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Zhou Y, Xue F. A comparative analysis and survival analysis of open versus minimally invasive radical antegrade modular pancreatosplenectomy for pancreatic cancer: a systematic review and meta-analysis. Front Oncol 2025; 14:1513520. [PMID: 39917364 PMCID: PMC11798776 DOI: 10.3389/fonc.2024.1513520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/31/2024] [Indexed: 02/09/2025] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is a major public health concern, ranking as the fourth leading cause of cancer-related mortality in the United States. Traditional surgical approaches often yield suboptimal outcomes, highlighting the need for innovative surgical strategies. Radical antegrade modular pancreatosplenectomy (RAMPS) has demonstrated improvements in surgical visualization and oncological outcomes. Recently, laparoscopic RAMPS (L-RAMPS) has been introduced as a minimally invasive alternative. Objectives This meta-analysis aims to compare the safety and efficacy of open RAMPS (O-RAMPS) versus L-RAMPS, focusing on operative outcomes, minimally invasive outcomes, intra-abdominal outcomes, overall postoperative outcomes, and oncologic outcomes. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. Eligible studies included prospective or retrospective cohort studies and randomized controlled trials comparing L-RAMPS with O-RAMPS. Data were extracted from EMBASE, PubMed, and the Cochrane Library databases through September 16, 2023. The ROBINS-I tool was used to assess the risk of bias. Statistical analyses included odds ratios (OR), risk differences (RD), mean differences (MD), and survival analyses. Results Eight studies involving 588 patients were included. O-RAMPS was associated with longer operative times (MD = 39.39 minutes, 95% CI = 22.93 to 55.84) and greater blood loss (MD = -231.84 mL, 95% CI = -312.00 to -151.69). No significant differences were observed in blood transfusion rates, pancreatic fistula rates, delayed gastric emptying, or length of hospital stay. L-RAMPS demonstrated a shorter time to oral feeding (MD = -0.79 days, 95% CI = -1.35 to -0.22). Survival analysis suggested a potentially improved long-term prognosis for L-RAMPS. Conclusion L-RAMPS offers advantages over O-RAMPS in terms of reduced blood loss, faster time to oral feeding, and potentially better long-term prognosis. Further research is warranted, particularly regarding the learning curve of L-RAMPS and its broader applicability. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier CRD42024498383.
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Affiliation(s)
| | - Fei Xue
- Kunshan Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
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Saponjski D, Djuric-Stefanovic A, Jovanovic MM, Jankovic A, Kovac J, Milosevic S, Stosic K, Pantovic J, Petrovic J, Kmezic S, Radenkovic D, Saranovic DS. Utility of MRI in detection of PET-CT proven local recurrence of pancreatic adenocarcinoma after surgery. Med Oncol 2024; 41:47. [PMID: 38175487 DOI: 10.1007/s12032-023-02271-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/24/2023] [Indexed: 01/05/2024]
Abstract
The aim of this prospective study was to investigate the accuracy and inter-observer reliability of MRI in detection of local recurrence (LR) of pancreatic adenocarcinoma (PAC) after surgery, which was proved by PET-CT and access correlation between functional MRI and PET parameters. Forty-five patients who underwent PET-CT and MRI for follow-up purposes after radical operation of PAC were included. Twenty-three were PET positive (study group) and 22 negative for LR (control group). MR examination was performed within one month after PET-CT and three readers who were blind for PET-CT findings searched LR in T2W, 3D-dynamic post-contrast T1W-FS and DWI sequences, respectively. Sensitivity and specificity were calculated while inter-reader agreement was estimated by Cronbach's Alpha reliability coefficient (CARC). Apparent diffusion coefficient (ADC) of LR was correlated with the size (maximal diameter) and functional PET-CT parameters: mean and maximum standardized uptake values (SUVmean, SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), using Spearman's correlation coefficient (rS). Sensitivity and specificity among three readers in detecting the LR were 70% and 77-84% in T2W (CARC 0.806), 91-100% and 100% in 3D post-contrast T1W-FS (CARC 0.980), and both 100% in DWI sequences (CARC 1.000). Moderate inverse correlation was found between the ADC and SUVmean (rS = - 0.484), MTV (rS = - 0.494), TLG (rS = - 0.519) and lesion size (rS = - 0.567). MRI with DWI shows high diagnostic accuracy in detecting the LR of PAC in comparison to PET-CT as reference standard. ADC significantly inversely correlates with standard and advanced PET parameters and size of LR.
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Affiliation(s)
- D Saponjski
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia.
| | - A Djuric-Stefanovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia
| | - M Mitrovic Jovanovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia
| | - A Jankovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia
| | - J Kovac
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia
| | - S Milosevic
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia
| | - K Stosic
- Department of Digestive Radiology (Clinic for Abdominal Surgery - First University Surgical Clinic), Center for Radiology, University Clinical Center of Serbia, Belgrade, Serbia
| | - J Pantovic
- Center for Nuclear Medicine, University Clinical Center of Serbia, Belgrade, Serbia
| | - J Petrovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Center for Nuclear Medicine, University Clinical Center of Serbia, Belgrade, Serbia
| | - S Kmezic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Abdominal Surgery - First University Surgical Clinic, University Clinical Center of Serbia, Belgrade, Serbia
| | - D Radenkovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Abdominal Surgery - First University Surgical Clinic, University Clinical Center of Serbia, Belgrade, Serbia
| | - D Sobic Saranovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Center for Nuclear Medicine, University Clinical Center of Serbia, Belgrade, Serbia
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Augustinus S, Latenstein AE, Bonsing BA, Busch OR, Groot Koerkamp B, de Hingh IH, de Meijer VE, Molenaar IQ, van Santvoort HC, de Vos-Geelen J, van Eijck CH, Besselink MG. Chyle Leak After Pancreatoduodenectomy: Clinical Impact and Risk Factors in a Nationwide Analysis. Ann Surg 2023; 277:e1299-e1305. [PMID: 35786606 PMCID: PMC10174101 DOI: 10.1097/sla.0000000000005449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to assess the clinical impact and risk factors of chyle leak (CL). BACKGROUND In 2017, the International Study Group for Pancreatic Surgery (ISGPS) published the consensus definition of CL. Multicenter series validating this definition are lacking and previous studies investigating risk factors have used different definitions and showed heterogeneous results. METHODS This observational cohort study included all consecutive patients after pancreatoduodenectomy in all 19 centers in the mandatory nationwide Dutch Pancreatic Cancer Audit (2017-2019). The primary endpoint was CL (ISGPS grade B/C). Multivariable logistic regression analyses were performed. RESULTS Overall, 2159 patients after pancreatoduodenectomy were included. The rate of CL was 7.0% (n=152), including 6.9% (n=150) grade B and 0.1% (n=2) grade C. CL was independently associated with a prolonged hospital stay [odds ratio (OR)=2.84, 95% confidence interval (CI): 1.85-4.36, P <0.001] but not with mortality (OR=0.3, 95% CI: 0.0-2.3, P =0.244). In multivariable analyses, independent predictors for CL were vascular resection (OR=2.1, 95% CI: 1.4-3.2, P <0.001) and open surgery (OR=3.5, 95% CI: 1.7-7.2, P =0.001). The number of resected lymph nodes and aortocaval lymph node sampling were not identified as predictors in multivariable analysis. CONCLUSIONS In this nationwide analysis, the rate of ISGPS grade B/C CL after pancreatoduodenectomy was 7.0%. Although CL is associated with a prolonged hospital stay, the clinical impact is relatively minor in the vast majority (>98%) of patients. Vascular resection and open surgery are predictors of CL.
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Affiliation(s)
- Simone Augustinus
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Anouk E.J. Latenstein
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Bert A. Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Olivier R. Busch
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | | | - Vincent E. de Meijer
- Department of Surgery, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
| | - I. Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht & St Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht & St Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Judith de Vos-Geelen
- Department of Internal Medicine, GROW—School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, The Netherlands
| | - Casper H. van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Marc G. Besselink
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
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Tang W, Zhang YF, Zhao YF, Wei XF, Xiao H, Wu Q, Du CY, Qiu JG. Comparison of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic cancer: A systematic review and meta-analysis. Int J Surg 2022; 103:106676. [PMID: 35577311 DOI: 10.1016/j.ijsu.2022.106676] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Laparoscopic radical antegrade modular pancreatosplenectomy (l-RAMPS) provides a new surgical approach for patients with pancreatic cancers of the body and tail. However, whether it can achieve comparable outcomes to the open RAMPS (o-RAMPS) remains an issue. METHODS To evaluate the safety and effectiveness of l-RAMPS, the studies in the databases of Medline, Embase, and the Cochrane Library published before September 13, 2021 were searched and a meta-analysis was performed using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. The perioperative and oncological outcomes were analyzed. RESULTS Five retrospective cohorts involving 189 patients were included for final pooled analysis. There were no significant differences in the patients' operation time, intra-abdominal bleeding rate, intra-abdominal infection rate, mild morbidity (Clavien-Dindo classification = 1), moderate to severe morbidity (Clavien-Dindo classification ≥2), overall morbidity, wound infection rate, pancreatic fistula rate, delayed gastric emptying rate, reoperation rate, length of hospital stay, postoperative mortality, R0 resection rate, and 2-year overall survival between the 2 approaches. Besides, l-RAMPS was associated with less blood loss (mean difference (MD) = -232.69, 95% confidence interval (CI) = -316.93 to -148.46, P < 0.00001) and shorter days until oral feeding (MD = -0.79, 95% CI = -1.35 to -0.22, P = 0.006). However, the pooled analysis also indicated a significantly fewer lymph nodes dissected (MD = -3.01, 95% CI = -5.59 to -0.43, P = 0.02) in l-RAMPS approach. CONCLUSIONS Although l-RAMPS provides similar outcomes associated with benefits of minimal invasiveness compared to o-RAMPS, it harvested significantly fewer lymph nodes which might have potentially negative influence on the patients' long-term survival. L-RAMPS is still in the infancy stage and further investigation is needed to verify its feasibility.
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Affiliation(s)
- Wei Tang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Yu-Fei Zhang
- Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Fei Zhao
- Department of General Surgery, the Ninth People's Hospital of Chongqing, Chongqing, China
| | - Xu-Fu Wei
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Heng Xiao
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qiao Wu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Cheng-You Du
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jian-Guo Qiu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Zhang H, Li Y, Liao Q, Xing C, Ding C, Zhang T, Guo J, Han X, Xu Q, Wu W, Zhao Y, Dai M. Comparison of minimal invasive versus open radical antegrade modular pancreatosplenectomy (RAMPS) for pancreatic ductal adenocarcinoma: a single center retrospective study. Surg Endosc 2020; 35:3763-3773. [PMID: 33033915 DOI: 10.1007/s00464-020-07938-1] [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: 05/19/2020] [Accepted: 08/25/2020] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Radical antegrade modular pancreatosplenectomy (RAMPS) was proposed a decade ago with the aim to achieve higher R0 tangential margin and radical N1 lymph node resection for left-sided pancreatic adenocarcinoma (PDAC), which has been widely accepted worldwide at present. Laparoscopic RAMPS (Lap-RAMPS) has been attempted for PDAC during last several years, however, no outcomes evaluation by comparison between laparoscopic vs open RAMPS has been reported yet. MATERIALS AND METHODS From August, 2012 to March, 2018, patients undergoing open or lap-RAMPS for the diagnosis of left-sided PDAC were reviewed from a prospective database. Patients excluded if they were related with combined organs or vessels resection, systematic metastasis as well as conversion from open RAMPS to lap RAMPS. The surgical and oncologic outcomes were compared. RESULTS A total of 48 PDAC patients were enrolled (25 underwent lap-RAMPS and 23 underwent open-RAMPS). There were no significant differences in demographic or perioperative morbidity. In the lap-RAMPS group, R0 transection margin and retroperitoneal margin were both achieved in 23 of 25 patients (92%). In the open RAMPS group, R0 transection margin was achieved in 21 of 23 patients (91.3%), R0 retroperitoneal margin was 22 of 23 patients (95.65%). There were no differences in pathological examinations. The number of lymph node (LN) retrieved between lap-RAMPS and open- RAMPS group was not significant difference (15.84 vs 18.22; P = 0.268). Median disease-free survival (DFS) was analogous in two groups (18.11 m vs 20.00 m, P = 0.999). Median overall survival (OS) was 24.53 m in lap-RAMPS group and 28.73 m in the open-RAMPS group (P = 0.633). CONCLUSIONS Lap-RAMPS is technically feasible, and has comparable long-term oncological outcome with open-RMAPS.
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Affiliation(s)
- Hanyu Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Yatong Li
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Quan Liao
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Cheng Xing
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Cheng Ding
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Junchao Guo
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Xianlin Han
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Wenming Wu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China
| | - Menghua Dai
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1, Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China.
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Bengtsson A, Andersson R, Ansari D. The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data. Sci Rep 2020; 10:16425. [PMID: 33009477 PMCID: PMC7532215 DOI: 10.1038/s41598-020-73525-y] [Citation(s) in RCA: 236] [Impact Index Per Article: 47.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 09/17/2020] [Indexed: 12/14/2022] Open
Abstract
Survival data for pancreatic cancer are usually based on actuarial calculations and actual long-term survival rates are rarely reported. Here we use population-level data from the Surveillance, Epidemiology, and End Results program for patients with microscopically confirmed pancreatic ductal adenocarcinoma diagnosed from 1975 to 2011. A total of 84,275 patients with at least 5 years of follow-up were evaluated (follow-up cutoff date: December 31, 2016). Actual 5-year survival for pancreatic cancer increased from 0.9% in 1975 to 4.2% in 2011 in patients of all stages (p < 0.001), while in surgically resected patients, it rose from 1.5% to 17.4% (p < 0.001). In non-resected patients, the actual 5-year survival remained unchanged over the same time period (0.8% vs 0.9%; p = 0.121). Multivariable analysis of surgically resected patients diagnosed in the recent time era (2004-2011) showed that age, gender, grade, tumour size, TNM-stage and chemotherapy were significant independent predictors of actual 5-year survival, while age, grade and TNM-stage were significant independent predictors in non-resected patients. However, unfavourable clinicopathological factors did not preclude long-term survival. Collectively, our findings indicate that actual 5-year survival for pancreatic cancer is still below 5% despite improvement of survival for the subset of patients undergoing surgical resection.
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Affiliation(s)
- Axel Bengtsson
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85, Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85, Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
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Kovač JD, Đurić-Stefanović A, Dugalić V, Lazić L, Stanisavljević D, Galun D, Mašulović D. CT perfusion and diffusion-weighted MR imaging of pancreatic adenocarcinoma: can we predict tumor grade using functional parameters? Acta Radiol 2019; 60:1065-1073. [PMID: 30428264 DOI: 10.1177/0284185118812202] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Jelena Djokić Kovač
- Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Đurić-Stefanović
- Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Dugalić
- First Surgical Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ljubica Lazić
- Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Dejana Stanisavljević
- Institute for Medical Statistics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Danijel Galun
- First Surgical Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Dragan Mašulović
- Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Kasahara N, Noda H, Kakizawa N, Kato T, Watanabe F, Ichida K, Endo Y, Aizawa H, Rikiyama T. A lack of postoperative complications after pancreatectomy contributes to the long-term survival of patients with pancreatic cancer. Pancreatology 2019; 19:686-694. [PMID: 31253497 DOI: 10.1016/j.pan.2019.06.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/01/2019] [Accepted: 06/21/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND /Objectives: The objectives of this study were to identify the factors affecting patients' survival and the characteristics of five-year survivors of pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy as well as to clarify the correlation between the development of postoperative complications and a five-year survival. METHODS A total of 104 patients underwent pancreatectomy for PDAC between April 2005 and March 2013 with curative intent. Patients who survived for more than five years after pancreatectomy were classified as long-term survivors. Sixteen demographic and clinical variables and 10 pathological variables were comprehensively assessed for their associations with the patients' survival time and long-term survival. RESULTS The presence of preoperative comorbidity (OR: 1.65, 95% CI 1.02-2.67, p = 0.042), postoperative overall complications (OR: 1.78, 95% CI 1.03-3.10, p = 0.041), a lymph node positivity ratio of ≥0.2 (OR: 3.04, 95% CI 1.51-6.11, p = 0.002), and portal invasion (OR: 2.58, 95% CI 1.48-4.49, p = 0.001) were identified as independent factors affecting the patients' survival. The absence of postoperative overall complications was identified as an independent factor related to long-term survival in the multivariate analysis (OR: 0.08, 95% CI 0.01-0.82, p = 0.034). CONCLUSIONS The presence of preoperative comorbidity, postoperative overall complications, LNR ≥0.2, and portal invasion were prognostic factors affecting the patients' survival, and avoiding postoperative complications after pancreatectomy might contribute to the long-term survival of PDAC patients after pancreatectomy. The further improvement of surgical procedures and perioperative care in order to reduce the rate of postoperative complications should be attempted.
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Affiliation(s)
- Naoya Kasahara
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Hiroshi Noda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan.
| | - Nao Kakizawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Takaharu Kato
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Kosuke Ichida
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Yuhei Endo
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Hidetoshi Aizawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Japan
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Kovač JD, Mayer P, Hackert T, Klauss M. The Time to and Type of Pancreatic Cancer Recurrence after Surgical Resection: Is Prediction Possible? Acad Radiol 2019; 26:775-781. [PMID: 30254003 DOI: 10.1016/j.acra.2018.07.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 07/29/2018] [Accepted: 07/30/2018] [Indexed: 12/14/2022]
Abstract
RATIONALE AND OBJECTIVES To evaluate factors predicting pancreatic cancer recurrence, and to determine the most common appearance of tumor relapse. MATERIALS AND METHODS Ninety patients with recurrent pancreatic cancer were retrospectively included in the study. 74.4% had pancreatic head tumors (group 1) and 25.6% pancreatic body and/or tail tumor (group 2). The tumor localization, operative technique, TNM stage, the R-status, tumor grade, lymphovascular, and perineural invasion were recorded. Location of local tumor recurrence, lymph node recurrence, or organ metastases were analyzed on the basis of follow-up CT imaging. RESULTS Mean recurrence time was 17.4 ± 13.2 months. The most common recurrence type was local recurrence (84.4%), followed by lymph node (15.5%), liver (14.4%), and lung metastasis (6.7%). The predominant site of local recurrence in pancreatic head tumors was close to superior mesenteric artery, common hepatic artery, and/or celiac artery (57.4%), followed by area defined by portal vein, inferior vena cava, CA or superior mesenteric artery (31.2%). Patients with pancreatic body and/or tail carcinoma had higher incidence (p = 0.003) of metastatic disease comparing to pancreatic head tumors, while resection margin was the most common type of local tumor recurrence, seen in 46.7% cases versus 8.2% of patients with pancreatic head tumors (p < 0.001). CONCLUSION The most common recurrence type in patients with resected pancreatic carcinoma was local recurrence along cardinal arteries. The localization of primary tumor influences the type of tumor relapse and site of local recurrence.
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Affiliation(s)
- Jelena Djokić Kovač
- Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.
| | - Philipp Mayer
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Miriam Klauss
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
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Choi MH, Lee YJ, Yoon SB, Choi JI, Jung SE, Rha SE. MRI of pancreatic ductal adenocarcinoma: texture analysis of T2-weighted images for predicting long-term outcome. Abdom Radiol (NY) 2019; 44:122-130. [PMID: 29980829 DOI: 10.1007/s00261-018-1681-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE To assess the association between T2-weighted imaging (T2WI) texture-analysis parameters and the pathological aggressiveness or long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS A total of 66 patients (mean age 65.3 ± 9.0 years) who underwent preoperative MRI followed by pancreatectomy for PDAC between 2013 and 2015 were included in this study. A radiologist performed a texture analysis twice on one axial image using commercial software. Differences in the tex parameters, according to pathological factors, were analyzed using a Student's t test or an ANOVA with Tukey's test. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the association between tex parameters and recurrence-free survival (RFS) or overall survival (OS). RESULTS The mean follow-up time was 18.5 months, and there were 58 recurrences and 39 deaths. The mean of the positive pixel (MPP)-related factors was significantly lower in poorly differentiated tumors than in well-differentiated tumors as well as in cases with perineural invasion. The univariate Cox proportional hazards analysis showed a significant association between the tex parameters and RFS or OS. However, only tumor size was statistically significant after the multivariate analysis. Only tumor size and entropy with medium texture were significantly associated with OS after the multivariate analysis. CONCLUSIONS Tumor size was a significant predictive factor for RFS and OS in PDAC patients. Although entropy with medium texture analysis was significantly associated with OS, there were also limitations in the texture analysis; thus, further study is necessary.
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Affiliation(s)
- Moon Hyung Choi
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young Joon Lee
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Seung Bae Yoon
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon-Il Choi
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Eun Jung
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Eun Rha
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
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Abstract
OBJECTIVES This study aimed to clarify the correlation between image classification and the pathological degree of portal system invasion (PSI) and to evaluate the prognostic impact of PSI in pancreatic cancer (PC). METHODS Pancreatic cancer patients with surgical resections (head, n = 244; body and tail, n = 80) were enrolled in this study. RESULTS Based on imaging findings, portal vein (PV) invasion was classified as type A (absent), B (unilateral narrowing), C (bilateral narrowing), or D (stenosis or obstruction with collaterals). Splenic vein (SPV) invasion was classified as type α (absent), β (stenosis), or γ (obstruction). The pathological grade of venous invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima). In PV and SPV invasions, image classification and pathological grade showed significant correlation (PV: ρ = 0.696; SPV: ρ = 0.681). Patients with PV invasion deeper than type B exhibited significantly poorer survival than type A (P < 0.0001). In contrast, there was no difference in survival among types α, β, and γ. CONCLUSIONS Image classification was correlated with the pathological grade of PSI in PC. Although not applicable for SPV invasion, image classification of PV invasion is a robust indicator for PC prognosis.
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Prognostic factors for actual long-term survival in the era of multidisciplinary treatment for pancreatic ductal adenocarcinoma. Langenbecks Arch Surg 2018; 403:693-700. [PMID: 30218193 DOI: 10.1007/s00423-018-1709-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 09/10/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Recent advances in multidisciplinary treatments are improving the postoperative prognosis of pancreatic ductal adenocarcinoma (PDAC). However, the prognosis even after potentially curative resection remains poor. The aim of this study was to identify the clinical and pathological features of actual 5-year survivors under current circumstances. METHODS A total of 128 patients who underwent pancreatectomy for PDAC at our institution between January 2006 and December 2011 were retrospectively analyzed. RESULTS The actual 5-year overall survival rate for all patients was 30.9%, with a median survival time of 33.1 months. Of 128 patients, 25 (19.5%) survived for 5 years after surgery without disease recurrence. A univariate analysis showed that the pretreatment serum CA19-9 value, tumor depth, lymph node metastasis, and UICC stage at resection were significant predictive factors for the actual long-term survival. A multivariate analysis showed that a pretreatment serum CA19-9 value ≥ 110 U/mL was a significant unfavorable prognostic indicator. In addition, all subjects in the 5-year survival group completed adjuvant chemotherapy. The recurrence rate in the liver was significantly lower and that in the lung significantly higher in the long-term survival group than in the short-term survival group. CONCLUSIONS The factors contributing to the long-term survival of PDAC were the pretreatment CA19-9 value and the completion of adjuvant chemotherapy. To achieve the actual long-term survival and cure after pancreatectomy for pancreatic cancer, further treatment strategies enhancing the completion rate of adjuvant chemotherapy are required.
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Shin SH, Kim SC, Song KB, Hwang DW, Lee JH, Park KM, Lee YJ. Chronologic changes in clinical and survival features of pancreatic ductal adenocarcinoma since 2000: A single-center experience with 2,029 patients. Surgery 2018; 164:432-442. [PMID: 29884479 DOI: 10.1016/j.surg.2018.04.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/20/2018] [Accepted: 04/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND To identify chronologic changes in clinical and survival features of pancreatic ductal adenocarcinoma based on diagnosis and treatment strategy development since 2000. METHODS Among 2,029 patients enrolled in this study, 746 and 1,283 were treated between 2000 and 2009 (group 1) and between 2010 and 2016 (group 2), respectively. We used patient clinicopathologic, biologic, and molecular factors to assess the prognostic factors. RESULTS Group 2 had a better survival outcome than group 1 (median survival time: 24.9 versus 18.4 months; 5-year survival rate: 27.6% versus 22.3%). The tendency for early diagnosis (lower CA19-9 levels, smaller size, and earlier T stage), use of neoadjuvant chemotherapy, decreased morbidity, early recovery (lesser hospital stay and more minimally invasive surgery), and standardization of surgical techniques appeared to improve patient survival. Multivariable analysis for prognosis revealed that tumor biologic factors (increased preoperative serum CA19-9 level, tumor size, tumor differentiation, N stage, and presence of lymphovascular invasion), operational factors (status of the resection margin, type of operation, and year of operation), and genetic factors (K-ras mutations) correlated with patient survival. CONCLUSION Early diagnosis and combined efforts, such as neoadjuvant chemotherapy and an established system of patient care, have gradually enhanced patient survival after operative resection for pancreatic ductal adenocarcinoma. Hence, multiplex prognostic parameters could provide additional information for improved prognostic estimation of pancreatic cancer exhibiting heterogeneous results.
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Affiliation(s)
- Sang Hyun Shin
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Song Cheol Kim
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Ki-Byung Song
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dae Wook Hwang
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kwang-Min Park
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Joo Lee
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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14
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Kanai T, Ito Z, Oji Y, Suka M, Nishida S, Takakura K, Kajihara M, Saruta M, Fujioka S, Misawa T, Akiba T, Yanagisawa H, Shimodaira S, Okamoto M, Sugiyama H, Koido S. Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma. Oncol Lett 2018; 16:2682-2692. [PMID: 30008944 DOI: 10.3892/ol.2018.8961] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 05/16/2018] [Indexed: 02/07/2023] Open
Abstract
The only current curative treatment for patients with pancreatic ductal adenocarcinoma (PDA) is surgical resection, and certain patients still succumb to disease shortly after complete surgical resection. Wilms' tumor 1 (WT1) serves an oncogenic role in various types of tumors; therefore, in the present study, WT1 protein expression in patients with PDA was analyzed and the association with overall survival (OS) and disease-free survival (DFS) time in patients with PDA was assessed following surgical resection. A total of 50 consecutive patients with PDA who received surgical resection between January 2005 and December 2015 at the Jikei University Kashiwa Hospital (Kashiwa, Chiba, Japan) were enrolled. WT1 protein expression in PDA tissue was measured using immunohistochemical staining. Furthermore, laboratory parameters were measured within 2 weeks of surgery, and systemic inflammatory response markers were evaluated. WT1 protein expression was detected in the nucleus and cytoplasm of all PDA cells and in tumor vessels. WT1 exhibited weak staining in the nuclei of all PDA cells; however, the cytoplasmic expression of WT1 levels was classified into four groups: Negative (n=0), weak (n=19), moderate (n=23) and strong (n=8). In patients with PDA, it was demonstrated that the OS and DFS times of patients with weak cytoplasmic WT1 expression were significantly prolonged compared with those of patients with moderate-to-strong cytoplasmic WT1 expression, as determined by log-rank test (P=0.0005 and P=0.0001, respectively). Furthermore, an association between the density of WT1-expressing tumor vessels and worse OS/DFS times was detected. Multivariate analysis also indicated a significant association between the overexpression of WT1 in PDA tissue and worse OS/DFS times. To the best of our knowledge, the present study is the first to demonstrate that moderate-to-strong overexpression of WT1 in the cytoplasm of PDA cells is significantly associated with worse OS/DFS times. Therefore, overexpression of WT1 in the cytoplasm of PDA cells may impact the recurrence and prognosis of patients with PDA following surgical resection. The results further support the development of WT1-targeted therapies to prolong survival in all patients with PDA.
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Affiliation(s)
- Tomoya Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Zensho Ito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Yusuke Oji
- Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Machi Suka
- Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo 105-8571, Japan
| | - Sumiyuki Nishida
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Kazuki Takakura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Mikio Kajihara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8571, Japan
| | - Shuichi Fujioka
- Department of Surgery, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Takeyuki Misawa
- Department of Surgery, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Tadashi Akiba
- Department of Surgery, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan
| | - Hiroyuki Yanagisawa
- Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo 105-8571, Japan
| | - Shigetaka Shimodaira
- Department of Regenerative Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan
| | - Masato Okamoto
- Department of Advanced Immunotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Haruo Sugiyama
- Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Shigeo Koido
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa, Chiba 277-8567, Japan.,Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Kashiwa, Chiba 277-8567, Japan
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Hsu CP, Hsu JT, Liao CH, Kang SC, Lin BC, Hsu YP, Yeh CN, Yeh TS, Hwang TL. Three-year and five-year outcomes of surgical resection for pancreatic ductal adenocarcinoma: Long-term experiences in one medical center. Asian J Surg 2018; 41:115-123. [PMID: 28010955 DOI: 10.1016/j.asjsur.2016.11.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Revised: 08/31/2016] [Accepted: 11/15/2016] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Pancreatic ductal adenocarcinoma is one of the most malignant types of cancer. This study evaluated the 3-year and 5-year surgical outcomes associated with the cancer and determined whether statistically identified factors can be used to predict survival. METHODS This retrospective review was conducted from 1995 to 2010. Patients who had resectable pancreatic ductal adenocarcinoma and received surgical treatment were included. Cases of hospital mortality were excluded. The relationships between several clinicopathological factors and the survival rate were analyzed. RESULTS A total of 223 patients were included in this study. The 3-year and 5-year survival rates were 21.4% and 10.1%, respectively, and the median survival was 16.1 months. Tumor size, N status, and resection margins were independent predictive factors for 3-year survival. Tumor size independently predicted 5-year survival. CONCLUSION Tumor size is the most important independent prognostic factor for 3-year and 5-year survival. Lymph node status and the resection margins also independently affected the 3-year survival. These patient outcomes might be improved by early diagnosis and radical resection. Future studies should focus on the tumor biology of this aggressive cancer.
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Affiliation(s)
- Chih-Po Hsu
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jun-Te Hsu
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chien-Hung Liao
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Shih-Ching Kang
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Being-Chuan Lin
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Pao Hsu
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chun-Nan Yeh
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ta-Sen Yeh
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsann-Long Hwang
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
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16
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Abstract
Pancreatic cancer is a challenging malignancy to treat, largely due to aggressive regional involvement, early systemic dissemination, high recurrence rate, and subsequent low patient survival. Generally, 15-20% of newly diagnosed pancreatic cancers are candidates for possible curative resection. Eighty percent of these patients, however, will experience locoregional or distant recurrence in first 2 years. Although there is no strong evidence-based guideline for optimal surveillance after pancreatic cancer resection, careful comparison of surveillance follow-up multi-detector CT (MDCT) studies with a postoperative baseline MDCT examination aids detection of early recurrent pancreatic cancer. In this review article, we describe imaging findings suggestive of recurrent pancreatic cancer and review routine and alternative imaging options.
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Yamamoto T, Uchida Y, Terajima H. Clinical impact of margin status on survival and recurrence pattern after curative-intent surgery for pancreatic cancer. Asian J Surg 2017; 42:93-99. [PMID: 29249392 DOI: 10.1016/j.asjsur.2017.09.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/01/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/OBJECTIVE The definition of R0 resection for invasive pancreatic ductal carcinoma (IPDC) is important. However, there are different definitions among several countries in the world. METHODS From 2001 to 2015, 100 consecutive patients with IPDC who underwent pancreatic resection in our hospital were enrolled. We compared survival and recurrence patterns between the R0 group and R1 group based on the UICC (Union for International Cancer Control) classification (current-R0 vs. current-R1) and based on our revised classification, which defines R0 as a surgical margin of >1 mm (revised-R0 vs. revised-R1). RESULTS The 100 patients comprised 58 males and 42 females, and their median age was 70 [32-87]. There were 84 patients in the current-R0 group and 43 in the revised-R0 group. There was no difference in overall survival (OS) or recurrence-free survival (RFS) between the current-R0 group and current-R1 group. However, there was a tendency toward a higher OS rate in the revised-R0 than revised-R1 group (log-rank p = 0.065), and RFS was significantly better in the revised-R0 than revised-R1 group (log-rank p = 0.002). There was no significant difference in the recurrence patterns between the current-R0 and current-R1 groups. In contrast, the local recurrence rate was significantly lower in the revised-R0 than revised-R1 group (21% vs. 42%, respectively; p = 0.026). CONCLUSION The revised classification of surgical resection may be more useful than the current UICC classification for prediction of prognosis and local recurrence of IPDC.
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Affiliation(s)
- Takehito Yamamoto
- Department of Gastroenterological Surgery and Oncology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20, Ogimachi, Kita-ku, Osaka 530-8480, Japan
| | - Yoichiro Uchida
- Department of Gastroenterological Surgery and Oncology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20, Ogimachi, Kita-ku, Osaka 530-8480, Japan.
| | - Hiroaki Terajima
- Department of Gastroenterological Surgery and Oncology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20, Ogimachi, Kita-ku, Osaka 530-8480, Japan
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18
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Early liver metastases in resectable periampullary cancer: Incidence and risk factors. Eur J Radiol 2017; 93:265-272. [DOI: 10.1016/j.ejrad.2017.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 06/07/2017] [Indexed: 01/15/2023]
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Han SH, Heo JS, Choi SH, Choi DW, Han IW, Han S, You YH. Actual long-term outcome of T1 and T2 pancreatic ductal adenocarcinoma after surgical resection. Int J Surg 2017; 40:68-72. [PMID: 28232032 DOI: 10.1016/j.ijsu.2017.02.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 02/05/2017] [Accepted: 02/07/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The prognosis for patients with pancreatic cancer is extremely poor. The diagnosis of pancreatic ductal adenocarcinoma at an early stage is uncommon. The purpose of this study was to analyze the clinicopathological characteristics of patients with pathologically proven pancreatic ductal adenocarcinoma following surgical resection and their actual 5 year survival rates, especially for those with T1 and T2 early stage cancer. METHODS Retrospective analysis was performed for 433 patients with pancreatic ductal adenocarcinoma who underwent resection at Samsung medical center between May 1995 and December 2010. The actual 5 year survival rates and prognostic factors were analyzed. RESULTS Multivariate analysis showed that positive resection margin, poor differentiation, large tumor size, large amount of blood loss, and T3/T4 were independent prognostic factors on overall survival. The median survival for T1/T2 stage was 71.7 months compared to 16.1 months for those with T3/T4 stage. The actual 5 year survival rates for T1/T2 and T3/T4 stages were 66.7% and 18.4%, respectively. CONCLUSIONS T stage is one of the strongest independent prognostic factor for overall survival of patients with pancreatic cancer. T1/T2 pancreatic ductal adenocarcinoma showed good survival outcome. Therefore, additional efforts are needed to improve the screening for early detection.
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Affiliation(s)
- San Hyup Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Seong Ho Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In Woong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sunjong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yung Hun You
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Pancreatic Cancer: 80 Years of Surgery-Percentage and Repetitions. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2016; 2016:6839687. [PMID: 27847403 PMCID: PMC5099466 DOI: 10.1155/2016/6839687] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 06/01/2016] [Indexed: 12/18/2022]
Abstract
Objective. The incidence of pancreatic cancer is estimated to be 48,960 in 2015 in the US and projected to become the second and third leading causes of cancer-related deaths by 2030. The mean costs in 2015 may be assumed to be $79,800 per patient and for each resection $164,100. Attempt is made to evaluate the results over the last 80 years, the number of survivors, and the overall survival percentage. Methods. Altogether 1230 papers have been found which deal with resections and reveal survival information. Only 621 of these report 5-year survivors. Reservation about surgery was first expressed in 1964 and five-year survival of nonresected survivors is well documented. Results. The survival percentage depends not only on the number of survivors but also on the subset from which it is calculated. Since the 1980s the papers have mainly reported the number of resections and survival as actuarial percentages, with or without the actual number of survivors being reported. The actuarial percentage is on average 2.75 higher. Detailed information on the original group (TN), number of resections, and actual number of survivors is reported in only 10.6% of the papers. Repetition occurs when the patients from a certain year are reported several times from the same institution or include survivors from many institutions or countries. Each 5-year survivor may be reported several times. Conclusion. Assuming a 10% resection rate and correcting for repetitions and the life table percentage the overall actual survival rate is hardly more than 0.3%.
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Effect of postoperative major complications on prognosis after pancreatectomy for pancreatic cancer: a retrospective review. Surg Today 2016; 47:555-567. [DOI: 10.1007/s00595-016-1426-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 07/26/2016] [Indexed: 02/07/2023]
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Long-term survival in patients with pancreatic ductal adenocarcinoma. Surgery 2016; 159:1520-1527. [PMID: 26847803 DOI: 10.1016/j.surg.2015.12.024] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 12/12/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Long-term survival (LTS) is uncommon for patients with pancreatic ductal adenocarcinoma (PDAC). We sought to identify factors that predict 10-year, LTS after resection of PDAC. METHODS We identified all patients with PDAC who underwent resection at UCLA after 1990 and included all patients eligible for observed LTS (1/1/1990-12/31/2004). An independent pathologist reconfirmed the diagnosis of PDAC in patients with LTS. Logistic regression was used to predict LTS on the basis of patient and tumor characteristics. RESULTS Of 173 included patients, 53% were male, median age at diagnosis was 66 years, and median survival was 23 months. The rate of observed LTS was 12.1% (n = 21). Age, sex, number of lymph nodes evaluated, margin status, lymphovascular invasion, and adjuvant chemotherapy and radiation were not associated with LTS. The following were associated with LTS on bivariate analysis: low AJCC stage (Ia, Ib, IIa) (P = .034), negative lymph node status (P = .034), low grade (well-, moderately-differentiated) (P = .001), and absence of perineural invasion (P = .019). Only low grade (odds ratio 7.17, P = .012) and absent perineural invasion (odds ratio 3.28, P = .036) were independently associated with increased odds of LTS. Our multivariate model demonstrated good discriminatory power for LTS, as indicated by a c-statistic of 0.7856. CONCLUSION Absence of perineural invasion and low tumor grade were associated with greater likelihood of LTS. Understanding the tumor biology of LTS may provide critical insight into a disease that is typically marked by aggressive behavior and limited survival.
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Balaj C, Ayav A, Oliver A, Jausset F, Sellal C, Claudon M, Laurent V. CT imaging of early local recurrence of pancreatic adenocarcinoma following pancreaticoduodenectomy. Abdom Radiol (NY) 2016; 41:273-82. [PMID: 26867909 DOI: 10.1007/s00261-015-0564-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE The objectives of this retrospective study were to describe the characteristics and topography of pancreatic ductal adenocarcinoma and its early local recurrence after pancreaticoduodenectomy and identify predictive factors of local early recurrence by imaging computed tomography (CT). METHODS The institutional review board approved the study and did require additional informed consent for reviewing the patients' medical records and images. Patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma, a preoperative CT scan, and adequate postoperative CT were included. After postoperative imaging, correlations among clinical and histological characteristics and preoperative imaging were evaluated. RESULTS Among the 123 patients who underwent pancreaticoduodenectomy, 48 patients had sufficient follow-up imaging and were included in this study. A total of 33 patients experienced local early recurrence (Group 1), and 15 exhibited no local recurrence (Group 2). Local recurrence consisted of two types of anomalies: tissue nodules on surgical clips (94%) and peri-arterial encasement (82%). On preoperative imaging, the tumor diameter (p = 0.02) and the presence of a venous borderline resectable tumor (p < 0.0001) were predictive of local recurrence. CONCLUSIONS Tissue nodules on surgical clips and arterial encasement characterize early local recurrence, and nodules and encasement should not be considered common post-operative infiltration. The role of the radiologist is essential to assess the predictive factors of recurrence and to identify early local recurrence.
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Affiliation(s)
- Clémence Balaj
- Department of Radiology Adults, Brabois Hospital, University of Nancy, Rue du Morvan, 54 511, Vandoeuvre les Nancy, France.
| | - Ahmet Ayav
- Department of HBP Surgery, Brabois Hospital, University of Nancy, Vandoeuvre les Nancy, France
| | - Alexandre Oliver
- Department of Radiology Adults, Brabois Hospital, University of Nancy, Rue du Morvan, 54 511, Vandoeuvre les Nancy, France
| | - François Jausset
- Department of Radiology Adults, Brabois Hospital, University of Nancy, Rue du Morvan, 54 511, Vandoeuvre les Nancy, France
| | - Caroline Sellal
- Department of Radiology Adults, Brabois Hospital, University of Nancy, Rue du Morvan, 54 511, Vandoeuvre les Nancy, France
| | - Michel Claudon
- Department of Radiology Adults, Brabois Hospital, University of Nancy, Rue du Morvan, 54 511, Vandoeuvre les Nancy, France
| | - Valérie Laurent
- Department of Radiology Adults, Brabois Hospital, University of Nancy, Rue du Morvan, 54 511, Vandoeuvre les Nancy, France
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Oh SY, Edwards A, Mandelson MT, Lin B, Dorer R, Helton WS, Kozarek RA, Picozzi VJ. Rare long-term survivors of pancreatic adenocarcinoma without curative resection. World J Gastroenterol 2015; 21:13574-13581. [PMID: 26730170 PMCID: PMC4690188 DOI: 10.3748/wjg.v21.i48.13574] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/11/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Long-term outcome data in pancreatic adenocarcinoma are predominantly based on surgical series, as resection is currently considered essential for long-term survival. In contrast, five-year survival in non-resected patients has rarely been reported. In this report, we examined the incidence and natural history of ≥ 5-year survivors with non-resected pancreatic adenocarcinoma. All patients with pancreatic adenocarcinoma who received oncologic therapy alone without surgery at our institution between 1995 and 2009 were identified. Non-resected ≥ 5-year survivors represented 2% (11/544) of all non-resected patients undergoing treatment for pancreatic adenocarcinoma, and 11% (11/98) of ≥ 5-year survivors. Nine patients had localized tumor and 2 metastatic disease at initial diagnosis. Disease progression occurred in 6 patients, and the local tumor bed was the most common site of progression. Six patients suffered from significant morbidities including recurrent cholangitis, second malignancy, malnutrition and bowel perforation. A rare subset of patients with pancreatic cancer achieve long-term survival without resection. Despite prolonged survival, morbidities unrelated to the primary cancer were frequently encountered and a close follow-up is warranted in these patients. Factors such as tumor biology and host immunity may play a key role in disease progression and survival.
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Onete VG, Besselink MG, Salsbach CM, Van Eijck CH, Busch OR, Gouma DJ, de Hingh IH, Sieders E, Dejong CH, Offerhaus JG, Molenaar IQ. Impact of centralization of pancreatoduodenectomy on reported radical resections rates in a nationwide pathology database. HPB (Oxford) 2015; 17:736-42. [PMID: 26037776 PMCID: PMC4527860 DOI: 10.1111/hpb.12425] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2015] [Accepted: 04/04/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Centralization of a pancreatoduodenectomy (PD) leads to a lower post-operative mortality, but is unclear whether it also leads to improved radical (R0) or overall resection rates. METHODS Between 2004 and 2009, pathology reports of 1736 PDs for pancreatic and peri-ampullary neoplasms from a nationwide pathology database were analysed. Pre-malignant lesions were excluded. High-volume hospitals were defined as performing ≥ 20 PDs annually. The relationship between R0 resections, PD-volume trends, quality of pathology reports and hospital volume was analysed. RESULTS During the study period, the number of hospitals performing PDs decreased from 39 to 23. High-volume hospitals reported more R0 resections in the pancreatic head and distal bile duct tumours than low-volume hospitals (60% versus 54%, P = 0.035) although they operated on more advanced (T3/T4) tumours (72% versus 58%, P < 0.001). The number of PDs increased from 258 in 2004 to 394 in 2009 which was partly explained by increased overall resection rates of pancreatic head and distal bile duct tumours (11.2% in 2004 versus 17.5% in 2009, P < 0.001). The overall reported R0 resection rate of pancreatic head and distal bile duct tumours increased (6% in 2004 versus 11% in 2009, P < 0.001). Pathology reports of low-volume hospitals lacked more data including tumour stage (25% versus 15%, P < 0.001). CONCLUSIONS Centralization of PD was associated with both higher resection rates and more reported R0 resections. The impact of this finding on overall survival should be further assessed.
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Affiliation(s)
- Veronica G Onete
- Department of Surgery, University Medical Center UtrechtUtrecht, The Netherlands,Department of Surgery, Academic Medical CenterAmsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Academic Medical CenterAmsterdam, The Netherlands,Correspondence Marc G. Besselink, Dutch Pancreatic Cancer Group, Academic Medical Center Amsterdam, Department of Surgery, Room G4-196, PO Box 22660, 1100 DD Amsterdam, The Netherlands. Tel.: +31-20-5669111. Fax: +31-20-5669243. E-mail:
| | - Chanielle M Salsbach
- Department of Surgery, University Medical Center UtrechtUtrecht, The Netherlands,Department of Surgery, Erasmus Medical CenterRotterdam, The Netherlands
| | | | - Olivier R Busch
- Department of Surgery, Academic Medical CenterAmsterdam, The Netherlands
| | - Dirk J Gouma
- Department of Surgery, Academic Medical CenterAmsterdam, The Netherlands
| | - Ignace H de Hingh
- Department of Surgery, Catharina Hospital EindhovenEindhoven, The Netherlands
| | - Egbert Sieders
- Department of Surgery, University Medical Center GroningenGroningen, The Netherlands
| | - Cornelis H Dejong
- Department of Surgery, University Medical Center Maastricht, Maastricht and NUTRIM School for Nutrition, Toxicology and MetabolismMaastricht, The Netherlands
| | - Johan G Offerhaus
- Department of Pathology, University Medical Center UtrechtUtrecht, The Netherlands,Department of Pathology, Academic Medical Center AmsterdamAmsterdam, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, University Medical Center UtrechtUtrecht, The Netherlands
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Dal Molin M, Zhang M, de Wilde RF, Ottenhof NA, Rezaee N, Wolfgang CL, Blackford A, Vogelstein B, Kinzler KW, Papadopoulos N, Hruban RH, Maitra A, Wood LD. Very Long-term Survival Following Resection for Pancreatic Cancer Is Not Explained by Commonly Mutated Genes: Results of Whole-Exome Sequencing Analysis. Clin Cancer Res 2015; 21:1944-50. [PMID: 25623214 DOI: 10.1158/1078-0432.ccr-14-2600] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 12/28/2014] [Indexed: 01/01/2023]
Abstract
PURPOSE The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTS). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival. EXPERIMENTAL DESIGN We sequenced the exomes of eight PDACs from patients who survived ≥10 years. On the basis of the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs. RESULTS KRAS mutations were identified in 33 of 35 cancers (94%) from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identified in four of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared with available data from PDACs unselected for survival. Comparison of clinicopathologic features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade, or nodal disease did not preclude long-term survival. CONCLUSIONS Our results suggest that in most patients, somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC.
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Affiliation(s)
- Marco Dal Molin
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ming Zhang
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Roeland F de Wilde
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Niki A Ottenhof
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Neda Rezaee
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Amanda Blackford
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Bert Vogelstein
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kenneth W Kinzler
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nickolas Papadopoulos
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ralph H Hruban
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Anirban Maitra
- Departments of Pathology and Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Laura D Wood
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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27
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Chen R, Dawson DW, Pan S, Ottenhof NA, de Wilde RF, Wolfgang CL, May DH, Crispin DA, Lai LA, Lay AR, Waghray M, Wang S, McIntosh MW, Simeone DM, Maitra A, Brentnall TA. Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma. J Transl Med 2015; 95:43-55. [PMID: 25347153 PMCID: PMC4281293 DOI: 10.1038/labinvest.2014.128] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 08/06/2014] [Accepted: 08/30/2014] [Indexed: 12/14/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated.
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Affiliation(s)
- Ru Chen
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - David W Dawson
- 1] Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, USA [2] Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Sheng Pan
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Niki A Ottenhof
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Roeland F de Wilde
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Christopher L Wolfgang
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Damon H May
- Fred Hutchinson Cancer Research Center, Molecular Diagnostics Program, Seattle, WA, USA
| | - David A Crispin
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Lisa A Lai
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Anna R Lay
- Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, USA
| | - Meghna Waghray
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Shouli Wang
- Department of Pathology, Soochow University School of Medicine, Suzhou, China
| | - Martin W McIntosh
- Fred Hutchinson Cancer Research Center, Molecular Diagnostics Program, Seattle, WA, USA
| | - Diane M Simeone
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Anirban Maitra
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Kimura K, Amano R, Nakata B, Yamazoe S, Hirata K, Murata A, Miura K, Nishio K, Hirakawa T, Ohira M, Hirakawa K. Clinical and pathological features of five-year survivors after pancreatectomy for pancreatic adenocarcinoma. World J Surg Oncol 2014; 12:360. [PMID: 25429841 PMCID: PMC4289316 DOI: 10.1186/1477-7819-12-360] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2014] [Accepted: 11/06/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Clinical factors determining short-term survival after pancreatectomy have been well studied, but factors predicting long-term survival with curative resection are poorly understood in pancreatic carcinoma. Our objective was to identify clinical and pathological features of five-year disease-free survivors after surgical resection of pancreatic adenocarcinoma. METHODS The clinical and pathological data from 147 patients who underwent a potentially curative resection for pancreatic adenocarcinoma at our institution between 1988 and 2012 were retrospectively analyzed. RESULTS Of 147 patients, 18 survived for more than five years after surgery without disease recurrence. A univariate analyses demonstrated that: two or fewer lymph node metastases (P=0.014), a preoperative serum carbohydrate antigen 19-9 (CA19-9) level of 40 U/mL or less (P=0.0018), an absence of intrapancreatic nerve invasion (P=0.028), and undergoing an R0 resection (P=0.011) were significantly associated with five-year survival. A logistic regression model identified the following independent cancer-related predictors of five-year survivors: having two or fewer lymph node metastases (odds ratio (OR): 6.02; 95% confidence interval (CI): 1.08 to 112.98; P=0.0385), a preoperative serum CA19-9 level of 40 U/mL or less (OR: 5.02; 95% CI: 1.68 to 16.48; P=0.0036), and undergoing an R0 resection (OR: 3.63; 95% CI: 1.12 to 14.28; P=0.0316). CONCLUSIONS We conclude that number of lymph node metastases being two or less, a preoperative serum CA19-9 level of 40 U/mL or less, and undergoing an R0 resection may be independent predictive factors to identify actual five-year survivors after pancreatectomy for pancreatic adenocarcinoma.
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Affiliation(s)
- Kenjiro Kimura
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
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Role of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the body and tail of the pancreas. World J Surg 2014; 38:186-93. [PMID: 24166024 DOI: 10.1007/s00268-013-2254-8] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND Studies have claimed that in the surgical treatment of pancreas body and tail cancer, radical antegrade modular pancreatosplenectomy (RAMPS) is associated with effective tangential margin and extensive lymph node dissection. In the present study, the authors have compared the surgical outcomes between RAMPS and conventional distal pancreatosplenectomy (DPS) in patients with adenocarcinoma of the pancreas body and tail, and also identified prognostic factors associated with survival after surgery. METHODS Retrospective review of 92 consecutive patients who underwent surgical resection for pancreas body and tail adenocarcinoma with curative intent between 1995 and 2010. Median follow-up duration was 16.1 months. RESULTS Of the 92 patients, 38 patients received RAMPS and 54 patients received DPS. Patients who underwent RAMPS had a greater number of retrieved lymph nodes than patients undergoing DPS [median 14 (5-52) vs. 9 (1-36), p < 0.05]. Conventional DPS, no adjuvant chemoradiation therapy (CRT), and non-curative resection were associated with poor overall survival (OS) on univariate analysis. After multivariate analysis for these variables, only the lack of adjuvant CRT and resection margin status were found to adversely affect OS. CONCLUSIONS While the RAMPS procedure is effective in performing an extensive LN dissection, it is not associated with better retroperitoneal resection margin or retrieval of more positive LNs, and it does not lead to better curability or OS survival compared to DPS. Lack of adjuvant CRT and resection margin status are poor prognostic factors in patients with pancreas body and tail cancer.
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30
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Shin SH, Kim SC, Hong SM, Song KB, Lee JH, Park KM, Lee YJ. Can statistically determined prognostic factors predict the long-term survival of patients with pancreatic ductal adenocarcinoma following surgical resection?: Clinicopathological analysis of 82 long-term survivors. Pancreas 2014; 43:571-577. [PMID: 24681875 DOI: 10.1097/mpa.0000000000000063] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The objective of this study were to analyze and describe the clinicopathological characteristics of long-term pancreatic ductal adenocarcinoma survivors and to determine if statistically identified prognostic factors can be used to predict the actual survival. METHODS Between January 2000 and December 2007, 537 patients with resectable pancreatic ductal adenocarcinoma underwent surgical resection at a single institute. Medical records were retrospectively reviewed, and 9 patients were excluded. Of the remaining 528, patients who survived for more than 5 years were classified as long-term survivors. RESULTS The actual 5-year survival rate of all 528 included patients was 15.5% (82 patients; median follow-up period, 82.7 months). Fifty-eight patients (70.7%) were diagnosed with cancers located in the head of pancreas, and the median size was 2.5 cm (range, 0.8-12.0 cm). Three patients had focal involvement noted on the resected surfaces. Poorly differentiated carcinoma (9.8%), lymph node metastasis (32.9%), lymphovascular invasion (25.6%), and perineural invasion (48.8%) were detected. Fifty-five of the 82 long-term survivors whose clinicopathological characteristics included several dismal predictors survived for more than 5 years without recurrence. CONCLUSIONS The long-term survivors identified in this study did not meet the appropriate prognostic criteria. Therefore, there are limitations in the use of statistically determined prognostic factors for estimating in the long term.
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Affiliation(s)
- Sang Hyun Shin
- From the Departments of *Surgery and †Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
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31
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Metildi CA, Kaushal S, Pu M, Messer KA, Luiken GA, Moossa AR, Hoffman RM, Bouvet M. Fluorescence-guided surgery with a fluorophore-conjugated antibody to carcinoembryonic antigen (CEA), that highlights the tumor, improves surgical resection and increases survival in orthotopic mouse models of human pancreatic cancer. Ann Surg Oncol 2014; 21:1405-11. [PMID: 24499827 DOI: 10.1245/s10434-014-3495-y] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND We have developed a method of distinguishing normal tissue from pancreatic cancer in vivo using fluorophore-conjugated antibody to carcinoembryonic antigen (CEA). The objective of this study was to evaluate whether fluorescence-guided surgery (FGS) with a fluorophore-conjugated antibody to CEA, to highlight the tumor, can improve surgical resection and increase disease-free survival (DFS) and overall survival (OS) in orthotopic mouse models of human pancreatic cancer. METHODS We established nude-mouse models of human pancreatic cancer with surgical orthotopic implantation of the human BxPC-3 pancreatic cancer. Orthotopic tumors were allowed to develop for 2 weeks. Mice then underwent bright-light surgery (BLS) or FGS 24 h after intravenous injection of anti-CEA-Alexa Fluor 488. Completeness of resection was assessed from postoperative imaging. Mice were followed postoperatively until premorbid to determine DFS and OS. RESULTS Complete resection was achieved in 92 % of mice in the FGS group compared to 45.5 % in the BLS group (p = 0.001). FGS resulted in a smaller postoperative tumor burden (p = 0.01). Cure rates with FGS compared to BLS improved from 4.5 to 40 %, respectively (p = 0.01), and 1-year postoperative survival rates increased from 0 % with BLS to 28 % with FGS (p = 0.01). Median DFS increased from 5 weeks with BLS to 11 weeks with FGS (p = 0.0003). Median OS increased from 13.5 weeks with BLS to 22 weeks with FGS (p = 0.001). CONCLUSIONS FGS resulted in greater cure rates and longer DFS and OS using a fluorophore-conjugated anti-CEA antibody. FGS has potential to improve the surgical treatment of pancreatic cancer.
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Affiliation(s)
- Cristina A Metildi
- Department of Surgery, University of California San Diego, San Diego, CA, USA
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32
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Lymph node involvement beyond peripancreatic region in pancreatic head cancers: when results belie expectations. Pancreas 2013; 42:239-48. [PMID: 23038054 DOI: 10.1097/mpa.0b013e31825f80a9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Surgery remains the standard therapy for curative management of pancreatic duct adenocarcinoma (PDA) involving the head of pancreas. This study aimed to report our experience in PDA about the prognostic value of lymph node (LN) invasion (N⁺) at the root of the superior mesenteric artery (SMA) and in N2 subgroup. METHODS From January 2005 to September 2009, 110 patients were included for pancreaticoduodenectomy or total pancreatectomy. RESULTS Etiologies were PDA (n = 87) or ampullary carcinomas (n = 23). Sixty-five percent of patients were N⁺, with N1/N2/N3 location, respectively, 63.6%, 9.1%, and 2.7%. Forty-four percent had a LN identified intraoperatively at the origin of the SMA, of whom only 12% were N⁺. In multivariate analysis (whole series), complication grade greater than II, location of positive LN (N1 to N3) and vascular resection were associated with a poorer survival. In the exocrine PDA subgroup, only location of positive LN and vascular resection were associated with a poorer survival. N⁺ SMA was not statistically correlated with survival, recurrence, or disease-free survival. CONCLUSIONS N⁺ at the origin of the SMA was not a significant prognostic factor for PDA and should no longer be considered as a formal contraindication for curative surgery. Conversely, N2 invasion remains an unfavorable prognostic.
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Yoshikawa K, Mitsunaga S, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Kato Y, Aizawa M, Ochiai A. Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head. Cancer Sci 2012; 103:2012-20. [PMID: 22931216 PMCID: PMC7659389 DOI: 10.1111/j.1349-7006.2012.02411.x] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2012] [Revised: 07/04/2012] [Accepted: 07/18/2012] [Indexed: 12/12/2022] Open
Abstract
Tumor-associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumor-associated macrophages can be affected by cancer-related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM-related factors and the clinical impact of TAMs. CD68 (a pan-macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease-free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC.
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Affiliation(s)
- Kiyoshi Yoshikawa
- Pathology Division, Research Center for Innovative Oncology, Kashiwa, Japan
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34
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Wylie N, Adib R, Barbour AP, Fawcett J, Hill A, Lynch S, Martin I, O'Rourke TR, Puhalla H, Rutherford L, Slater K, Whiteman DC, Neale RE. Surgical management in patients with pancreatic cancer: a Queensland perspective. ANZ J Surg 2012; 83:859-64. [PMID: 23095039 DOI: 10.1111/j.1445-2197.2012.06312.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Little has been published regarding presenting symptoms, investigations and outcomes for patients with pancreatic cancer in Australia. Data from a series of patients undergoing attempted resection in Queensland, Australia, are presented with the aim of assisting development of consistent strategies in disease management. METHODS We reviewed the medical records of 121 patients who underwent attempted surgical resection and who took part in a case-control study between 2007 and 2009. Information relating to symptoms, investigations, surgical procedures and outcomes was captured. RESULTS The mean age was 63 years and 60% were men. The most common presenting symptoms were jaundice (64%) and pain (63%). Over 80% of patients had multiple imaging investigations or laparoscopy prior to surgery. Seventy-eight patients (64%) had a completed resection and 23% of these had involved margins. The presence of metastases and/or involvement of vessels or adjacent structures precluded resection in the remaining patients. The 1-year survival for patients whose resections were completed was 77% compared with 51% for those whose tumours were not resectable (P = 0.004). There was no 30-day mortality and 68% of patients were alive 1 year after diagnosis. Resections were performed in 11 different hospitals but over 90% of patients underwent their surgery in one of five high-volume centres. CONCLUSION The Queensland experience is consistent with that reported internationally. A significant proportion of attempted resections was not completed because preoperative staging underestimated disease extent. Most patients with potentially resectable disease are being treated in high-volume centres.
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Affiliation(s)
- Neil Wylie
- Queensland Institute of Medical Research, Brisbane, Queensland, Australia
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Chen R, Pan S, Ottenhof NA, de Wilde RF, Wolfgang CL, Lane Z, Post J, Bronner MP, Willmann JK, Maitra A, Brentnall TA. Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. Cancer Biol Ther 2012; 13:899-907. [PMID: 22785208 DOI: 10.4161/cbt.20842] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The overall 5 year survival rate for pancreatic ductal adenocarcinoma (i.e., PDAC) is a dismal 5%, although patients that have undergone surgical resection have a somewhat better survival rate of up to 20%. Very long-term survivors of PDAC (defined as patients with ≥ 10 year survival following apparently curative resection), on the other hand, are considerably less frequent. The molecular characteristics of very long-term survivors (VLTS) are poorly understood, but might provide novel insights into prognostication for this disease. In this study, a panel of five VLTS and stage-matched short-term survivors (STS, defined as disease-specific mortality within 14 months of resection) were identified, and quantitative proteomics was applied to comparatively profile tumor tissues from both cohorts. Differentially expressed proteins were identified in cancers from VLTS vs. STS patients. Specifically, the expression of galectin-1 was 2-fold lower in VLTS compared with STS tumors. Validation studies were performed by immunohistochemistry (IHC) in two additional cohorts of resected PDAC, including: 1) an independent cohort of VLTS and 2) a panel of sporadic PDAC with a considerable range of overall survival following surgery. Immunolabeling analysis confirmed that significantly lower expression of stromal galectin-1 was associated with VLTS (p = 0.02) and also correlated with longer survival in sporadic, surgically-treated PDAC cases (hazard ratio = 4.9, p = 0.002). The results from this study provide new insights to better understand the role of galectin-1 in PDAC survival, and might be useful for rendering prognostic information, and developing more effective therapeutic strategies aimed at improving survival.
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Affiliation(s)
- Ru Chen
- Department of Medicine, University of Washington, Seattle, WA, USA
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Crippa S, Partelli S, Zamboni G, Barugola G, Capelli P, Inama M, Bassi C, Pederzoli P, Falconi M. Poorly differentiated resectable pancreatic cancer: is upfront resection worthwhile? Surgery 2012; 152:S112-9. [PMID: 22766365 DOI: 10.1016/j.surg.2012.05.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Accepted: 05/11/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Poorly differentiated, resectable pancreatic ductal adenocarcinoma is associated with early recurrence and may benefit from neoadjuvant treatment. The aim of this study was to evaluate clinicopathologic characteristics and survival of patients with resectable pancreatic ductal adenocarcinoma according to histologic grading. METHODS A total of 502 patients who underwent resection for pancreatic ductal adenocarcinoma between 1990 and 2008 were analyzed via the use of different histologic grading. RESULTS Well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) pancreatic ductal adenocarcinomas were found in 23 (4.5%), 310 (62%), and 169 (33.5%) patients. Adjuvant therapy, N status, grading, and R status were independent predictors of disease-specific survival for the entire cohort, with 1- and 5-year disease-specific survival rates of 81% and 21%, respectively. Only the presence of symptoms was a significant clinical predictor of G3 status (P = .035). G3 neoplasms were characterized by a greater rate of lymph node metastases, microvascular/perineural invasion, and R2 resections. Median disease-specific survival was 77, 26, and 20 months for G1, G2, and G3 neoplasms (P < .0001). Median disease-free survival was 63, 14, and 9 months for G1, G2, and G3 pancreatic ductal adenocarcinoma (P < .0001). Adjuvant therapy improved disease-specific survival in G2 (P < .04) and G3 (P < .0001) pancreatic ductal adenocarcinoma, with a greater survival benefit for G3 neoplasms (hazard ratio: 1.334 vs 2.116). CONCLUSION G3 pancreatic ductal adenocarcinoma is associated with a lesser rate of disease-free survival after resection and with the presence of other poor prognostic factors. The benefit of adjuvant therapy is greater in G3 than in G1 and G2 neoplasms. On the basis of these findings, patients with resectable G3 PDAC can be considered as possible targets for neoadjuvant treatment.
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Affiliation(s)
- Stefano Crippa
- Department of Surgery, University of Verona, Verona, Italy.
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Metildi CA, Kaushal S, Hardamon C, Snyder CS, Pu M, Messer KS, Talamini MA, Hoffman RM, Bouvet M. Fluorescence-guided surgery allows for more complete resection of pancreatic cancer, resulting in longer disease-free survival compared with standard surgery in orthotopic mouse models. J Am Coll Surg 2012; 215:126-35; discussion 135-6. [PMID: 22632917 PMCID: PMC3383387 DOI: 10.1016/j.jamcollsurg.2012.02.021] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2011] [Revised: 02/19/2012] [Accepted: 02/20/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND Negative surgical margins are vital to achieve cure and prolong survival in patients with pancreatic cancer. We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes and reduce recurrence rates in orthotopic mouse models of human pancreatic cancer. STUDY DESIGN A randomized active-control preclinical trial comparing bright light surgery (BLS) to FGS was used. Orthotopic mouse models of human pancreatic cancer were established using the BxPC-3 pancreatic cancer cell line expressing red fluorescent protein (RFP). Two weeks after orthotopic implantation, tumors were resected with BLS or FGS. Pre- and postoperative images were obtained with the OV-100 Small Animal Imaging System to assess completeness of surgical resection in real time. Postoperatively, noninvasive whole body imaging was done to assess recurrence and follow tumor progression. Six weeks postoperatively, mice were sacrificed to evaluate primary pancreatic and metastatic tumor burden at autopsy. RESULTS A more complete resection of pancreatic cancer was achieved using FGS compared with BLS: 98.9% vs 77.1%, p = 0.005. The majority of mice undergoing BLS (63.2%) had evidence of gross disease with no complete resections; 20% of mice undergoing FGS had complete resection and an additional 75% had only minimal residual disease (p = 0.0001). The mean postoperative tumor burden was significantly less with FGS compared with BLS: 0.08 ± 0.06 mm(2) vs 2.64 ± 0.63 mm(2), p = 0.001. The primary tumor burden at termination was significantly less with FGS compared with BLS: 19.3 ± 5.3 mm(2) vs 6.2 ± 3.6 mm(2), p = 0.048. FGS resulted in significantly longer disease-free survival than BLS (p = 0.02, hazard ratio = 0.39, 95% CI 0.17, 0.88). CONCLUSIONS Surgical outcomes were improved in pancreatic cancer using fluorescence-guidance. This novel approach has significant potential to improve surgical treatment of cancer.
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Affiliation(s)
- Cristina A Metildi
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Sharmeela Kaushal
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Chanae Hardamon
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Cynthia S Snyder
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Minya Pu
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Karen S Messer
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Mark A Talamini
- Department of Surgery, University of California San Diego, San Diego, CA
| | - Robert M Hoffman
- Department of Surgery, University of California San Diego, San Diego, CA
- AntiCancer, Inc, San Diego, CA
| | - Michael Bouvet
- Department of Surgery, University of California San Diego, San Diego, CA
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Adjuvant surgical therapy for patients with initially-unresectable pancreatic cancer with long-term favorable responses to chemotherapy. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2011; 18:712-6. [PMID: 21455748 DOI: 10.1007/s00534-011-0391-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND To evaluate the prognostic impact of surgical intervention for initially-unresectable pancreatic ductal adenocarcinomas with long-term favorable responses to chemotherapy. METHOD Twelve patients with initially-unresectable pancreatic ductal carcinomas who underwent radical surgery after a favorable response to chemotherapy for six months or longer in principle were enrolled in this study. We retrospectively reviewed the charts of these 12 patients and performed a survival analysis. RESULTS Initially, the included patients were unable to undergo resection secondary to locally-advanced disease in eight patients and metastatic disease in four patients. The length of preoperative therapy was five to 44 months (median 12). The operative procedure included resection of the area initially involved by tumor and regional major vessels. The postoperative mortality and morbidity rates were 0% for patients with locally-advanced disease and 50% in those with metastatic disease. R0 resection was achieved in nine patients (75%) and pathological CR was seen in one patient. Estimated overall five-year survival from initial therapy was 50.0%. The survival rate (0% at 5 years) of the four patients with metastatic disease as the cause of initial unresectability was significantly worse than that (100% at 5 years) of the eight patients with locally-advanced disease (P = 0.0014). CONCLUSION Surgical intervention should be considered for patients with initially-unresectable pancreatic cancers who demonstrate long-term favorable responses to chemotherapy. R0 resection may significantly contribute to cure, especially in patients with initially locally-advanced disease. Large cohort prospective studies will be necessary to demonstrate the efficacy of this strategy.
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Benckert C, Thelen A, Cramer T, Weichert W, Gaebelein G, Gessner R, Jonas S. Impact of microvessel density on lymph node metastasis and survival after curative resection of pancreatic cancer. Surg Today 2011; 42:169-76. [DOI: 10.1007/s00595-011-0045-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2010] [Accepted: 02/18/2011] [Indexed: 12/30/2022]
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Shrikhande SV, Arya S, Barreto SG, Ingle S, D'Souza MA, Hawaldar R, Shukla PJ. Borderline resectable pancreatic tumors: is there a need for further refinement of this stage? Hepatobiliary Pancreat Dis Int 2011; 10:319-324. [PMID: 21669578 DOI: 10.1016/s1499-3872(11)60053-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The ideal treatment of patients with "borderline resectable pancreatic tumors (BRTs)" needs to be established. Current protocols advise neoadjuvant chemo(radio)therapy, although some patients may appear to have BRT on preoperative imaging and a complete resection may be achieved without the need for vascular resection. The aim of the present study was to identify specific findings on preoperative imaging that could help predict in which patients with BRT a complete resection, with or without vascular resection (VR), could be achieved. METHODS Twelve patients with BRTs were identified. Tumor location, maximum degree of circumferential contact (CC), length of contact of the tumor with major vessels (LC), and luminal narrowing of vessels at the point of contact with the tumor (venous deformity, VD) were graded on preoperatively acquired multidetector computed tomography (MDCT) images and then compared with the intraoperative findings and need for VR. RESULTS A complete resection (R0) was achieved in 10 patients with 2 having microscopic positive margins (R1) on histopathology at the uncinate margin. Four of the 10 patients required VR (40%). In 3 of the 4 patients whose tumors required VRs, CC was ≥grade III and VD was grade 2. LC did not influence the need for VR. CONCLUSIONS It is possible to achieve a complete resection at the first instance in patients found to have BRTs on preoperative imaging. Preoperative MDCT-based grading systems and our proposed criteria may help identify such patients, thus avoiding any delay in curative resections in such patients.
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Affiliation(s)
- Shailesh V Shrikhande
- Department of Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Hospital, Mumbai, India.
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de Jong MC, Li F, Cameron JL, Wolfgang CL, Edil BH, Herman JM, Choti MA, Eckhauser F, Hirose K, Schulick RD, Pawlik TM. Re-evaluating the impact of tumor size on survival following pancreaticoduodenectomy for pancreatic adenocarcinoma. J Surg Oncol 2011; 103:656-62. [PMID: 21283994 DOI: 10.1002/jso.21883] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2010] [Accepted: 01/10/2011] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES Following resection of pancreatic adenocarcinoma, tumor size has been considered a key prognostic feature; however, this remains controversial. We sought to examine the association of size with outcomes following resection of pancreatic adenocarcinoma. METHODS Between 1970 and 2010, 1,697 patients with pancreatic adenocarcinoma at the Johns Hopkins Hospital underwent curative intent pancreaticoduodenectomy. Prognostic factors were identified by univariate and multivariate analyses. RESULTS Of 1,697 patients, tumor size was ≤ 2 cm in 418 (24.6%) patients, 2-5 cm in 1,070 (63.1%) patients, and ≥ 5 cm in 209 (12.3%) patients. On univariate analyses, 5-year survival was inversely proportional to tumor size (≤ 2 cm: 28.8% vs. 2-5 cm: 19.4% vs. ≥ 5 cm: 14.2%; P < 0.001). Size correlated with the risk of other adverse factors, with larger tumors being more likely to be associated with nodal disease and poor differentiation (both P < 0.05). On multivariate analysis, the 2 cm cut-off was not associated with survival, while nodal disease (HR = 1.59; P = 0.006) and poor differentiation (HR = 1.59; P = 0.04) remained predictive of outcome, regardless of size. CONCLUSION The cut-off value of 2 cm is not independently associated with outcome, however, tumor size was strongly associated with the risk of other adverse prognostic factors. The effect of size on prognosis was largely attributable to these other biologic factors rather than tumor size itself.
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Affiliation(s)
- Mechteld C de Jong
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
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Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on genome-wide DNA methylation profiling by bacterial artificial chromosome array-based methylated CpG island amplification. J Biomed Biotechnol 2010; 2011:780836. [PMID: 21197409 PMCID: PMC3010700 DOI: 10.1155/2011/780836] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2010] [Accepted: 11/12/2010] [Indexed: 12/31/2022] Open
Abstract
To establish diagnostic criteria for ductal adenocarcinomas of the pancreas (PCs), bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using 139 tissue samples. Twelve BAC clones, for which DNA methylation status was able to discriminate cancerous tissue (T) from noncancerous pancreatic tissue in the learning cohort with a specificity of 100%, were identified. Using criteria that combined the 12 BAC clones, T-samples were diagnosed as cancers with 100% sensitivity and specificity in both the learning and validation cohorts. DNA methylation status on 11 of the BAC clones, which was able to discriminate patients showing early relapse from those with no relapse in the learning cohort with 100% specificity, was correlated with the recurrence-free and overall survival rates in the validation cohort and was an independent prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling may provide optimal diagnostic markers and prognostic indicators for patients with PCs.
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