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Park Y, Hwang DW, Lee JH, Song KB, Jun E, Lee W, Sung MK, Kim SC. Oncological outcomes of palliative minimally invasive distal pancreatectomy for unexpected metastatic pancreatic ductal adenocarcinoma: A single-center experience. Surgery 2025; 182:109331. [PMID: 40138876 DOI: 10.1016/j.surg.2025.109331] [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: 09/30/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND The benefits of palliative minimally invasive distal pancreatectomy for patients with unexpectedly metastatic pancreatic ductal adenocarcinoma have not been previously studied. This retrospective study compared the outcomes of palliative minimally invasive distal pancreatectomy with those of minimally invasive biopsy in these patients. METHODS We reviewed the records of 46 patients with unexpected metastasis of left-sided pancreatic ductal adenocarcinoma that were discovered during surgery between 2005 and 2019. Nineteen patients underwent palliative resection (minimally invasive distal pancreatectomy group), whereas 27 patients underwent only minimally invasive biopsy (minimally invasive biopsy group). Demographic, clinical, and operative data, as well as survival rates, were compared between the 2 groups. RESULTS Major complications (Clavien-Dindo grade ≥3) were comparable between the 2 groups (11.8% vs 5.6%; P = .603). Postoperative chemotherapy was administered to 84.2% of the minimally invasive distal pancreatectomy group and 77.8% of the minimally invasive biopsy group (P = .716). The minimally invasive distal pancreatectomy group had a higher completion rate of first-line palliative chemotherapy (42.9% vs 8.7%; P = .007) and a higher 2-year survival rate (36.8% vs 18.8%; P = .004). In multivariate analysis, survival was associated with completion of first-line chemotherapy (hazard ratio: 2.962; P = .003) and maintenance chemotherapy for over 12 months (hazard ratio: 2.339; P = .010). Gastric outlet obstruction was less prevalent in the minimally invasive distal pancreatectomy group (5.3% vs 25.9%, P = .037). CONCLUSION Palliative minimally invasive distal pancreatectomy may improve survival and facilitate the continuation of chemotherapy in selected patients with unexpected metastatic pancreatic ductal adenocarcinoma. However, the small sample size and potential selection bias limit the generalizability of these findings. Larger, prospective, multicenter studies are needed to confirm the role of minimally invasive distal pancreatectomy and to establish optimal management strategies for these patients.
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Affiliation(s)
- Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Kyu Sung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, BK21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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D'Ambra V, Ricci C, Ingaldi C, Alberici L, Minghetti M, Casadei R. Stage IV pancreatic ductal adenocarcinoma (PDAC) with synchronous liver metastasis: are there survival benefits in liver resection? A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109598. [PMID: 39837137 DOI: 10.1016/j.ejso.2025.109598] [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: 09/25/2024] [Revised: 01/01/2025] [Accepted: 01/10/2025] [Indexed: 01/23/2025]
Abstract
OBJECTIVE Metastatic PDAC has a very poor prognosis, and surgery has a limited role. The study aims to evaluate the OS of patients with PDAC and synchronous liver metastasis who undergo surgical therapy (ST) versus non-surgical therapies (NST). METHODS We performed a random effects meta-analysis. Inclusion criteria were: PDAC histology; studies reporting technically resectable cases with liver metastasis and survival data; absence of extra-hepatic disease. The primary endpoint was to evaluate OS. Results were reported as HR and 95 % CI. We performed a meta-regression analysis to identify factors influencing heterogeneity. We analyzed key covariates in order to predict how changes in these factors affect HR. RESULTS Six studies were included. The OS was significantly better in group ST than NST, with HR = 0.41 (95 % CI: 0.32-0.52). Heterogeneity was high (I2 = 64.50 %). As the rate of patients who underwent postoperative CT in the ST group decreased, the difference between the two groups decreased (β = -1.28 ± 0.67; p = 0.003), with almost 87.10 % heterogeneity. The adjusted effect based on meta-regression showed an improved OS in ST group only when both pre- and post-operative systemic CT were administrated (HR 0.18, 95 % CI: 0.08-0.40). CONCLUSIONS In highly selected patients with metastatic PDAC who respond to systemic CT and receive post-operative systemic CT, ST could be associated with improved OS. However, the high heterogeneity and retrospective design of included studies limit the ability to draw definitive conclusions.
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Affiliation(s)
- Vincenzo D'Ambra
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Italy.
| | - Carlo Ingaldi
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Italy
| | - Laura Alberici
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Italy
| | - Margherita Minghetti
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Italy; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Italy
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Fonseca GM, Braghiroli MIFM, Pirola Kruger JA, Coelho FF, Herman P. Is There a Role for Locoregional Therapies for Non-colorectal Gastrointestinal Malignancies? Hematol Oncol Clin North Am 2025; 39:125-141. [PMID: 39510669 DOI: 10.1016/j.hoc.2024.08.004] [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] [Indexed: 11/15/2024]
Abstract
The liver is the most common site of metastases from solid gastrointestinal tract tumors. Over the past few decades, the role of locoregional therapies, resection and thermal ablation, for neuroendocrine and colorectal liver metastases has been widely studied. However, for liver metastases originating from other gastrointestinal organs, the role of locoregional treatment remains unclear. This review summarizes and discusses the available evidence regarding benefits, risks, and indications for locoregional therapies for non-colorectal and non-neuroendocrine gastrointestinal liver metastases, highlighting the importance of multidisciplinary approach and patient selection.
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Affiliation(s)
- Gilton Marques Fonseca
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Maria Ignez Freitas Melro Braghiroli
- Instituto do Cancer do Estado de Sao Paulo (ICESP), University of Sao Paulo, and Rede D'Or Sao Paulo, Av. Dr. Arnaldo, 251 - São Paulo, SP, Brazil. CEP: 01246-000, Brazil
| | - Jaime Arthur Pirola Kruger
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Fabricio Ferreira Coelho
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Paulo Herman
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil.
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Giuliante F, Panettieri E, Campisi A, Coppola A, Vellone M, De Rose AM, Ardito F. Treatment of oligo-metastatic pancreatic ductal adenocarcinoma to the liver: is there a role for surgery? A narrative review. Int J Surg 2024; 110:6163-6169. [PMID: 38818688 PMCID: PMC11486948 DOI: 10.1097/js9.0000000000001665] [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: 12/30/2023] [Accepted: 05/09/2024] [Indexed: 06/01/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.
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Affiliation(s)
- Felice Giuliante
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Elena Panettieri
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Andrea Campisi
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | | | - Maria Vellone
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Agostino M. De Rose
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Francesco Ardito
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
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5
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Hewitt DB, Wolfgang CL. The Role of Surgery in "Oligometastatic" Pancreas Cancer. Surg Clin North Am 2024; 104:1065-1081. [PMID: 39237164 DOI: 10.1016/j.suc.2024.04.009] [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] [Indexed: 09/07/2024]
Abstract
The majority of patients diagnosed with pancreatic cancer already have metastatic disease at the time of presentation, which results in a 5-year survival rate of only 13%. However, multiagent chemotherapy regimens can stabilize the disease in select patients with limited metastatic disease. For such patients, a combination of curative-intent therapy and systemic therapy may potentially enhance outcomes compared to using systemic therapy alone. Of note, the evidence supporting this approach is primarily derived from retrospective studies and may carry a significant selection bias. Looking ahead, ongoing prospective trials are exploring the efficacy of curative-intent therapy in managing oligometastatic pancreatic cancer and the implementation of treatment strategies based on specific biomarkers. The emergence of these trials, coupled with the development of less invasive therapeutic modalities, provides hope for patients with oligometastatic pancreatic cancer.
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Affiliation(s)
- D Brock Hewitt
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The NYU Grossman School of Medicine, 577 1st Avenue, 2nd Floor, New York, NY 10016, USA.
| | - Christopher L Wolfgang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The NYU Grossman School of Medicine, 577 1st Avenue, 2nd Floor, New York, NY 10016, USA
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Levine JM, Rompen IF, Franco JC, Swett B, Kryschi MC, Habib JR, Diskin B, Hewitt DB, Sacks GD, Kaplan B, Berman RS, Cohen SM, Wolfgang CL, Javed AA. The impact of metastatic sites on survival Rates and predictors of extended survival in patients with metastatic pancreatic cancer. Pancreatology 2024; 24:887-893. [PMID: 38969544 PMCID: PMC11462613 DOI: 10.1016/j.pan.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 06/07/2024] [Accepted: 06/10/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND OBJECTIVES The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. METHODS We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016-2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. RESULTS Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). CONCLUSION While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.
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Affiliation(s)
- Jonah M Levine
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Ingmar F Rompen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA; Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Jorge Campos Franco
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Ben Swett
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Maximilian C Kryschi
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Joseph R Habib
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Brian Diskin
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - D Brock Hewitt
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Greg D Sacks
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Brian Kaplan
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Russel S Berman
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Steven M Cohen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Christopher L Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Ammar A Javed
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA.
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Funo T, Hashimoto D, Yamaki S, Matsumura K, Miyazaki H, Matsui Y, Tsybulskyi D, Sang NT, Yaolin X, Satoi S. Conversion surgery for BRCA-mutated pancreatic ductal adenocarcinoma with liver metastasis treated with platinum-based chemotherapy followed by olaparib. Surg Case Rep 2024; 10:179. [PMID: 39078424 PMCID: PMC11289193 DOI: 10.1186/s40792-024-01975-x] [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: 05/20/2024] [Accepted: 07/13/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND With recent dramatic developments in chemotherapy, attempts to incorporate surgery into the multidisciplinary treatment of unresectable pancreatic ductal adenocarcinoma with metastasis (UR-M PDAC) have emerged. Maintenance therapy with olaparib after chemotherapy including a platinum-based regimen, which inhibits the poly ADP-ribose polymerase (PARP) involved in DNA repair, was approved for UR-M PDAC with positive BRCA mutations. CASE PRESENTATION A 47-year-old male patient with a high carbohydrate antigen 19-9 (CA19-9) level was diagnosed with PDAC in the pancreatic tail. Staging laparoscopy revealed occult liver metastasis. Because BRCA2 mutation was confirmed, triple combination chemotherapy with SOXIRI (S-1/oxaliplatin/irinotecan) was introduced and continued for 16 weeks, followed by 14 weeks of olaparib. After that, CA19-9 was normalized, and no obvious liver metastases of any size could be seen on imaging studies during chemotherapy. Since staging laparoscopy after chemotherapy proved that the liver metastasis had disappeared, laparoscopic distal pancreatectomy was performed, and curative resection was completed. After adjuvant chemotherapy with olaparib for 12 months, the patient is alive 36 months from his initial diagnosis and 27 months postoperatively without recurrence. CONCLUSION We report a case of PDAC with liver metastasis and BRCA mutation-positivity who underwent conversion surgery and achieved long-term survival after irinotecan-based chemotherapy followed by maintenance therapy with olaparib.
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Affiliation(s)
- Takumi Funo
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Daisuke Hashimoto
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - So Yamaki
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Kazuki Matsumura
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Hidetaka Miyazaki
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Yuki Matsui
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Denys Tsybulskyi
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Nguyen Thanh Sang
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Xu Yaolin
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan
| | - Sohei Satoi
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan.
- Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
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Saito R, Ban D, Mizui T, Takamoto T, Nara S, Esaki M, Shimada K. Oligo-like liver metastasis: A novel prognostic indicator to improve survival in pancreatic cancer. Ann Gastroenterol Surg 2024; 8:481-489. [PMID: 38707220 PMCID: PMC11066487 DOI: 10.1002/ags3.12753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 10/10/2023] [Accepted: 10/24/2023] [Indexed: 05/07/2024] Open
Abstract
Purpose Whether surgical intervention for patients with oligometastatic recurrence can improve their post-recurrent prognosis is unclear. In this study, we introduce a novel concept of oligometastasis in post-surgical pancreatic ductal adenocarcinoma (PDAC) patients with hepatic recurrence, which we call "oligo-like liver metastasis (OLLM)." Patients with OLLM have better post-recurrence prognosis and could therefore be eligible for surgical intervention. Methods A total of 121 PDAC patients who underwent radical resection, and who had an initial and single-organ metastasis to the liver, were analyzed. Independent prognostic factors for overall survival after recurrence (OSAR) were examined, and patients with all of these factors were defined as OLLM. The clinicopathological features and post-recurrent prognosis of OLLM patients were evaluated. In addition, a detailed analysis using the oligo-score, which was based on the prognostic factors, was performed. Results The prognostic analysis revealed that short recurrence-free interval (RFI) (<6 months), short stable disease interval (SDI) (≤3 months), and four or more recurrent tumors were independent poor prognostic factors. OLLM patients were defined as those with all three conditions: long RFI (≥6 months), long SDI (>3 months), and three or less recurrent tumors. OLLM patients had a significantly better prognosis for OSAR than non-OLLM patients (HR = 0.272, p < 0.001). Further analysis demonstrated that the OSAR of patients could be stratified using the oligo-score, which was calculated based on the prognostic factors. Conclusion We recommend that OLLM should be used to predict which patients are most likely to experience better post-recurrent prognosis after surgery with curative intent.
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Affiliation(s)
- Ryo Saito
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
- First Department of Surgery, Faculty of MedicineUniversity of YamanashiYamanashiJapan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
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Su K, Duan R, Wu Y. Identifying Optimal Candidates for Primary Tumor Resection Among Metastatic Pancreatic Cancer Patients: A Population-Based Predictive Model. Cancer Invest 2024; 42:333-344. [PMID: 38712480 DOI: 10.1080/07357907.2024.2349585] [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: 07/08/2023] [Accepted: 04/25/2024] [Indexed: 05/08/2024]
Abstract
BACKGROUND There is a controversy about whether surgery should proceed among metastatic pancreatic cancer (mPC) patients. A survival benefit was observed in mPC patients who underwent primary tumor resection; however, determining which patients would benefit from surgery is complex. For this purpose, we created a model to identify mPC patients who may benefit from primary tumor excision. METHODS Patients with mPC were extracted from the Surveillance, Epidemiology, and End Results database, and separated into surgery and nonsurgery groups based on whether the primary tumor was resected. Propensity score matching (PSM) was applied to balance confounding factors between the two groups. A nomogram was developed using multivariable logistic regression to estimate surgical benefit. Our model is evaluated using multiple methods. RESULTS About 662 of 14,183 mPC patients had primary tumor surgery. Kaplan-Meier analyses showed that the surgery group had a better prognosis. After PSM, a survival benefit was still observed in the surgery group. Among the surgery cohort, 202 patients survived longer than 4 months (surgery-beneficial group). The nomogram discriminated better in training and validation sets under the receiver operating characteristic (ROC) curve (AUC), and calibration curves were consistent. Decision curve analysis (DCA) revealed that it was clinically valuable. This model is better at identifying candidates for primary tumor excision. CONCLUSION A helpful prediction model was developed and validated to identify ideal candidates who may benefit from primary tumor resection in mPC.
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Affiliation(s)
- Kaifeng Su
- Medical Faculty of Ludwig Maximilians University of Munich, University Hospital of LMU Munich, Munich, Germany
| | - Ruifeng Duan
- Department of Gastroenterology and Digestive Endoscopy Center, The Second Hospital of Jilin University, Changchun, China
| | - Yang Wu
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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10
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Tohyama T, Tanno Y, Murakami T, Hayashi T, Fujimoto Y, Takehara K, Seshimo K, Fukuhara R, Omori M, Matsumoto T. A case of metachronous oligo-hepatic and peritoneal metastases of pancreatic cancer with a favorable outcome after conversion surgery combined with perioperative sequential chemotherapy. Clin J Gastroenterol 2024; 17:371-381. [PMID: 38291249 DOI: 10.1007/s12328-023-01917-4] [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: 10/06/2023] [Accepted: 12/24/2023] [Indexed: 02/01/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, and the prognosis for its recurrence after surgery is very poor. Here, we report a case of metachronous oligo-hepatic and peritoneal metastases in a patient who survived without recurrence for 3 years after conversion surgery combined with perioperative sequential chemotherapy using gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFOLFIRINOX). The patient was a 70-year-old man with pancreatic ductal carcinoma, classified as cT3N0M0, cStage IIA, who underwent a distal pancreatosplenectomy. At 1 year and 4 months later, two liver metastases and one peritoneal metastasis were detected. A systemic 9-month course of chemotherapy was administered with GnP and mFOLFIRINOX as the first- and second-line chemotherapeutic agents, respectively. The two liver metastases were judged as showing a partial response, but one dissemination was considered stable disease. After receiving informed consent from the patient, we performed resection of the disseminated tumor and lateral segmentectomy of the liver. Adjuvant chemotherapy using mFOLFIRINOX and GnP was administered for 10 months. The patient has now been alive for 5 years and 6 months after the initial pancreatosplenectomy, and 3 years and 3 months after the conversion surgery, without subsequent tumor recurrence. Thus, a multidisciplinary treatment approach including surgery and perioperative sequential chemotherapy using GnP and mFOLFIRINOX may be beneficial for treating metachronous oligo-hepatic and peritoneal metastases, depending on the patient's condition.
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Affiliation(s)
- Taiji Tohyama
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan.
| | - Yuto Tanno
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Takayoshi Murakami
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Tatsuro Hayashi
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Yoshimi Fujimoto
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Kiyoto Takehara
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Ken Seshimo
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Ryuichiro Fukuhara
- Department of Radiology, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Masako Omori
- Department of Pathology, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
| | - Takamasa Matsumoto
- Department of Surgery, Kurashiki Medical Center, Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan
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11
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Kong Q, Teng F, Li H, Chen Z. Radical resection benefits patients suffering pancreatic ductal adenocarcinoma with liver oligometastases. Ann Surg Treat Res 2024; 106:51-60. [PMID: 38205094 PMCID: PMC10774701 DOI: 10.4174/astr.2024.106.1.51] [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: 08/11/2023] [Revised: 10/16/2023] [Accepted: 11/15/2023] [Indexed: 01/12/2024] Open
Abstract
Purpose Whether patients suffering liver oligometastases from pancreatic ductal adenocarcinoma (LOPDA) should undergo surgical treatment remains controversial. Methods PubMed and Embase databases were systematically reviewed until 2023 June. Survival data were collected from the Kaplan-Meier curves. Safety and survival were evaluated using primary outcomes such as 1-year, 3-year, and 5-year survival rates, and 30-day mortality and morbidity. A subgroup meta-analysis was conducted to compare survival rates post-synchronous resection and resection post-neoadjuvant chemotherapy in LOPDA. Results Our analysis of 15 studies involving 1,818 patients (surgical group, 648 and nonsurgical group, 1,170) indicates that radical hepatectomy for LOPDA notably improved 1-year (odds ratio [OR], 3.24; 95% confidence interval [CI], 2.45-4.28; P < 0.001), 3-year (OR, 5.74; 95% CI, 3.36-8.90; P < 0.001), and 5-year (OR, 4.89; 95% CI, 2.56-9.35; P < 0.001) overall survival (OS) rates. A separate analysis of 6 studies with 750 patients demonstrated the safety of LOPDA surgery, with no increase in postoperative complications (P = 0.26 for overall morbidity and P = 0.99 for mortality) compared to the patients with no metastatic disease from the pancreatic ductal adenocarcinoma (NMPDA) group. The NMPDA group showed superior 1-year and 3-year OS rates, but not 5-year OS rates compared to the LOPDA group. Conclusion Surgical treatment apparently offers a survival advantage to LOPDA by comparing with nonsurgical groups in 1-, 3-, and 5-year OS rates. Radical resection for LOPDA is a safe treatment without more postoperative complications than NMPDA.
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Affiliation(s)
- Qingyan Kong
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Fei Teng
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hang Li
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zheyu Chen
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
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12
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Leonhardt CS, Stamm T, Hank T, Prager G, Strobel O. Defining oligometastatic pancreatic cancer: a systematic review and critical synthesis of consensus. ESMO Open 2023; 8:102067. [PMID: 37988953 PMCID: PMC10774968 DOI: 10.1016/j.esmoop.2023.102067] [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: 08/05/2023] [Accepted: 10/14/2023] [Indexed: 11/23/2023] Open
Abstract
BACKGROUND Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no uniform definition of oligometastatic disease (OMD) in PDAC exists; this impedes meaningful conclusions. PATIENTS AND METHODS A systematic literature search using PubMed, Web of Science, and Cochrane CENTRAL registries for studies and protocols reporting on definitions and/or LCT of OMD in PDAC was performed. The primary endpoint was the definition of OMD. Levels of agreement were categorized as consensus (≥75% agreement between studies), fair agreement (50%-74%), and absent/poor agreement (<50%). RESULTS After screening of 5374 abstracts, the full text of 218 studies was assessed, of which 76 were included in the qualitative synthesis. The majority of studies were retrospective (n = 66, 87%), two were prospective studies and eight were study protocols. Studies investigated mostly liver (n = 38, 51%) and lung metastases (n = 15, 20%). Across studies, less than one-half (n = 32, 42%) reported a definition of OMD, while 44 (58%) did not. Involvement was limited to a single organ (consensus). Additional criteria for defining OMD were the number of lesions (consensus), metastatic site (poor agreement), metastatic size (poor agreement), treatment possibilities (poor agreement), and biomarker response (poor agreement). Liver OMD could involve three or fewer lesions (consensus) and synchronous disease (fair agreement), while lung metastases could involve two or fewer lesions and metachronous disease (consensus). The large majority of studies were at a high risk of bias or did not include any control groups. CONCLUSION Definitions of OMD were not used or varied widely between studies hampering across-study comparability and highlighting an unmet need for a consensus. The present study is part of a multistep process that aims to develop an interdisciplinary consensus on OMD in pancreatic cancer.
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Affiliation(s)
- C-S Leonhardt
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna
| | - T Stamm
- Institute of Outcomes Research, Center for Medical Data Science, Medical University of Vienna; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna
| | - T Hank
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna
| | - G Prager
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - O Strobel
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna.
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13
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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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14
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Kaslow SR, Sacks GD, Berman RS, Lee AY, Correa-Gallego C. Natural History of Stage IV Pancreatic Cancer. Identifying Survival Benchmarks for Curative-intent Resection in Patients With Synchronous Liver-only Metastases. Ann Surg 2023; 278:e798-e804. [PMID: 36353987 DOI: 10.1097/sla.0000000000005753] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients. BACKGROUND Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups. METHODS We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan-Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis. RESULTS We identified 241 patients. Median OS was 7 months (95% CI, 5-9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17-39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR). CONCLUSIONS The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.
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Affiliation(s)
- Sarah R Kaslow
- Department of Surgery, New York University Grossman School of Medicine, New York City, NY
| | - Greg D Sacks
- Department of Surgery, New York University Grossman School of Medicine, New York City, NY
| | - Russell S Berman
- Department of Surgery, New York University Grossman School of Medicine, New York City, NY
| | - Ann Y Lee
- Department of Surgery, New York University Grossman School of Medicine, New York City, NY
| | - Camilo Correa-Gallego
- Department of Surgery, New York University Grossman School of Medicine, New York City, NY
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York City, NY
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15
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Hashimoto D, Satoi S, Fujii T, Sho M, He J, Hackert T, Del Chiaro M, Jang JY, Gulla A, Yoon YS, Shan YS, Lou W, Valente R, Furuse J, Oba A, Nagai M, Terai T, Tanaka H, Sakai A, Yamamoto T, Yamaki S, Matsumoto I, Murakami Y, Takaori K, Takeyama Y. Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto. Pancreatology 2023; 23:682-688. [PMID: 37507301 DOI: 10.1016/j.pan.2023.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/09/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.
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Affiliation(s)
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan; Division of Surgical Oncology, Department of Surgery, University of Colorado of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
| | - Tsutomu Fujii
- Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, Nara, Japan
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg Eppendorf, Hamburg, Germany
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado of Medicine, Anschutz Medical Campus, Aurora, CO, USA
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Aiste Gulla
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yan-Shen Shan
- Department of Surgery, National Cheng Kung University Hospital, Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wenhui Lou
- Department of General Surgery, Fudan University Zhongshan Hospital, Shanghai, China
| | - Roberto Valente
- Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden
| | - Junji Furuse
- Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Minako Nagai
- Department of Surgery, Nara Medical University, Nara, Japan
| | - Taichi Terai
- Department of Surgery, Nara Medical University, Nara, Japan
| | - Haruyoshi Tanaka
- Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
| | - Ayano Sakai
- Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
| | | | - So Yamaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Ippei Matsumoto
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kyoichi Takaori
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Surgery, Nagahama City Hospital, Shiga, Japan
| | - Yoshifumi Takeyama
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
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16
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Nagai M, Wright MJ, Ding D, Thompson ED, Javed AA, Weiss MJ, Hruban RH, Yu J, Burkhart RA, He J, Cameron JL, Wolfgang CL, Burns WR. Oncologic resection of pancreatic cancer with isolated liver metastasis: Favorable outcomes in select patients. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:1025-1035. [PMID: 36652559 PMCID: PMC10548446 DOI: 10.1002/jhbp.1303] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 12/23/2022] [Accepted: 01/12/2023] [Indexed: 01/19/2023]
Abstract
BACKGROUND Patients with pancreatic ductal adenocarcinoma (PDAC) and liver metastasis are treated with palliative chemotherapy, whereas similar patients with metastatic colorectal cancer are considered for aggressive surgery. METHODS Using an institutional database, PDAC patients undergoing liver resection for isolated metastasis were identified. Their overall survival (OS), treatment factors, and clinicopathological variables associated with survival were also evaluated. RESULTS Forty-seven patients underwent curative-intent surgery for metastatic PDAC to the liver between 2000 and 2019. Median OS was 21.9 months from diagnosis. Fourteen patients underwent unplanned resection of radiographically occult liver metastasis during pancreatectomy with median OS of 8.7 months. On the other hand, 29 patients received systemic chemotherapy followed by planned resection; this cohort had the most favorable prognosis following aggressive surgery with median OS being 38.1 months from diagnosis and 24.1 months from surgery. Preoperative chemotherapy (HR = 7.1; p = .002) and moderate to well differentiation of the primary tumor (HR = 3.7; p = .003) were associated with prolonged survival in multivariate analysis, whereas lymph node metastases, response to preoperative therapy, number of liver metastasis, and extent of liver surgery were not. CONCLUSIONS In select patients with PDAC and isolated liver metastasis, curative-intent surgery can result in meaningful survival. This aggressive approach seems most beneficial in patients following induction chemotherapy.
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Affiliation(s)
- Minako Nagai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Surgery, Nara Medical University, Nara, Japan
| | - Michael J. Wright
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ding Ding
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elizabeth D. Thompson
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ammar A. Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Matthew J. Weiss
- Department of Hepatobiliary Surgery, Pancreas, Oncology, Northwell Health Cancer Institute, New Hyde Park, New York, USA
| | - Ralph H. Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Richard A. Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - John L. Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Christopher L. Wolfgang
- Department of Surgery, New York University Grossman School of Medicine and NYU-Langone Medical Center, New York, New York, USA
| | - William R. Burns
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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17
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Halle-Smith JM, Powell-Brett S, Roberts K, Chatzizacharias NA. Resection of isolated liver oligometastatic disease in pancreatic ductal adenocarcinoma: Is there a survival benefit? A systematic review. World J Gastrointest Surg 2023; 15:1512-1521. [PMID: 37555114 PMCID: PMC10405113 DOI: 10.4240/wjgs.v15.i7.1512] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/22/2023] [Accepted: 05/05/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma (PDAC), either synchronous or metachronous after pancreatic resection, is a terminal diagnosis that warrants management with palliative intent as per all international practice guidelines. However, there is an increasing interest on any potential value of surgical treatment of isolated oligometastatic disease in selected cases. AIM To present the published evidence on surgical management of PDAC liver metastases, synchronous and metachronous, and compare the outcomes of these treatments to the current standard of care. METHODS A systematic review was performed in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to compare the outcomes of both synchronous and metachronous liver metastases resection to standard care. RESULTS 356 studies were identified, 31 studies underwent full-text review and of these 10 were suitable for inclusion. When synchronous resection of liver metastases was compared to standard care, most studies did not demonstrate a survival benefit with the exception of one study that utilised neoadjuvant treatment. However, resection of metachronous disease appeared to confer a survival advantage when compared to treatment with chemotherapy alone. CONCLUSION A survival benefit may exist in resection of selected cases of metachronous liver oligometastatic PDAC disease, after disease biology has been tested with time and systemic treatment. Any survival benefit is less clear in synchronous cases; however an approach with neoadjuvant treatment and consideration of resection in some selected cases may confer some benefit. Future studies should focus on pathways for selection of cases that may benefit from an aggressive approach.
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Affiliation(s)
- James M Halle-Smith
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Sarah Powell-Brett
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith Roberts
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nikolaos A Chatzizacharias
- Department of HPB and Liver Transplant, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2GW, United Kingdom
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18
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Yasuda S, Nagai M, Terai T, Kohara Y, Sho M. Essential updates 2021/2022: Surgical outcomes of oligometastasis in pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 2023; 7:358-366. [PMID: 37152775 PMCID: PMC10154895 DOI: 10.1002/ags3.12655] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/25/2022] [Accepted: 01/01/2023] [Indexed: 01/20/2023] Open
Abstract
Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including surgery. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma, although there is still little evidence. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarized the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives. In liver oligometastasis, multimodal treatment including surgery achieved favorable long-term survival, especially in patients with good responses to preoperative chemotherapy, with a median survival time from 25.5 to 54.6 months. In addition, the data from the National Cancer Database in the United States showed that patients who underwent surgery for oligometastatic liver metastases had a significantly longer overall survival than those who received chemotherapy alone. Prognostic biomarkers were identified, including carbohydrate antigen 19-9 (CA19-9) levels at diagnosis and preoperative chemotherapy with normalization of CA19-9 levels or favorable radiological response. Patients with lung oligometastasis had a more favorable long-term prognosis than those with other recurrence sites, and the updated literature further confirmed the previous studies. Overall survival was favorable, with 84 months after initial surgery and 29.2 months after metastasectomy, and a 5-year survival rate of 60.6% was also reported. In peritoneal oligometastasis, the results of conversion surgery after good responses to preoperative treatment with intraperitoneal therapy or systematic chemotherapy were reported, and the conversion rate and long-term prognosis were favorable. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarize the current status of surgery in multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives.
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Affiliation(s)
| | - Minako Nagai
- Department of SurgeryNara Medical UniversityNaraJapan
| | - Taichi Terai
- Department of SurgeryNara Medical UniversityNaraJapan
| | | | - Masayuki Sho
- Department of SurgeryNara Medical UniversityNaraJapan
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19
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Hank T, Klaiber U, Hinz U, Schütte D, Leonhardt CS, Bergmann F, Hackert T, Jäger D, Büchler MW, Strobel O. Oncological Outcome of Conversion Surgery After Preoperative Chemotherapy for Metastatic Pancreatic Cancer. Ann Surg 2023; 277:e1089-e1098. [PMID: 35758505 PMCID: PMC10082047 DOI: 10.1097/sla.0000000000005481] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To investigate the outcome of conversion surgery in patients with metastatic pancreatic cancer (mPDAC) and to identify patients who may benefit from this approach. BACKGROUND The role of conversion surgery in patients with mPDAC and exceptional response to chemotherapy remains unclear. METHODS Patients who underwent surgical exploration for mPDAC following chemotherapy between 2006 and 2019 were included. Data on demographics, oncologic treatment, pathology, and postoperative outcomes were analyzed. Univariate and multivariate survival analyses were performed. RESULTS Some 173 patients received preoperative chemotherapy and underwent surgical exploration. Ninety-three patients underwent resection of the primary tumor and metastatic sites, 80 patients underwent exploration only. In the resection subgroup, 45 patients had complete pathological response of metastases (ypM0) and 48 patients had residual metastases (ypM1). ypM0 status was associated with lower carcinoembryonic antigen levels and lower ypN stage. Overall survival after resection was 25.5 months in ypM0, 10.7 months in ypM1, and 8.1 months in patients without resection ( P <0.001). Additional adjuvant chemotherapy was significantly associated with prolonged survival in resected patients (29.0 vs 14.8 mo, P =0.024) as well as in ypM0 (29.1 vs 19.2 mo, P =0.047). Multivariable analysis identified conversion surgery, carbohydrate antigen 19-9 (CA19-9) and time of resection as independent prognostic markers for the entire cohort. CA19-9, ypM0 and adjuvant treatment were independent predictors of survival in the resection subgroup. CONCLUSION In patients with mPDAC and ypM0 status after chemotherapy, surgical resection is associated with encouraging survival. mPDAC patients with exceptional response to chemotherapy may be candidates for exploration and for resection in ypM0. Adjuvant chemotherapy may provide an additional survival advantage.
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Affiliation(s)
- Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Denise Schütte
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Carl-Stephan Leonhardt
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Frank Bergmann
- Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Dirk Jäger
- Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
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20
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Zhang H, Dong H, Pan Z, Du X, Liu S, Xu W, Zhang Y. Risk factors and predictive nomograms for early death of patients with pancreatic cancer liver metastasis: A large cohort study based on the SEER database and Chinese population. Front Oncol 2022; 12:998445. [PMID: 36212438 PMCID: PMC9539004 DOI: 10.3389/fonc.2022.998445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/23/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundThe liver is the most common organ for distant metastasis of pancreatic cancer, and patients with pancreatic cancer liver metastases (PCLM) often die in a short period of time. As such, the establishment of an effective nomogram to predict the probability of early death (survival time ≤3 months) in PCLM patients is of considerable significance.MethodsPatients diagnosed with PCLM in the Surveillance, Epidemiology, and End Result (SEER) database between 2010 and 2015 were included for model construction and internal validation. A data set was obtained from the Chinese population for external validation. Risk factors that contributed to all-cause and cancer-specific early death were determined by means of univariable and multivariable logistic regression. The accuracy of the nomogram was verified by means of receiver operating characteristic (ROC) curves, and the true consistency of the model was assessed by calibration curves. The clinical applicability of the model was evaluated by means of decision curve analysis (DCA).ResultsA total of 12,955 patients were included in the present study, of whom 7,219 (55.7%) experienced early death and 6,973 (53.8%) patients died of PCLM. Through multivariable logistic regression analysis, 11 risk factors associated with all-cause early death and 12 risk factors associated with cancer-specific early death were identified. The area under the curves (AUCs) for all-cause and cancer-specific early death were 0.806 (95% CI: 0.785- 0.827) and 0.808 (95% CI: 0.787- 0.829), respectively. Internal validation showed that the C-indexes of all-cause and cancer-specific early death after bootstrapping (5,000 re-samplings) were 0.805 (95% CI: 0.784-0.826) and 0.807 (95% CI: 0.786-0.828), respectively. As revealed by the calibration curves, the constructed nomograms exhibited good consistency. The decision curve analysis (DCA) indicated the nomograms had significant clinical applicability.ConclusionIn the present study, reliable nomograms were developed for predicting the early death probability in patients with PCLM. Such tools can help clinicians identify high-risk patients and develop individualized treatment plans as early as possible.
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Affiliation(s)
- Haidong Zhang
- School of Medicine, Southeast University, Nanjing, China
| | - Hui Dong
- School of Medicine, Southeast University, Nanjing, China
| | - Zheng Pan
- Hepatopancreatobiliary Center, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xuanlong Du
- School of Medicine, Southeast University, Nanjing, China
| | - Shiwei Liu
- School of Medicine, Southeast University, Nanjing, China
| | - Wenjing Xu
- School of Medicine, Southeast University, Nanjing, China
| | - Yewei Zhang
- Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Yewei Zhang,
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21
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Li Q, Bai L, Xing J, Liu X, Liu D, Hu X. Risk Assessment of Liver Metastasis in Pancreatic Cancer Patients Using Multiple Models Based on Machine Learning: A Large Population-Based Study. DISEASE MARKERS 2022; 2022:1586074. [PMID: 35634443 PMCID: PMC9132665 DOI: 10.1155/2022/1586074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/26/2022] [Accepted: 04/30/2022] [Indexed: 11/18/2022]
Abstract
Background A more accurate prediction of liver metastasis (LM) in pancreatic cancer (PC) would help improve clinical therapeutic effects and follow-up strategies for the management of this disease. This study was to assess various prediction models to evaluate the risk of LM based on machine learning algorithms. Methods We retrospectively reviewed clinicopathological characteristics of PC patients from the Surveillance, Epidemiology, and End Results database from 2010 to 2018. The logistic regression, extreme gradient boosting, support vector, random forest (RF), and deep neural network machine algorithms were used to establish models to predict the risk of LM in PC patients. Specificity, sensitivity, and receiver operating characteristic (ROC) curves were used to determine the discriminatory capacity of the prediction models. Results A total of 47,919 PC patients were identified; 15,909 (33.2%) of which developed LM. After iterative filtering, a total of nine features were included to establish the risk model for LM based on machine learning. The RF showed the most promising results in the prediction of complications among the models (ROC 0.871 for training and 0.832 for test sets). In risk stratification analysis, the LM rate and 5-year cancer-specific survival (CSS) in the high-risk group were worse than those in the intermediate- and low-risk groups. Surgery, radiotherapy, and chemotherapy were found to significantly improve the CSS in the high- and intermediate-risk groups. Conclusion In this study, the RF model constructed could accurately predict the risk of LM in PC patients, which has the potential to provide clinicians with more personalized clinical decision-making recommendations.
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Affiliation(s)
- Qinggang Li
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
| | - Lu Bai
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
| | - Jiyuan Xing
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
| | - Xiaorui Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
| | - Dan Liu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
| | - Xiaobo Hu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
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22
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Macfie R, Berger Y, Sarpel U, Hiotis S, Golas B, Labow D, Cohen N. Surgical management of pancreatic cancer liver oligometastases. Crit Rev Oncol Hematol 2022; 173:103654. [PMID: 35301097 DOI: 10.1016/j.critrevonc.2022.103654] [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: 10/26/2021] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 11/20/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, which commonly metastasizes to the liver. The current standard of care for metastatic PDAC is systemic chemotherapy, however there are limited emerging data regarding surgical resection of pancreatic oligometastases in select patients. Here we review the literature addressing resection of PDAC liver oligometastases.
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Affiliation(s)
| | | | | | | | | | | | - Noah Cohen
- The Mount Sinai Hospital, United States.
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23
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Lee SE, Han SS, Kang CM, Kwon W, Paik KY, Song KB, Yang JD, Chung JC, Jeong CY, Kim SW. Korean Surgical Practice Guideline for Pancreatic Cancer 2021: A summary of evidence-based surgical approaches. Ann Hepatobiliary Pancreat Surg 2022; 26:1-16. [PMID: 35220285 PMCID: PMC8901981 DOI: 10.14701/ahbps.22-009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/17/2022] [Accepted: 02/17/2022] [Indexed: 11/17/2022] Open
Abstract
Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2021. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.
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Affiliation(s)
- Seung Eun Lee
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sung-Sik Han
- Department of Surgery, National Cancer Center, Goyang, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang Yeol Paik
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Do Yang
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Korea
| | - Jun Chul Chung
- Department of Surgery, Soon Chun Hyang University School of Medicine, Cheonan, Korea
| | - Chi-Young Jeong
- Department of Surgery, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Sun-Whe Kim
- Department of Surgery, National Cancer Center, Goyang, Korea
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24
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Fu N, Jiang Y, Weng Y, Chen H, Deng X, Shen B. Worth it or not? Primary tumor resection for stage IV pancreatic cancer patients: A SEER-based analysis of 15,836 cases. Cancer Med 2021; 10:5948-5963. [PMID: 34288562 PMCID: PMC8419755 DOI: 10.1002/cam4.4147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/19/2021] [Accepted: 06/27/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Primary tumor resection (PTR) as a treatment option for patients with stage IV pancreatic cancer (PC) is controversial. PATIENTS AND METHODS Stage IV PC patients, with treatment data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER), were screened. The main outcomes were overall survival (OS) and cancer-specific survival (CSS). RESULTS We enrolled 15,836 stage IV PC patients in this study. Propensity score-matched analyses revealed improved OS and CSS of patients receiving chemotherapy plus PTR versus chemotherapy (median survival time [MSTOS ]: 13 vs. 9 months, p = 0.024; MSTCSS : 14 vs. 10 months, p = 0.035), and chemoradiotherapy plus PTR versus chemoradiotherapy (MSTOS : 14 vs. 7 months, p = 0.044; MSTCSS : 14 vs. 7 months, p = 0.066). Multivariate adjusted analyses further confirmed these results. Stratified with different metastatic modalities, multivariate analyses suggested that PTR significantly improved the OS and CSS among patients with ≤1 metastatic organ, and that patients with brain metastasis might not benefit from chemotherapy treatment. CONCLUSION PTR improves the OS and CSS of stage IV PC patients on the basis of chemotherapy or chemoradiotherapy, provided that the metastases involve ≤1 organ. Chemotherapy, however, should be carefully considered in patients with metastases involving the brain.
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Affiliation(s)
- Ningzhen Fu
- Department of General SurgeryPancreatic Disease CenterRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic DiseaseShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghaiChina
- Shanghai Jiao Tong UniversityInstitute of Translational MedicineShanghaiChina
| | - Yu Jiang
- Department of General SurgeryPancreatic Disease CenterRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic DiseaseShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghaiChina
- Shanghai Jiao Tong UniversityInstitute of Translational MedicineShanghaiChina
| | - Yuanchi Weng
- Department of General SurgeryPancreatic Disease CenterRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic DiseaseShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghaiChina
- Shanghai Jiao Tong UniversityInstitute of Translational MedicineShanghaiChina
| | - Hao Chen
- Department of General SurgeryPancreatic Disease CenterRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic DiseaseShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghaiChina
- Shanghai Jiao Tong UniversityInstitute of Translational MedicineShanghaiChina
| | - Xiaxing Deng
- Department of General SurgeryPancreatic Disease CenterRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic DiseaseShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghaiChina
- Shanghai Jiao Tong UniversityInstitute of Translational MedicineShanghaiChina
| | - Baiyong Shen
- Department of General SurgeryPancreatic Disease CenterRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
- Shanghai Jiao Tong University School of MedicineResearch Institute of Pancreatic DiseaseShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghaiChina
- Shanghai Jiao Tong UniversityInstitute of Translational MedicineShanghaiChina
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25
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Zhou W, Wang D, Lou W. Current Role of Surgery in Pancreatic Cancer With Synchronous Liver Metastasis. Cancer Control 2021; 27:1073274820976593. [PMID: 33238715 PMCID: PMC7791445 DOI: 10.1177/1073274820976593] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer with synchronous liver metastasis has an extremely poor
prognosis, and surgery is not recommended for such patients by the current
guidelines. However, an increasing body of studies have shown that concurrent
resection of pancreatic cancer and liver metastasis is not only technically
feasible but also beneficial to the survival in the selected patients. In this
review, we aim to summarize the short- and long-term outcomes following
synchronous liver metastasectomy for pancreatic cancer patients, and discuss the
potential criteria in selecting appropriate surgical candidates, which might be
helpful in clinical decision-making.
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Affiliation(s)
- Wentao Zhou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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26
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Safi SA, Fluegen G, Rehders A, Haeberle L, Fung S, Keitel V, Krieg A, Knoefel WT, Lehwald-Tywuschik N. Surgical margin clearance and extended chemotherapy defines survival for synchronous oligometastatic liver lesions of the ductal adenocarcinoma of the pancreas. Int J Clin Oncol 2021; 26:1911-1921. [PMID: 34132929 PMCID: PMC8449759 DOI: 10.1007/s10147-021-01961-5] [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: 01/14/2021] [Accepted: 06/03/2021] [Indexed: 11/28/2022]
Abstract
Background The role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease. Methods Correlation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available. Results Out of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed. Conclusion This is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results. Supplementary Information The online version contains supplementary material available at 10.1007/s10147-021-01961-5.
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Affiliation(s)
- S A Safi
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany
| | - G Fluegen
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany
| | - A Rehders
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany
| | - L Haeberle
- Institute of Pathology, Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Dusseldorf, Germany
| | - S Fung
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany
| | - V Keitel
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Dusseldorf, Germany
| | - A Krieg
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany
| | - W T Knoefel
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.
| | - N Lehwald-Tywuschik
- Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany
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Timmer FEF, Geboers B, Nieuwenhuizen S, Schouten EAC, Dijkstra M, de Vries JJJ, van den Tol MP, Meijerink MR, Scheffer HJ. Locoregional Treatment of Metastatic Pancreatic Cancer Utilizing Resection, Ablation and Embolization: A Systematic Review. Cancers (Basel) 2021; 13:cancers13071608. [PMID: 33807220 PMCID: PMC8036519 DOI: 10.3390/cancers13071608] [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: 01/31/2021] [Revised: 03/20/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a dismal prognosis. In selected patients with limited metastatic disease, locoregional therapy, in addition to systemic chemotherapy, may improve survival. This systematic review sought to examine current evidence on the value of additional locoregional treatment, including resection, ablation and embolization, in patients with hepatic or pulmonary mPDAC. The results, although liable to substantial bias, demonstrated superior survival from metastatic diagnosis or treatment in a subset of patients after radical-intent local primary and metastatic treatment (hepatic mPDAC 7.8–19 months; pulmonary mPDAC 22.8–47 months) compared to chemotherapy or best supportive care (hepatic mPDAC 4.3–7.6 months; pulmonary mPDAC 11.8 months). However, as a consequence of the bias, definitive conclusions regarding the seemingly beneficial effect of locoregional treatment cannot be endorsed. Randomized controlled trials with strictly selected oligometastatic PDAC patients are required to deduce final recommendations on this notion. Abstract The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains universally poor, requiring new and innovative treatment approaches. In a subset of oligometastatic PDAC patients, locoregional therapy, in addition to systemic chemotherapy, may improve survival. The aim of this systematic review was to explore and evaluate the current evidence on locoregional treatments for mPDAC. A systematic literature search was conducted on locoregional techniques, including resection, ablation and embolization, for mPDAC with a focus on hepatic and pulmonary metastases. A total of 59 studies were identified, including 63,453 patients. Although subject to significant bias, radical-intent local therapy for both the primary and metastatic sites was associated with a superior median overall survival from metastatic diagnosis or treatment (hepatic mPDAC 7.8–19 months; pulmonary mPDAC 22.8–47 months) compared to control groups receiving chemotherapy or best supportive care (hepatic mPDAC 4.3–7.6 months; pulmonary mPDAC 11.8 months). To recruit patients that may benefit from these local treatments, selection appears essential. Most significant is the upfront possibility of local radical pancreatic and metastatic treatment. In addition, a patient’s response to neoadjuvant systemic chemotherapy, performance status, metastatic disease load and, to a lesser degree, histological differentiation grade and tumor marker CA19-9 serum levels, are powerful prognostic factors that help identify eligible subjects. Although the exact additive value of locoregional treatments for mPDAC patients cannot be distillated from the results, locoregional primary pancreatic and metastatic treatment seems beneficial for a highly selected group of oligometastatic PDAC patients. For definite recommendations, well-designed prospective randomized controlled trials with strict in- and exclusion criteria are needed to validate these results.
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Affiliation(s)
- Florentine E. F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
- Correspondence: ; Tel.: +31-20-444-4571
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
| | - Evelien A. C. Schouten
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
| | - Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
| | - Jan J. J. de Vries
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
| | - M. Petrousjka van den Tol
- Department of Surgery, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
| | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (Location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (B.G.); (S.N.); (E.A.C.S.); (M.D.); (J.J.J.d.V.); (M.R.M.); (H.J.S.)
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28
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Prognostic Nomogram for pancreatic cancer with lung metastasis: a SEER database-based study. JOURNAL OF PANCREATOLOGY 2021. [DOI: 10.1097/jp9.0000000000000059] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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Su BB, Bai DS, Yu JQ, Zhang C, Jin SJ, Zhou BH, Jiang GQ. Can Patients with Pancreatic Cancer and Liver Metastases Obtain Survival Benefit from Surgery? A Population-Based Study. J Cancer 2021; 12:539-552. [PMID: 33391450 PMCID: PMC7739005 DOI: 10.7150/jca.51218] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 10/29/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Surgery for pancreatic cancer with liver metastases (PCL) is not recommended in the international guidelines, and investigation of its clinical significance in patients with PCL is very limited. This study explored whether surgery, especially synchronous resection of the primary tumor and liver metastases (SPL), could improve survival in PCL. Methods: Data of 14,248 patients with PCL from Surveillance, Epidemiology, and End Results database was analyzed. Patients were divided into following groups: SPL, synchronous primary site, and other resection (SPO), single resection of the primary site (SPS), and no resection (NR). Results: In this study, only 93 (0.7%) underwent SPL, 88 (0.6%) for SPO, and 232 (1.6%) for SPS. Multivariate Cox analysis showed surgical procedures of both the primary site and other sites were independent protective prognostic factors for pancreatic cancer cause-specific survival (PCSS) (all P < 0.001). Patients in the SPL group showed the most survival benefit, with a significant and gradually increased difference as compared with the SPO, SPS, and NR groups (median survival: 54, 34, 15, and 3 months, respectively, all P < 0.001). Compared with the NR group, mortalities were significant and gradually declining in the SPS, SPO, and SPL groups, with hazard ratio 0.329 (95% confidence interval [CI], 0.281 to 0.386), 0.220 (95% CI, 0.164 to 0.294), and 0.162 (95% CI, 0.118 to 0.222), respectively (all P < 0.001). Conclusions: Surgical procedures for both primary site and other sites improved survival. SPL, particularly, showed a considerable survival benefit in well-selected patients with PCL.
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Affiliation(s)
- Bing-Bing Su
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Dou-Sheng Bai
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Jiang-Quan Yu
- Department of Intensive Care Unit, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Chi Zhang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Sheng-Jie Jin
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Bao-Huan Zhou
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Guo-Qing Jiang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
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Fonseca GM, Braghiroli MIFM, Pirola Kruger JA, Coelho FF, Herman P. Is There a Role for Locoregional Therapies for Non-colorectal Gastrointestinal Malignancies? Surg Oncol Clin N Am 2020; 30:125-142. [PMID: 33220801 DOI: 10.1016/j.soc.2020.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The liver is the most common site of metastases from solid gastrointestinal tract tumors. Over the past few decades, the role of locoregional therapies, resection and thermal ablation, for neuroendocrine and colorectal liver metastases has been widely studied. However, for liver metastases originating from other gastrointestinal organs, the role of locoregional treatment remains unclear. This review summarizes and discusses the available evidence regarding benefits, risks, and indications for locoregional therapies for non-colorectal and non-neuroendocrine gastrointestinal liver metastases, highlighting the importance of multidisciplinary approach and patient selection.
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Affiliation(s)
- Gilton Marques Fonseca
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Maria Ignez Freitas Melro Braghiroli
- Instituto do Cancer do Estado de Sao Paulo (ICESP), University of Sao Paulo, and Rede D'Or Sao Paulo, Av. Dr. Arnaldo, 251 - São Paulo, SP, Brazil. CEP: 01246-000, Brazil
| | - Jaime Arthur Pirola Kruger
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Fabricio Ferreira Coelho
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil
| | - Paulo Herman
- Digestive Surgery Division, Liver Surgery Unit, Department of Gastroenterology, University of Sao Paulo Medical School, Avenida Doutor Enéas de Carvalho Aguiar, 255, Instituto Central, 9° andar, Sala 9074, Cerqueira Cesar, São Paulo, São Paulo CEP: 05403-900, Brazil.
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Ricke J, Westphalen CB, Seidensticker M. Therapeutic Concepts for Oligometastatic Gastrointestinal Tumours. Visc Med 2020; 36:359-363. [PMID: 33178732 DOI: 10.1159/000509897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 07/02/2020] [Indexed: 12/25/2022] Open
Abstract
Background Clinical trials have proven a survival benefit from applying local therapies for oligometastatic cancers of various origin. Summary Today, the definition of oligometa-static disease is based on limited lesion numbers and organ systems involved. Treatment guidelines by the European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO) and several other groups suggest a threshold of up to 5 tumours. Established biological markers indicating the aggressiveness of a given tumour (and therefore suggesting local treatment only or the addition of or complete switch to systemic therapies) are missing, except for disease-free survival, the only recommended parameter for patient selection beyond lesion count. Key Message The following article discusses clinical implications as well as local techniques established for the treatment of oligometastatic disease.
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Affiliation(s)
- Jens Ricke
- Klinik und Poliklinik für Radiologie, LMU Klinikum, Munich, Germany
| | - Christoph Benedikt Westphalen
- Medizinische Klinik und Poliklinik III und CCC München, Klinikum der Universität München, LMU München, Munich, Germany
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D'Haese JG, Renz BW, Ilmer M, Werner J. [Surgery for isolated local recurrence and metachronous oligometastasis in pancreatic cancer]. Chirurg 2020; 91:628-635. [PMID: 32424598 DOI: 10.1007/s00104-020-01190-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Most patients with pancreatic cancer suffer a relapse, which occurs either locally or systemically in the sense of liver and the lung metastases. Surgery for pancreatic cancer has become more radical due to the increased use of multimodal treatment concepts; however, the role of surgery in cases of recurrence remains controversial. OBJECTIVE This review summarizes the surgical treatment options for isolated local recurrence and metachronous oligometastatic pancreatic cancer. MATERIAL AND METHODS A selective literature search was carried out and the current evidence for surgical treatment is summarized. RESULTS There are currently no randomized studies on surgery for metastatic pancreatic cancer. Currently available data, however, show that after surgery long-term survival of up to 32-47 months after metastasectomy can be achieved, especially in patients with local recurrence or isolated pulmonary metastases with low morbidity and mortality. Individualized treatment concepts including surgical resection after initial systemic therapy seem promising even for liver metastases. The greatest survival benefits are consistently shown for all localizations in patients with a long as possible disease-free interval after the first operation. CONCLUSION The treatment of isolated local recurrence or metachronous oligometastatic pancreatic cancer is an interdisciplinary challenge that should be performed in specialized pancreatic treatment centers only. Surgical resection embedded in a multimodal treatment concept can be meaningful in selected cases.
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Affiliation(s)
- J G D'Haese
- Klinik für Allgemein, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, Standort Großhadern, Marchioninistr. 15, 81377, München, Deutschland.
| | - B W Renz
- Klinik für Allgemein, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, Standort Großhadern, Marchioninistr. 15, 81377, München, Deutschland
| | - M Ilmer
- Klinik für Allgemein, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, Standort Großhadern, Marchioninistr. 15, 81377, München, Deutschland
| | - J Werner
- Klinik für Allgemein, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, Standort Großhadern, Marchioninistr. 15, 81377, München, Deutschland
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Feng F, Cai W, Wang G, Chen W, Yang H, Sun M, Zhou L. Metastatic pancreatic adenocarcinomas could be classified into M1a and M1b category by the number of metastatic organs. BMC Gastroenterol 2020; 20:289. [PMID: 32854631 PMCID: PMC7457242 DOI: 10.1186/s12876-020-01431-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/20/2020] [Indexed: 11/17/2022] Open
Abstract
Background With the improvement of treatment and prognosis for patients with late malignant diseases, certain malignancies with distant metastasis (M1 category) have been further classified into M1a (single metastatic site) and M1b (multiple metastatic sites) category in the staging system. We aimed to assess the feasibility of sub-classifying metastatic pancreatic adenocarcinoma (mPA) into M1a and M1b category depending on the number of metastatic organs. Methods Patient records were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). Univariable and multivariable analyses were performed using the Cox regression model. Then survival analysis was determined using the Kaplan–Meier method. Results A total of 11,885 patients were included in this analysis, including 9425 patients with single metastasis and 2460 patients with multiple metastases. Multivariable analysis showed that gender, age, marital status, grade, surgery, chemotherapy, and radiotherapy were independent prognostic factors for patients with single metastasis; gender, age, marital status, grade, chemotherapy and radiotherapy were independent prognostic factors for patients with multiple metastases. Notably, surgery was an independent prognostic factor for patients with single metastasis (P < 0.001) but not for patients with multiple metastases (P = 0.134). Kaplan–Meier analysis showed that patients with single metastasis (M1a) had better survival outcomes than patients with multiple metastases (M1b) (P < 0.001). Conclusions PA patients with M1 diseases could be divided into M1a (single metastasis) category and M1b (multiple metastases) category by the number of metastatic organs. The subclassification would facilitate individualized treatment for late PA patients. Surgery was associated with lower mortality in M1a patients but not significantly in M1b patients.
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Affiliation(s)
- Fang Feng
- Department of Oncology, Suzhou Ninth People's Hospital, Suzhou, 215200, China
| | - Wei Cai
- Department of Thoracic Surgery, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, 221009, China
| | - Gaoming Wang
- Department of Thoracic Surgery, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, 221009, China
| | - Weigang Chen
- Department of Thoracic Surgery, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, 221009, China
| | - Haochang Yang
- College of Clinical Medicine, Binzhou Medical University, Yantai, 264003, China
| | - Mingyu Sun
- Department of Breast Surgery, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, 221009, China
| | - Li Zhou
- Department of Oncology, Suzhou Ninth People's Hospital, Suzhou, 215200, China.
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Jin T, Dai C, Xu F. Surgical and local treatment of hepatic metastasis in pancreatic ductal adenocarcinoma: recent advances and future prospects. Ther Adv Med Oncol 2020; 12:1758835920933034. [PMID: 32636941 PMCID: PMC7313332 DOI: 10.1177/1758835920933034] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 05/07/2020] [Indexed: 12/19/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with increasing incidence and mortality. More than half of PDAC patients develop metastases, with the liver being the most common site. Patients with pancreatic ductal adenocarcinoma with liver metastases (PCLM) have a very limited scope for surgery due to aggressive tumor behavior and poor prognosis. However, with the improvements in preoperative systemic therapy and perioperative outcomes, an increasing number of patients are being considered for surgical management. However, the best choice of surgical treatment and criteria for selecting suitable PCLM patients who may benefit from surgical treatment remains controversial. Palliative local treatments, such as ablation, locoregional chemotherapy, and brachytherapy, which are less invasive and have fewer contraindications and complications, are the preferred alternatives to surgery. The present study reviews the advances in the management of PCLM, with focus on resection and local therapies.
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Affiliation(s)
- Tianqiang Jin
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chaoliu Dai
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feng Xu
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, China
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35
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Liver metastases from pancreatic ductal adenocarcinoma: is there a place for surgery in the modern era? JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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Yang J, Zhang J, Lui W, Huo Y, Fu X, Yang M, Hua R, Wang L, Sun Y. Patients with hepatic oligometastatic pancreatic body/tail ductal adenocarcinoma may benefit from synchronous resection. HPB (Oxford) 2020; 22:91-101. [PMID: 31262486 DOI: 10.1016/j.hpb.2019.05.015] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 05/20/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Synchronous resection of primary pancreatic ductal adenocarcinoma (PDAC) and liver metastases in highly selective patients is being accepted based on oncology research progress showing safe surgical outcomes with low morbidity and mortality. We also tried to determine patients who would benefit from the operation. METHODS From January 2012 to October 2017, 48 patients who underwent synchronous resection of primary PDAC and liver metastases were retrospectively evaluated. Twenty-three of them underwent oligometastatic synchronous resection. RESULTS The majority of synchronous resection PDAC patients underwent hepatic wedge resection, and no oligometastatic patient was treated with hemihepatectomy. The median overall survival (OS) of the synchronous resection patients was 7.8 months. Hepatic oligometastatic PDAC patients had a longer OS than that of non-oligometastatic synchronous resection patients, systemic chemotherapy patients and palliative patients (16.1 vs 6.4 months, P = 0.02; 16.1 vs 7.6 months, P = 0.02; 16.1 vs 4.3 months, P < 0.0001; respectively). Further analysis showed that localized pancreatic body/tail PDAC had a better OS in oligometastatic patients than in non-oligometastatic synchronous resection patients (16.8 months vs 7.05 months, P = 0.0004) and systemic chemotherapy patients (16.8 months vs 8 months, P = 0.003). CONCLUSION Patients with pancreatic body/tail PDAC with liver oligometastases can benefit from synchronous resection.
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Affiliation(s)
- Jianyu Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China
| | - Junfeng Zhang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China
| | - Wei Lui
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China
| | - Yanmiao Huo
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China
| | - Xueliang Fu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China
| | - Minwei Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China
| | - Rong Hua
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China.
| | - Liwei Wang
- Department of Oncology, State Key Laboratory for Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China.
| | - Yongwei Sun
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240 Shanghai, PR China.
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Wei M, Shi S, Hua J, Xu J, Yu X. Simultaneous resection of the primary tumour and liver metastases after conversion chemotherapy versus standard therapy in pancreatic cancer with liver oligometastasis: protocol of a multicentre, prospective, randomised phase III control trial (CSPAC-1). BMJ Open 2019; 9:e033452. [PMID: 31818843 PMCID: PMC6924808 DOI: 10.1136/bmjopen-2019-033452] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 10/24/2019] [Accepted: 11/18/2019] [Indexed: 12/27/2022] Open
Abstract
INTRODUCTION Approximately 50% of pancreatic ductal adenocarcinoma (PDAC) patients are diagnosed with distant metastasis, especially liver metastasis. The current standard treatment for these stage IV patients is palliative chemotherapy. There is increasing agreement that synchronous PDAC and liver metastasis resection may benefit highly selected patients. Thus, the Chinese Study Group for Pancreatic Cancer (CSPAC)-1 trial is being launched to establish a strategy for selecting PDAC patients with liver oligometastases who may benefit from synchronous resection after conversion chemotherapy. METHODS AND ANALYSIS In this study, liver oligometastasis is defined as no more than three metastatic lesions irrespective of their distribution within the liver lobes. The trial contains two steps. In the first step, 1000 to 1200 needle biopsy-confirmed PDAC patients with liver oligometastases are eligible for inclusion. Candidates will receive first-line chemotherapy. The RECIST V.1.1 criteria combined with tumour markers will be applied to evaluate the tumour response to chemotherapy every two cycles. Pancreatic cancer and hepatic metastasis resectability will be identified by multidisciplinary teams. Approximately 300 patients who meet our criteria will enter the second step and be randomly assigned at a 1:1 ratio to simultaneous resection of the primary pancreatic cancer lesion and liver oligometastases if no extensive metastatic sites are found during surgery or standard chemotherapy. Postoperative chemotherapy is recommended, and regimen selection should be based on the preoperative chemotherapy regimen. The primary endpoint is real overall survival (from enrolment to death). This study was activated in July 2018 and is expected to complete accrual within 5 years. ETHICS AND DISSEMINATION This trial has been approved by the Clinical Research Ethics Committee of Fudan University Shanghai Cancer Centre. Written informed consent will be obtained from all participants. Serious adverse events will be reported. Trial results will be submitted for peer-reviewed publication. TRIAL REGISTRATION NUMBER NCT03398291; Pre-results.
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Affiliation(s)
- Miaoyan Wei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
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Wang L, Yang L, Chen L, Chen Z. Do Patients Diagnosed with Metastatic Pancreatic Cancer Benefit from Primary Tumor Surgery? A Propensity-Adjusted, Population-Based Surveillance, Epidemiology and End Results (SEER) Analysis. Med Sci Monit 2019; 25:8230-8241. [PMID: 31677259 PMCID: PMC6852709 DOI: 10.12659/msm.917106] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background With the progress in surgical techniques and management of complications, pancreatic resection can be safely performed in experienced hospitals. Pancreatic resection enables surgeons to assess the effect of surgery for metastatic cases, even when there is limited information. In the present study we evaluated the role of primary tumor resection for metastatic pancreatic cancer (mPC) by using the Surveillance, Epidemiology and End Results (SEER) database. Material/Methods Metastatic pancreatic cancer patients treated at our hospital from 2004 to 2015 were identified. The effect of surgery on cancer-specific survival was assessed by restricted mean survival time (RMST) and stabilized inverse probability of treatment weight-adjusted analysis after propensity score matching (PSM). Results A total of 2694 mPC patients were included. Of this population, 365 adults underwent primary tumor resection. After propensity matching, postsurgical patients had longer RMST than non-surgery patients (1: 1 PSM 11.60 months vs. 8.98 months; 1: 2 PSM 11.61 months vs. 9.10 months; p<0.01). Stabilized inverse probability of treatment weight-adjusted analysis yielded similar results (p<0.01). Conclusions Our study supports the hypothesis that patients with mPC can benefit from primary tumor surgery. However, the surgical inclusion criteria and the appropriate role of surgery, such as its effect on symptom control, quality of life, and the extent to which it prolongs survival for metastatic pancreatic cancer, remain to be completely assessed by well-designed, prospective, randomized clinical trials.
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Affiliation(s)
- Lai Wang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China (mainland).,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China (mainland)
| | - Lina Yang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China (mainland).,Cancer Institute, Fudan University, Shanghai, China (mainland)
| | - Lianyu Chen
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China (mainland).,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China (mainland)
| | - Zhen Chen
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China (mainland).,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China (mainland)
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Surgery or Locoregional Approaches for Hepatic Oligometastatic Pancreatic Cancer: Myth, Hope, or Reality? Cancers (Basel) 2019; 11:cancers11081095. [PMID: 31374916 PMCID: PMC6721290 DOI: 10.3390/cancers11081095] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 07/27/2019] [Accepted: 07/28/2019] [Indexed: 12/15/2022] Open
Abstract
Despite extensive research, pancreatic ductal adenocarcinoma (PDAC) remains a difficult-to-treat cancer associated with poor survival. Due to the known aggressive disease biology, palliative chemotherapy is the only routinely recommended treatment in the metastatic setting in patients with adequate performance status. However, in a subset of patients with oligometastatic disease, multimodality treatment with surgery and/or locoregional approaches may provide long-term disease control and prolong survival. In fact, in highly selected cases, median overall survival has been reported to extend to 56 months in patients treated with surgery. In particular, liver and extraregional nodal resections may provide long-term tumor control with acceptable morbidity. Current guidelines do not recommend surgery for patients with metastatic PDAC and, in the case of PDAC with oligometastases, there are no published randomized controlled trials regarding locoregional or surgical approaches. Here we review the literature on surgical and locoregional approaches including radiofrequency ablation, irreversible electroporation, and stereotactic body radiation, and focus on patients with hepatic oligometastatic pancreatic cancer. We provide a summary regarding survival outcomes, morbidity and mortality and discuss selection criteria that may be useful to predict the best outcomes for such strategies.
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Moletta L, Serafini S, Valmasoni M, Pierobon ES, Ponzoni A, Sperti C. Surgery for Recurrent Pancreatic Cancer: Is It Effective? Cancers (Basel) 2019; 11:991. [PMID: 31315222 PMCID: PMC6679234 DOI: 10.3390/cancers11070991] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 07/10/2019] [Accepted: 07/12/2019] [Indexed: 02/06/2023] Open
Abstract
Despite improvements to surgical procedures and novel combinations of drugs for adjuvant and neoadjuvant therapies for pancreatic adenocarcinoma, the recurrence rate after radical surgery is still high. Little is known about the role of surgery in the treatment of isolated recurrences of pancreatic cancer. The aim of this study was to review the current literature dealing with surgery for recurrent pancreatic cancer in order to examine its feasibility and effectiveness. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 14 articles dealing with re-resections for recurrent pancreatic adenocarcinoma were analyzed, focusing on the characteristics of the primary neoplasm and its recurrence, the surgical procedures used, and patient outcomes. Data were retrieved on a total of 301 patients. The interval between surgery for primary pancreatic cancer and the detection of a recurrence ranged from 2 to 120 months. The recurrence was local or regional in 230 patients, and distant in 71. The median overall survival was 68.9 months (range 3-152) after resection of the primary tumor, and 26.0 months (range 0-112) after surgery for recurrent disease. The disease-free interval after the resection of recurrences was 14.2 months (range 4-29). Although data analysis was performed on a heterogeneous and limited number of patients, some of these may benefit from surgery for isolated recurrence of pancreatic adenocarcinoma. Further studies are needed to identify these cases.
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Affiliation(s)
- Lucia Moletta
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy
| | - Simone Serafini
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy
| | - Michele Valmasoni
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy
| | - Elisa Sefora Pierobon
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy
| | - Alberto Ponzoni
- Department of Radiology, Padua General Hospital, 35128 Padua, Italy
| | - Cosimo Sperti
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy.
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Voss N, Izbicki JR, Nentwich MF. Oligometastases in pancreatic cancer (Synchronous resections of hepatic oligometastatic pancreatic cancer: Disputing a principle in a time of safe pancreatic operations in a retrospective multicenter analysis). Ann Gastroenterol Surg 2019; 3:373-377. [PMID: 31346576 PMCID: PMC6635688 DOI: 10.1002/ags3.12255] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/02/2019] [Accepted: 04/03/2019] [Indexed: 12/25/2022] Open
Abstract
The aim of the present review was to analyze the current data on surgery of synchronous liver metastases in pancreatic ductal adenocarcinoma (PDAC) in curative intent. A review of the literature was carried out to identify the current international concepts regarding surgery of liver metastases of PDAC and, furthermore, we addressed the current challenges of resection of liver metastases of PDAC. Resection of liver metastases in PDAC may provide survival benefit without compromising safety and quality of life in a highly selected group of patients.
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Affiliation(s)
- Nina Voss
- Department of General, Visceral and Thoracic SurgeryUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Jakob R. Izbicki
- Department of General, Visceral and Thoracic SurgeryUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Michael F. Nentwich
- Department of General, Visceral and Thoracic SurgeryUniversity Medical Center Hamburg‐EppendorfHamburgGermany
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Sakaguchi T, Valente R, Tanaka K, Satoi S, Del Chiaro M. Surgical treatment of metastatic pancreatic ductal adenocarcinoma: A review of current literature. Pancreatology 2019; 19:672-680. [PMID: 31285145 DOI: 10.1016/j.pan.2019.05.466] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 05/05/2019] [Accepted: 05/29/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND There is no international consensus concerning the role of surgical treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), but favorable prognoses can be expected for highly selected patients. METHODS A comprehensive literature search of the PubMed and Cochrane databases was conducted using combinations of keywords to 4 July 2018. Eligible studies were those reporting on patients with histologically confirmed mPDAC undergoing surgery with curative intent. We excluded case reports with fewer than five patients, insufficient descriptions of survival data, and palliative or cytoreductive surgery as well as studies that assessed para-aortic lymph node metastasis or peritoneal washing cytology. RESULTS Thirteen studies were deemed eligible, and six studies were identified from their references. The studies involved 428 patients who underwent surgical resection for liver metastases (n = 343), lung metastases (n = 57), and peritoneal dissemination (n = 28). Median overall survival (OS) in patients with synchronous liver metastases who underwent conversion surgery following favorable response to initial chemotherapy was 27 or 34 months, and peritoneum metastases was 28 months. Median OS after the initial treatment was varied from 51 to 121 months in metachronous lung metastasis and from 24 to 40 months in metachronous liver metastasis, respectively. CONCLUSION Encouraging OS was indicated in patients with synchronous mPDAC of liver and peritoneum who underwent conversion surgery. Metastasectomy for metachronous lung and liver oligometastases could be considered a practical treatment option.
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Affiliation(s)
| | - Roberto Valente
- Division of Surgery, HPB Disease Unit, Karolinska University Hospital, Stockholm, Sweden.
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Sapporo, Japan
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Denver, USA
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Lopez-Lopez V, Robles-Campos R, López-Conesa A, Brusadin R, Carbonel G, Gomez-Ruiz A, Ruiz JJ, Parrilla P. Surgical resection of liver metastasis in pancreatic and periampullary carcinoma. MINERVA CHIR 2019; 74:253-262. [PMID: 30600968 DOI: 10.23736/s0026-4733.18.07972-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
INTRODUCTION Once liver metastases in pancreatic and periampullary carcinoma are diagnosed, guidelines do not recommend resection of the primary tumor. In this stage of the disease, therapeutic regimes with chemotherapy are the standard treatment. However, it is unclear whether combinations of extensive surgery and novel chemotherapy treatments confer a survival benefit in selected patients. EVIDENCE ACQUISITION We provide a systematic review about liver metastases in pancreatic and periampullary carcinoma treated by surgery utilizing EMBASE, Medline/PubMed, Cochrane and Scopus databases according to PRISMA guidelines. EVIDENCE SYNTHESIS In pancreatic and periampullary carcinoma, the number of lesions that can be resected includes a mean or median of 1-3; the size of the lesions should not exceed 3 cm and the most frequent surgical technique used were wedge or atypical resections. Overall morbidity and mortality after liver resection from pancreatic tumors were 0-68% and 0-9.1%, respectively, and from periampullary carcinomas were 0-82% and 0-21%, respectively. Considering both types of carcinomas, the rate of recurrence was up to 91%. Median overall survival ranged from 5.5 to 16.6 months for liver metastases from pancreas carcinoma, and from 5 to 23 months for periampullary carcinoma, with better prognosis for duodenal carcinomas. CONCLUSIONS Perioperative chemotherapy is the cornerstone of treatment in patients with liver metastasis from pancreatic and periampullary carcinoma. Liver resection from early liver metastases could be acceptable in selected patients with oligometastatic disease and small single lesions taking into account the individual risk of complications.
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Affiliation(s)
- Victor Lopez-Lopez
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Ricardo Robles-Campos
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain -
| | - Asunción López-Conesa
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Roberto Brusadin
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Guillermo Carbonel
- Department of Radiology, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Alvaro Gomez-Ruiz
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Juan J Ruiz
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
| | - Pascual Parrilla
- Department of Surgery, Virgen de la Arrixaca Clinic and University Hospital, Murcia, Spain
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Conversion surgery for initially unresectable pancreatic cancer: current status and unresolved issues. Surg Today 2019; 49:894-906. [PMID: 30949842 DOI: 10.1007/s00595-019-01804-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 02/17/2019] [Indexed: 12/16/2022]
Abstract
Pancreatic cancer is one of the most lethal of all malignancies. One of the reasons for the dismal prognosis is that most diagnoses are made when the disease is either locally advanced or metastatic. Recent advances in chemotherapy and chemoradiotherapy (CRT) enable "conversion surgery" to be performed for selected patients with initially unresectable pancreatic cancer following favorable responses to preoperative treatment. Using FOLFIRINOX as preoperative treatment, the resection rate was reported as 6-44% of patients with locally advanced cancer and the prognosis of these patients was favorable. Even for metastasized cancer, recent reports show the effectiveness of conversion surgery, which has achieved 27-56 months of median overall survival. However, there are many unanswered questions about conversion surgery. The optimal regimen and duration of preoperative treatment remain unclear and there is still debate regarding the safety and effectiveness of vascular resection, which is often required for curative resection of locally advanced cancer. Accumulation of more data on conversion surgery is required to establish the safety and effectiveness of this treatment. In this review, we summarize the current status and unresolved issues about conversion surgery for initially unresectable pancreatic cancer.
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Andreou A, Knitter S, Klein F, Malinka T, Schmelzle M, Struecker B, Schmuck RB, Noltsch AR, Lee D, Pelzer U, Denecke T, Pratschke J, Bahra M. The role of hepatectomy for synchronous liver metastases from pancreatic adenocarcinoma. Surg Oncol 2018; 27:688-694. [PMID: 30449494 DOI: 10.1016/j.suronc.2018.09.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 08/27/2018] [Accepted: 09/17/2018] [Indexed: 01/04/2023]
Abstract
BACKGROUND The role of hepatectomy for patients with liver metastases from ductal adenocarcinoma of the pancreas (PLM) remains controversial. Therefore, the aim of our study was to examine the postoperative morbidity, mortality, and long-term survivals after liver resection for synchronous PLM. METHODS Clinicopathological data of patients who underwent hepatectomy for PLM between 1993 and 2015 were assessed. Major endpoint of this study was to identify predictors of overall survival (OS). RESULTS During the study period, 76 patients underwent resection for pancreatic cancer and concomitant hepatectomy for synchronous PLM. Pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were performed in 67%, 25%, and 8% of the patients, respectively. The median PLM size was 1 (1-13) cm and 36% of patients had multiple PLM. The majority of patients (96%) underwent a minor liver resection. After a median follow-up time of 130 months, 1-, 3-, and 5-year OS rates were 41%, 13%, and 7%, respectively. Postoperative morbidity and mortality rates were 50% and 5%, respectively. Preoperative and postoperative chemotherapy was administered to 5% and 72% of patients, respectively. In univariate analysis, type of pancreatic procedure (P = .020), resection and reconstruction of the superior mesenteric artery (P = .016), T4 stage (P = .086), R1 margin status at liver resection (P = .001), lymph node metastases (P = .016), poorly differentiated cancer (G3) (P = .037), no preoperative chemotherapy (P = .013), and no postoperative chemotherapy (P = .005) were significantly associated with worse OS. In the multivariate analysis, poorly differentiated cancer (G3) (hazard ratio [HR] = 1.87; 95% confidence interval [CI] = 1.08-3.24; P = .026), R1 margin status at liver resection (HR = 4.97; 95% CI = 1.46-16.86; P = .010), no preoperative chemotherapy (HR = 4.07; 95% CI = 1.40-11.83; P = .010), and no postoperative chemotherapy (HR = 1.88; 95% CI = 1.06-3.29; P = .030) independently predicted worse OS. CONCLUSIONS Liver resection for PLM is feasible and safe and may be recommended within the framework of an individualized cancer therapy. Multimodal treatment strategy including perioperative chemotherapy and hepatectomy may provide prolonged survival in selected patients with metastatic pancreatic cancer.
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Affiliation(s)
- Andreas Andreou
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany.
| | - Sebastian Knitter
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Fritz Klein
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Thomas Malinka
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Moritz Schmelzle
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Benjamin Struecker
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Rosa B Schmuck
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Alina Roxana Noltsch
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Daniela Lee
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Uwe Pelzer
- Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Timm Denecke
- Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
| | - Marcus Bahra
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Germany
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Lee RC, Kanhere H, Trochsler M, Broadbridge V, Maddern G, Price TJ. Pancreatic, periampullary and biliary cancer with liver metastases: Should we consider resection in selected cases? World J Gastrointest Oncol 2018; 10:211-220. [PMID: 30147847 PMCID: PMC6107475 DOI: 10.4251/wjgo.v10.i8.211] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 05/14/2018] [Accepted: 06/28/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To analyse the safety and efficacy of curative intent surgery in biliary and pancreatic cancer.
METHODS An extensive literature review was performed using MEDLINE, Google Scholar and EMBASE to identify articles regarding hepato-pancreatoduodenectomy or resection of liver metastasis in patients with pancreatic, biliary tract, periampullary and gallbladder cancers.
RESULTS A total of 19 studies were identified and reviewed. Major hepatectomy was undertaken in 391 patients. The median overall survival for pancreatic cancer ranged from 5-36 mo and for biliary tract/gallbladder cancer, it was 8-38 mo. The 30 d mortality rate was only 1%-9%. Overall Survival was significantly better for patients, who had good response to neoadjuvant chemotherapy, underwent metachronous liver resection and who had intestinal type tumours.
CONCLUSION Resection of liver metastases in pancreatic and biliary cancers may provide survival benefit without compromising safety and quality of life in a very select group of patients. These data may be utilised to formulate selection criteria that may allow future investigation of resection in the era of more effective systemic therapy.
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Affiliation(s)
- Rachael Chang Lee
- Department of Medical Oncology, the Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Harsh Kanhere
- Department of Surgery, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| | - Markus Trochsler
- Department of Surgery, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| | - Vy Broadbridge
- Department of Medical Oncology, the Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Guy Maddern
- Department of Surgery, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
| | - Timothy J Price
- Department of Medical Oncology, the Queen Elizabeth Hospital, Adelaide 5011, Australia
- School of Medicine, University of Adelaide, Adelaide 5000, Australia
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Yu X, Gu J, Fu D, Jin C. Dose surgical resection of hepatic metastases bring benefits to pancreatic ductal adenocarcinoma? A systematic review and meta-analysis. Int J Surg 2017; 48:149-154. [PMID: 29081375 DOI: 10.1016/j.ijsu.2017.10.066] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/07/2017] [Accepted: 10/21/2017] [Indexed: 01/11/2023]
Abstract
OBJECTIVE The objectives of this systematic review and meta-analysis were to examine morbidity, mortality, and long-term survival after surgical resection of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC) patients. BACKGROUND Patients with hepatic metastases from pancreatic ductal adenocarcinoma are facing a dilemma of whether to make hepatic resection. METHODS A systematic literature research was undertaken through computerized databases as well as manually research from unpublished data. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and non-surgical treatments based on the evaluation of morbidity, 30-day mortality, and 1-, 3-, or 5-year survival. RESULTS 11 cohort studies with 1147 patients were identified in the pool. Compared with the non-surgical approach, hepatic resection can be performed in a safe and feasible manner for all pancreatic cancer patients with liver metastases (p = 0.13 for overall morbidity; p = 0.63 for mortality). For surgical group, the median 1-year, 3-year, and 5-year survival were 40.9%, 13.3%, 2.9%, respectively, with a median survival of 9.9 months. Surgical resection of hepatic metastases was associated with a significantly improved overall 1-year and 3-year survival (p < 0.001). CONCLUSIONS Hepatic resection is a safe procedure; furthermore, it is worth doing such an extended surgery for PDAC patients due to additional survival benefit in the medium-term (less than 3 years). However, further randomized, controlled trials are urgently needed.
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Affiliation(s)
- Xinzhe Yu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China
| | - Jichun Gu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China
| | - Deliang Fu
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China
| | - Chen Jin
- Pancreatic Surgery Department, Huashan Hospital Affiliated to Fudan University, PR China.
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Oweira H, Petrausch U, Helbling D, Schmidt J, Mannhart M, Mehrabi A, Schöb O, Giryes A, Decker M, Abdel-Rahman O. Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis. World J Gastroenterol 2017; 23:1872-1880. [PMID: 28348494 PMCID: PMC5352929 DOI: 10.3748/wjg.v23.i10.1872] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 12/20/2016] [Accepted: 02/07/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database. METHODS SEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. RESULTS A total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001) (for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival. CONCLUSION Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.
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Renz BW, Boeck S, Roeder F, Trumm C, Heinemann V, Werner J. Oligometastatic Disease in Pancreatic Cancer - How to Proceed? Visc Med 2017; 33:36-41. [PMID: 28612015 DOI: 10.1159/000455027] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Pancreatic cancer is a highly aggressive malignancy and will become the second leading cause of cancer-related death in the USA and also in Germany by 2030. Furthermore, the majority of patients with pancreatic ductal adenocarcinoma (PDAC) will present with distant metastases, limiting surgical management in this population as there is little evidence available to support surgical or ablative treatment options for advanced-stage disease. However, highly selected patients suffering from synchronous and metachronous oligometastatic PDAC may potentially benefit from a surgical resection with an acceptable morbidity. METHODS This review summarizes and discusses the current literature on the management of oligometastatic disease regarding PDAC, focusing on para-aortic lymph nodes as well as isolated hepatic and pulmonary metastases. RESULTS AND CONCLUSION In order to further investigate the feasibility and efficacy of such an approach, a prospective multicenter trial, in which survival and quality of life after metastatic resection and systemic chemotherapy is evaluated, has to be initiated. Additionally, local and locoregional ablation techniques or stereotactic body radiation therapy as therapeutic options for isolated metastases in PDAC need further research in order to determine their significance and benefit.
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Affiliation(s)
- Bernhard W Renz
- Department of General, Visceral and Transplantation Surgery, Hospital of the University of Munich, Munich, Germany, Munich, Germany.,Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany, Munich, Germany
| | - Stefan Boeck
- Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany, Munich, Germany.,Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany, Munich, Germany
| | - Falk Roeder
- Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany, Munich, Germany.,Department of Radiation Oncology, Hospital of the University of Munich, Munich, Germany, Munich, Germany.,Department of Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany, Munich, Germany
| | - Christoph Trumm
- Department of Clinical Radiology, Hospital of the University of Munich, Munich, Germany
| | - Volker Heinemann
- Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany, Munich, Germany.,Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany, Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, Hospital of the University of Munich, Munich, Germany, Munich, Germany.,Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany, Munich, Germany
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Shi HJ, Jin C, Fu DL. Preoperative evaluation of pancreatic ductal adenocarcinoma with synchronous liver metastasis: Diagnosis and assessment of unresectability. World J Gastroenterol 2016; 22:10024-10037. [PMID: 28018110 PMCID: PMC5143749 DOI: 10.3748/wjg.v22.i45.10024] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 09/09/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma (PDAC) and assess unresectability of synchronous liver metastasis. METHODS Retrospective records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group. RESULTS CA125 > 38 U/mL (OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus (OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL (OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years (OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with post-operatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels (7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone (7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula (P = 0.072) or other complications (P = 0.230) and no greater impacts on length of hospital stay (P = 0.602) or post-operative diabetic control (P = 0.479). CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.
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