|
1
|
Lan CC, Chiu TJ, Hung CY, Yeh KY, Lu CH, Chen YY, Chen JS, Hung YS, Chou WC. The efficacy and safety profile of third-line treatment in patients with metastatic pancreatic adenocarcinoma. Pancreatology 2025; 25:266-274. [PMID: 39915162 DOI: 10.1016/j.pan.2025.01.012] [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: 05/29/2024] [Revised: 10/01/2024] [Accepted: 01/31/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND For metastatic pancreatic ductal adenocarcinoma (mPDAC), there are no established third-line chemotherapy options. We examined the efficacy and safety of third-line chemotherapy in patients with mPDAC in real-world practice. METHODS We retrospectively analyzed 257 patients with mPDAC and progressive disease after first-line treatment with gemcitabine-based regimens and second-line treatment with liposomal irinotecan plus 5-fluorouracil and leucovorin at five Taiwanese medical centers from 2018 to 2022. Treatment efficacy and toxicity were analyzed in 77 of 257 patients receiving third-line treatment subsequently. We performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) in patients receiving third-line treatment. RESULTS Patients receiving third-line treatment had a median OS of 4.5 months (95 % confidence interval [CI], 3.6-5.4), compared to 1.6 months (95 % CI, 1.3-1.9) for those who did not. Independent poor prognostic factors for OS included the absence of previous pancreatectomy (adjusted hazard ratio [aHR] 3.03, 95 % CI, 1.30-7.14, P = 0.001), an ECOG score of ≥2 ((aHR 9.81, 95 % CI 4.34-22.1, P < 0.001), and progressive disease response during second-line treatment (aHR 1.90, 95 % CI 1.21-8.91, P = 0.020, P = 0.020). Median OS for patients with none, one, two, and three poor prognostic factors were 15.9 (95 % CI, 12.3-19.6), 7.0 (2.6-13.3), 4.4 (3.5-5.2), and 2.0 (1.7-2.2) months, respectively. 43 of 77 patients (56 %) experienced at least one grade 3 or 4 toxicity. CONCLUSION In real-world settings, patients with mPDAC receiving third-line chemotherapy may have a moderate survival advantage, although clinicians should carefully select patients owing to high incidence of grade 3/4 toxicities.
Collapse
Affiliation(s)
- Chi-Chen Lan
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Tai-Jan Chiu
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Kaohsiung Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Chia-Yen Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Kun-Yun Yeh
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Keelung Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Chang-Hsien Lu
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Yen-Yang Chen
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Kaohsiung Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Jen-Shi Chen
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Yu-Shin Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan
| | - Wen-Chi Chou
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyaun, Taiwan.
| |
Collapse
|
|
2
|
Zhu S, Yang H, Liu L, Jiang Z, Ji J, Wang X, Zhong L, Liu F, Gao X, Wang H, Zhou Y. CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma. JOURNAL OF BIOINFORMATICS AND SYSTEMS BIOLOGY : OPEN ACCESS 2023; 6:187-200. [PMID: 37744402 PMCID: PMC10516534 DOI: 10.26502/jbsb.5107060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a poor prognosis and growing incidence. In this study, we explored the potential roles of CDK1, CDK2, CDK4, and CDK6 in the progression of early-stage PDAC. Clinicopathologic and mRNA expression data and treatment information of 140 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy were obtained from the Cancer Genome Atlas data set. Our bioinformatic analysis showed that higher CDK1, CDK2, CDK4, or CDK6 expression was associated with a shorter median survival of the early-stage PDAC patients. Of note, in the low-proliferating pancreatic cancer group, CDKs expressions were significantly associated with proteins functioning in apoptosis, metastasis, immunity, or stemness. Among the low-proliferating PDAC, higher expression of CDK1 was associated with the shorter survival of patients, suggesting that CDK1 may regulate PDAC progression through cell cycle-independent mechanisms. Our experimental data showed that CDK1 knockdown/inhibition significantly suppressed the expression levels of AHR and POU5F1, two critical proteins functioning in cancer cell metastasis and stemness, in low-proliferating, but not in high-proliferating pancreatic cancer cells. In all, our study suggests that CDKs regulate PDAC progression not only through cell proliferation but also through apoptosis, metastasis, immunity, and stemness.
Collapse
Affiliation(s)
- Shikai Zhu
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
- Organ Transplant Center, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Huining Yang
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Lingling Liu
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics
| | - Zhilin Jiang
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Juanjuan Ji
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Xiao Wang
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Lin Zhong
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Fulin Liu
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| | - Xueliang Gao
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics
- Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Haizhen Wang
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics
- Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Yu Zhou
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine,University of Electronic Science and Technology of China, Chengdu, China
| |
Collapse
|
|
3
|
Singh M, Pal P, Dutta RS, Marbaniang D, Ray S, Mazumder B. Nanodiamond Mediated Molecular Targeting in Pancreatic Ductal Adenocarcinoma: Disrupting the Tumor-stromal Cross-talk, Next Hope on the Horizon? Curr Cancer Drug Targets 2023; 23:620-633. [PMID: 36843367 DOI: 10.2174/1568009623666230227120837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 12/21/2022] [Accepted: 12/21/2022] [Indexed: 02/28/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the foremost causes of cancer-related morbidities worldwide. Novel nanotechnology-backed drug delivery stratagems, including molecular targeting of the chemotherapeutic payload, have been considered. However, no quantum leap in the gross survival rate of patients with PDAC has been realized. One of the predominant causes behind this is tumor desmoplasia, a dense and heterogenous stromal extracellular matrix of the tumor, aptly termed tumor microenvironment (TME). It plays a pivotal role in the tumor pathogenesis of PDAC as it occupies most of the tumor mass, making PDAC one of the most stromal-rich cancers. The complex crosstalk between the tumor and dynamic components of the TME impacts tumor progression and poses a potential barrier to drug delivery. Understanding and deciphering the complex cascade of tumorstromal interactions are the need of the hour so that we can develop neoteric nano-carriers to disrupt the stroma and target the tumor. Nanodiamonds (NDs), due to their unique surface characteristics, have emerged as a promising nano delivery system in various pre-clinical cancer models and have the potential to deliver the chemotherapeutic payload by moving beyond the dynamic tumor-stromal barrier. It can be the next revolution in nanoparticle-mediated pancreatic cancer targeting.
Collapse
Affiliation(s)
- Mohini Singh
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Paulami Pal
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Rajat Subhra Dutta
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Daphisha Marbaniang
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Subhabrata Ray
- Dr. B.C. Roy College of Pharmacy & AHS, Durgapur, WB, India
| | - Bhaskar Mazumder
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, India
| |
Collapse
|
|
4
|
Marino MV, Giovinazzo F, Podda M, Gomez Ruiz M, Gomez Fleitas M, Pisanu A, Latteri MA, Takaori K. Robotic-assisted pancreaticoduodenectomy with vascular resection. Description of the surgical technique and analysis of early outcomes. Surg Oncol 2020; 35:344-350. [PMID: 32979700 DOI: 10.1016/j.suronc.2020.08.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 05/03/2020] [Accepted: 08/19/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Despite the potential benefits, the adoption of the minimally invasive surgery for the treatment of borderline resectable pancreatic cancer is still in the initial phase. We investigated the safety and feasibility of the robotic pancreaticoduodenectomy with venous resection/reconstruction (RPD SMV/PV). METHODS Since March 2013 to October 2019, a total of 73 RPD and 10 RPD SMV/PV were performed. The two groups were case-matched according to the preoperative characteristics. RESULTS Mean operative times and estimated blood loss were less in the RPD group in comparison to that in the RPD with SMV-PV group (525 vs 642 min, p = 0.003 and 290 vs 620 ml, p = 0.002, respectively). The mean length of hospital stay was similar in the RPD group in comparison to that in the RPD with SMV-PV group (10 days vs 13 days, p = 0.313). The two groups had similar overall postoperative morbidity rate (57.5% vs 60%, p = 0.686), although the severe complication rate was lower in the RPD group (11% vs 40%, p = 0.004). CONCLUSIONS RPD with SMV-PV is associated with increased operative time, estimated blood loss, higher major complication rate compared with RPD.
Collapse
Affiliation(s)
- Marco Vito Marino
- Department of Emergency and General Surgery, Azienda Ospedaliera, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy; Department of General and Digestive Surgery, Hospital Universitario Marqués de Valdecilla, Santander, Spain; Department of Surgical, Oncological and Oral Science, Palermo University Hospital, Palermo, Italy; General Surgery Department, Policlinico Abano Terme, Padova, Italy.
| | - Francesco Giovinazzo
- Department of Surgery, Transplantation Service, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Mauro Podda
- Department of Surgery, Cagliari University Hospital D. Casula, Cagliari, Italy
| | - Marcos Gomez Ruiz
- Department of General and Digestive Surgery, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Manuel Gomez Fleitas
- Department of Robotics and Surgical Innovation, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Adolfo Pisanu
- Department of Surgery, Cagliari University Hospital D. Casula, Cagliari, Italy
| | - Mario Adelfio Latteri
- Department of Surgical, Oncological and Oral Science, Palermo University Hospital, Palermo, Italy
| | - Kyoichi Takaori
- Department of General Surgery, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto, Japan
| |
Collapse
|
|
5
|
Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center propensity score matching study. Updates Surg 2020; 72:387-397. [PMID: 32266660 DOI: 10.1007/s13304-020-00742-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 03/04/2020] [Indexed: 12/17/2022]
Abstract
Laparoscopic distal pancreatectomy (LDP) for benign and low-grade malignant pancreatic diseases has been increasingly utilized. However, the use of LDP for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not been widely accepted. In this study, the outcomes of LDP versus conventional open distal pancreatectomy (ODP) for left-sided PDAC were examined. A retrospective review of patients who underwent LDP or ODP for left-sided PDAC between January 2010 and January 2019 was conducted. One-to-one propensity score matching (PSM) was used to minimize selection biases by balancing factors including age, sex, ASA grade, tumor size, and combined resection. Demographic data, their pathological and short-term clinical parameters, and long-term oncological outcomes were compared between the LDP and ODP groups. A total of 197 patients with PDAC were enrolled. There were 115 (58.4%) patients in the LDP group and 82 (41.6%) patients in the ODP group. After 1:1 PSM, 66 well-matched patients in each group were evaluated. The LDP group had lesser blood loss (195 vs. 210 mL, p < 0.01), shorter operative time (193.6 vs. 217.5 min; p = 0.02), and shorter hospital stay (12 vs. 15 days, p < 0.01), whereas the overall complication rates were comparable between groups (10.6% vs.16.7%, p = 0.31). There were no significant differences between the LDP and ODP groups regarding 3-year recurrence-free or overall survival rate (p = 0.89 and p = 0.33, respectively). LDP in the treatment of left-sided PDAC is a technically safe, feasible and favorable approach in short-term surgical outcomes. Moreover, patients undergoing LDP than ODP for PDAC had comparable oncological metrics and similar middle-term survival rate.
Collapse
|
|
6
|
Heiberg T, Baekelandt B, Kvien TK, Buanes T. Psychometric performance of the PAncreatic CAncer disease impact (PACADI) score. Pancreatology 2019; 19:971-978. [PMID: 31530448 DOI: 10.1016/j.pan.2019.09.001] [Citation(s) in RCA: 3] [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: 02/13/2019] [Revised: 08/30/2019] [Accepted: 09/01/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVE Pancreatic Cancer Disease Impact (PACADI) score measures the impact of pancreatic cancer (PC) on important health dimensions, selected by patients. The aim of this single center study was to test the psychometric performance of the Pancreatic Cancer Disease Impact (PACADI) score. METHODS Patients with suspected pancreatic cancer (PC) completed PACADI, the EuroQol-5D (EQ-5D index) and Edmonton Symptom Assessment System (ESAS) in this longitudinal observational study. Measures were compared across patients with PC (n = 210), other malignant lesions (OML) (n = 109) and non-malignant lesions (NML) (n = 41). Associations, test-retest and internal consistency reliability, longitudinal changes, sensitivity to change and prediction of mortality during the first year were examined in patients with PC. RESULTS The three measures discriminated between PC and OML. The PACADI score correlated strongly at baseline (n = 199)/after three months (n = 85) with the EQ-5D index and ESAS "sense of well-being" (0.64 and 0.66/0.73 and 0.69, p < 0.001, respectively), showed high test-retest reliability (ICC 0.84) and very good internal consistency reliability (Cronbach's alpha 0.81-0.85) across all visits. Scores improved over time at 3, 6, 9 and 12 months for survivors, and standardized response mean (SRM) for improvement between 2 and 3 months (n = 44) was 0.80 (PACADI), -0.59 (EQ-5D index) and 0.69 (ESAS "sense of well-being"). The PACADI score significantly predicted mortality within the first year (p = 0.02) in contrast to the EQ-5D index and ESAS "sense of well-being". CONCLUSION This study showed satisfactory psychometric performance of the PACADI score. The results support its use in clinical practice and intervention trials.
Collapse
Affiliation(s)
- Turid Heiberg
- Regional Research Support, Oslo University Hospital, Oslo, Norway; Østfold University College, Halden, Norway.
| | - Bart Baekelandt
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Tore K Kvien
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
| | - Trond Buanes
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| |
Collapse
|
|
7
|
Beesley VL, Janda M, Burmeister EA, Goldstein D, Gooden H, Merrett ND, O'Connell DL, Wyld DK, Chan RJ, Young JM, Neale RE. Association between pancreatic cancer patients' perception of their care coordination and patient-reported and survival outcomes. Palliat Support Care 2018; 16:534-543. [PMID: 28669376 DOI: 10.1017/s1478951517000608] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE People with pancreatic cancer have poor survival, and management is challenging. Pancreatic cancer patients' perceptions of their care coordination and its association with their outcomes have not been well-studied. Our objective was to determine if perception of care coordination is associated with patient-reported outcomes or survival. METHODS People with pancreatic cancer who were 1-8 months postdiagnosis (52 with completed resection and 58 with no resection) completed a patient-reported questionnaire that assessed their perceptions of care coordination, quality of life, anxiety, and depression using validated instruments. Mean scores for 15 care-coordination items were calculated and then ranked from highest (best experience) to lowest (worst experience). Associations between care-coordination scores (including communication and navigation domains) and patient-reported outcomes and survival were investigated using general linear regression and Cox regression, respectively. All analyses were stratified by whether or not the tumor had been resected. RESULTS In both groups, the highest-ranked care-coordination items were: knowing who was responsible for coordinating care, health professionals being informed about their history, and waiting times. The worst-ranked items related to: how often patients were asked about visits with other health professionals and how well they and their family were coping, knowing the symptoms they should monitor, having sufficient emotional help from staff, and access to additional specialist services. For people who had a resection, better communication and navigation scores were significantly associated with higher quality of life and less anxiety and depression. However, these associations were not statistically significant for those with no resection. Perception of cancer care coordination was not associated with survival in either group. SIGNIFICANCE OF RESULTS Our results suggest that, while many core clinical aspects of care are perceived to be done well for pancreatic cancer patients, improvements in emotional support, referral to specialist services, and self-management education may improve patient-reported outcomes.
Collapse
Affiliation(s)
- Vanessa L Beesley
- Population Health Department,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia
| | - Monika Janda
- School of Public Health and Social Work,Queensland University of Technology,Brisbane,Queensland,Australia
| | - Elizabeth A Burmeister
- Population Health Department,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia
| | - David Goldstein
- Department of Medical Oncology,Prince of Wales Hospital,Sydney,New South Wales,Australia
| | - Helen Gooden
- Cancer Nursing Research Unit, University of Sydney,New South Wales,Sydney,Australia
| | - Neil D Merrett
- Discipline of Surgery,Western Sydney University,Sydney,New South Wales,Australia
| | - Dianne L O'Connell
- Cancer Research Division,Cancer Council of New South Wales,Sydney,New South Wales,Australia
| | - David K Wyld
- Department of Medical Oncology and Cancer Care Services,Royal Brisbane and Women's Hospital,Brisbane,Queensland,Australia
| | - Raymond J Chan
- Department of Medical Oncology and Cancer Care Services,Royal Brisbane and Women's Hospital,Brisbane,Queensland,Australia
| | - Jane M Young
- RPA Institute of Academic Surgery and Surgical Outcomes Research Centre,Sydney Local Health District,Sydney,New South Wales,Australia
| | - Rachel E Neale
- Population Health Department,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia
| |
Collapse
|
|
8
|
Mariglia J, Momin S, Coe IR, Karshafian R. Analysis of the cytotoxic effects of combined ultrasound, microbubble and nucleoside analog combinations on pancreatic cells in vitro. ULTRASONICS 2018; 89:110-117. [PMID: 29775835 DOI: 10.1016/j.ultras.2018.05.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 05/02/2018] [Accepted: 05/04/2018] [Indexed: 06/08/2023]
Abstract
Ultrasonically-stimulated microbubbles enhance the therapeutic effects of various chemotherapy drugs. However, the application of ultrasound and microbubbles (USMB) for enhancing the therapeutic effect of nucleoside analogs, which are used as front-line treatments in a range of cancers, and its underlying mechanism is not well understood. This study investigated the effect of gemcitabine, a nucleoside analog drug, in combination with USMB in increasing cell cytotoxicity relative to either treatment alone in BxPC3 pancreatic cancer cells. Cells were sonicated using low frequency (0.5 MHz) ultrasound in combination with Definity® microbubbles (1.7% v/v) in the presence of 1 µM of gemcitabine for a total of 2 h. USMB in combination with gemcitabine decreased cell viability (48 h) to 44.7 ± 5.2%, 27.7 ± 4.3%, and 12.5 ± 3.4% with increasing ultrasound peak negative pressures (220, 360, 530 kPa) from 84.7 ± 3.6%, 54.2 ± 3.8%, and 26.8 ± 3.0%, respectively, when USMB was applied in the absence of drug. We further confirmed that USMB did not enhance the internalization of 1 µM of a radiolabeled nucleoside analog (2-chloroadenosine) at each of the three chosen ultrasound PNPs, determined by radiolabeled scintillation counting. These data suggest that USMB in combination with nucleoside analog drugs leads to an additive effect on cell toxicity and that USMB does not impair transporter-mediated uptake of nucleoside analogs.
Collapse
Affiliation(s)
- Julia Mariglia
- Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada
| | - Shadab Momin
- Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada
| | - Imogen R Coe
- Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada; St. Michael's Hospital, Keenan Research Centre of LKSKI, 209 Victoria Street, Toronto, ON M5B 1W8, Canada
| | - Raffi Karshafian
- Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada; St. Michael's Hospital, Keenan Research Centre of LKSKI, 209 Victoria Street, Toronto, ON M5B 1W8, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), a partnership between Ryerson University and St. Michael's Hospital, Toronto, Ontario, Canada.
| |
Collapse
|
|
9
|
Qu L, Zhiming Z, Xianglong T, Yuanxing G, Yong X, Rong L, Yee LW. Short- and mid-term outcomes of robotic versus laparoscopic distal pancreatosplenectomy for pancreatic ductal adenocarcinoma: A retrospective propensity score-matched study. Int J Surg 2018; 55:81-86. [PMID: 29802919 DOI: 10.1016/j.ijsu.2018.05.024] [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: 12/16/2017] [Revised: 05/07/2018] [Accepted: 05/19/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Robotic distal pancreatectomy exhibits short-term benefits over laparoscopic distal pancreatectomy. The use of minimal invasive techniques to carry out distal pancreatosplenectomy (DPS) for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not gained popular acceptance. A comparative study was designed to analyze the short- and mid-term outcomes of robotic DPS (RDPS) versus laparoscopic DPS (LDPS) on patients with PDAC. METHODS The baseline characteristics, perioperative outcomes and survival data among patients who underwent RDPS (n = 35) versus LDPS (n = 35) for PDAC between December 2011 and December 2015 were compared after a 1:1 propensity score matching. RESULTS There were no significant differences in the operative time, blood loss, blood transfusion rate, and morbidity and pancreatic fistula rates between the RDPS and LDPS groups. RDPS significantly reduced the rate of conversion to laparotomy (5.7% vs. 22.9% when compared with LDPS, p = 0.04). There were no significant differences in R0 resection rates, number of harvested lymph nodes, positive to harvested lymph node ratios, and disease-free survival and overall survival rates between the two groups. A Cox proportional hazards analysis showed N1 stage to be significantly associated with worse survival and suggested that chemotherapy might prolong overall survival in these PDAC patients. CONCLUSIONS This single-center study demonstrated that RDPS was safe and efficacious in treatment of PDAC. When compared with LDPS, RDPS was associated with a reduced rate of conversion to open surgery. There were no significantly differences in oncological outcomes and mid-term survival rates between the groups of patients who underwent RDPS or LDPS.
Collapse
Affiliation(s)
- Liu Qu
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Zhao Zhiming
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Tan Xianglong
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Gao Yuanxing
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Xu Yong
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Liu Rong
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
| | - Lau Wan Yee
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, China.
| |
Collapse
|
|
10
|
Huang HC, Rizvi I, Liu J, Anbil S, Kalra A, Lee H, Baglo Y, Paz N, Hayden D, Pereira S, Pogue BW, Fitzgerald J, Hasan T. Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves Drug Delivery. Cancer Res 2018; 78:558-571. [PMID: 29187403 PMCID: PMC5771811 DOI: 10.1158/0008-5472.can-17-1700] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 09/13/2017] [Accepted: 11/15/2017] [Indexed: 12/27/2022]
Abstract
Physiologic barriers to drug delivery and selection for drug resistance limit survival outcomes in cancer patients. In this study, we present preclinical evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve drug delivery barriers in the tumor microenvironment to safely widen the therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal-IRI) prevented tumor relapse, reduced metastasis, and increased both progression-free survival and 1-year disease-free survival. PDP enabled these durable improvements by targeting multiple tumor compartments to (i) increase intratumoral drug accumulation by >10-fold, (ii) increase the duration of drug exposure above a critical therapeutic threshold, and (iii) attenuate surges in CD44 and CXCR4 expression, which mediate chemoresistance often observed after multicycle chemotherapy. Overall, our results offer preclinical proof of concept for the effectiveness of PDP to minimize risks of tumor relapse, progression, and drug resistance and to extend patient survival.Significance: A biophysical priming approach overcomes key treatment barriers, significantly reduces metastases, and prolongs survival in orthotopic models of human pancreatic cancer. Cancer Res; 78(2); 558-71. ©2017 AACR.
Collapse
Affiliation(s)
- Huang-Chiao Huang
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Imran Rizvi
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Joyce Liu
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Sriram Anbil
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
- The University of Texas School of Medicine at San Antonio, San Antonio, Texas
| | - Ashish Kalra
- Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
| | - Helen Lee
- Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
| | - Yan Baglo
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Nancy Paz
- Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
| | - Douglas Hayden
- MGH Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Steve Pereira
- UCL Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Brian W Pogue
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire
| | | | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
- Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts
| |
Collapse
|
|
11
|
Buanes TA. Role of surgery in pancreatic cancer. World J Gastroenterol 2017; 23:3765-3770. [PMID: 28638216 PMCID: PMC5467062 DOI: 10.3748/wjg.v23.i21.3765] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/17/2017] [Accepted: 04/21/2017] [Indexed: 02/06/2023] Open
Abstract
Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious postoperative complications or rapid disease progression may preclude completion of multimodal treatment. The sequence of treatment interventions has therefore become an important concern, and numerous ongoing randomized controlled trials compare clinical outcome after upfront surgery and neoadjuvant treatment with subsequent resection. In previous years, borderline resectable and locally advanced pancreatic cancer was most often considered unresectable. More effective chemotherapy together with the latest improvements in surgical expertise has resulted in extended operations, pushing the borders of resectability. Multivisceral resections with or without resection of major mesenteric vessels are now performed in numerous patients, resulting in better outcome, recorded as overall survival and/or patient reported outcome. But postoperative morbidity increases concurrently, and clinical benefit must be carefully evaluated against risk of potential harm, associated with new comprehensive multimodal treatment sequences. Even though cost/utility analyses are deficient, extended surgery has resulted in significantly longer and better life for many patients with no other treatment alternative. Improved selection of patients to surgery and/or chemotherapy will in the near future be possible, based on better tumor biology insight. Clinically available biomarkers enabling personalized treatment are forthcoming, but these options are still limited. The importance of surgical resection for each patient's prognosis is presently increasing, justifying sustained expansion of the surgical treatment modality.
Collapse
|
|
12
|
Velez-Serrano JF, Velez-Serrano D, Hernandez-Barrera V, Jimenez-Garcia R, Lopez de Andres A, Garrido PC, Álvaro-Meca A. Prediction of in-hospital mortality after pancreatic resection in pancreatic cancer patients: A boosting approach via a population-based study using health administrative data. PLoS One 2017; 12:e0178757. [PMID: 28591154 PMCID: PMC5462391 DOI: 10.1371/journal.pone.0178757] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 05/18/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND One reason for the aggressiveness of the pancreatic cancer is that it is diagnosed late, which often limits both the therapeutic options that are available and patient survival. The long-term survival of pancreatic cancer patients is not possible if the tumor is not resected, even among patients who receive chemotherapy in the earliest stages. The main objective of this study was to create a prediction model for in-hospital mortality after a pancreatectomy in pancreatic cancer patients. METHODS We performed a retrospective study of all pancreatic resections in pancreatic cancer patients in Spanish public hospitals (2013). Data were obtained from records in the Minimum Basic Data Set. To develop the prediction model, we used a boosting method. RESULTS The in-hospital mortality of pancreatic resections in pancreatic cancer patients was 8.48% in Spain. Our model showed high predictive accuracy, with an AUC of 0.91 and a Brier score of 0.09, which indicated that the probabilities were well calibrated. In addition, a sensitivity analysis of the information available prior to the surgery revealed that our model has high predictive accuracy, with an AUC of 0.802. CONCLUSIONS In this study, we developed a nation-wide system that is capable of generating accurate and reliable predictions of in-hospital mortality after pancreatic resection in patients with pancreatic cancer. Our model could help surgeons understand the importance of the patients' characteristics prior to surgery and the health effects that may follow resection.
Collapse
Affiliation(s)
| | - Daniel Velez-Serrano
- Department of Statistics and Operations Research, Complutense University, Madrid, Spain
| | | | - Rodrigo Jimenez-Garcia
- Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain
| | - Ana Lopez de Andres
- Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain
| | - Pilar Carrasco Garrido
- Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain
| | - Alejandro Álvaro-Meca
- Department of Preventive Medicine & Public Health, Rey Juan Carlos University, Madrid, Spain
- * E-mail:
| |
Collapse
|
|
13
|
Angelico R, Khan S, Dasari B, Marudanayagam R, Sutcliffe RP, Muiesan P, Isaac J, Mirza D, Roberts KJ. Is routine hepaticojejunostomy at the time of unplanned surgical bypass required in the era of self-expanding metal stents? HPB (Oxford) 2017; 19:365-370. [PMID: 28223041 DOI: 10.1016/j.hpb.2016.12.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 12/11/2016] [Accepted: 12/22/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepaticojejunostomy is routinely performed in patients when inoperable disease is found at planned pancreatoduodenectomy; however, in the presence of self-expanding metal stent (SEMS) hepaticojejunostomy may not be required. The aim of this study was to assess biliary complications and outcomes in patients with unresectable disease at time of planned pancreaticoduodenectomy stratified by the management of the biliary tract. MATERIAL AND METHODS Retrospective analysis of patients undergoing surgery in January 2010-December 2015. Complications were measured using the Clavien-Dindo scale. RESULTS Of 149 patients, 111 (75%) received gastrojejunostomy and hepaticojejunostomy (double bypass group) and 38 (26%) received a single bypass in the presence of SEMS (single bypass group). Post-operative non-biliary [7 (18%) vs 43 (38%), (p = 0.028)] and biliary [0% vs 12 (11%), (p = 0.037)] complications were lower in the single bypass group. Hospital readmissions were significantly higher in the double bypass group (p = 0.021). Overall survival and the time to start chemotherapy were equivalent (p = n.s.). CONCLUSIONS Complications are more common following double bypass compared to single bypass with SEMS suggesting that gastric bypass is adequate surgical palliation in presence of SEMS. This study adds further evidence that preoperative SEMS should be used in preference to plastic stents for suspected periampullary malignancy.
Collapse
Affiliation(s)
- Roberta Angelico
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom; Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00146 Rome, Italy
| | - Shakeeb Khan
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Bobby Dasari
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Ravi Marudanayagam
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Robert P Sutcliffe
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Paolo Muiesan
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - John Isaac
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Darius Mirza
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | - Keith J Roberts
- The Liver and Pancreas Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom.
| |
Collapse
|
|
14
|
Gong YF, Zhou QB, Liao YD, Mai C, Chen TJ, Tang YQ, Chen RF. Optimized construction of MUC1-VNTR n DNA vaccine and its anti-pancreatic cancer efficacy. Oncol Lett 2017; 13:2198-2206. [PMID: 28454381 PMCID: PMC5403551 DOI: 10.3892/ol.2017.5717] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/03/2016] [Indexed: 12/11/2022] Open
Abstract
Considering mucin 1-variable number tandem repeat (MUC1-VNTRn) as a novel target for pancreatic cancer immunotherapy, the present study aimed to screen and identify the pVAX1-MUC1-VNTRn DNA vaccine with the strongest immunogenicity. Following construction of a pVAX1-MUC1-VNTRn plasmid, immature dendritic cells (DCs) were subjected to transfection, and mature DCs were then co-cultured with autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting interferon (IFN)-γ were determined using an enzyme-linked immunospot assay, and CytoTox® was also used to examine the MUC1-VNTRn-specific Lethal effect of CTLs on Capan2 cells. Additional in vivo experiments in mice were performed to confirm the antitumor effect of the DNA vaccine candidate. The present study successfully constructed the pVAX1-MUC1-VNTRn plasmid, which expresses the target protein in eukaryotic cells. Additionally, upon uptake of the pVAX1-MUC1-VNTRn plasmid, the immature DCs differentiated into mature DCs. The levels of the DC surface molecules cluster of differentiation (CD) 80, CD86, human leukocyte antigen-antigen D related, interleukin (IL)-12, IL-17 and IFN-γ were significantly higher, while the levels of IL-10 and IL-14 were lower, in mature DCs of the stimulated groups compared with the immature DCs of the non-stimulated groups (all P<0.01). In addition, the MUC1-VNTR6 and MUC1-VNTR9 groups, in which DCs were capable of activating autologous T-cells, showed increased IFN-γ-producing T-cells compared with the other groups (strong MUC1-VNTR1, weak VNTR1, VNTR3, VNTR4 and MUC1-cDNA groups; all P<0.001). In addition, the Lethal effect of CTLs on Capan2 cells in these two groups was stronger compared with the other groups (all P<0.001). Furthermore, the induced protective and therapeutic immune responses in mouse experiments showed that the pVAX1-MUC1-VNTR6DNA vaccine likely possessed the strongest immunogenicity, and its ability to inhibit panc02-MUC1 tumor growth was superior to other DNA vaccines (P<0.01). The present study provides compelling evidence that pVAX1-MUC1-VNTRn has the potential to express the target protein in eukaryotic cells, and thatpVAX1-MUC1-VNTR6 was characterized by the strongest Lethal effect in both in vivo and in vitro experiments.
Collapse
Affiliation(s)
- Yuan-Feng Gong
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Quan-Bo Zhou
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China
| | - Ya-Di Liao
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Cong Mai
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Tie-Jun Chen
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Yun-Qiang Tang
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Ru-Fu Chen
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China
| |
Collapse
|
|
15
|
Kauffmann EF, Napoli N, Menonna F, Vistoli F, Amorese G, Campani D, Pollina LE, Funel N, Cappelli C, Caramella D, Boggi U. Robotic pancreatoduodenectomy with vascular resection. Langenbecks Arch Surg 2016; 401:1111-1122. [PMID: 27553112 DOI: 10.1007/s00423-016-1499-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 08/11/2016] [Indexed: 12/16/2022]
Abstract
PURPOSE This study aims to define the current status of robotic pancreatoduodenectomy (RPD) with resection and reconstruction of the superior mesenteric/portal vein (RPD-SMV/PV). METHODS Our experience on RPD, including RPD-SMV/PV, is presented along with a description of the surgical technique and a systematic review of the literature on RPD-SMV/PV. RESULTS We have performed 116 RPD and 14 RPD-SMV/PV. Seven additional cases of RPD-SMV/PV were identified in the literature. In our experience, RPD and RPD-SMV/PV were similar in all baseline variables, but lower mean body mass and higher prevalence of pancreatic cancer in RPD-SMV/PV. Regarding the type of vein resection, there were one type 2 (7.1 %), five type 3 (35.7 %) and eight type 4 (57.2 %) resections. As compared to RPD, RPD-SMV/PV required longer operative time, had higher median estimated blood loss, and blood transfusions were required more frequently. Incidence and severity of post-operative complications were not increased in RPD-SMV/PV, but post-pancreatectomy hemorrhage occurred more frequently after this procedure. In pancreatic cancer, RPD-SMV/PV was associated with a higher mean number of examined lymph nodes (60.0 ± 13.9 vs 44.6 ± 11.0; p = 0.02) and with the same rate of microscopic margin positivity (25.0 % vs 26.1 %). Mean length or resected vein was 23.1 ± 8.08 mm. Actual tumour infiltration was discovered in ten patients (71.4 %), reaching the adventitia in four patients (40.0 %), the media in two patients (20.0 %), and the intima in four patients (40.0 %). Literature review identified seven additional cases, all reported to have successful outcome. CONCLUSIONS RPD-SMV/PV is feasible in carefully selected patients. The generalization of these results remains to be demonstrated.
Collapse
Affiliation(s)
- Emanuele F Kauffmann
- Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy
| | - Niccolò Napoli
- Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy
| | - Francesca Menonna
- Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy
| | - Fabio Vistoli
- Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy
| | - Gabriella Amorese
- Division of Anesthesia and Intensive Care, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Daniela Campani
- Division of Pathology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Luca Emanuele Pollina
- Division of Pathology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Niccola Funel
- Division of Pathology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Carla Cappelli
- Division of Radiology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Davide Caramella
- Division of Radiology, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa and Azienda Ospedaliero Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy.
| |
Collapse
|
|
16
|
Sahakyan MA, Kazaryan AM, Rawashdeh M, Fuks D, Shmavonyan M, Haugvik SP, Labori KJ, Buanes T, Røsok BI, Ignjatovic D, Abu Hilal M, Gayet B, Kim SC, Edwin B. Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: results of a multicenter cohort study on 196 patients. Surg Endosc 2016; 30:3409-3418. [PMID: 26514135 DOI: 10.1007/s00464-015-4623-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Accepted: 10/14/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Laparoscopy is widely accepted as a feasible option for distal pancreatectomy. However, the experience in laparoscopic distal pancreatectomy (LDP) for pancreatic ductal adenocarcinoma (PDAC) is limited to a small number of studies, reported by expert centers. The present study aimed to evaluate perioperative and oncological outcomes after LDP for PDAC in a large, multicenter cohort of patients. METHODS A retrospective analysis of the data on 196 patients with histologically verified PDAC, operated at Oslo University Hospital-Rikshospitalet (Oslo, Norway), Asan Medical Center (Seoul, Republic of Korea), Institut Mutualiste Montsouris (Paris, France) and University Hospital Southampton (Southampton, UK) between January 2002 and April 2015 was conducted. The patients with standard (SLDP) and extended (i.e., en bloc with adjacent organ, ELDP) resections were compared in terms of perioperative and oncological outcomes. RESULTS Out of 196 LDP procedures, 191 (97.4 %) were completed through laparoscopy, while five (2.6 %) were converted to open surgery. ELDP was performed in 30 (15.7 %) cases. Sixty-one (31.9 %) patients experienced postoperative complications, including 48 (25.1 %) with pancreatic fistula. The rate of clinically relevant fistula (grade B/C) was 15.7 %. Median postoperative hospital stay was 8 (2-63) days. Median follow-up was 16 months. Median survival was 31.3 months (95 % CI 22.9-39.6). Three- and 5-year actuarial survival rates were 42.4 and 30 %, respectively. SLDP was associated with significantly higher survival compared with ELDP (p = 0.032). CONCLUSIONS LDP seems to be a feasible and safe procedure, providing satisfactory oncological outcomes in patients with PDAC.
Collapse
Affiliation(s)
- Mushegh A Sahakyan
- The Intervention Centre, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway.
- Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.
- Department of Surgery No 1, Yerevan State Medical University After M. Heratsi, Yerevan, Armenia.
| | - Airazat M Kazaryan
- The Intervention Centre, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway
- Department of Surgery, Finnmark Hospital, Kirkenes, Norway
| | - Majd Rawashdeh
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - David Fuks
- Department of Digestive Diseases, Institut Mutualiste Montsouris, Université Paris Descartes, Paris, France
- Institut des Systèmes Intelligents et Robotique (ISIR), Université Pierre et Marie Curie, Paris, France
| | - Mark Shmavonyan
- The Intervention Centre, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway
- Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
| | - Sven-Petter Haugvik
- Department of Hepato-Pancreato-Billiary Sugery, Oslo University Hospital-Rikshospitalet, Oslo, Norway
- Department of Surgery, Vestre Viken Hospital Trust, Drammen, Norway
| | - Knut Jørgen Labori
- Department of Hepato-Pancreato-Billiary Sugery, Oslo University Hospital-Rikshospitalet, Oslo, Norway
| | - Trond Buanes
- Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
- Department of Hepato-Pancreato-Billiary Sugery, Oslo University Hospital-Rikshospitalet, Oslo, Norway
| | - Bård Ingvald Røsok
- Department of Hepato-Pancreato-Billiary Sugery, Oslo University Hospital-Rikshospitalet, Oslo, Norway
| | - Dejan Ignjatovic
- Department of Digestive Surgery, Akershus University Hospital, University of Oslo, Lørenskog, Norway
| | | | - Brice Gayet
- Department of Digestive Diseases, Institut Mutualiste Montsouris, Université Paris Descartes, Paris, France
- Institut des Systèmes Intelligents et Robotique (ISIR), Université Pierre et Marie Curie, Paris, France
| | - Song Cheol Kim
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
| | - Bjørn Edwin
- The Intervention Centre, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway
- Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
- Department of Hepato-Pancreato-Billiary Sugery, Oslo University Hospital-Rikshospitalet, Oslo, Norway
| |
Collapse
|
|
17
|
Burmeister EA, Jordan SJ, O'Connell DL, Beesley VL, Goldstein D, Gooden HM, Janda M, Merrett ND, Wyld D, Neale RE. Using a Delphi process to determine optimal care for patients with pancreatic cancer. Asia Pac J Clin Oncol 2016; 12:105-114. [PMID: 26800012 DOI: 10.1111/ajco.12450] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 10/07/2015] [Accepted: 11/23/2015] [Indexed: 02/07/2023]
Abstract
AIM Overall 5-year survival for pancreatic cancer is ∼5%. Optimizing the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. METHODS Using a Delphi process, a multidisciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one [no importance/disagree] to 10 [very important/agree]) the factors. The mean and coefficient of variation scores were calculated and categorized into three levels of importance. RESULTS Overall, 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from nine disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multidisciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and interdisciplinary variation in views about MDT membership and roles. CONCLUSION Overall, the opinions of Australian health professionals reflect international guideline recommended care; however, they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multidisciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified.
Collapse
Affiliation(s)
| | | | - Dianne L O'Connell
- Cancer Council NSW
- University of Newcastle
- University of New South Wales
- University of Sydney
| | | | | | | | | | - Neil D Merrett
- University of Western Sydney
- Bankstown Hospital, NSW, Australia
| | - David Wyld
- Royal Brisbane and Women's Hospital, Brisbane
- School of Medicine, University of Queensland, Queensland
| | | |
Collapse
|