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Kim HS, Chae H, Lim SY, Jeong H, Yoon SJ, Shin SH, Han IW, Heo JS, Kim H. Prognostic Accuracy of ypTNM Stage in Patients with Pancreatic Cancer in the Era of Modern Neoadjuvant Therapy. Ann Surg Oncol 2025; 32:2799-2808. [PMID: 39757338 DOI: 10.1245/s10434-024-16792-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) 8th edition TNM staging manual, which provided ypTNM for patients undergoing neoadjuvant therapy (NAT), has not been comparatively assessed against pTNM for prognosis in pancreatic cancer. This study aimed to compare the prognosis between ypTNM and pTNM stages. PATIENTS AND METHODS Clinicopathological data from 586 patients who underwent pancreatic cancer surgery at a tertiary center between 2018 and 2022 were analyzed to compare survival outcomes between ypTNM and pTNM stages and identify prognostic factors. RESULTS The analysis included 541 patients (100 ypTNM, 441 pTNM). Significant differences in overall survival (OS) were observed among patients stratified by TNM stage (p < 0.001). However, no significant difference in OS was found between the ypTNM and pTNM groups (2-year survival rate (YSR): 76.8% vs. 66.7%, p = 0.094). Subgroup analysis by stage I (82.4% vs. 76.2%, p = 0.577) and II (68.8% vs. 61.6%, p = 0.715), and III (53.0% vs. 49.8%, p = 0.596) revealed similar survival rates. Multivariate analysis identified factors associated with OS: age > 65 years (HR 1.763, p < 0.001), CA19-9 > 150 U/mL (HR 1.439, p = 0.014), preoperative biliary drainage (HR 1.405, p = 0.029), pathologic T2 stage (HR 1.961, p = 0.004) and T3/4 stage (HR 2.830, p < 0.001) versus T0/1 stage, lymphovascular invasion (HR 2.220, p < 0.001), and adjuvant treatment (HR 0.251, p < 0.001). CONCLUSIONS This study confirms comparable survival outcomes between ypTNM and pTNM stages in surgically resected pancreatic cancer, affirming the applicability of the TNM staging system after NAT. The results highlight the utility of TNM staging in guiding therapeutic decisions for patients undergoing NAT.
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Affiliation(s)
- Hyeong Seok Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hochang Chae
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Soo Yeun Lim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea
| | - HyeJeong Jeong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University School of Medicine, Daejeon, South Korea
| | - So Jeong Yoon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Hyun Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In Woong Han
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin Seok Heo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hongbeom Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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Aploks K, Kim M, Stroever S, Ostapenko A, Sim YB, Sooriyakumar A, Rahimi-Ardabily A, Seshadri R, Dong XD. Radiation therapy prior to a pancreaticoduodenectomy for adenocarcinoma is associated with longer operative times and higher blood loss. World J Gastrointest Surg 2023; 15:1663-1672. [PMID: 37701691 PMCID: PMC10494586 DOI: 10.4240/wjgs.v15.i8.1663] [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: 03/29/2023] [Revised: 05/12/2023] [Accepted: 06/12/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma is currently the fourth leading cause of cancer-related deaths in the United States. In patients with "borderline resectable" disease, current National Comprehensive Cancer Center guidelines recommend the use of neoadjuvant chemoradiation prior to a pancreaticoduodenectomy. Although neoadjuvant radiotherapy may improve negative margin resection rate, it is theorized that its administration increases operative times and complexity. AIM To investigate the association between neoadjuvant radiotherapy and 30-d morbidity and mortality outcomes among patients receiving a pancreaticoduodenectomy for pancreatic adenocarcinoma. METHODS Patients listed in the 2015-2019 National Surgery Quality Improvement Program data set, who received a pancreaticoduodenectomy for pancreatic adenocarcinoma, were divided into two groups based off neoadjuvant radiotherapy status. Multivariable regression was used to determine if there is a significant correlation between neoadjuvant radiotherapy, perioperative blood transfusion status, total operative time, and other perioperative outcomes. RESULTS Of the 11458 patients included in the study, 1470 (12.8%) underwent neoadjuvant radiotherapy. Patients who received neoadjuvant radiotherapy were significantly more likely to require a perioperative blood transfusion [adjusted odds ratio (aOR) = 1.58, 95% confidence interval (CI): 1.37-1.82; P < 0.001] and have longer surgeries (insulin receptor-related receptor = 1.14, 95%CI: 1.11-1.16; P < 0.001), while simultaneously having lower rates of organ space infections (aOR = 0.80, 95%CI: 0.66-0.97; P = 0.02) and pancreatic fistula formation (aOR = 0.50, 95%CI: 0.40-0.63; P < 0.001) compared to those who underwent surgery alone. CONCLUSION Neoadjuvant radiotherapy, while not associated with increased mortality, will impact the complexity of surgical resection in patients with pancreatic adenocarcinoma.
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Affiliation(s)
- Krist Aploks
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Minha Kim
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Stephanie Stroever
- Department of Research and Innovation, Nuvance Health, Danbury, CT 06810, United States
| | - Alexander Ostapenko
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Young Bo Sim
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | | | | | - Ramanathan Seshadri
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Xiang Da Dong
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
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Cassese G, Han HS, Yoon YS, Lee JS, Lee B, Cubisino A, Panaro F, Troisi RI. Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives. World J Gastrointest Oncol 2023; 15:911-924. [PMID: 37389109 PMCID: PMC10302990 DOI: 10.4251/wjgo.v15.i6.911] [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: 12/28/2022] [Revised: 02/17/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Pancreatic adenocarcinoma (PDAC) is one of the most common and lethal human cancers worldwide. Surgery followed by adjuvant chemotherapy offers the best chance of a long-term survival for patients with PDAC, although only approximately 20% of the patients have resectable tumors when diagnosed. Neoadjuvant chemotherapy (NACT) is recommended for borderline resectable pancreatic cancer. Several studies have investigated the role of NACT in treating resectable tumors based on the recent advances in PDAC biology, as NACT provides the potential benefit of selecting patients with favorable tumor biology and controls potential micro-metastases in high-risk patients with resectable PDAC. In such challenging cases, new potential tools, such as ct-DNA and molecular targeted therapy, are emerging as novel therapeutic options that may improve old paradigms. This review aims to summarize the current evidence regarding the role of NACT in treating non-metastatic pancreatic cancer while focusing on future perspectives in light of recent evidence.
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Affiliation(s)
- Gianluca Cassese
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive HPB Surgery and Transplantation Service, Federico II University Hospital, Naples 80131, Italy
| | - Ho-Seong Han
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Boram Lee
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Antonio Cubisino
- Department of HPB Surgery and Transplantation, Beaujon Hospital, Clichy 92110, France
| | - Fabrizio Panaro
- Department of Digestive Surgery and Liver Transplantation, CHU Montpellier, Montpellier 34100, France
| | - Roberto Ivan Troisi
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive HPB Surgery and Transplantation Service, Federico II University Hospital, Naples 80131, Italy
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de Geus SWL, Sachs TE. A Paradigm Shifts: Neoadjuvant Therapy for Clearly Resectable Pancreatic Cancer. Ann Surg Oncol 2023; 30:3427-3436. [PMID: 36869916 DOI: 10.1245/s10434-023-13281-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 02/12/2023] [Indexed: 03/05/2023]
Abstract
Over the past decade, neoadjuvant therapy has become the standard of care for patients with borderline resectable and locally advanced pancreatic cancer. The surgical community remains divided regarding the value of neoadjuvant therapy for patients who present with clearly resectable disease. Thus far, randomized controlled trials comparing neoadjuvant therapy with conventional upfront surgical strategies for patients with clearly resectable pancreatic cancer have been plagued by poor accrual, and are often underpowered. Nonetheless, meta-analyses of the results of these trials suggest that neoadjuvant therapy can be offered as an acceptable standard of care for patients with clearly resectable pancreatic cancer. Previous trials used neoadjuvant gemcitabine, but more recent studies have demonstrated superior survival for patients who were able to tolerate neoadjuvant FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan hydrochloride, and oxaliplatin). The increased utilization of FOLFIRINOX may be shifting the treatment paradigm in favor of neoadjuvant therapy among patients with clearly resectable disease. Randomized controlled trials assessing the value of neoadjuvant FOLFIRINOX in clearly resectable pancreatic cancer, which are expected to provide more conclusive recommendations, are still ongoing. This review outlines the rationale, considerations, and current level of evidence for the use of neoadjuvant therapy in patients with clearly resectable pancreatic cancer.
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Affiliation(s)
- Susanna W L de Geus
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
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Hsu DS, Kwak HV, Le ST, Kazantsev G, Chang AL, Spitzer AL, Peng PD, Chang CK. Predicting early discharge and readmission following pancreaticoduodenectomy [S079]. Surg Endosc 2022; 36:9329-9334. [PMID: 35411457 DOI: 10.1007/s00464-022-09207-9] [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: 08/24/2021] [Accepted: 02/17/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Implementing enhanced recovery after surgery (ERAS) protocols for major abdominal surgery has been shown to decrease length of stay (LOS) and postoperative complications, including mortality and readmission. Little is known to guide which patients undergoing pancreaticoduodenectomy (PD) should be eligible for ERAS protocols. METHODS AND PROCEDURES A retrospective chart review of all PD performed from 2010 to 2018 within an integrated healthcare system was conducted. A predictive score that ranges from 0 to 4 was developed, with one point assigned to each of the following: obesity (BMI > 30), operating time > 400 min, estimated blood loss (EBL) > 400 mL, low- or high-risk pancreatic remnant (based on the presence of soft gland or small duct). Chi-squared tests and ANOVA were used to assess the relationship between this score and LOS, discharge before postoperative day 7, readmission, mortality, delayed gastric emptying (DGE), and pancreatic leak/fistula. RESULTS 291 patients were identified. Mean length of stay was 8.5 days in those patients who scored 0 compared to 16.2 days for those who scored 4 (p = 0.001). 30% of patients who scored 0 were discharged before postoperative day 7 compared to 0% of those who scored 4 (p = 0.019). Readmission rates for patients who scored 0 and 4 were 12% and 33%, respectively (p = 0.017). Similarly, postoperative pancreatic fistula occurred in 2% versus 25% in these groups (p = 0.007). CONCLUSION A simple scoring system using BMI, operating time, EBL, and pancreatic remnant quality can help risk-stratify postoperative PD patients. Those with lower scores could potentially be managed via an ERAS protocol. Patients with higher scores required longer hospitalizations, and adjunctive therapy such as medication and surgical technique to decrease risk of delayed gastric emptying and pancreatic fistula could be considered.
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Affiliation(s)
- Diana S Hsu
- UCSF East Bay Surgery, Highland Hospital, 1411 E 31st St., QIC 22134, Oakland, CA, 94602, USA.
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA.
| | - Hyunjee V Kwak
- UCSF East Bay Surgery, Highland Hospital, 1411 E 31st St., QIC 22134, Oakland, CA, 94602, USA
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Sidney T Le
- UCSF East Bay Surgery, Highland Hospital, 1411 E 31st St., QIC 22134, Oakland, CA, 94602, USA
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - George Kazantsev
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Alex L Chang
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Austin L Spitzer
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Peter D Peng
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Ching-Kuo Chang
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
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Fossaert V, Mimmo A, Rhaiem R, Rached LJ, Brasseur M, Brugel M, Pegoraro F, Sanchez S, Bouché O, Kianmanesh R, Piardi T. Neoadjuvant chemotherapy for borderline resectable and upfront resectable pancreatic cancer increasing overall survival and disease-free survival? Front Oncol 2022; 12:980659. [PMID: 36387257 PMCID: PMC9640996 DOI: 10.3389/fonc.2022.980659] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/06/2022] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease. In order to increase resectability, results of neoadjuvant chemotherapy (NAC) on metastatic disease were extrapolated to the neoadjuvant setting by many centers. The aim of our study was to retrospectively evaluate the outcome of patients who underwent upfront surgery (US)-PDAC and borderline (BR)-PDAC, and those resected after NAC to determine prognostic factors that might affect the outcome in these resected patients. METHODS One hundred fifty-one patients between January 2012 and March 2021 in our department were reviewed. Epidemiological characteristics and pre-operative induction treatment were assessed. Pathological reports were analyzed to evaluate the quality of oncological resection (R0/R1). Post-operative mortality and morbidity and survival data were reviewed. RESULTS One hundred thirteen patients were addressed for US, and 38 were considered BR and referred for surgery after induction chemotherapy. The pancreatic resection R0 was 71.5% and R1 28.5%. pT3 rate was significantly higher in the US than BR (58,4% vs 34,2%, p= 0.005). The mean OS and DFS rates were 29.4 months 15.9 months respectively. There was no difference between OS and DFS of US vs BR patients. N0 patients had significantly longer OS and DFS (p=<0.001). R0 patients had significantly longer OS (p=0.03) and longer DFS (P=0.08). In the multivariate analysis, the presence of postoperative pancreatic fistula, R1 resection, N+ and not access to adjuvant chemotherapy were bad prognostic factors of OS. CONCLUSIONS Our study suggests the benefits of NAC for BR patients in downstaging tumors and rendering them amenable to resection, with same oncological result compared to US.
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Affiliation(s)
- Violette Fossaert
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Antonio Mimmo
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Rami Rhaiem
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Linda J. Rached
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Mathilde Brasseur
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Mathias Brugel
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Francesca Pegoraro
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
- Division of Hepato-Bilio-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy
| | - Stephane Sanchez
- Pôle Territorial Santé Publique et Performance des Hôpitaux Champagne Sud, University Reims Champagne-Ardenne, Troyes, France
| | - Olivier Bouché
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Reza Kianmanesh
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Tullio Piardi
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
- Department of Surgery, Hepato-Bilio-Pancreatic and Metabolic Unit, University Reims Champagne-Ardenne, Troyes, France
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Trends in pancreatic surgery in Switzerland: a survey and nationwide analysis over two decades. Langenbecks Arch Surg 2022; 407:3423-3435. [DOI: 10.1007/s00423-022-02679-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 09/08/2022] [Indexed: 12/24/2022]
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Neoadjuvant Treatment Strategies in Resectable Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13184724. [PMID: 34572951 PMCID: PMC8469083 DOI: 10.3390/cancers13184724] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/15/2021] [Accepted: 09/15/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Only 10–20% of patients with newly diagnosed resectable pancreatic adenocarcinoma have potentially resectable disease. Upfront surgery is the gold standard, but it is rarely curative. After surgical extirpation of tumors, up to 80% of patients will develop cancer recurrence, and the initial relapse is metastatic in 50–70% of these patients. Adjuvant chemotherapy offers the best strategy to date to improve overall survival but faces real challenges; some patients will experience rapid disease progression within 3 months of surgery and patients who do not receive all planned cycles of chemotherapy have unfavourable oncological outcomes. The neoadjuvant approach is therefore logical but requires further investigation. This approach shows favourable trends regarding disease-free survival and overall survival but, in the absence of rigorous published phase III trials, is not validated to date. Here, we intend to provide a comprehensive analysis of the literature to provide direction for future studies. Abstract Complete surgical resection is the cornerstone of curative therapy for resectable pancreatic adenocarcinoma. Upfront surgery is the gold standard, but it is rarely curative. Neoadjuvant treatment is a logical option, as it may overcome some of the limitations of adjuvant therapy and has already shown some encouraging results. The main concern regarding neoadjuvant therapy is the risk of disease progression during chemotherapy, meaning the opportunity to undergo the intended curative surgery is missed. We reviewed all recent literature in the following areas: major surveys, retrospective studies, meta-analyses, and randomized trials. We then selected the ongoing trials that we believe are of interest in this field and report here the results of a comprehensive review of the literature. Meta-analyses and randomized trials suggest that neoadjuvant treatment has a positive effect. However, no study to date can be considered practice changing. We considered design, endpoints, inclusion criteria and results of available randomized trials. Neoadjuvant treatment appears to be at least a feasible strategy for patients with resectable pancreatic cancer.
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Hashimoto D, Satoi S, Yamamoto T, Yamaki S, Ishida M, Sakaguchi T, Hirooka S, Ikeura T, Inoue K, Sekimoto M. Validation of the triple-checked criteria for drain management after pancreatectomy. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 29:271-281. [PMID: 34330147 DOI: 10.1002/jhbp.1030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/18/2021] [Accepted: 07/26/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND Drain management is important for the detection and treatment of clinically relevant postoperative pancreatic fistula (CR-POPF). We previously established the triple-checked criteria for drain removal: drain fluid amylase (DFA) <5000 U/L on postoperative day (POD) 1 and DFA <3000 U/L on POD 3, or C-reactive protein <15 mg/dL on POD 3. This study aimed to validate the efficacy of the triple-checked criteria. METHODS In this study, 681 patients who underwent pancreatectomy were included. Drains were removed according to our previous criteria (sequentially checked criteria: DFA <5000 U/L on POD 1 and DFA <3000 U/L on POD 3) from 2012 to 2016 (control group) and the triple-checked criteria from 2017 to 2019 (intervention group). RESULTS The control group included 406 patients, and the intervention group included 275 patients. Significantly more patients (n = 237, 86.2%) met the triple-checked criteria in the intervention group, relative to the sequentially checked criteria for early drain removal policy (n = 309, 76.1%; P = .001). Sensitivity, accuracy, and negative predictive value were significantly higher in the intervention group than in the control group (P < .001). The incidence of CR-POPF was not significantly different (11.1% vs 13.8%, P = .285). CONCLUSIONS The triple-checked criteria contributed to effective drain removal after pancreatectomy without increasing CR-POPF.
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Affiliation(s)
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Hirakata, Japan
| | | | - So Yamaki
- Department of Surgery, Kansai Medical University, Hirakata, Japan
| | - Mitsuaki Ishida
- Department of Pathology and Clinical Laboratory, Kansai Medical University, Hirakata, Japan
| | | | - Satoshi Hirooka
- Department of Surgery, Kansai Medical University, Hirakata, Japan
| | - Tsukasa Ikeura
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan
| | - Kentaro Inoue
- Department of Surgery, Kansai Medical University, Hirakata, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Hirakata, Japan
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10
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Vitello DJ, Bentrem DJ. A review of response in neoadjuvant therapy for exocrine pancreatic cancer. J Surg Oncol 2021; 123:1449-1459. [PMID: 33831249 DOI: 10.1002/jso.26369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 12/27/2020] [Indexed: 11/11/2022]
Abstract
Despite overall advances in cancer therapy, patients with pancreatic ductal adenocarcinoma continue to have a poor prognosis. While adjuvant therapy is still considered standard, there is mounting evidence that neoadjuvant therapy confers similar benefits in patients with locally advanced disease. The primary measures of response are radiographic, biochemical, margin status, and pathologic. Given overall low response rates and the need for new treatment strategies, standard metrics remain important to the investigation of new systemic agents.
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Affiliation(s)
- Dominic J Vitello
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - David J Bentrem
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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Kamarajah SK, Naffouje SA, Salti GI, Dahdaleh FS. Neoadjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma is Associated with Lower Post-Pancreatectomy Readmission Rates: A Population-Based Cohort Study. Ann Surg Oncol 2021; 28:1896-1905. [PMID: 33398644 DOI: 10.1245/s10434-020-09470-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 10/20/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Despite neoadjuvant chemotherapy (NAC) being increasingly utilized and possibly associated with improved oncological outcomes, the impact of NAC on textbook outcomes following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) remains debated. METHODS A retrospective review of the National Cancer Database of patients undergoing resection of non-metastatic PDAC from 2004 to 2016 was performed. Propensity score matching was used to account for treatment selection bias in patients with and without NAC (noNAC). A multivariable binary logistic regression model was used to analyze the association of NAC with length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. RESULTS Of 7975 (11%) NAC patients and 65,338 (89%) noNAC patients, 2911 NAC and 2911 noNAC patients remained in the cohort after matching. Clinicopathologic and demographic variables were well-balanced after matching. After matching, NAC was associated with significantly lower rates of 30-day readmission (5.5% vs. 7.4%; p = 0.006), which remained after multivariable adjustment (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.60-0.92; p = 0.006). There were no significant differences in LOS and 30- and 90-day mortality in patients receiving NAC and noNAC. Stratified analyses by surgery type (i.e. pancreaticoduodenectomy [PD] and distal pancreatectomy [DP]) demonstrated consistent results. CONCLUSION Receipt of NAC in PDAC patients undergoing DP or PD is associated with lower readmission rates and does not otherwise compromise short-term outcomes. These data reaffirm the safety of strategies incorporating NAC and is important to consider when devising policies aimed at quality improvement in achieving textbook outcomes.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, Newcastle, UK
| | - Samer A Naffouje
- Department of Surgical Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - George I Salti
- Department of General Surgery, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA.,Department of Surgical Oncology, Edward-Elmhurst Health, Naperville, IL, USA
| | - Fadi S Dahdaleh
- Department of Surgical Oncology, Edward-Elmhurst Health, Naperville, IL, USA.
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12
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Kamarajah SK, Bundred JR, Boyle C, Oo J, Pandanaboyana S, Loveday B. Impact of neoadjuvant therapy on post-operative pancreatic fistula: a systematic review and meta-analysis. ANZ J Surg 2020; 90:2201-2210. [PMID: 32418344 DOI: 10.1111/ans.15885] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/07/2020] [Accepted: 03/09/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The use of neoadjuvant therapy (NAT) for pancreatic cancer is increasing, although its impact on post-operative pancreatic fistula (POPF) is variably reported. This systematic review and meta-analysis aimed to assess the impact of NAT on POPF. METHODS A systematic literature search until October 2019 identified studies reporting POPF following NAT (radiotherapy, chemotherapy or chemoradiotherapy) versus upfront resection. The primary outcome was overall POPF. Secondary outcomes included grade B/C POPF, delayed gastric emptying (DGE), post-operative pancreatic haemorrhage (PPH) and overall and major complications. RESULTS The search identified 24 studies: pancreatoduodenectomy (PD), 19 studies (n = 19 416) and distal pancreatectomy (DP), five studies (n = 477). Local staging was reported in 17 studies, with borderline resectable and locally advanced disease comprising 6% (0-100%) and 1% (0-33%) of the population, respectively. For PD, any NAT was significantly associated with lower rates of overall POPF (OR: 0.57, P < 0.001) and grade B/C POPF (OR: 0.55, P < 0.001). In DP, NAT was not associated with significantly lower rates of overall or grade B/C POPF. CONCLUSION NAT is associated with significantly lower rates of POPF after PD but not after DP. Further studies are required to determine whether NAT should be added to POPF risk calculators.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, Newcastle, UK
| | - James R Bundred
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Charles Boyle
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
| | - June Oo
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Sanjay Pandanaboyana
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
| | - Benjamin Loveday
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Surgery, University of Auckland, Auckland, New Zealand
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13
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Nassour I, Adam MA, Kowalsky S, Al Masri S, Bahary N, Singhi AD, Lee K, Zureikat A, Paniccia A. Neoadjuvant therapy versus upfront surgery for early-stage left-sided pancreatic adenocarcinoma: A propensity-matched analysis from a national cohort of distal pancreatectomies. J Surg Oncol 2020; 123:245-251. [PMID: 33103242 DOI: 10.1002/jso.26267] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/27/2020] [Accepted: 10/05/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND There are limited data on the efficacy of neoadjuvant therapy (NAT) for early-stage distal pancreas adenocarcinoma (PDAC). Previous studies focused on adenocarcinoma of the head of the pancreas or dealt with borderline and locally advanced tumors of the body and tail. METHODS This is a retrospective study of the National Cancer Database between 2006 and 2015. A propensity-matched analysis was performed to compare overall survival estimates between NAT and upfront resection (UR) groups. RESULTS A total of 5003 distal pancreatectomies for PDAC were identified, of whom 408 (9%) received NAT. After 1:1 matching, 353 NAT patients were compared with 353 UR patients. NAT was associated with lower 90-day mortality. There were no differences in the number of lymph nodes retrieved, or length of stay. With matching, the NAT group had higher median overall survival compared with UR (33.0 vs. 27.0 months; p = 0.009) and adjusted overall survival (hazard ratio = 0.63, 95% confidence interval = 0.51-0.77; p < 0.001). CONCLUSION The receipt of NAT followed by distal pancreatectomy for early-stage distal PDAC is associated with improved overall survival compared with UR. This study supports the use of NAT in the multimodal therapy paradigm of early-stage adenocarcinoma of the body and tail of the pancreas.
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Affiliation(s)
- Ibrahim Nassour
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Mohamed A Adam
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Stacy Kowalsky
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Samer Al Masri
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Nathan Bahary
- Department of Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Kenneth Lee
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Amer Zureikat
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Alessandro Paniccia
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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14
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Mangieri CW, Strode MA, Moaven O, Clark CJ, Shen P. Utilization of chemoradiation therapy provides strongest protective effect for avoidance of postoperative pancreatic fistula following pancreaticoduodenectomy: A NSQIP analysis. J Surg Oncol 2020; 122:1604-1611. [PMID: 32935353 DOI: 10.1002/jso.26202] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/05/2020] [Accepted: 08/20/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND The utilization of neoadjuvant therapy (NAT) before performing pancreaticoduodenectomy for malignancy has been well established as a protective factor for the prevention of postoperative pancreatic fistula (POPF). However, there is a paucity of published data evaluating the specific NAT regimen that is the most protective against POPF development. We evaluated the differences between neoadjuvant chemotherapy (CT) and chemoradiation therapy (CRT) with regard to the effect on POPF rates. METHODS The main and targeted pancreatectomy American College of Surgeons National Surgical Quality Improvement Program registries for 2014-2016 were retrospectively reviewed. A total of 10,665 pancreaticoduodenectomy cases were present. The primary outcome was POPF development. The factors that have previously been shown to be associated with or suspected to be associated with POPF were evaluated. The factors included NAT, sex, age, body mass index (BMI), diabetes, smoking, steroid therapy, preoperative weight loss, preoperative albumin level, perioperative blood transfusions, wound classification, American Society of Anesthesiologists classification, duct size (<3 mm, 3-6 mm, and >6 mm), gland texture (soft, intermediate, and hard), and anastomotic technique. The factors identified to be statistically significant were then used for propensity score matching to compare POPF development between the cases utilizing CT versus CRT. RESULTS A total of 10,117 cases met the inclusion criteria. The development of POPF was significantly associated, on multivariate analysis, with a lack of NAT, male sex, higher BMI, nondiabetic status, nonsmoker status, decreased weight loss, preoperative albumin level, decreased duct size, and soft gland texture. NAT, duct size, and gland texture had the strongest associations with the development of POPF (p < .0001). The overall 1765 cases (17.45%) received NAT and the POPF rate for cases with NAT was 10.20% versus 20.10% for cases without NAT (p < .0001). A total of 1031 cases underwent CT and 734 cases underwent CRT, respectively. A total of 708 paired cases were selected for analysis based on propensity score matching. The POPF rates were 11.20% versus 3.50% for CT and CRT, respectively (p < .0001). There was no difference in the frequencies of specific POPF grades. The decreased POPF rate with CRT correlated with firmer gland texture rates. CONCLUSIONS To our knowledge, this is the largest analysis of specific NAT regimens with regard to the development of POPF following pancreaticoduodenectomy. CRT provided the strongest protective effect. That protective effect is most likely due to increased fibrosis in the pancreatic parenchyma from radiation therapy. These findings provide additional support to consider CRT over CT alone in the treatment of pancreatic cancer when NAT will be utilized.
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Affiliation(s)
- Christopher W Mangieri
- Department of Surgical Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA
- Department of General Surgery, Dwight D. Eisenhower Army Medical Center, Fort Gordon, Georgia, USA
| | - Matthew A Strode
- Department of Surgery, Womack Army Medical Center, Fort Bragg, North Carolina, USA
| | - Omeed Moaven
- Department of Surgical Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Clancy J Clark
- Department of Surgical Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Perry Shen
- Department of Surgical Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA
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Scheufele F, Schirren R, Friess H, Reim D. Selective decontamination of the digestive tract in upper gastrointestinal surgery: systematic review with meta-analysis of randomized clinical trials. BJS Open 2020; 4:1015-1021. [PMID: 32749070 PMCID: PMC7709368 DOI: 10.1002/bjs5.50332] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/29/2020] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Infectious complications are common after gastrointestinal surgery. Selective decontamination of the digestive tract (SDD) might reduce their incidence. SDD is used widely in colorectal resections, but its role in upper gastrointestinal resection is less clear. The aim of this study was to investigate the impact of SDD on postoperative outcome in upper gastrointestinal surgery. METHODS Studies investigating SDD in upper gastrointestinal surgery were included after search of medical databases (PubMed, Ovid, Cochrane Library and Google Scholar). Results were analysed according to predefined criteria. The incidence of perioperative overall complications and death was pooled. Risk of bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS Some 1384 studies were identified, of which four RCTs were included in the final analysis. These studies included 415 patients, of whom 213 (51·3 per cent) received standard treatment/placebo and 202 (48·7 per cent) had SDD. The incidence of anastomotic leakage (odds ratio (OR) 0·39, 95 per cent c.i. 0·19 to 0·80; P = 0·010) and pneumonia (OR 0·42, 0·23 to 0·78; P = 0·006) was reduced in patients receiving SDD. Rates of surgical-site infection (P = 0·750) and mortality (P = 0·130) were not affected by SDD. CONCLUSION SDD seems to be associated with reduction of anastomotic leakage and pneumonia following upper gastrointestinal resection, without affecting postoperative mortality.
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Affiliation(s)
- F. Scheufele
- Department of Surgery, Klinikum rechts der Isar, School of MedicineTechnical University of MunichIsmaningerstrasse 22D‐81675 MunichGermany
| | - R. Schirren
- Department of Surgery, Klinikum rechts der Isar, School of MedicineTechnical University of MunichIsmaningerstrasse 22D‐81675 MunichGermany
| | - H. Friess
- Department of Surgery, Klinikum rechts der Isar, School of MedicineTechnical University of MunichIsmaningerstrasse 22D‐81675 MunichGermany
| | - D. Reim
- Department of Surgery, Klinikum rechts der Isar, School of MedicineTechnical University of MunichIsmaningerstrasse 22D‐81675 MunichGermany
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16
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Lof S, Korrel M, van Hilst J, Alseidi A, Balzano G, Boggi U, Butturini G, Casadei R, Dokmak S, Edwin B, Falconi M, Keck T, Malleo G, de Pastena M, Tomazic A, Wilmink H, Zerbi A, Besselink MG, Abu Hilal M. Impact of Neoadjuvant Therapy in Resected Pancreatic Ductal Adenocarcinoma of the Pancreatic Body or Tail on Surgical and Oncological Outcome: A Propensity-Score Matched Multicenter Study. Ann Surg Oncol 2020; 27:1986-1996. [PMID: 31848815 PMCID: PMC7210228 DOI: 10.1245/s10434-019-08137-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. METHODS Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007-2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. RESULTS Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien-Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14-39) versus 31 months (95% CI 19-42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18-53) versus 20 months (95% CI 15-24), P = 0.049], as compared with upfront resection. CONCLUSION In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.
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Affiliation(s)
- Sanne Lof
- Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, UK
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Maarten Korrel
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jony van Hilst
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Gianpaolo Balzano
- Pancreatic Surgery, San Raffaele Hospital IRCCS, Università Vita-Salute, Milan, Italy
| | - Ugo Boggi
- Department of Surgery, Universitá di Pisa, Pisa, Italy
| | | | - Riccardo Casadei
- Department of Surgery, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Safi Dokmak
- Department of Surgery, Hospital of Beaujon, Clichy, France
| | - Bjørn Edwin
- Department of Surgery, Oslo University Hospital and Institute for Clinical Medicine, Oslo, Norway
| | - Massimo Falconi
- Pancreatic Surgery, San Raffaele Hospital IRCCS, Università Vita-Salute, Milan, Italy
| | - Tobias Keck
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Giuseppe Malleo
- Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Matteo de Pastena
- Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Ales Tomazic
- Department of Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Hanneke Wilmink
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Alessandro Zerbi
- Department of Surgery, Humanitas University Hospital, Milan, Italy
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Mohammed Abu Hilal
- Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, UK.
- Department of General Surgery, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.
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17
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Flick KF, Al-Temimi MH, Maatman TK, Sublette CM, Swensson JK, Nakeeb A, Ceppa EP, Nguyen TK, Schmidt CM, Zyromski NJ, Tann MA, House MG. Hepatic Steatosis After Neoadjuvant Chemotherapy for Pancreatic Cancer: Incidence and Implications for Outcomes After Pancreatoduodenectomy. J Gastrointest Surg 2020; 24:2008-2014. [PMID: 32671796 PMCID: PMC7363010 DOI: 10.1007/s11605-020-04723-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 06/28/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND This study aimed to determine the incidence of new onset hepatic steatosis after neoadjuvant chemotherapy for pancreatic cancer and its impact on outcomes after pancreatoduodenectomy. METHODS Retrospective review identified patients who received neoadjuvant chemotherapy for pancreatic adenocarcinoma and underwent pancreatoduodenectomy from 2013 to 2018. Preoperative computed tomography scans were evaluated for the development of hepatic steatosis after neoadjuvant chemotherapy. Hypoattenuation included liver attenuation greater than or equal to 10 Hounsfield units less than tissue density of spleen on noncontrast computed tomography and greater than or equal to 20 Hounsfield units less on contrast-enhanced computed tomography. RESULTS One hundred forty-nine patients received neoadjuvant chemotherapy for a median of 5 cycles (interquartile range (IQR), 4-6). FOLFIRINOX was the regimen in 78% of patients. Hepatic steatosis developed in 36 (24%) patients. The median time from neoadjuvant chemotherapy completion to pancreatoduodenectomy was 40 days (IQR, 29-51). Preoperative biliary stenting was performed in 126 (86%) patients. Neoadjuvant radiotherapy was delivered to 23 (15%) patients. Female gender, obesity, and prolonged exposure to chemotherapy were identified as risk factors for chemotherapy-associated hepatic steatosis. Compared with control patients without neoadjuvant chemotherapy-associated hepatic steatosis, patients developing steatosis had similar rates of postoperative pancreatic fistula (8% (control) vs. 4%, p = 0.3), delayed gastric emptying (8% vs. 14%, p = 0.4), and major morbidity (11% vs. 15%, p = 0.6). Ninety-day mortality was similar between groups (8% vs. 2%, p = 0.08). CONCLUSION Hepatic steatosis developed in 24% of patients who received neoadjuvant chemotherapy but was not associated with increased morbidity or mortality after pancreatoduodenectomy.
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Affiliation(s)
- K. F. Flick
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - M. H. Al-Temimi
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - T. K. Maatman
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - C. M. Sublette
- Indiana University School of Medicine, Indianapolis, IN USA
| | - J. K. Swensson
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN USA
| | - A. Nakeeb
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - E. P. Ceppa
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - T. K. Nguyen
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - C. M. Schmidt
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - N. J. Zyromski
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
| | - M. A. Tann
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN USA
| | - M. G. House
- Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 515, Indianapolis, IN 46202 USA
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Pecorelli N, Pagnanelli M, Cinelli L, Di Salvo F, Partelli S, Crippa S, Tamburrino D, Castoldi R, Belfiori G, Reni M, Falconi M, Balzano G. Postoperative Outcomes and Functional Recovery After Preoperative Combination Chemotherapy for Pancreatic Cancer: A Propensity Score-Matched Study. Front Oncol 2019; 9:1299. [PMID: 31850203 PMCID: PMC6901953 DOI: 10.3389/fonc.2019.01299] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 11/11/2019] [Indexed: 12/12/2022] Open
Abstract
Introduction: Previous studies show encouraging oncologic outcomes for neoadjuvant chemotherapy (NACT) in the setting of pancreatic ductal adenocarcinoma (PDAC). However, recent literature reported an increased clinical burden in patients undergoing pancreaticoduodenectomy (PD) following NACT. Therefore, the aim of our study was to assess the impact of NACT on postoperative outcomes and recovery after PD. Methods: A retrospective propensity score-matched study was performed including all patients who underwent PD for PDAC in a single center between 2015 and 2018. Patients treated with NACT for resectable, borderline resectable or locally advanced PDAC were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients who underwent upfront resection. Propensity scores were calculated using 7 perioperative variables, including gender, age, BMI, ASA score, Charlson-Deyo comorbidity score, fistula risk score (FRS), vascular resection. Primary outcome was the number and severity of complications at 90-days after surgery measured by the comprehensive complication index (CCI). Data are reported as median (IQR) or number of patients (%). Results: Of 283 resected patients, 95 (34%) were treated with NACT. Before matching, NACT patients were younger, had less comorbidities (Charlson-Deyo score 0 vs. 1, p = 0.04), similar FRS [2 (0–3) for both groups], and more vascular resections performed [n = 28 (30%) vs. n = 26 (14%), p < 0.01]. After propensity-score matching, preoperative and intraoperative characteristics were comparable. Postoperatively, CCI was similar between groups [8.7 (0–29.6) for both groups, p = 0.59]. NACT patients had a non-statistically significant increase in superficial incisional surgical site infections [n = 12 (13%) vs. 6 (6%), p = 0.14], while no difference was found for overall infectious complications and organ-space SSI. The occurrence of clinically-relevant pancreatic fistula was similar between groups [10 (11%) vs. 13 (14%), p = 0.51]. No difference was found between groups for length of hospital stay [8 (7–15) vs. 8 (7–14) days, p = 0.62], and functional recovery outcomes. Conclusion: After propensity score adjustment for perioperative risk factors, NACT did not worsen postoperative outcomes and functional recovery following PD for PDAC compared to upfront resection.
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Affiliation(s)
- Nicolò Pecorelli
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | | | | | - Francesca Di Salvo
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Stefano Crippa
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Domenico Tamburrino
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Renato Castoldi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Giulio Belfiori
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Michele Reni
- Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Gianpaolo Balzano
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
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19
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Song KB, Kwon J, Kim YW, Hwang DW, Lee JH, Hong S, Lee JW, Hwang K, Yoo D, Kim SC. Prognostic value of adjacent organ resection in patients with left-sided pancreatic ductal adenocarcinoma following distal pancreatectomy. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:227-234. [PMID: 30980486 DOI: 10.1002/jhbp.627] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND We evaluated whether distal pancreatectomy (DP) with adjacent organ resection (AOR) affected perioperative outcomes and survival in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). METHODS Retrospective cohort study was conducted at single large volume academic medical center from January 2000 to December 2016. RESULTS Five hundred and twenty-three patients had undergone standard DP (without additional vessel/organ resection) and 40 had undergone DP with AOR due to adjacent organ infiltration. There were no differences of postoperative morbidity and hospital stay between the two groups. In the patients with AJCC 8th stage I and II PDAC, there were significant differences of median disease-specific and progression-free survivals between the standard and AOR groups (37.9 vs. 20.2 months; P = 0.05, 20 vs. 10 months; P = 0.028, respectively). DP with AOR was identified as independent prognostic factor of stage I and II PDAC by multivariate Cox regression analysis. CONCLUSIONS Distal pancreatectomy with AOR could be an acceptable surgical treatment for left-sided PDAC. However, AOR group shows poor prognosis than that of the standard group in patients with AJCC 8th stage I and II PDAC. AOR should be considered indicative of a more aggressive tumor in AJCC 8th stage I and II PDAC.
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Affiliation(s)
- Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jaewoo Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yong Woon Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jong Woo Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kyungyeon Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Daegwang Yoo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Scheufele F, Hartmann D, Friess H. Treatment of pancreatic cancer-neoadjuvant treatment in borderline resectable/locally advanced pancreatic cancer. Transl Gastroenterol Hepatol 2019; 4:32. [PMID: 31231699 PMCID: PMC6556697 DOI: 10.21037/tgh.2019.04.09] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 04/25/2019] [Indexed: 12/17/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.
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Affiliation(s)
- Florian Scheufele
- Department of Surgery, Klinikum rechts der Isar, School of Medicine Technical University of Munich, D-81675 Munich, Germany
| | - Daniel Hartmann
- Department of Surgery, Klinikum rechts der Isar, School of Medicine Technical University of Munich, D-81675 Munich, Germany
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, School of Medicine Technical University of Munich, D-81675 Munich, Germany
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