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Westerhoff JM, Scheepens JCM, van Wolffelaar FF, Bernchou U, Bahij R, Erickson BA, Christodouleas JP, Ng SSW, Gani C, Choudhury A, Alongi F, Renz P, Colonias AT, Meijer GJ, Schytte T, Intven MPW, Verkooijen HM, Daamen LA, Hall WA. Quality of Life and Toxicity in Patients With Pancreatic Ductal Adenocarcinoma Treated With Online Adaptive Stereotactic Magnetic Resonance Guided Radiation Therapy. Int J Radiat Oncol Biol Phys 2025:S0360-3016(25)00307-4. [PMID: 40180057 DOI: 10.1016/j.ijrobp.2025.03.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 03/19/2025] [Accepted: 03/22/2025] [Indexed: 04/05/2025]
Abstract
PURPOSE Online adaptive magnetic resonance guided radiation therapy (MRgRT) using a hybrid magnetic resonance imaging and linear accelerator enables stereotactic ablative radiation doses to pancreatic tumors. We evaluated patient-reported quality of life (QoL) and clinician-reported toxicity in patients with pancreatic ductal adenocarcinoma after stereotactic MRgRT. METHOD Patients with nonmetastatic pancreatic ductal adenocarcinoma treated with stereotactic MRgRT on a 1.5-Tesla magnetic resonance imaging and linear accelerator according to local standard practices between May 2019 and December 2023 were identified using the international, prospective observational Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-Linac study (MOMENTUM, NCT04075305). Patient-reported QoL and clinician-reported toxicity were assessed using the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaires and National Cancer Institute Common Terminology Criteria for Adverse Events at baseline, 3, 6, and 12 months of follow-up. Patients with new systemic therapy or resection were censored. Patients with disease progression were additionally censored for a sensitivity analysis. Mean difference (MD) QoL scores from baseline were estimated using a linear mixed model, which were evaluated for clinical relevance (MD ≥ 10) and statistical significance (P ≤ .05). Acute (≤3 months follow-up) and late (3-12 months follow-up) toxicity was captured if grade ≥3. RESULTS A total of 127 patients were included from 8 centers. Treatment dose ranged from 30 to 50 Gy in 5 fractions. Functional QoL domains remained stable over time. A statistically significant and clinically relevant improvement was found for nausea and vomiting (MD -10; 95% CI, -17 to -3; P < .001), and in the sensitivity analysis for nausea and vomiting (MD -11; 95% CI -18 to -3; P < .001) and appetite (MD -14; 95% CI -28 to 0; P = .05), all at 6 months follow-up. No clinically relevant and statistically significant deterioration was found in other domains. New-onset acute and late grade 3 toxicity occurred in 2 patients and 1 patient, respectively. CONCLUSION Stereotactic MRgRT for patients with nonmetastatic pancreatic ductal adenocarcinoma was associated with stable functioning, improved disease-related symptoms, and minimal toxicity up to 12 months after treatment.
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Affiliation(s)
- Jasmijn M Westerhoff
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jacobien C M Scheepens
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Uffe Bernchou
- Department of Oncology, Odense University Hospital, Odense, Denmark; Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Denmark
| | - Rana Bahij
- Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Beth A Erickson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - John P Christodouleas
- Elekta AB, Stockholm, Sweden; Department of Radiation Oncology, Hospital of the University of Pennsylvania, Pennsylvania, Philadelphia
| | - Sylvia S W Ng
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, Ontario, Canada
| | - Cihan Gani
- Department of Radiation Oncology, University Hospital Tubingen, University of Tubingen, Tubingen, Germany
| | - Ananya Choudhury
- Department of Clinical Oncology, The University of Manchester and The Christie National Health Service Foundation Trust, Manchester, United Kingdom
| | - Filippo Alongi
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar-Verona, Italy; University of Brescia, Brescia, Italy
| | - Paul Renz
- Radiation Oncology, Allegheny Health Network, Pittsburgh, Pennsylvania
| | | | - Gert J Meijer
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Tine Schytte
- Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Martijn P W Intven
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Helena M Verkooijen
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Lois A Daamen
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
| | - William A Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
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Shimamaki Y, Takahashi M, Higashihara T, Hayashi T, Morita Y, Azuma T, Inoue D, Okada H, Ohtsuka M. Long-Term Survival after Curative Resection for Postoperative Dissemination of Pancreatic Ductal Adenocarcinoma: A Case Report. Surg Case Rep 2025; 11:24-0022. [PMID: 40196210 PMCID: PMC11975445 DOI: 10.70352/scrj.cr.24-0022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 03/16/2025] [Indexed: 04/09/2025] Open
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis and high mortality. The prognosis for recurrence after surgery is extremely poor. Resection for disseminations of PDAC is not recommended. CASE PRESENTATION The patient was a 69-year-old woman with a pancreatic tumor that was detected with computed tomography (CT) during a postoperative colon cancer checkup. She was suspected of having pancreatic body cancer without distant metastasis. Distal pancreatectomy with celiac axis resection was performed. Postoperative pathological examination revealed an invasive ductal adenocarcinoma with lymph node metastasis (pT4N1M0, stage III). Postoperatively, she received adjuvant chemotherapy containing gemcitabine and S-1 for 1 year and 4 months, and S-1 monotherapy for 1 year. Six years and 2 months after the initial surgery, her serum carbohydrate antigen 19-9 level elevated, and CT revealed soft tissue in front of the left kidney. Positron emission tomography/CT also revealed high fluorine-18 fluorodeoxyglucose uptake in the tissue. Accordingly, the patient was diagnosed with dissemination of PDAC. The patient was administered chemotherapy with gemcitabine and S-1. One year and 6 months after the diagnosis of dissemination, CT revealed reduction of the nodule. Therefore, we decided to eliminate this dissemination. A left nephrectomy and partial gastrectomy were performed. Histopathological examination confirmed dissemination of PDAC. The patient refused adjuvant chemotherapy. No evidence of recurrence has been observed for 13 years and 3 months since the initial surgery, and 5 years and 1 month since the resection of the dissemination. CONCLUSIONS This case showed a recurrence of dissemination after radical PDAC surgery, and the patient showed long-term survival without recurrence after dissemination resection. Resection of dissemination may confer long-term survival in selected patients.
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Affiliation(s)
- Yoshitaka Shimamaki
- Department of General Surgery, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Makoto Takahashi
- Department of General Surgery, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Taku Higashihara
- Department of General Surgery, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Tatsuya Hayashi
- Department of General Surgery, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Yasuhiro Morita
- Department of General Surgery, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Takeshi Azuma
- Division of Urology, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Dai Inoue
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
- Department of Clinical Genomics, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Haruka Okada
- Department of Pathology, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba, Japan
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Schorn S, Fritz A, Kaissis G, Gaida MM, Steiger K, Jäger C, Schlitter AM, Braren R, Friess H, Demir IE, Ceyhan GO. Neural invasion severity is a strong predictor of local recurrence in pancreatic ductal adenocarcinoma. Surgery 2025; 180:109018. [PMID: 39798180 DOI: 10.1016/j.surg.2024.109018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 10/20/2024] [Accepted: 11/26/2024] [Indexed: 01/15/2025]
Abstract
BACKGROUND In pancreatic ductal adenocarcinoma, neural invasion is being increasingly recognized as an unfavorable predictor of patient outcomes. Neural invasion severity seems to have a stronger clinical impact on patient prognosis than neural invasion status alone. Therefore, this study aims to assess the impact of severity of neural invasion on overall survival and disease-free survival in pancreatic ductal adenocarcinoma. MATERIALS To assess the impact of intrapancreatic neural invasion severity, tumor specimens resected from patients with pancreatic ductal adenocarcinoma between 2007 and 2014 were systematically re-evaluated, and neural invasion severity was determined using the standardized neural invasion severity score. RESULTS In our cohort (n = 216), an increased neural invasion severity score was associated with markedly shorter overall survival in pancreatic head ductal adenocarcinoma (neural invasion severity score low: 22.8 months vs neural invasion severity score high: 17.6 months: P = .001). An external European validation cohort confirmed these results and showed significantly better survival of patients with lower neural invasion (20.5 vs 15.4 months, P = .026). The disease-free survival time was also substantially decreased in patients with pancreatic head pancreatic ductal adenocarcinoma and increased neural invasion severity (neural invasion severity score low: 19.1 months vs neural invasion severity score high: 10.4 months; P = .004). Moreover, the neural invasion severity score was an important independent factor influencing overall survival (hazards ratio 1.024, P = .04) and disease-free survival (hazards ratio 1.03, P = .01) using an adjusted Cox proportional hazards model. Importantly, higher neural invasion severity score leads to significantly more and earlier local recurrence than to distant tumor recurrence. CONCLUSION Neural invasion severity is a powerful independent factor influencing overall survival and local recurrence in patients with pancreatic ductal adenocarcinoma. Therefore, individuals with high neural invasion severity score values should be regarded as a specific subgroup of pancreatic ductal adenocarcinoma patients and may benefit from more tailored postoperative oncologic therapy.
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Affiliation(s)
- Stephan Schorn
- Department of Surgery, School of Medicine and Health, Technical University Munich, TUM University Hospital, Klinikum rechts der Isar, Munich, Germany
| | - Anouk Fritz
- Department of Surgery, School of Medicine and Health, Technical University Munich, TUM University Hospital, Klinikum rechts der Isar, Munich, Germany
| | - Georgios Kaissis
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Department of Computing, Imperial College London, London, United Kingdom
| | - Matthias M Gaida
- Institute of Pathology, JGU-Mainz, University Medical Center Mainz, Mainz, Germany; TRON, Translational Oncology at the University Medical Center, Mainz, Germany; Collaborative Research Center 1292, Mainz, Germany
| | - Katja Steiger
- Institute of Pathology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Carsten Jäger
- Department of Surgery, School of Medicine and Health, Technical University Munich, TUM University Hospital, Klinikum rechts der Isar, Munich, Germany
| | - Anna Melissa Schlitter
- Institute of Pathology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Rickmer Braren
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Helmut Friess
- Department of Surgery, School of Medicine and Health, Technical University Munich, TUM University Hospital, Klinikum rechts der Isar, Munich, Germany.
| | - Ihsan Ekin Demir
- Department of Surgery, School of Medicine and Health, Technical University Munich, TUM University Hospital, Klinikum rechts der Isar, Munich, Germany; Department of General Surgery, HPB-Unit, School of Medicine, Acibadem Mehmet Ali Aydınlar University, Istanbul, Turkey; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany; CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany; Else Kröner Clinician Scientist Professor for Translational Pancreatic Surgery, Munich, Germany. https://twitter.com/PancNeuropathy
| | - Güralp Onur Ceyhan
- Department of Surgery, School of Medicine and Health, Technical University Munich, TUM University Hospital, Klinikum rechts der Isar, Munich, Germany; Institute of Pathology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
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Zhao P, Jiang Q, Xue K, Liu X, Tian B. The role of pulmonary metastasectomy in patients suffering pancreatic ductal adenocarcinoma with lung metastases: a systematic review and meta-analysis. Front Surg 2025; 12:1535212. [PMID: 40084343 PMCID: PMC11903735 DOI: 10.3389/fsurg.2025.1535212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 02/12/2025] [Indexed: 03/16/2025] Open
Abstract
Background Because of the high rate of recurrence, the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is still very poor despite underwent pancreatectomy and adjuvant chemotherapy. A few reports have suggested the feasibility and efficacy of surgical resection for pulmonary metastases of PDAC. However, the role of metastasectomy of recurrent PDAC remains controversial. The aim of this study is to evaluate the benefits of pulmonary metastasectomy in PDAC patients with lung metastases. Methods We searched the PubMed, Embase, and Cochrane Library databases and extracted the hazard ratio (HR) with 95% confidence interval (CI) from eligible studies. Pooled HR with 95% CI were used to reveal the association between pulmonary metastasectomy and survival. Results The meta-analysis encompassed data from nine studies, comprising 467 patients suffered PDAC with lung metastasis. The results (the pooled HR: 0.637, 95% CI: 0.531-0.764, I 2 = 61.5%, p value = 0.008) indicated that patients with lung metastasis who underwent pulmonary metastasectomy seemed to have better survival when compared with patients who underwent only chemotherapy. The robustness of these pooled results was verified by our subgroup analysis and sensitivity analysis. Moreover, the varying sample sizes among studies contribute to the heterogeneity in the pooled hazard ratio (HR) for survival, as indicated by the meta-regression analysis (p value = 0.045). Conclusion Pulmonary metastasectomy could prolong the survival in patients with lung metastases from PDAC. However, the present study is based on a relatively small number of patients and may include a selection bias. More multi-institutional prospective study is needed to evaluated the clinical value of pulmonary metastasectomy.
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Affiliation(s)
- Pengcheng Zhao
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Pediatric Surgery, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qiaoqi Jiang
- Department of Anesthesiology, West China Xiamen Hospital, Sichuan University, Xiamen, Fujian, China
| | - Kang Xue
- Department of General Surgery, Division of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaofeng Liu
- Department of General Surgery, Division of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bole Tian
- Department of General Surgery, Division of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Hayat U, Croce PS, Saadeh A, Desai K, Appiah J, Khan S, Khan YI, Kumar K, Hanif A. Current and Emerging Treatment Options for Pancreatic Cancer: A Comprehensive Review. J Clin Med 2025; 14:1129. [PMID: 40004658 PMCID: PMC11856716 DOI: 10.3390/jcm14041129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of death worldwide, and its global burden has increased significantly over the past few years. The incidence of pancreatic cancer has also increased in the United States, and most of this increase is attributed to the population's aging process in addition to the rise in the prevalence of risk factors such as obesity, diabetes, smoking, and alcohol intake. Most patients with pancreatic cancer present with advanced unresectable or metastatic disease. Only a few patients present at an early stage with localized disease, and a multidisciplinary approach is required to maximize survival and outcomes. The surgical approach is an option for localized disease, and surgery's safety and efficacy have also been improved in recent years due to the increasing use of minimally invasive surgical techniques. Moreover, systematic chemotherapy has also been used and has had a significant impact on survival. More recently, neoadjuvant therapy has been used for pancreatic cancer along with radiation therapy, optimizing survival among those patients. Targeted therapies have been introduced based on genetic testing in metastatic pancreatic cancer and have shown promising results. Moreover, immune checkpoint inhibitors and targeted agents such as PARP inhibitors and vaccines have emerged with optimal results in terms of survival. To conclude, pancreatic cancer is considered a disease with poor long-term survival; however, recent developments in pharmacotherapy have changed its treatment and have improved outcomes with improved survival. Our review summarizes ongoing therapeutic options for local and metastatic pancreatic cancer. It also summarizes new state-of-the-art therapies that have emerged or are in trials, which can change the pancreatic cancer treatment perspective.
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Affiliation(s)
- Umar Hayat
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Phillip S. Croce
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Aseel Saadeh
- Department of Internal Medicine, Geisinger Medical Center, Danville, PA 18711, USA;
| | - Karna Desai
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - John Appiah
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Sidrah Khan
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (P.S.C.); (K.D.); (J.A.); (S.K.)
| | - Yakub I. Khan
- Department of Internal Medicine, Division of Gastroenterology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (Y.I.K.); (K.K.)
| | - Kishore Kumar
- Department of Internal Medicine, Division of Gastroenterology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA; (Y.I.K.); (K.K.)
| | - Ahmad Hanif
- Department of Internal Medicine, Division of Hematology/Oncology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, USA;
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Yao L, Qin W, Hu L, Shi T, Yu Yang J, Li Q, Nie H, Li J, Wang X, Zhu L, Liu D, Zhang Y, Jiang S, Zhang Z, Yang X, Li D, Zhang X. Reciprocal tumor-platelet interaction through the EPHB1-EFNB1 axis in the liver metastatic niche promotes metastatic tumor outgrowth in pancreatic ductal adenocarcinoma. Cancer Commun (Lond) 2025; 45:143-166. [PMID: 39648610 PMCID: PMC11833672 DOI: 10.1002/cac2.12637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 11/08/2024] [Accepted: 11/27/2024] [Indexed: 12/10/2024] Open
Abstract
BACKGROUND The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation. Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver. However, the role of platelet in the liver metastatic niche of PDAC remains elusive. This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC. METHODS An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC. Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis. Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1 (Ephb1), tumor cell-platelet adhesion, recombinant protein, and tryptophan hydroxylase 1 (Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche. RESULTS The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients. Platelet depletion decreased liver metastatic tumor growth in mice. Mechanistically, tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1 (EFNB1) mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation, and in turn, activated platelet-released 5-HT, further enhancing tumor growth. CONCLUSION We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC. Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver. Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.
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Affiliation(s)
- Lin‐Li Yao
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Wei‐Ting Qin
- Department of Radiation OncologyRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Li‐Peng Hu
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Tie‐Zhu Shi
- Department of UrologyShanghai General HospitalShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Jian Yu Yang
- Department of Biliary‐Pancreatic SurgeryRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Qing Li
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Hui‐Zhen Nie
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Jun Li
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Xu Wang
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Lei Zhu
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - De‐Jun Liu
- Department of Biliary‐Pancreatic SurgeryRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Yan‐Li Zhang
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Shu‐Heng Jiang
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Zhi‐Gang Zhang
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Xiao‐Mei Yang
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Dong‐Xue Li
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Xue‐Li Zhang
- State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiP. R. China
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Sakamoto T, Kishino M, Murakami Y, Miyatani K, Hanaki T, Shishido Y, Kihara K, Matsunaga T, Yamamoto M, Tokuyasu N, Fujiwara Y. The cachexia index is a prognostic factor for patients with recurrent pancreatic cancer. Surg Today 2024; 54:1498-1504. [PMID: 38822841 DOI: 10.1007/s00595-024-02877-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 05/03/2024] [Indexed: 06/03/2024]
Abstract
PURPOSE Cancer cachexia leads to poor outcomes, especially for patients with advanced stage disease. The cachexia index (CXI), a novel biomarker for cancer cachexia, has been identified as a prognostic indicator for several malignancies. The present study aimed to clarify the prognostic significance of the CXI for patients with recurrent pancreatic cancer. METHODS This retrospective study enrolled 113 patients diagnosed with recurrence following pancreatectomy for pancreatic cancer, to analyze the association between the CXI and prognostic survival. RESULTS The 2-year overall survival rate and median survival of all patients were 28.5% and 12.6 months, respectively. The 2-year overall survival curve in the high CXI group was significantly better than that in the low CXI group (p < 0.001). The rate of chemotherapy after recurrence was significantly lower in the low CXI group than in the high CXI group (p = 0.002). Multivariate analysis identified the CXI as an independent prognostic factor for patients with recurrent pancreatic cancer (p = 0.011). CONCLUSIONS The CXI proved useful for predicting the post-recurrence prognosis of patients with recurrent pancreatic cancer. Patients with a low CXI at the time of recurrence have poorer prognostic outcomes than those with a high CXI.
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Affiliation(s)
- Teruhisa Sakamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan.
| | - Mikiya Kishino
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Yuki Murakami
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Kozo Miyatani
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Takehiko Hanaki
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Yuji Shishido
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Kyoichi Kihara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Tomoyuki Matsunaga
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Manabu Yamamoto
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Naruo Tokuyasu
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
| | - Yoshiyuki Fujiwara
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, Faculty of Medicine, Tottori University, 36-1 Nichi-Cho, Yonago, 683-8504, Japan
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Suto H, Nagao M, Matsukawa H, Fuke T, Ando Y, Oshima M, Takahashi S, Shibata T, Kamada H, Kobara H, Okuyama H, Hirao T, Kumamoto K, Okano K. Relationships between postoperative recurrences and standardized uptake value on 18F-fluorodeoxyglucose-positron emission tomography in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma who underwent curative pancreatic resection after neoadjuvant chemoradiotherapy. Pancreatology 2024; 24:1133-1140. [PMID: 39160121 DOI: 10.1016/j.pan.2024.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 08/07/2024] [Accepted: 08/12/2024] [Indexed: 08/21/2024]
Abstract
BACKGROUND This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHOD The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed. RESULTS After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis. CONCLUSION R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.
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Affiliation(s)
- Hironobu Suto
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
| | - Mina Nagao
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hiroyuki Matsukawa
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Takuro Fuke
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Yasuhisa Ando
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Minoru Oshima
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Shigeo Takahashi
- Department of Radiation Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Toru Shibata
- Department of Radiation Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hideki Kamada
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Hiroyuki Okuyama
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Tomohiro Hirao
- Department of Public Health, Kagawa University, Kagawa, Japan
| | - Kensuke Kumamoto
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
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Zheng Z, Li M, Yang J, Zhou X, Chen Y, Silli EK, Tang J, Gong S, Yuan Y, Zong Y, Kong J, Chen P, Yu L, Luo S, Wang Y, Tan C. Growth inhibition of pancreatic cancer by targeted delivery of gemcitabine via fucoidan-coated pH-sensitive liposomes. Int J Biol Macromol 2024; 277:134517. [PMID: 39111497 DOI: 10.1016/j.ijbiomac.2024.134517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 08/02/2024] [Accepted: 08/03/2024] [Indexed: 08/10/2024]
Abstract
Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.
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Affiliation(s)
- Zhenjiang Zheng
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Mengfei Li
- School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Jianchen Yang
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
| | - Xintao Zhou
- School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Yonghua Chen
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Epiphane K Silli
- School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Jiali Tang
- School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Songlin Gong
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yuan Yuan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yihao Zong
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Jianping Kong
- School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Pu Chen
- School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Lingxi Yu
- School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Shujun Luo
- School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
| | - Ying Wang
- School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
| | - Chunlu Tan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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10
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Dee EC, Ng VC, O’Reilly EM, Wei AC, Lobaugh SM, Varghese AM, Zinovoy M, Romesser PB, Wu AJ, Hajj C, Cuaron JJ, Khalil DN, Park W, Yu KH, Zhang Z, Drebin JA, Jarnagin WR, Crane CH, Reyngold M. Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery. J Clin Med 2024; 13:2631. [PMID: 38731159 PMCID: PMC11084663 DOI: 10.3390/jcm13092631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Marsha Reyngold
- Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (E.C.D.); (V.C.N.); (C.H.C.)
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11
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López JC, Ielpo B, Iglesias M, Pinilla FB, Sánchez-Velázquez P. The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma. Langenbecks Arch Surg 2024; 409:122. [PMID: 38607450 PMCID: PMC11009726 DOI: 10.1007/s00423-024-03301-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 03/26/2024] [Indexed: 04/13/2024]
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival. METHODS Eighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan-Meier method and prognostic factors assessed using Cox regression hazards model. RESULTS LR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031). CONCLUSIONS Arterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.
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Affiliation(s)
| | - Benedetto Ielpo
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain
| | - Mar Iglesias
- Pompeu-Fabra University, Barcelona, Spain
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain
- Department of Pathology, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu-Fabra, Barcelona, Spain
| | - Fernando Burdío Pinilla
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain
| | - Patricia Sánchez-Velázquez
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain.
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12
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Shouman MA, Fuchs F, Walter F, Corradini S, Westphalen CB, Vornhülz M, Beyer G, Andrade D, Belka C, Niyazi M, Rogowski P. Stereotactic body radiotherapy for pancreatic cancer - A systematic review of prospective data. Clin Transl Radiat Oncol 2024; 45:100738. [PMID: 38370495 PMCID: PMC10873666 DOI: 10.1016/j.ctro.2024.100738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 01/05/2024] [Accepted: 01/26/2024] [Indexed: 02/20/2024] Open
Abstract
Purpose This systematic review aims to comprehensively summarize the current prospective evidence regarding Stereotactic Body Radiotherapy (SBRT) in various clinical contexts for pancreatic cancer including its use as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC), induction therapy for locally advanced pancreatic cancer (LAPC), salvage therapy for isolated local recurrence (ILR), adjuvant therapy after radical resection, and as a palliative treatment. Special attention is given to the application of magnetic resonance-guided radiotherapy (MRgRT). Methods Following PRISMA guidelines, a systematic review of the Medline database via PubMed was conducted focusing on prospective studies published within the past decade. Data were extracted concerning study characteristics, outcome measures, toxicity profiles, SBRT dosage and fractionation regimens, as well as additional systemic therapies. Results and conclusion 31 studies with in total 1,571 patients were included in this review encompassing 14 studies for LAPC, 9 for neoadjuvant treatment, 2 for adjuvant treatment, 2 for ILR, with an additional 4 studies evaluating MRgRT. In LAPC, SBRT demonstrates encouraging results, characterized by favorable local control rates. Several studies even report conversion to resectable disease with substantial resection rates reaching 39%. The adoption of MRgRT may provide a solution to the challenge to deliver ablative doses while minimizing severe toxicities. In BRPC, select prospective studies combining preoperative ablative-dose SBRT with modern induction systemic therapies have achieved remarkable resection rates of up to 80%. MRgRT also holds potential in this context. Adjuvant SBRT does not appear to confer relevant advantages over chemotherapy. While prospective data for SBRT in ILR and for palliative pain relief are limited, they corroborate positive findings from retrospective studies.
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Affiliation(s)
- Mohamed A Shouman
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Frederik Fuchs
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
| | - Franziska Walter
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
| | - Stefanie Corradini
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
| | - C Benedikt Westphalen
- Department of Medicine III and Comprehensive Cancer Center (CCC Munich LMU), University Hospital LMU, Munich, Germany
| | - Marlies Vornhülz
- Bavarian Cancer Research Center (BZKF), Munich, Germany
- Department of Internal Medicine II, LMU University Hospital, Munich, Germany
| | - Georg Beyer
- Bavarian Cancer Research Center (BZKF), Munich, Germany
- Department of Internal Medicine II, LMU University Hospital, Munich, Germany
| | - Dorian Andrade
- Department of General, Visceral, and Transplant Surgery, University Hospital LMU, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
| | - Maximilian Niyazi
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
- Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany
- German Cancer Consortium (DKTK), Partner Site Tübingen, Germany
| | - Paul Rogowski
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
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13
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Philipp LM, Yesilyurt UU, Surrow A, Künstner A, Mehdorn AS, Hauser C, Gundlach JP, Will O, Hoffmann P, Stahmer L, Franzenburg S, Knaack H, Schumacher U, Busch H, Sebens S. Epithelial and Mesenchymal-like Pancreatic Cancer Cells Exhibit Different Stem Cell Phenotypes Associated with Different Metastatic Propensities. Cancers (Basel) 2024; 16:686. [PMID: 38398077 PMCID: PMC10886860 DOI: 10.3390/cancers16040686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages, limiting the prognoses of patients. Metastasis requires high tumor cell plasticity, implying phenotypic switching in response to changing environments. Here, epithelial-mesenchymal transition (EMT), being associated with an increase in cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC phenotypes exist along the EMT axis and how these impact malignancy-associated properties, we aimed to characterize CSC populations of epithelial and mesenchymal-like PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. The Panc1 Holoclone cells showed a mesenchymal-like phenotype, dominated by a high expression of the stemness marker Nestin, while the Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. The Panc89 Holoclone cells showed enhanced cell growth and a self-renewal capacity but slow cluster-like invasion. Contrarily, the Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, the Panc1 and Panc89 cell variants significantly differed regarding the number and size of metastases, as well as organ manifestation, leading to different survival outcomes. Overall, these data support the existence of different CSC phenotypes along the EMT axis in PDAC, manifesting different metastatic propensities.
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Affiliation(s)
- Lisa-Marie Philipp
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
| | - Umut-Ulas Yesilyurt
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
| | - Arne Surrow
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
| | - Axel Künstner
- Medical Systems Biology Group, Lübeck Institute of Experimental Dermatology, University of Lübeck, 23538 Lübeck, Germany
- Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany
| | - Anne-Sophie Mehdorn
- Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, UKSH, Campus Kiel, 24105 Kiel, Germany
| | - Charlotte Hauser
- Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, UKSH, Campus Kiel, 24105 Kiel, Germany
| | - Jan-Paul Gundlach
- Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, UKSH, Campus Kiel, 24105 Kiel, Germany
| | - Olga Will
- Molecular Imaging North Competence Center, Clinic of Radiology and Neuroradiology, Kiel University, UKSH, Campus Kiel, 24118 Kiel, Germany
| | - Patrick Hoffmann
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
| | - Lea Stahmer
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
| | - Sören Franzenburg
- Institute of Clinical Molecular Biology, Kiel University, 24118 Kiel, Germany
| | - Hendrike Knaack
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
- Academic Affairs Office, Hannover Medical School, 30625 Hannover, Germany
| | - Udo Schumacher
- Department of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Hauke Busch
- Medical Systems Biology Group, Lübeck Institute of Experimental Dermatology, University of Lübeck, 23538 Lübeck, Germany
- Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany
| | - Susanne Sebens
- Institute for Experimental Cancer Research, Kiel University, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, 23562 Kiel, Germany
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14
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Zhang HW, Huang DL, Wang YR, Zhong HS, Pang HW. CT radiomics based on different machine learning models for classifying gross tumor volume and normal liver tissue in hepatocellular carcinoma. Cancer Imaging 2024; 24:20. [PMID: 38279133 PMCID: PMC10811872 DOI: 10.1186/s40644-024-00652-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/29/2023] [Indexed: 01/28/2024] Open
Abstract
BACKGROUND & AIMS The present study utilized extracted computed tomography radiomics features to classify the gross tumor volume and normal liver tissue in hepatocellular carcinoma by mainstream machine learning methods, aiming to establish an automatic classification model. METHODS We recruited 104 pathologically confirmed hepatocellular carcinoma patients for this study. GTV and normal liver tissue samples were manually segmented into regions of interest and randomly divided into five-fold cross-validation groups. Dimensionality reduction using LASSO regression. Radiomics models were constructed via logistic regression, support vector machine (SVM), random forest, Xgboost, and Adaboost algorithms. The diagnostic efficacy, discrimination, and calibration of algorithms were verified using area under the receiver operating characteristic curve (AUC) analyses and calibration plot comparison. RESULTS Seven screened radiomics features excelled at distinguishing the gross tumor area. The Xgboost machine learning algorithm had the best discrimination and comprehensive diagnostic performance with an AUC of 0.9975 [95% confidence interval (CI): 0.9973-0.9978] and mean MCC of 0.9369. SVM had the second best discrimination and diagnostic performance with an AUC of 0.9846 (95% CI: 0.9835- 0.9857), mean Matthews correlation coefficient (MCC)of 0.9105, and a better calibration. All other algorithms showed an excellent ability to distinguish between gross tumor area and normal liver tissue (mean AUC 0.9825, 0.9861,0.9727,0.9644 for Adaboost, random forest, logistic regression, naivem Bayes algorithm respectively). CONCLUSION CT radiomics based on machine learning algorithms can accurately classify GTV and normal liver tissue, while the Xgboost and SVM algorithms served as the best complementary algorithms.
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Affiliation(s)
- Huai-Wen Zhang
- Department of Radiotherapy, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, 330029, Nanchang, China
- Department of Oncology, The third people's hospital of Jingdezhen, The third people's hospital of Jingdezhen affiliated to Nanchang Medical College, 333000, Jingdezhen, China
| | - De-Long Huang
- School of Clinical Medicine, Southwest Medical University, 646000, Luzhou, China
| | - Yi-Ren Wang
- School of Nursing, Southwest Medical University, 646000, Luzhou, China
| | - Hao-Shu Zhong
- Department of Hematology, Huashan Hospital, Fudan University, 200040, Shanghai, China.
| | - Hao-Wen Pang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, 646000, Luzhou, China.
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15
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Kolbeinsson HM, Chandana S, Wright GP, Chung M. Pancreatic Cancer: A Review of Current Treatment and Novel Therapies. J INVEST SURG 2023; 36:2129884. [PMID: 36191926 DOI: 10.1080/08941939.2022.2129884] [Citation(s) in RCA: 169] [Impact Index Per Article: 84.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Pancreatic cancer is one of the leading causes for cancer-related deaths in the United States. Majority of patients present with unresectable or metastatic disease. For those that present with localized disease, a multidisciplinary approach is necessary to maximize survival and optimize outcomes. The quality and safety of surgery for pancreatic cancer have improved in recent years with increasing adoption of minimally invasive techniques and surgical adjuncts. Systemic chemotherapy has also evolved to impact survival. It is now increasingly being utilized in the neoadjuvant setting, often with concomitant radiation. Increased utilization of genomic testing in metastatic pancreatic cancer has led to better understanding of their biology, thereby allowing clinicians to consider potential targeted therapies. Similarly, targeted agents such as PARP inhibitors and immune checkpoint- inhibitors have emerged with promising results. In summary, pancreatic cancer remains a disease with poor long-term survival. However, recent developments have led to improved outcomes and have changed practice in the past decade. This review summarizes current practices in pancreatic cancer treatment and the milestones that brought us to where we are today, along with emerging therapies.
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Affiliation(s)
- Hordur Mar Kolbeinsson
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA
| | - Sreenivasa Chandana
- Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.,Cancer and Hematology Centers of Western Michigan, PC, Grand Rapids, Michigan, USA
| | - G Paul Wright
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
| | - Mathew Chung
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
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16
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Kayashima H, Itoh S, Shimokawa M, Hayashi H, Takamori H, Fukuzawa K, Ninomiya M, Araki K, Yamashita YI, Sugimachi K, Uchiyama H, Morine Y, Utsunomiya T, Uwagawa T, Maeda T, Baba H, Yoshizumi T. Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial. Int J Clin Oncol 2023; 28:1520-1529. [PMID: 37552354 DOI: 10.1007/s10147-023-02399-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 07/29/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.
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Affiliation(s)
- Hiroto Kayashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan.
| | - Mototsugu Shimokawa
- Department of Biostatistics, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8511, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hiroshi Takamori
- Department of Surgery, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Kumamoto, 861-4193, Japan
| | - Kengo Fukuzawa
- Department of Surgery, Oita Red Cross Hospital, 3-2-37 Chiyo-machi, Oita, 870-0033, Japan
| | - Mizuki Ninomiya
- Department of Surgery, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Kenichiro Araki
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, 4-2 Aramaki-machi, Maebashi, Gunma, 371-8510, Japan
| | - Yo-Ichi Yamashita
- Department of Surgery, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Keishi Sugimachi
- Department of Hepatobiliary-Pancreatic Surgery, Kyushu Cancer Center, 3-1-1 Notame, Fukuoka, 811-1395, Japan
| | - Hideaki Uchiyama
- Department of Surgery, Saiseikai Fukuoka General Hospital, 1-3-46 Tenjin, Fukuoka, 810-0001, Japan
| | - Yuji Morine
- Department of Surgery, Tokushima University, 2-24 Shinkuracho, Tokushima, 770-0855, Japan
| | - Tohru Utsunomiya
- Department of Surgery, Oita Prefectural Hospital, 2-8-1 Bunyo, Oita, 870-8511, Japan
| | - Tadashi Uwagawa
- Department of Hepato-Biliary-Pancreatic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takashi Maeda
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, 1-9-6 Senda-machi, Hiroshima, 730-8619, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan
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Pedrazzoli S. Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor. J Clin Med 2023; 12:6461. [PMID: 37892599 PMCID: PMC10607532 DOI: 10.3390/jcm12206461] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks to advances in chemo/radiotherapy and the reduction in operative mortality. METHODS This narrative review presents a chosen literature selection, giving a picture of the current state of treatment of these patients. RESULTS Neoadjuvant therapy (NAT) is generally recognized as the treatment of choice before surgery. However, despite the increased efficacy, the best pathological response is still limited to 10.9-27.9% of patients. There are still limited data on the selection of possible NAT responders and how to diagnose non-responders early. Multidetector computed tomography has high sensitivity and low specificity in evaluating resectability after NAT, limiting the resection rate of resectable patients. Ca 19-9 and Positron emission tomography are giving promising results. The prediction of early recurrence after a radical resection of synchronous or metachronous metastatic PDAC, thus identifying patients with poor prognosis and saving them from a resection of little benefit, is still ongoing, although some promising data are available. CONCLUSION In conclusion, high-level evidence demonstrating the benefit of the surgical treatment of such patients is still lacking and should not be performed outside of high-volume centers with interdisciplinary teams of surgeons and oncologists.
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18
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van Oosten AF, Daamen LA, Groot VP, Biesma NC, Habib JR, van Goor IWJM, Kinny-Köster B, Burkhart RA, Wolfgang CL, van Santvoort HC, He J, Molenaar IQ. Predicting post-recurrence survival for patients with pancreatic cancer recurrence after primary resection: A Bi-institutional validated risk classification. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106910. [PMID: 37173152 DOI: 10.1016/j.ejso.2023.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 03/07/2023] [Accepted: 04/19/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND Over 80% of patients will develop disease recurrence after radical resection of pancreatic ductal adenocarcinoma (PDAC). This study aims to develop and validate a clinical risk score predicting post-recurrence survival (PRS) at time of recurrence. METHODS All patients who had recurrence after undergoing pancreatectomy for PDAC at the Johns Hopkins Hospital or at the Regional Academic Cancer Center Utrecht during the study period were included. Cox proportional hazard model was used to develop the risk model. Performance of the final model was assessed in a test set after internal validation. RESULTS Of 718 resected PDAC patients, 72% had recurrence after a median follow-up of 32 months. The median overall survival was 21 months and the median PRS was 9 months. Prognostic factors associated with shorter PRS were age (hazard ratio [HR] 1.02; 95% confidence interval [95%CI] 1.00-1.04), multiple-site recurrence (HR 1.57; 95%CI 1.08-2.28), and symptoms at time of recurrence (HR 2.33; 95%CI 1.59-3.41). Recurrence-free survival longer than 12 months (HR 0.55; 95%CI 0.36-0.83), FOLFIRINOX and gemcitabine-based adjuvant chemotherapy (HR 0.45; 95%CI 0.25-0.81; HR 0.58; 95%CI 0.26-0.93, respectively) were associated with a longer PRS. The resulting risk score had a good predictive accuracy (C-index: 0.73). CONCLUSION This study developed a clinical risk score based on an international cohort that predicts PRS in patients who underwent surgical resection for PDAC. This risk score will become available on www.evidencio.com and can help clinicians with patient counseling on prognosis.
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Affiliation(s)
- A Floortje van Oosten
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lois A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands; Division of Imaging and Oncology, University Medical Center Utrecht Cancer Center, Utrecht University, Utrecht, the Netherlands
| | - Vincent P Groot
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands
| | - Nanske C Biesma
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands
| | - Joseph R Habib
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Iris W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands
| | - Benedict Kinny-Köster
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery, New York University Langone Medical Center, New York City, NY, USA
| | - Richard A Burkhart
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christopher L Wolfgang
- Department of Surgery, New York University Langone Medical Center, New York City, NY, USA
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands
| | - Jin He
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, the Netherlands.
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19
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Hirai K, Takeshima J, Ichikawa J, Okabe A, Ohe H, Mitsuyoshi A. Advanced pancreatic cancer with long-term recurrence-free survival after radical pancreatic resection and subsequent resection of lung metastases twice: A case report. Int J Surg Case Rep 2023; 110:108724. [PMID: 37660495 PMCID: PMC10509926 DOI: 10.1016/j.ijscr.2023.108724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/20/2023] [Accepted: 08/21/2023] [Indexed: 09/05/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Reports on lung resection for recurrence with lung metastases after the surgical treatment of pancreatic cancer have been sporadic, and limited information is currently available on the long-term postoperative course. Furthermore, the significance of the surgical resection of recurrent/metastatic lesions after the resection of pancreatic cancer has not been sufficiently established. We herein present a long-term recurrence-free survivor after perioperative chemotherapy and pancreatic resection for primary pancreatic body cancer who underwent resection for isolated lung metastases twice. CASE PRESENTATION A 66-year-old woman with locally advanced pancreatic cancer accompanied by invasion of the splenic artery underwent distal pancreatectomy with celiac axis resection following preoperative S1 + gemcitabine therapy. Recurrence with lung metastasis was detected 42 and 62 months after resection of the primary lesion, and lung resection was performed both times. As postoperative adjuvant therapies, S1 + gemcitabine therapy was performed after lung resection. The patient has survived free of recurrence for 11 years after resection of the primary lesion and 5 years and 9 months after the second lung resection. CLINICAL DISCUSSION A long interval from resection of the primary lesion to the occurrence of lung metastases and the high responsiveness of the patient to chemotherapy may have contributed to her long-term survival. CONCLUSION This case suggests that if lung metastasis occurring after radical resection of the primary lesion is resected without remnants, aggressive multidisciplinary treatment, including surgical resection with the appropriate selection of cases, may contribute to improvements in patient outcomes.
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Affiliation(s)
- Kenjiro Hirai
- Department of Surgery, Japanese Red Cross Otsu Hospital, 1-1-35 Nagara, Otsu City, Siga 520-8511, Japan; Department of Surgery, Otsu City Hospital, 2-9-9 Motomiya, Otsu city, Shiga 520-0804, Japan.
| | - Jun Takeshima
- Department of Surgery, Otsu City Hospital, 2-9-9 Motomiya, Otsu city, Shiga 520-0804, Japan
| | - Jun Ichikawa
- Department of Surgery, Otsu City Hospital, 2-9-9 Motomiya, Otsu city, Shiga 520-0804, Japan
| | - Asami Okabe
- Department of Surgery, Otsu City Hospital, 2-9-9 Motomiya, Otsu city, Shiga 520-0804, Japan
| | - Hidenori Ohe
- Department of Surgery, Otsu City Hospital, 2-9-9 Motomiya, Otsu city, Shiga 520-0804, Japan
| | - Akira Mitsuyoshi
- Department of Surgery, Otsu City Hospital, 2-9-9 Motomiya, Otsu city, Shiga 520-0804, Japan
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20
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Shibata Y, Uemura K, Sumiyoshi T, Okada K, Otsuka H, Serikawa M, Ishii Y, Murakami Y, Arihiro K, Takahashi S. Surgical resection for liver recurrence after curative resection of pancreatic ductal adenocarcinoma. Langenbecks Arch Surg 2023; 408:280. [PMID: 37458812 DOI: 10.1007/s00423-023-03009-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 07/02/2023] [Indexed: 07/20/2023]
Abstract
PURPOSE This study aimed to evaluate the clinical significance of surgical resection for liver recurrence in patients with curatively resected pancreatic ductal adenocarcinoma. METHODS The medical records of patients with a liver recurrence after undergoing curative pancreatectomy for pancreatic ductal adenocarcinoma were retrospectively reviewed. Clinicopathological and prognostic factors were analyzed, as was the clinical impact of surgical resection for liver recurrence. RESULTS Overall, 502 patients underwent curative pancreatic ductal adenocarcinoma resection. Of the 311 patients with recurrence after curative pancreatectomy, 71 (23%) had an initial recurrence in the liver, with 35 having solitary recurrence (11%). Patients with solitary, two or three, or more than four recurrences had median overall survival times of 28.5, 18.0, and 12.2 months, respectively (p < 0.001). Surgical indications for liver recurrence in our institution included solitary tumor, good disease control under chemotherapy after recurrence for > 6 months, and sufficient remnant liver function. Ten patients who met our institutional policy inclusion criteria underwent liver resection. Among 35 patients with initially solitary liver recurrence, those who underwent liver resection outlived those who did not (57.6 months vs. 20.1 months, p < 0.001). In multivariate analysis of overall survival, solitary liver recurrence and liver resection were independent favorable prognostic factors in patients with initial liver recurrence. CONCLUSION In selected patients with solitary liver recurrence after curatively resected pancreatic ductal adenocarcinoma, liver resection may be a treatment option.
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Affiliation(s)
- Yoshiyuki Shibata
- Department of Surgery, Graduate School of Biochemical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biochemical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan.
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biochemical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biochemical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biochemical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Digestive Disease Center, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University, Hiroshima, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biochemical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
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21
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Xia T, Xu P, Mou Y, Zhang X, Song S, Zhou Y, Lu C, Zhu Q, Xu Y, Jin W, Wang Y. Factors predicting recurrence after left‑sided pancreatectomy for pancreatic ductal adenocarcinoma. World J Surg Oncol 2023; 21:191. [PMID: 37349737 DOI: 10.1186/s12957-023-03080-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 06/17/2023] [Indexed: 06/24/2023] Open
Abstract
BACKGROUND Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately. METHODS Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified. RESULTS One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019). CONCLUSIONS Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.
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Affiliation(s)
- Tao Xia
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Peng Xu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Surgery, Qingdao University, Qingdao, China
| | - Yiping Mou
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
- Department of Surgery, Qingdao University, Qingdao, China.
- Department of Surgery, Wenzhou Medical University, Wenzhou, China.
| | - Xizhou Zhang
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Shihao Song
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Surgery, Wenzhou Medical University, Wenzhou, China
| | - Yucheng Zhou
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Chao Lu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Qicong Zhu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Yunyun Xu
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Weiwei Jin
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Yuanyu Wang
- Department of General Surgery, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
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22
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van Goor IWJM, Daamen LA, Besselink MG, Bruynzeel AME, Busch OR, Cirkel GA, Groot Koerkamp B, Haj Mohammed N, Heerkens HD, van Laarhoven HWM, Meijer GJ, Nuyttens J, van Santvoort HC, van Tienhoven G, Verkooijen HM, Wilmink JW, Molenaar IQ, Intven MPW. A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE). Trials 2022; 23:913. [PMID: 36307892 PMCID: PMC9617359 DOI: 10.1186/s13063-022-06829-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/06/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Disease recurrence is the main cause of mortality after resection of pancreatic ductal adenocarcinoma (PDAC). In 20-30% of resected patients, isolated local PDAC recurrence occurs. Retrospective studies have suggested that stereotactic body radiation therapy (SBRT) might lead to improved local control in these patients, potentially having a beneficial effect on both survival and quality of life. The "nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy" (ARCADE) will investigate the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence compared to standard of care alone, regarding both survival and quality of life outcomes. METHODS The ARCADE trial is nested within a prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'Trials within Cohorts' design. All PACAP participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies are eligible. Patients will be randomized for local therapy (5 fractions of 8 Gy SBRT) in addition to standard of care or standard of care alone. In total, 174 patients will be included. The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. DISCUSSION It is hypothesized that additional SBRT, compared to standard of care alone, improves survival and quality of life in patients with isolated local recurrence after PDAC resection. TRIAL REGISTRATION ClinicalTrials.gov registration NCT04881487 . Registered on May 11, 2021.
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Affiliation(s)
- I W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.
| | - L A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - M G Besselink
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - A M E Bruynzeel
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, the Netherlands
| | - O R Busch
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - G A Cirkel
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - B Groot Koerkamp
- Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands
| | - N Haj Mohammed
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - H D Heerkens
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - H W M van Laarhoven
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands
| | - G J Meijer
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - J Nuyttens
- Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - H C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - G van Tienhoven
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - H M Verkooijen
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - J W Wilmink
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands
| | - I Q Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - M P W Intven
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.
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23
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Ueberroth BE, Jones JC, Bekaii-Saab TS. Circulating tumor DNA (ctDNA) to evaluate minimal residual disease (MRD), treatment response, and posttreatment prognosis in pancreatic adenocarcinoma. Pancreatology 2022; 22:741-748. [PMID: 35725696 DOI: 10.1016/j.pan.2022.06.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/03/2022] [Accepted: 06/09/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Circulating tumor DNA (ctDNA) has emerged as a blood-based test with multiple utilities in oncology. In the past few years, multiple studies of varying designs, methods, and quality have emerged which show promise for ctDNA as a tool to assess response to treatment and detect minimal residual disease (MRD) across various gastrointestinal (GI) malignancies. We aim to review the current literature for ctDNA as it pertains to assessing treatment response, MRD, prognosis, and risk of recurrence for pancreatic adenocarcinoma. METHODS PubMed was queried with a combination of terms regarding pancreatic adenocarcinoma, minimal residual disease, resection, and prognosis. All resultant articles were reviewed by the authors for appropriate fit with scope. RESULTS Fourteen articles were identified that fit with the scope of this review. CONCLUSIONS Detectable ctDNA after definitive resection, specifically mutated KRAS, correlates with shorter recurrence-free survival (RFS), overall survival (OS), and overall prognosis. Limited data also suggests ctDNA may provide a noninvasive means to assess response to chemotherapy. Whether this information is actionable in terms of altering neoadjuvant or postresection treatment regimens remains an open question requiring further study.
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Affiliation(s)
- Benjamin E Ueberroth
- Department of Internal Medicine, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.
| | - Jeremy C Jones
- Mayo Clinic Comprehensive Cancer Center, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Tanios S Bekaii-Saab
- Mayo Clinic Comprehensive Cancer Center, 5881 E Mayo Blvd, Phoenix, AZ, 85054, USA
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24
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Chen G, Jiao D, Peng S, Chen X, Zhang Y, Lin L, Zhong Z, Li Y, Xu K, Zhang F. Peritumoral abnormalities on dynamic-enhanced CT after brachytherapy for hepatic malignancies: local progression or benign changes? Eur Radiol 2022; 32:7307-7319. [PMID: 35980429 PMCID: PMC9474341 DOI: 10.1007/s00330-022-09074-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 11/06/2022]
Abstract
Objectives To determine if dynamic CT can differentiate local progression from radioactive seed-induced peritumoral reaction (RSIPR) after brachytherapy with iodine-125 radioactive seeds (BIRS) for advanced hepatic malignancies. Methods Enhanced CT images of seed-implanted lesions between 2006 and 2018 were retrospectively evaluated. Hounsfield units of peritumoral parenchyma were measured and assessed quantitatively. The classification, conversion, consequences, and serological indicators during follow-up were recorded and quantified. Statistical differences were analyzed using a Pearson χ2 test. Results RSIPR was observed in 201 of 290 (69.3%) lesions (161 patients; median age, 55 years; range, 26–79 years), while local progression occurred in 53 lesions. The low density of local progression was much lower than that of RSIPR (p < 0.001), and the former did not exhibit iso-/high density in the portal or equilibrium phase. Ring-like enhancement in progressive lesions was also quite different from RSIPR. Local progression rate was lower for lesions with RSIPR than for those without RSIPR (14.9% vs 25.8%; p = 0.03), and their doses were different (397.2 Gy vs 120.3 Gy, p < 0.001). Conclusions Radioactive seed-induced peritumoral reaction has characteristic manifestations on CT images, which is associated with a higher dose of lesions and lower local progression rate. Notably, the enhancement pattern of local progression was distinct from RSIPR and was clearly distinguishable on dynamic-enhanced CT. Key Points • Radioactive seed-induced peritumoral reaction after brachytherapy with125I seeds for liver malignancies has characteristic manifestations on CT images, which is associated with a higher dose of lesions (397.2 Gy vs 120.3 Gy, p < 0.001), as a focal radiation injury. • Lesions with RSIPR were less likely to develop local progression, while those without RSIPR had a higher rate of local progression (14.9% vs 25.8%; p = 0.03). • The enhancement pattern of local progression after brachytherapy was distinct from radioactive seed-induced peritumoral reaction and was clearly distinguishable on dynamic-enhanced CT. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-022-09074-x.
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Affiliation(s)
- Guanyu Chen
- Department of Minimally Invasive & Interventional Radiology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Dechao Jiao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China
| | - Sheng Peng
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Xi Chen
- Department of Minimally Invasive & Interventional Radiology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Yanling Zhang
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510000, People's Republic of China
| | - Letao Lin
- Department of Minimally Invasive & Interventional Radiology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Zhihui Zhong
- Department of Minimally Invasive & Interventional Radiology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Yong Li
- Department of Intervention, Zhuhai People's Hospital, Zhuhai, 519000, People's Republic of China
| | - Kaihao Xu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China
| | - Fujun Zhang
- Department of Minimally Invasive & Interventional Radiology, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China.
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25
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Nakajima T, Ikuta S, Nakamura I, Aihara T, Kasai M, Iwama H, Fujimoto Y, Hatano E, Yamanaka N. Impact of the aberrant right hepatic artery on local recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy. Surgery 2022; 172:691-699. [PMID: 35337684 DOI: 10.1016/j.surg.2022.02.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/12/2022] [Accepted: 02/15/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND The influence and risk associated with an aberrant right hepatic artery, a common anatomical variation, during pancreatoduodenectomy for pancreatic ductal adenocarcinoma has not been fully investigated. The present study analyzed the impact of an aberrant right hepatic artery on local recurrence after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. METHODS A total of 169 patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy at 2 separate Japanese medical institutions were retrospectively analyzed. RESULTS Thirty of 169 patients (17.7%) presented with an aberrant right hepatic artery. The incidence of local recurrence was higher in the aberrant right hepatic artery group than in the normal right hepatic artery group (43.3 vs 21.5%, P = .017). The local recurrence-free survival was significantly poorer in the aberrant right hepatic artery group than in the normal right hepatic artery group (P = .011). A multivariate analysis found that the aberrant right hepatic artery was an independent risk factor for local recurrence (hazard ratio: 3.74, P = .017). In the aberrant right hepatic artery group, more frequent local recurrence was observed in patients with tumors situated ≤10 mm from the aberrant right hepatic artery root. However, local recurrence was not observed in 2 out of 3 patients with tumors ≤10 mm from the aberrant right hepatic artery root who underwent pancreatoduodenectomy with combined resection of the aberrant right hepatic artery. CONCLUSION The presence of an aberrant right hepatic artery in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma may be associated with an increased risk of postoperative local recurrence. Combined resection of the aberrant right hepatic artery may reduce local recurrence, especially for tumors near the root of the aberrant right hepatic artery.
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Affiliation(s)
| | | | - Ikuo Nakamura
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Japan
| | | | - Meidai Kasai
- Department of Surgery, Meiwa Hospital, Hyogo, Japan
| | - Hideaki Iwama
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Japan
| | - Yasuhiro Fujimoto
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Japan
| | - Etsuro Hatano
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Japan
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26
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Hanada K, Shimizu A, Kurihara K, Ikeda M, Yamamoto T, Okuda Y, Tazuma S. Endoscopic approach in the diagnosis of high-grade pancreatic intraepithelial neoplasia. Dig Endosc 2022; 34:927-937. [PMID: 35165942 DOI: 10.1111/den.14240] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 01/02/2022] [Accepted: 01/16/2022] [Indexed: 02/08/2023]
Abstract
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high-grade pancreatic intraepithelial neoplasia (HG-PanIN), whose tumorous lesion is undetectable on cross-sectional images such as computed tomography or magnetic resonance image, long-term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG-PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG-PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG-PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post-ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4-Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early-stage PDAC.
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Affiliation(s)
- Keiji Hanada
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Akihiro Shimizu
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Keisuke Kurihara
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Morito Ikeda
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Takuya Yamamoto
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Yasuhiro Okuda
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Susumu Tazuma
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
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Szymoński K, Milian-Ciesielska K, Lipiec E, Adamek D. Current Pathology Model of Pancreatic Cancer. Cancers (Basel) 2022; 14:2321. [PMID: 35565450 PMCID: PMC9105915 DOI: 10.3390/cancers14092321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/29/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. Daily reports reveal new aspects of tumor biology, including its molecular and morphological heterogeneity, explain complicated "cross-talk" that happens between the cancer cells and tumor stroma, or the nature of the PC-associated neural remodeling (PANR). Staying up-to-date is hard and crucial at the same time. In this review, we are focusing on a comprehensive summary of PC aspects that are important in pathologic reporting, impact patients' outcomes, and bring meaningful information for clinicians. Finally, we show promising new trends in diagnostic technologies that might bring a difference in PC early diagnosis.
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Affiliation(s)
- Krzysztof Szymoński
- Department of Pathomorphology, Jagiellonian University Medical College, 31-531 Cracow, Poland;
- Department of Pathomorphology, University Hospital, 30-688 Cracow, Poland;
| | | | - Ewelina Lipiec
- M. Smoluchowski Institute of Physics, Jagiellonian University, 30-348 Cracow, Poland;
| | - Dariusz Adamek
- Department of Pathomorphology, Jagiellonian University Medical College, 31-531 Cracow, Poland;
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28
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Luan H, He Y, Zhang T, Su Y, Zhou L. The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma. BMC Cancer 2022; 22:463. [PMID: 35477379 PMCID: PMC9047343 DOI: 10.1186/s12885-022-09577-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 04/18/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candidate biomarkers are unknown. METHODS We performed mRNA profiling comparisons in 8 primary tumors (T) and 12 liver metastases (M) samples using the Gene Expression Omnibus (GEO) database. After determining differentially expressed genes (DEG), gene ontology (GO), pathway enrichment and protein-protein interaction (PPI) network analyses were performed to determine DEG functions. Then, Cytoscape was used to screen out significant hub genes, after which their clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Furthermore, prognosis-associated gene expression was validated using Oncomine and TCGA database. Lastly, associations between prognosis-associated genes, immune cells and immunological checkpoint genes were evaluated using the Tumor Immune Estimation Resource (TIMER). RESULTS In total, 102 genes were related to liver metastasis and predominantly involved in cell migration, motility, and adhesion. Using Cytoscape, this number was narrowed down to 16 hub genes. Elevated mRNA expression levels for two of these genes, SPARC (P = 0.019) and TPM1 (P = 0.037) were significantly correlated with poor disease prognosis. For the remaining 14, expression was not related to overall patient survival. SPARC had higher expression in patients with metastatic PDAC than those with non-metastatic PDAC in TCGA dataset. SPARC and TPM1 levels were also positively correlated with the immune infiltration of specific cell types. Additionally, both genes exhibited strong co-expression associations with immune checkpoint genes. CONCLUSIONS Combined, we suggest SPARC has high potential as biomarker to predict liver metastasis during PDAC. Additionally, both SPARC and TPM1 appeared to recruit and regulate immune-infiltrating cells during these pathophysiological processes.
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Affiliation(s)
- Hong Luan
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China
| | - Ye He
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China
| | - Tuo Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China
| | - Yanna Su
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China
| | - Liping Zhou
- Department of Post Graduation Training, The First Affiliated Hospital of China Medical University, No. 155, Nanjingbei Street, Heping District, Shenyang, Liaoning Province, 110001, People's Republic of China.
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29
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Kumar AA, Buckley BJ, Ranson M. The Urokinase Plasminogen Activation System in Pancreatic Cancer: Prospective Diagnostic and Therapeutic Targets. Biomolecules 2022; 12:152. [PMID: 35204653 PMCID: PMC8961517 DOI: 10.3390/biom12020152] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/13/2022] [Accepted: 01/16/2022] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer is a highly aggressive malignancy that features high recurrence rates and the poorest prognosis of all solid cancers. The urokinase plasminogen activation system (uPAS) is strongly implicated in the pathophysiology and clinical outcomes of patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic cancers. Overexpression of the urokinase-type plasminogen activator (uPA) or its cell surface receptor uPAR is a key step in the acquisition of a metastatic phenotype via multiple mechanisms, including the increased activation of cell surface localised plasminogen which generates the serine protease plasmin. This triggers multiple downstream processes that promote tumour cell migration and invasion. Increasing clinical evidence shows that the overexpression of uPA, uPAR, or of both is strongly associated with worse clinicopathological features and poor prognosis in PDAC patients. This review provides an overview of the current understanding of the uPAS in the pathogenesis and progression of pancreatic cancer, with a focus on PDAC, and summarises the substantial body of evidence that supports the role of uPAS components, including plasminogen receptors, in this disease. The review further outlines the clinical utility of uPAS components as prospective diagnostic and prognostic biomarkers for PDAC, as well as a rationale for the development of novel uPAS-targeted therapeutics.
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Affiliation(s)
- Ashna A. Kumar
- Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; (A.A.K.); (B.J.B.)
- School of Chemistry and Molecular Biosciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia
| | - Benjamin J. Buckley
- Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; (A.A.K.); (B.J.B.)
- School of Chemistry and Molecular Biosciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia
| | - Marie Ranson
- Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; (A.A.K.); (B.J.B.)
- School of Chemistry and Molecular Biosciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia
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30
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Xu J, Lyu S, Zhao Y, Zhang X, Liu Z, Zhao X, He Q. Ratio of CA19-9 Level to Total Tumor Volume as a Prognostic Predictor of Pancreatic Carcinoma After Curative Resection. Technol Cancer Res Treat 2022; 21:15330338221078438. [PMID: 35138217 PMCID: PMC8832591 DOI: 10.1177/15330338221078438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 01/16/2022] [Accepted: 01/19/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is known to have a poor prognosis, early local invasion, and distant metastasis. Surgical resection is the most effective treatment, and tumor recurrence can be the key factor affecting the surgical outcome. Serum carbohydrate antigen 19-9 (CA19-9) is a tumor marker with high sensitivity to pancreatic cancer; elevated CA19-9 levels often indicate poor biological behavior. Tumor size is also a crucial factor that affects the prognosis. Therefore, we developed a program to evaluate the effect of the ratio of CA19-9 to total tumor volume (CA19-9/TTV) as a prognostic marker on tumor recurrence and long-term survival in patients with PDAC following pancreaticoduodenectomy (PD). Methods: Data from 200 patients who underwent PD for PDAC were retrospectively analyzed. CA19-9/TTV was calculated according to preoperative CA19-9 and TTV, and patients were divided into two groups according to the optimal cut-off value. Univariate and multivariate analyses were performed on the clinicopathological data to screen the risk factors affecting postoperative recurrence and long-term prognosis of patients with PDAC undergoing PD. Results: The receiver operating characteristic curve showed that the best cut-off value was 5.62 (area under curve [AUC], 0.633; 95% CI: 0.548-0.718). Multivariate analysis showed that tumor differentiation and CA19-9/TTV were independent risk factors for the long-term prognosis of PDAC (P = 0.004, P = 0.007), as well as for tumor recurrence (P = 0.008, P = 0.008). Conclusion: CA19-9/TTV is an independent risk factor for the prognosis of PDAC and may be a new marker for lower survival benefits.
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Affiliation(s)
- Junming Xu
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Shaocheng Lyu
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Yang Zhao
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Xinxue Zhang
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Zhe Liu
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Xin Zhao
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Qiang He
- Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
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Odisho T, Joseph S, Shahait A, Choi-Kim L, McGee J, Kim S. OUP accepted manuscript. J Surg Case Rep 2022; 2022:rjac138. [PMID: 35495083 PMCID: PMC9048657 DOI: 10.1093/jscr/rjac138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 03/14/2022] [Indexed: 11/25/2022] Open
Abstract
Pancreatic cancer has a low survival rate even after ostensible complete resection, and treatment for recurrence is usually only palliative. However, rare solitary metastasis can occur and may be operable. In this report, we describe such a case and review the literature on metastasectomy for pancreatic adenocarcinoma. A 66-year-old female underwent Whipple procedure at our institution in 2014 for a pT3N0 pancreatic adenocarcinoma. A slowly growing umbilical mass was noted 6 years later with concomitant rise in her CA 19-9 levels. CT-guided biopsy of her abdominal wall mass confirmed a well-differentiated adenocarcinoma consistent with her primary pancreatic cancer. The patient underwent metastasectomy of the isolated abdominal wall mass, with negative margins. She received no further postoperative treatment. The patient remains disease and symptom-free over 18 months after resection of the metastasis. In highly selected cases of pancreatic adenocarcinoma, resection of solitary metastasis may be therapeutic.
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Affiliation(s)
- Tanya Odisho
- Correspondence address. Department of Surgery, Detroit Medical Center, Sinai Grace Hospital, 6071 Outer Dr. W, Detroit, MI 48235, USA. E-mail:
| | - Stephanie Joseph
- Department of Surgery, Detroit Medical Center, Detroit, MI, USA
- The Michael and Marian Ilitch Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA
| | - Awni Shahait
- Department of Surgery, Detroit Medical Center, Detroit, MI, USA
- The Michael and Marian Ilitch Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA
| | - Lydia Choi-Kim
- The Michael and Marian Ilitch Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA
| | - Jessica McGee
- The Michael and Marian Ilitch Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA
| | - Steve Kim
- The Michael and Marian Ilitch Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA
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Usefulness of Inflammation-Based Prognostic Scores in Patients with Surgically Treated Pancreatic Ductal Adenocarcinoma. J Clin Med 2021; 10:jcm10245784. [PMID: 34945079 PMCID: PMC8708028 DOI: 10.3390/jcm10245784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/08/2021] [Accepted: 12/08/2021] [Indexed: 11/17/2022] Open
Abstract
In this study, we evaluated the prognostic value of inflammation-based prognostic scores in patients undergoing curative surgery for pancreatic ductal adenocarcinoma (PDAC). A retrospective analysis was conducted for 914 patients undergoing curative surgical resection for PDAC between January 2011 and April 2016. Inflammation-based scores of modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio were assessed. mGPS was classified as high (1 or 2) or low (0). Median age was 63 (range, 33–88) years; 538 patients (58.9%) were male. A high mGPS was independently associated with poor overall survival (OS) and disease-free survival (DFS) (median OS: 25.4 months vs. 20.4 months, p = 0.001; median DFS: 11.6 months vs. 9.3 months, p = 0.002), poor OS in patients with TNM stage I PDAC (44 months vs. 24.8 months, p = 0.001), and poor OS and DFS in patients with tumors located at the pancreatic head or uncinate process (OS: 25.4 months vs. 20.4 months; p = 0.007, DFS: 11.4 months vs. 8.87 months; p = 0.005). Preoperative mGPS was a significant prognostic factor for PDAC after curative resection; thus, mGPS can be a useful prognostic predictive factor in patients with TNM stage I PDAC, especially for tumors located at the head and uncinate.
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Hong S, Song KB, Hwang DW, Lee JH, Lee W, Jun E, Kwon J, Park Y, Park SY, Kim N, Shin D, Kim H, Sung M, Ryu Y, Kim SC. Preoperative serum carbohydrate antigen 19-9 levels predict early recurrence after the resection of early-stage pancreatic ductal adenocarcinoma. World J Gastrointest Surg 2021; 13:1423-1435. [PMID: 34950431 PMCID: PMC8649558 DOI: 10.4240/wjgs.v13.i11.1423] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 05/31/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a serious disease with a poor prognosis. Only a minority of patients undergo surgery due to the advanced stage of the disease, and patients with early-stage disease, who are expected to have a better prognosis, often experience recurrence. Thus, it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan. AIM To evaluate the predictive factors associated with the early recurrence of early-stage PDAC. METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016. Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery. The optimal cutoff values were determined by receiver operating characteristic (ROC) analyses. Univariate and multivariate analyses were performed to identify the risk factors for early recurrence. RESULTS Of the 407 patients, 98 patients (24.1%) experienced early disease recurrence: 26 (26.5%) local and 72 (73.5%) distant sites. In total, 253 (62.2%) patients received adjuvant chemotherapy. On ROC curve analysis, the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9 (CA 19-9) levels and tumor size, respectively. Of the 181 patients with CA 19-9 level > 70 U/mL, 59 (32.6%) had early recurrence, compared to 39 (17.4%) of 226 patients with CA 19-9 level ≤ 70 U/mL (P < 0.001). Multivariate analysis revealed that CA 19-9 level > 70 U/mL (P = 0.006), tumor size > 2.85 cm (P = 0.004), poor differentiation (P = 0.008), and non-adjuvant chemotherapy (P = 0.025) were significant risk factors for early recurrence in early-stage PDAC. CONCLUSION Elevated CA 19-9 level (cutoff value > 70 U/mL) can be a reliable predictive factor for early recurrence in early-stage PDAC. As adjuvant chemotherapy can prevent early recurrence, it should be recommended for patients susceptible to early recurrence.
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Affiliation(s)
- Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Jaewoo Kwon
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, South Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Seo Young Park
- Department of Statistics and Data Science, Korea National Open University, Seoul 03087, South Korea
| | - Naru Kim
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, Gyeonggido 11765, South Korea
| | - Dakyum Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Hyeyeon Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Minkyu Sung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Yunbeom Ryu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
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Igarashi C, Yoshii Y, Tashima H, Iwao Y, Sakurai K, Hihara F, Tachibana T, Yoshida E, Wakizaka H, Akamatsu G, Yamaya T, Yoshimoto M, Matsumoto H, Zhang MR, Nagatsu K, Sugyo A, Tsuji AB, Higashi T. Usefulness of PET-guided surgery with 64Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer. Nucl Med Commun 2021; 42:1112-1121. [PMID: 34100794 DOI: 10.1097/mnm.0000000000001442] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery. METHODS A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations. RESULTS Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3-10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group. CONCLUSIONS OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival.
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Affiliation(s)
| | - Yukie Yoshii
- Department of Molecular Imaging and Theranostics
| | - Hideaki Tashima
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | - Yuma Iwao
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | | | | | | | - Eiji Yoshida
- Department of Molecular Imaging and Theranostics
| | - Hidekatsu Wakizaka
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | - Go Akamatsu
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | - Taiga Yamaya
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | - Mitsuyoshi Yoshimoto
- Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | | | - Ming-Rong Zhang
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | - Kotaro Nagatsu
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba
| | - Aya Sugyo
- Department of Molecular Imaging and Theranostics
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Wang G, Dai S, Gao H, Gao Y, Yin L, Zhang K, Huang X, Lu Z, Miao Y. Opposite Roles of Tumor Cell Proliferation and Immune Cell Infiltration in Postoperative Liver Metastasis of PDAC. Front Cell Dev Biol 2021; 9:714718. [PMID: 34485300 PMCID: PMC8415276 DOI: 10.3389/fcell.2021.714718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/20/2021] [Indexed: 11/13/2022] Open
Abstract
Background Recurrence of liver metastasis after pancreatectomy is often a predictor of poor prognosis. Comprehensive genomic analysis may contribute to a better understanding of the molecular mechanisms of postoperative liver metastasis and provide new therapeutic targets. Methods A total of 67 patients from The Cancer Genome Atlas (TCGA) were included in this study. We analyzed differentially expressed genes (DEGs) by R package "DESeq2." Weighted gene co-expression network analysis (WGCNA) was applied to investigate the key modules and hub genes. Immunohistochemistry was used to analyze tumor cell proliferation index and CD4+ T cells infiltration. Results Functional analysis of DEGs between the liver metastatic and recurrence-free groups was mainly concentrated in the immune response. The liver metastasis group had lower immune and stroma scores and a higher TP53 mutation rate. WGCNA showed that the genes in key modules related to disease-free survival (DFS) and overall survival (OS) were mainly enriched in the cell proliferation process and tumor immune response. Immunohistochemical analysis showed that the pancreatic cancer cells of patients with early postoperative liver metastasis had higher proliferative activity, while the infiltration of CD4+ T cells in tumor specimens was less. Conclusion Our study suggested that increased immune cell infiltration (especially CD4+ T cells) and tumor cell proliferation may play an opposite role in liver metastasis recurrence after pancreatic cancer.
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Affiliation(s)
- Guangfu Wang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Shangnan Dai
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Hao Gao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Yong Gao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Lingdi Yin
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Kai Zhang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Xumin Huang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Zipeng Lu
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Yi Miao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China.,Pancreas Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China
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Lee B, Han HS, Lee JS, Yoon YS. Surgical Resection or Ablation for Recurrent Pancreatic Ductal Adenocarcinoma: An Analysis of Oncologic Outcomes According to the Recurrence Type. ANNALS OF SURGERY OPEN 2021; 2:e096. [PMID: 37635830 PMCID: PMC10455453 DOI: 10.1097/as9.0000000000000096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 08/08/2021] [Indexed: 11/27/2022] Open
Abstract
Objective To evaluate the survival benefits of curative-intent treatment (CIT, including surgery or ablation) for recurrent pancreatic ductal adenocarcinoma (PDAC) depending on the recurrence type and compared the survival outcomes with other treatment modalities. Background The treatment for recurrent PDAC is mostly chemotherapy or best supportive care (BSC). Still, the role of CIT for recurrent PDAC is not well established. Methods PDAC patients who underwent pancreatectomy between 2004 and 2019 were included. Recurrences were categorized as locoregional (LR), distant, or disseminated. Recurrent PDAC management was classified as CIT, chemotherapy ± radiation therapy (CTX ± RTX), or BSC. The survival after recurrence (SAR) rate was measured from the first day of recurrence to the date of death or last follow-up. Results Two hundred eighteen patients had recurrent PDAC and were analyzed (27 CIT, 128 CTX ± RTX, 63 BSC). The 1-, 3-, and 5-year SAR rates were 65.4%, 11.5%, and 11.5% for CIT, 42.1%, 4.0%, and 0% for CTX ± RTX, and 15.9%, 1.6%, and 0% for BSC, respectively. Subgroup analysis indicated the SAR rate was significantly better in the CIT group than in the CTX ± RTX and BSC groups in LR type (P = 0.027) and distant type (P < 0.001). In multivariate analysis, the albumin level at recurrence (hazard ratio, 2.14; 95% confidence interval, 1.15-18.3, P = 0.038) and operation time of the second operation (hazard ratio, 0.98; 95% confidence interval, 0.97-0.99, P = 0.021) were associated with a favorable prognosis of SAR in the CIT group. Conclusions CIT should be considered in recurrent PDAC for LR and distant metastases in selected patients.
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Affiliation(s)
- Boram Lee
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
| | - Ho-Seong Han
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
| | - Jun Suh Lee
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
| | - Yoo-Seok Yoon
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
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Safi SA, Haeberle L, Fluegen G, Lehwald-Tywuschik N, Krieg A, Keitel V, Luedde T, Esposito I, Rehders A, Knoefel WT. Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival. Pancreatology 2021; 21:787-795. [PMID: 33775563 DOI: 10.1016/j.pan.2021.02.024] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 02/11/2021] [Accepted: 02/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Survival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. METHOD Clinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. RESULTS The rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). CONCLUSION Mesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.
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Affiliation(s)
- S-A Safi
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - L Haeberle
- Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - G Fluegen
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - N Lehwald-Tywuschik
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - A Krieg
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - V Keitel
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - T Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - I Esposito
- Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - A Rehders
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - W T Knoefel
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany.
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Vining CC, Skowron KB, Hogg ME. Robotic gastrointestinal surgery: learning curve, educational programs and outcomes. Updates Surg 2021; 73:799-814. [PMID: 33484423 DOI: 10.1007/s13304-021-00973-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 01/06/2021] [Indexed: 02/07/2023]
Abstract
The use of the robotic platform for gastrointestinal surgery was introduced nearly 20 years ago. However, significant growth and advancement has occurred primarily in the last decade. This is due to several advantages over traditional laparoscopic surgery allowing for more complex dissections and reconstructions. Several randomized controlled trials and retrospective reviews have demonstrated equivalent oncologic outcomes compared to open surgery with improved short-term outcomes. Unfortunately, there are currently no universally accepted or implemented training programs for robotic surgery and robotic surgery experience varies greatly. Additionally, several limitations to the robotic platform exist resulting in a distinct learning curve associated with various procedures. Therefore, implementation of robotic surgery requires a multidisciplinary team approach with commitment and investment from clinical faculty, operating room staff and hospital administrators. Additionally, there is a need for wider distribution of educational modules to train more surgeons and reduce the associated learning curve. This article will focus on the implementation of the robotic platform for surgery of the pancreas, stomach, liver, colon and rectum with an emphasis on the associated learning curve, educational platforms to develop proficiency and perioperative outcomes.
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Affiliation(s)
- Charles C Vining
- Department of Surgery, University of Chicago Medical Center, Chicago, IL, USA
| | - Kinga B Skowron
- Department of Surgery, University of Chicago Medical Center, Chicago, IL, USA
| | - Melissa E Hogg
- Department of Surgery, NorthShore University HealthSystem, Walgreens Building, Floor 2, 2650 Ridge Road, Evanston, IL, 60201, USA.
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Perioperative Predictors of Early Recurrence for Resectable and Borderline-Resectable Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13102285. [PMID: 34064540 PMCID: PMC8151140 DOI: 10.3390/cancers13102285] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/30/2021] [Accepted: 05/06/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Most patients with a pancreatic ductal adenocarcinoma develop a recurrence after surgery. Predictive factors may therefore guide therapeutic decision-making. We aimed to identify perioperative predictors of the early recurrence of pancreatic ductal adenocarcinomas. We found that preoperative (>52 U/mL) and postoperative (>37 U/mL) elevated carbohydrate antigen 19-9 levels as well as a tumor size >3.0 cm were independently associated with an early recurrence after a pancreatectomy. Furthermore, an early recurrence resulted in a more frequent liver metastasis than a late recurrence, suggesting that patients experiencing a recurrence within 12 months had undetectable micrometastases. Further studies are needed to identify new biomarkers for the detection of clinically occult micrometastases during surgery as current preoperative risk factors are inadequate to accurately identify patients susceptible to an early recurrence of pancreatic ductal adenocarcinomas. Abstract We aimed to identify the perioperative predictors of the early recurrence (ER) of resectable and borderline-resectable pancreatic ductal adenocarcinomas (PDACs). After surgery for a PDAC, most patients develop a recurrence. Predictive factors may therefore guide therapeutic decision-making. Patients (n = 234) who underwent a pancreatectomy for a PDAC between 2006 and 2019 were included. The postrecurrence survival (PRS) was estimated using Kaplan–Meier curves. Predictive factors for an ER were assessed using logistic regression analyses; 93 patients (39.7%) were recurrence-free at the last follow-up. Patients with an ER (n = 85, 36.3%), defined as a recurrence within the first 12 months after surgery, had 1- and 2-year PRS rates of 38.7% and 9.5%, respectively, compared with 66.9% and 37.2% for those with a late recurrence (n = 56, 23.9%; both p < 0.001). The most common site of an ER was the liver (55.3%) with a significantly shorter median overall survival time than that with either a local or a lung recurrence (14.5 months; p < 0.001). Preoperative and postoperative risk factors for an ER included a tumor size >3.0 cm (odds ratio (OR): 3.11, 95% confidence interval (CI): 1.35–7.14) and preoperative carbohydrate antigen 19-9 (CA19-9) levels >52 U/mL (OR: 3.25, 95% CI: 1.67–6.30) and a pathological tumor size >3.0 cm (OR: 2.00, 95% CI: 1.03–3.90) and postoperative carbohydrate antigen 19-9 levels >37 U/mL (OR: 2.11, 95% CI: 1.02–4.36), respectively. Preoperatively (>52 U/mL) and postoperatively (>37 U/mL) elevated CA19-9 and a tumor size >3.0 cm were independent predictors for an ER after a pancreatectomy for a PDAC.
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Nappo G, Borzomati D, Zerbi A, Spaggiari P, Boggi U, Campani D, Mrowiec S, Liszka Ł, Coppola A, Amato M, Petitti T, Vistoli F, Montorsi M, Perrone G, Coppola R, Caputo D. The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial. Cancers (Basel) 2021; 13:2097. [PMID: 33926138 PMCID: PMC8123600 DOI: 10.3390/cancers13092097] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. METHODS PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. RESULTS One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. CONCLUSIONS The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (G.N.); (A.Z.)
| | - Domenico Borzomati
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (G.N.); (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
| | - Paola Spaggiari
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
| | - Ugo Boggi
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
- Division of General and Transplant Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy
| | - Daniela Campani
- Pathology Unit, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy;
| | - Sławomir Mrowiec
- Department of Gastrointestinal Surgery, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Łukasz Liszka
- Department of Pathomorphology and Molecular Diagnostics, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Alessandro Coppola
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Michela Amato
- Pathology Unit, Campus Bio-Medico University of Rome, 00128 Rome, Italy; (M.A.); (G.P.)
| | - Tommasangelo Petitti
- Department of Public Health, Hygiene and Statistics, Campus Bio-Medico University of Rome, 00128 Rome, Italy;
| | - Fabio Vistoli
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
- Division of General and Transplant Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy
| | - Marco Montorsi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
- Department of Surgery, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Giuseppe Perrone
- Pathology Unit, Campus Bio-Medico University of Rome, 00128 Rome, Italy; (M.A.); (G.P.)
| | - Roberto Coppola
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Damiano Caputo
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
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Preoperative CTC-Detection by CellSearch ® Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13030485. [PMID: 33513877 PMCID: PMC7865868 DOI: 10.3390/cancers13030485] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 12/23/2022] Open
Abstract
In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5-10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.
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Hussung S, Akhoundova D, Hipp J, Follo M, Klar RFU, Philipp U, Scherer F, von Bubnoff N, Duyster J, Boerries M, Wittel U, Fritsch RM. Longitudinal analysis of cell-free mutated KRAS and CA 19-9 predicts survival following curative resection of pancreatic cancer. BMC Cancer 2021; 21:49. [PMID: 33430810 PMCID: PMC7802224 DOI: 10.1186/s12885-020-07736-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 12/15/2020] [Indexed: 02/06/2023] Open
Abstract
Background Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRASmut) and CA 19–9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters. Methods Between 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Highly sensitive discriminatory multi-target ddPCR assays were employed to screen plasma samples for cfKRASmut. cfKRASmut and CA 19–9 dynamics were correlated with recurrence-free survival (RFS) and overall survival (OS). Patients were followed-up until 01/2020. Results Out of 25 enrolled patients, 76% had undergone R0 resection and 48% of resected PDACs were pN0. 17/25 (68%) of patients underwent adjuvant chemotherapy. Median follow-up was 22.0 months, with 19 out of 25 (76%) patients relapsing during study period. Median RFS was 10.0 months, median OS was 22.0 months. Out of clinicopathologic variables, only postoperative CA 19–9 levels and administration of adjuvant chemotherapy correlated with survival endpoints. cfKRASmut. was detected in 12/25 (48%) of patients, and detection of high levels inversely correlated with survival endpoint. Integration of cfKRASmut and CA 19–9 levels outperformed either individual marker. cfKRASmut outperformed CA 19–9 as dynamic marker since increase during adjuvant chemotherapy and follow-up was highly predictive of early relapse and poor OS. Conclusions Integrated analysis of cfKRASmut and CA 19–9 levels is a promising approach for molecular monitoring of patients following resection of PDAC. Larger prospective studies are needed to further develop this approach and dissect each marker’s specific potential. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07736-x.
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Affiliation(s)
- Saskia Hussung
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany.,Department of Medical Oncology and Hematology, Zurich University Hospital, Raemistrasse 100, 8091, Zürich, Switzerland
| | - Dilara Akhoundova
- Department of Medical Oncology and Hematology, Zurich University Hospital, Raemistrasse 100, 8091, Zürich, Switzerland
| | - Julian Hipp
- Department of Surgery, Freiburg University Medical Center, Freiburg, Germany
| | - Marie Follo
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany
| | - Rhena F U Klar
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany
| | - Ulrike Philipp
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany
| | - Florian Scherer
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany
| | - Nikolas von Bubnoff
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany
| | - Justus Duyster
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany.,German Cancer Consortium (DKTK), partner site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Comprehensive Cancer Center Freiburg (CCCF), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Melanie Boerries
- German Cancer Consortium (DKTK), partner site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Comprehensive Cancer Center Freiburg (CCCF), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Institute of Medical Bioinformatics and Systems Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Uwe Wittel
- Department of Surgery, Freiburg University Medical Center, Freiburg, Germany
| | - Ralph M Fritsch
- Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Freiburg University Medical Center, Freiburg, Germany. .,Department of Medical Oncology and Hematology, Zurich University Hospital, Raemistrasse 100, 8091, Zürich, Switzerland. .,Comprehensive Cancer Center Freiburg (CCCF), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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43
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Lei Y, Yu T, Li C, Li J, Liang Y, Wang X, Chen Y, Wang X. Expression of CAMK1 and its association with clinicopathologic characteristics in pancreatic cancer. J Cell Mol Med 2020; 25:1198-1206. [PMID: 33342045 PMCID: PMC7812292 DOI: 10.1111/jcmm.16188] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 11/08/2020] [Accepted: 11/21/2020] [Indexed: 12/11/2022] Open
Abstract
Calcium/calmodulin‐dependent protein kinase (CAMKs) can control a wide range of cancer‐related functions in multiple tumour types. Herein, we explore the expressions and clinical significances of calcium/calmodulin‐dependent protein kinase 1 (CAMK1) in pancreatic cancer (PC). The expression of CAMK1 in PC was analysed by Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database and the Oncomine database. For further validation, the protein level of CAMK1 in PC tissues was also detected in the Human Protein Atlas (HPA) database and the tissue microarray (TMA)‐based immunohistochemistry (IHC). GEPIA 2 and Kaplan‐Meier Plotter (KM Plotter) databases were used to explore the prognostic significances of CAMK1 in overall survival (OS) and disease‐free survival (DFS) of PC at mRNA level. The relationship between CAMK1 expression and the clinicopathological characteristics of PC was further explored. Additionally, the Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyse protein‐protein interactions (PPI). We found CAMK1 was highly expressed in PC both in bioinformatics analyses and TMA‐IHC results. The prognostic analyses from the public databases also showed consistent results with follow‐up data. The PPI network suggested that CALM1, CALM3, CREB1, CALM2, SYN1, NOS3, ATF1, GAPDH, PPM1F and FBXL12 were important significant genes associated with CAMK1. Our finding revealed CAMK1 has prognostic value in PC patients, suggesting that CAMK1 may has a distinct role in PC patients and can be used as a candidate marker for investigating clinical prognosis of PC.
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Affiliation(s)
- Yangyang Lei
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Tianzhu Yu
- Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Changyu Li
- Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Jianke Li
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Yicheng Liang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyuan Wang
- Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Maynooth, Ireland
| | - Yi Chen
- Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Xiaolin Wang
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
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44
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Hagiwara K, Harimoto N, Araki K, Watanabe A, Kubo N, Nakazawa S, Yajima T, Uchida N, Shirabe K. Long-term survival of two patients with pancreatic cancer after resection of liver and lung oligometastases: a case report. Surg Case Rep 2020; 6:309. [PMID: 33284401 PMCID: PMC7721952 DOI: 10.1186/s40792-020-01029-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/23/2020] [Indexed: 12/13/2022] Open
Abstract
Background The efficacy of resection of pancreatic cancer metastases has not been established. We here report two patients with long-term survival after resection of lung and liver metastases. Case presentation The first patient underwent distal pancreatectomy for pancreatic cancer. One year later, she underwent partial hepatectomy for a single liver metastasis. She subsequently underwent pulmonary resections 7, 7.5, 9, and 10 years later for pulmonary metastases from pancreatic cancer. Thus, this patient underwent five surgeries for metastases, one for a liver metastasis and four for lung metastases. All of the tumors were pathologically diagnosed as metastatic pancreatic cancer. She is currently alive without new recurrence 10 years after the initial diagnosis. The second patient underwent pancreaticoduodenectomy for pancreatic cancer. Four years later, she underwent a thoracoscopic partial resection for lung metastasis. The tumor was similar to the pancreatic cancer on pathological examination. She is currently alive without new recurrences 6 years after the initial diagnosis. Conclusion Long-term survival can be achieved in some patients with pancreatic cancer by resection of metachronous liver or lung metastases.
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Affiliation(s)
- Kei Hagiwara
- Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan
| | - Norifumi Harimoto
- Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan. .,Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
| | - Kenichiro Araki
- Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan
| | - Akira Watanabe
- Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan
| | - Norio Kubo
- Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan
| | - Seshiru Nakazawa
- Division of General Thoracic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Japan
| | - Toshiki Yajima
- Division of General Thoracic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Japan
| | - Nobuyuki Uchida
- Haramachi Red Cross Hospital, 698 Haramachi, Agatsuma, Gunma, Japan
| | - Ken Shirabe
- Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan
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45
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Weibel P, Pavic M, Lombriser N, Gutknecht S, Weber M. Chemoradiotherapy after curative surgery for locally advanced pancreatic cancer: A 20-year single center experience. Surg Oncol 2020; 36:36-41. [PMID: 33285435 DOI: 10.1016/j.suronc.2020.11.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 09/29/2020] [Accepted: 11/15/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Pancreatic adenocarcinoma (PAC) is a highly malignant tumor with relevant morbidity and mortality. The role of adjuvant chemoradiotherapy (CRT) for primarily resected tumors remains controversial. We aimed to assess the outcome of patients treated at our institution with postoperative CRT for PAC. METHODS We present a retrospective case series of patients with pancreatic adenocarcinoma at a single center in Switzerland. These patients were treated by primary surgery followed by adjuvant CRT between 1995 and 2015. The results were compared with published data. RESULTS Median follow-up for the 60 patients was 33 months (range 19.9-193.9); median overall survival (OS) for patients undergoing a resection followed by combined CRT was 25.5 months. Overall, disease-free survival (DFS) was 15.2 months. A local recurrence occurred in 14 patients (23.3%) after a median time of 8.8 months, and in 43 patients (71.7%) distant metastasis was demonstrated with a median time to metastasis of 10.6 months. CONCLUSION This retrospective study represents one of the sole reviews of outcome data after adjuvant CRT in resected PAC in Europe within the past years. OS was comparable to that of other institutional outcome data published previously but inferior when compared to most recent published results with an intense chemotherapy. However, not all patients are suitable to undergo such an intense chemotherapy with modified FOLFIRINOX after the extensive surgery for the PAC - these patients could benefit from adding adjuvant CRT to a less intensive chemotherapy with gemcitabine to enhance the benefit regarding locoregional recurrence-free survival.
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Affiliation(s)
- P Weibel
- Department for Abdominal, Thoracic, and Vascular Surgery, Triemli Hospital Zurich, Switzerland.
| | - M Pavic
- Department for Radiation Oncology, Triemli Hospital Zurich, Zurich, Switzerland.
| | - N Lombriser
- Department for Radiation Oncology, Triemli Hospital Zurich, Zurich, Switzerland.
| | - S Gutknecht
- Department for Abdominal, Thoracic, and Vascular Surgery, Triemli Hospital Zurich, Switzerland.
| | - M Weber
- Department for Abdominal, Thoracic, and Vascular Surgery, Triemli Hospital Zurich, Switzerland.
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46
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Kim JR, Kim H, Kwon W, Jang JY, Kim SW. Pattern of local recurrence after curative resection in pancreatic ductal adenocarcinoma according to the initial location of the tumor. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 28:105-114. [PMID: 33084211 DOI: 10.1002/jhbp.854] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 09/18/2020] [Accepted: 09/22/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND/PURPOSE The aim of the present study was to identify the types of recurrence in pancreatic ductal adenocarcinoma (PDAC) and discover the frequent location of the local recurrence. METHODS This study included 361 patients with PDAC who underwent curative-intent surgery between 2007-2014. RESULTS Among 361 patients, 75.1% (n = 271) developed recurrence during the follow-up period. The 5-year overall survival rate of recurred patients was 8.3%. The patterns of recurrence were classified as local (17.7%), systemic (62.0%), and loco-systemic (20.3%). According to the preoperative tumor locations, patients with uncinate and head cancer showed higher rates of local recurrence than those with body and tail cancer (47.8% vs 17.2%, P < .001). When comparing uncinate and head cancer only, patients with uncinate cancer had much more frequent local recurrence around the superior mesenteric artery/vein (M zone) than around the hepatoduodenal ligament/common hepatic artery (H zone). Patients with head cancer had a higher rate of local recurrence in the H zone (H zone vs M zone; 53.5% vs 81.4% in uncinate cancer, P = .001; 66.7% vs 44.4% in head cancer, P = .056). CONCLUSION Discovering the patterns of recurrence and frequent locations of recurrence may assist in local control as well as in the development of a customized individual approach for each patient.
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Affiliation(s)
- Jae Ri Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Department of Surgery, Pusan National University Hospital, Busan, South Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sun-Whe Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
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Leon P, Giannone F, Belfiori G, Falconi M, Crippa S, Boggi U, Menonna F, Al Sadairi AR, Piardi T, Sulpice L, Gardini A, Sega V, Chirica M, Ravazzoni F, Giannandrea G, Pessaux P, de Blasi V, Navarro F, Panaro F. The Oncologic Impact of Pancreatic Fistula After Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma of the Body and the Tail: A Multicenter Retrospective Cohort Analysis. Ann Surg Oncol 2020; 28:3171-3183. [PMID: 33156465 DOI: 10.1245/s10434-020-09310-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 10/13/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The aim of this study was to assess the impact of clinically relevant postoperative pancreatic fistula (CR-POPF) on patient disease-specific survival and recurrence after curative distal pancreatectomy (DP) for pancreatic cancer. DESIGN This was a retrospective case-control analysis. METHODS We examined the data of adult patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) of the body and tail of the pancreas undergoing curative DP, over a 10-year period in 12 European surgical departments, from a prospectively implemented database. RESULTS Among the 382 included patients, 283 met the strict inclusion criteria; 139 were males (49.1%) and the median age of the entire population was 70 years (range 37-88). A total of 121 POPFs were observed (42.8%), 42 (14.9%) of which were CR-POPFs. The median follow-up period was 24 months (range 3-120). Although poorer in the POPF group, overall survival (OS) and disease-free survival (DFS) did not differ significantly between patients with and without CR-POPF (p = 0.224 and p = 0.165, respectively). CR-POPF was not significantly associated with local or peritoneal recurrence (p = 0.559 and p = 0.302, respectively). A smaller percentage of patients benefited from adjuvant chemotherapy after POPF (76.2% vs. 83.8%), but the difference was not significant (p = 0.228). CONCLUSIONS CR-POPF is a major complication after DP but it did not affect the postoperative therapeutic path or long-term oncologic outcomes. CR-POPF was not a predictive factor for disease recurrence and was not associated with an increased incidence of peritoneal or local relapse. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT04348084.
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Affiliation(s)
- Piera Leon
- Department of Surgery/Division of HBP Surgery and Transplantation, "Saint Eloi" Montpellier University Hospital, Montpellier, France.
| | - Fabio Giannone
- Department of Surgery/Division of HBP Surgery and Transplantation, "Saint Eloi" Montpellier University Hospital, Montpellier, France
| | - Giulio Belfiori
- "San Raffaele" IRCCS Hospital, Università Vita - Salute, Milan, Italy
| | - Massimo Falconi
- "San Raffaele" IRCCS Hospital, Università Vita - Salute, Milan, Italy
| | - Stefano Crippa
- "San Raffaele" IRCCS Hospital, Università Vita - Salute, Milan, Italy
| | - Ugo Boggi
- "Cisanello" University Hospital, Pisa, Italy
| | | | | | | | | | | | | | | | | | | | | | - Vito de Blasi
- Hospital Centre of Luxembourg, Luxembourg City, Luxembourg
| | - Francis Navarro
- Department of Surgery/Division of HBP Surgery and Transplantation, "Saint Eloi" Montpellier University Hospital, Montpellier, France
| | - Fabrizio Panaro
- Department of Surgery/Division of HBP Surgery and Transplantation, "Saint Eloi" Montpellier University Hospital, Montpellier, France
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48
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Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis. Cancer Lett 2020; 497:1-13. [PMID: 33065249 DOI: 10.1016/j.canlet.2020.10.015] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/02/2020] [Accepted: 10/09/2020] [Indexed: 12/18/2022]
Abstract
Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients.
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Guerra F, Barucca V, Coletta D. Metastases or primary recurrence to the lung is related to improved survival of pancreatic cancer as compared to other sites of dissemination. Results of a systematic review with meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1789-1794. [PMID: 32753117 DOI: 10.1016/j.ejso.2020.06.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/22/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023]
Abstract
There are demonstrations that the prognosis of patients with isolated pulmonary dissemination of pancreatic cancer is more favorable than that of patients with other patterns of disease progression. The aim of this systematic review with meta-analysis was to evaluate the oncological outcomes of pulmonary vs. non-pulmonary metastasis of patients with pancreatic cancer. A total of 11 916 patients with secondary spread of pancreatic cancer were included from 15 primary reports. In the setting of single-organ disease dissemination, the lung demonstrated a significant survival advantage over hepatic, locoregional, or peritoneal localization. In particular, patients who recurred in the lung after pancreatectomy, showed a significant survival benefit as compared to those patients with hepatic and locoregional relapse in terms of disease-free survival, survival after recurrence and overall survival.
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Affiliation(s)
| | | | - Diego Coletta
- Hepatopancreatobiliary Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
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50
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Comprehensive histological evaluation with clinical analysis of venous invasion in pancreatic ductal adenocarcinoma: From histology to clinical implications. Pancreatology 2020; 20:1486-1494. [PMID: 32948429 DOI: 10.1016/j.pan.2020.08.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 07/31/2020] [Accepted: 08/18/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Venous invasion is a poor prognostic factor for pancreatic ductal adenocarcinoma (PDAC). However, our understanding of various features of venous invasion is limited. Our aim is to comprehensively evaluate various histopathologic features of venous invasion, including status, type (lymphatic or venous), number of invasion foci, and histologic pattern (pancreatic intraepithelial neoplasia [PanIN]-like, conventional) in PDACs. METHODS Various features of venous invasion, including status, number of invasion foci, histologic patterns [pancreatic intraepithelial neoplasia (PanIN)-like, conventional], and size of involved vessels in 471 surgically resected PDACs were evaluated with all available hematoxylin and eosin (H&E)-stained slides. RESULTS Venous invasion was observed in 319 cases (67.7%) and was more frequently associated with increased tumor size, extrapancreatic extension, resection margin involvement, diffuse tumor distribution, lymph node metastasis, and perineural invasion (all Ps < .05). High frequency (≥3 foci) of venous invasion was associated with shorter overall survival both in the entire group and in the early stage subgroup (stage I; all Ps < .05). Multivariate analysis indicated that a high frequency (≥3 foci) of venous invasion, large tumor size (>4 cm), higher histologic grade, and lymph node metastasis, were independent prognostic factors of worse overall survival (all Ps < .05). CONCLUSION Precise evaluation of venous invasion status, including foci number of invasion, can provide additional prognostic information for patients undergoing surgical resection of PDAC, especially for those with early disease stage.
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