The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Overall survival, recurrence, and sites of recurrence.Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.

To describe accurately the pattern, timing, and predictors of disease recurrence after a potentially curative resection for pancreatic ductal adenocarcinoma (PDAC).After surgery for PDAC, most patients will develop disease recurrence. Understanding the patterns and timing of disease failure can help guide improvements in therapy.Patients who underwent pancreatectomy for PDAC at the Johns Hopkins Hospital between 2000 and 2010 were included. Exclusion criteria were incomplete follow-up records, follow-up <24 months, and neoadjuvant therapy. The first recurrence site was recorded and recurrence-free survival (RFS) was estimated using Kaplan-Meier curves. Predictive factors for specific recurrence patterns were assessed by univariate and multivariate analyses using Cox-proportional hazard regression models.From the identified cohort of 1103 patients, 692 patients had comprehensive and detailed follow-up data available. At a median follow-up of 25.3 months, 531 (76.7%) of the 692 had recurred after a median RFS of 11.7 months. Most patients recurred at isolated distant sites (n = 307, 57.8%), while isolated local recurrence was seen in 126 patients (23.7%). Liver-only recurrence (n = 134, 25.2%) tended to occur early (median 6.9 mo), while lung-only recurrence (n = 78, 14.7%) occurred later (median 18.6 mo). A positive lymph node ratio >0.2 was a strong predictor for all distant disease recurrence. Patients receiving adjuvant chemotherapy or chemoradiotherapy had fewer recurrences and a longer RFS of 18.0 and 17.2 months, respectively.Specific recurrence locations have different predictive factors and possess distinct RFS curves, supporting the hypothesis that unique biological differences exist among tumors leading to distinct patterns of recurrence.

Retro pancreatic invasion is a major concern in pancreatic head carcinoma. Posterior clearance has been recognized as an independent risk factor for disease recurrence and hence patient survival. The aim of this study was to report a standardized method that ensures posterior clearance with Total Mesopancreas Excision (TMpE).Our procedure consisted in a posterior approach with cranio-caudal dissection at the origin of the superior mesenteric artery and the celiac trunk all along their right semi-circumference. This allowed a complete clearance of retro pancreatic tissues with safe control of pancreaticoduodenal arteries at their origin.Fifty-two consecutive pancreatic resections with TMpE were performed. Sixteen cases were associated to vascular resection. Pathology revealed an adenocarcinoma of the pancreatic duct, distal bile duct, periampullary and neuroendocrine carcinoma. Mesopancreas was invaded by cancer in 12 cases, of these, 3 had invaded margins and 7 had a margin less than 1 mm. Mesopancreas was the only site of tumour infiltration. Applying the International Union Against Cancer criteria, an R0 resection was thus achieved in 42 patients.Our procedure is feasible and safe in experienced hand. It is a description of a standardized method for TMpE that clearly shows an advantage in improving posterior clearance and R0 resection.© 2011 Elsevier Ltd. All rights reserved.

Continuous theoretical and technological progress in the face of increasing expectations for quality health care has transformed the surgical paradigm. The authors systematically review these historical trends and propose the novel paradigm of "precision surgery," featuring certainty-based practice to ensure the best result for each patient with multiobjective optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. The main characteristics of precision surgery may be summarized as determinacy, predictability, controllability, integration, standardization, and individualization. The strategy of precision in liver surgery is to seek a balance of maximizing the removal of the target lesion, while maximizing the functional liver remnant and minimizing surgical invasiveness. In this article, the authors demonstrate the application of precision approaches in specific settings in complex liver surgery. They propose that the concept of precision surgery should be considered for wider application in liver surgery and other fields as a step toward the ultimate goal of perfect surgery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prognosis after surgical therapy for pancreatic cancer is poor and has been attributed to early lymph node involvement as well as to a strong tendency of cancer cells to infiltrate into the retropancreatic tissue and to spread along the peripancreatic neural plexuses. The objective of our study was to classify the anatomical-surgical layer of the mesopancreas and to describe the surgical principles relevant for resection of the mesopancreas (RMP). Immunohistochemical investigation of the mesopancreatic-perineural lymphogenic structures was carried out with the purpose of identifying possible routes of metastatic spread.Resection of the mesopancreas (RMP) was performed in fresh corpses. Pancreas and mesopancreas were separated from each other and the mesopancreas was immunohistochemically investigated.The mesopancreas strains itself dorsally of the mesenteric vessels as a whitish-firm, fatty tissue-like layer. Macroscopically, in the dissected en-bloc specimens of pancreas and mesopancreas nerve plexuses were found running from the dorsal site of the pancreatic head to the mesopancreas to establish a perineural plane. Immunohistochemical examinations revealed the lymphatic vessels localized in direct vicinity of the neuronal plexuses between pancreas and mesopancreas.The mesopancreas as a perineural lymphatic layer located dorsally to the pancreas and reaching beyond the mesenteric vessels has not been classified in the anatomical or surgical literature before. The aim to ensure the greatest possible distance from the retropancreatic lymphatic tissue which drains the carcinomatous focus can be achieved in patients with pancreatic cancer only by complete resection of the mesopancreas (RMP).

Mesopancreas is a controversial structure. This study aimed to explore the anatomical characteristics of the mesopancreas, define the range of the total mesopancreas excision (TMpE), and evaluate the feasibility, safety and effectivity of TMpE in the treatment of pancreatic head cancer. The clinical and pathological data of 58 consecutive patients undergoing TMpE for pancreatic head carcinoma from January 2013 to December 2015 were analyzed prospectively. The perioperative morbidity, mortality and clinical outcomes of patients undergoing TMpE were compared with the patients undergoing conventional pancreaticoduodenectomy. The mesopancreas was located in the retropancreatic area, extending from the head, neck, and uncinated process of pancreas to the aorto-caval groove, in which there were loose areolar tissue, adipose tissue, nerve plexus, lymphatic and capillaries. We observed significantly higher R0 rate (94.8% vs. 81.4%, P=0.035), more lymph nodes (16.2 vs. 11.4, P=0.000), lower total and local recurrence rate (half-year local recurrence rate 7.8% vs. 23.7%, P=0.036, one-year 18.2% vs. 39.5%, P=0.018) and longer disease-free survival (16.9 vs. 13.4 months, P=0.044) in TMpE group than in control group. In conclusion, mesopancreas is different from mesorectum because there is no fascial envelop or anatomical boundary in this area. TMpE could be safely and feasibly performed for the treatment of pancreatic head cancer to increase the R0 resection rate and improve the clinical outcomes.

Pancreatic head cancer patients who undergo pancreatoduodenectomy (PD) often experience disease recurrence, frequently associated with a positive margin status (R1). Total mesopancreas excision (TMpE) has emerged as a potential approach to increase surgical radicality and minimize locoregional recurrence. However, its effectiveness and safety remain under evaluation.We conducted a systematic review and meta-analysis to synthesize current evidence on TMpE outcomes. A systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases was conducted up to March 2024 to identify studies comparing TMpE with standard pancreatoduodenectomy (sPD). The risk ratio (RR) or mean difference (MD) was pooled using a random effects model.From 452 studies identified, 9 studies with a total of 738 patients were included, with 361 (49%) undergoing TMpE. TMpE significantly improved the R0 resection rate (RR 1.24; 95% CI 1.11-1.38; P < 0.05), reduced blood loss (MD -143.70 ml; 95% CI -247.92, -39.49; P < 0.05), and increased lymph node harvest (MD 7.27 nodes; 95% CI 4.81, 9.73; P < 0.05). No significant differences were observed in hospital stay, postoperative complications, or mortality between TMpE and sPD. TMpE also significantly reduced overall recurrence (RR 0.53; 95% CI 0.35-0.81; P < 0.05) and local recurrence (RR 0.39; 95% CI 0.24-0.63; P < 0.05). Additionally, the risk of pancreatic fistula was lower in the TMpE group (RR 0.66; 95% CI 0.52-0.85; P < 0.05).Total mesopancreas excision significantly increases the R0 resection rate and reduces locoregional recurrence while maintaining an acceptable safety profile when compared with standard pancreatoduodenectomy. Further prospective randomized studies are warranted to determine the optimal surgical approach for total mesopancreatic resection.© 2024. The Author(s).

Despite its importance in pancreatic head carcinoma, the retroportal lamina is still under studied, with only two anatomical cadaveric dissections in the English literature, with recent controversies about the concept of a mesopancreas.Resection of the mesopancreas was performed in 33 fresh cadavers. The pancreas and mesopancreas were separated from each other and the mesopancreas was immunohistochemically investigated.The retroportal lamina is roughly rectangular in shape. Its dimensions are: height 6.2 cm (5-8), 2.5 cm wide (1.5-4). It contains a right hepatic artery arising from the superior mesenteric artery in 13.3% of cases. Microscopic examination revealed areolar tissue, adipose tissue, peripheral nerve, nerve plexus, lymphatics and capillaries. However, fibrous sheath and fascia were not found around these structures.A right hepatic artery arising from the superior mesenteric artery is a frequent anatomic variation. Surgeons must be aware of this to ensure the integrity of the hepatic artery blood supply in patients treated by pancreaticoduodenectomy. Despite controversy about the reality of the mesopancreas (postulated in analogy to the mesorectum), because of the absence of fibrous sheath or fascia, its complete removal in pancreatic head carcinoma is feasible by a subadventitial dissection of the superior mesenteric artery which can be considered as the real limit of the mesopancreas.Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

To describe the details of the surgical technique of pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD), using a supracolic anterior artery-first approach.An artery-first approach in PD has been advocated in pancreatic cancer to judge resectability, clear the superior mesenteric artery margin from invasion, or reduce blood loss. However, the efficacy of an artery-first approach in mesopancreas dissection remains unclear.This study involved 162 consecutive patients who underwent PD with curative intent. The patients were divided into 82 SMD-PDs and 80 conventional PDs (CoPD) and then stratified further according to the dissection level, that is, level 1 was applied to 24 simple mesopancreas divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a hemicircumferential superior mesenteric artery plexus resection to keep the margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results were collected to assess the feasibility and validity of SMD-PD with an artery-first approach.Blood loss and operation duration were significantly less in the SMD-PD group than in the CoPD group among the total 162 patients. The imaging analysis showed that four fifths of pancreatic arterial branches came from the right dorsal aspect of the superior mesenteric artery and cancer abutment occurred exclusively from the same direction indicating the validity of an artery-first approach.SMD-PD using an SAA is feasible across PD cases, with acceptable short-term outcomes, and we propose this procedure as a promising option for PD.

We describe the short- and long-term outcomes for PDAC patients after tailored mesopancreas dissection using supracolic artery-first approach followed by adjuvant therapy.This study analyzed 233 consecutive patients who underwent artery-first pancreaticoduodenectomy for PDAC. Dissection extent for the superior mesenteric artery (SMA) was categorized into three levels: level 2 (LV2) including regional lymph nodes, level 3 (LV3) with hemicircumferential nerve plexus dissection, and extended-level 3 (E-LV3) including borderline resectable cases for the SMA. All clinical, pathological, and survival outcomes were reviewed.LV2/3/E-LV3 dissection was performed in 77/115/41 patients. The short-term outcomes were similar among groups without mortality. Although postoperative diarrhea requiring opioids was significantly more frequent in the E-LV3 group (76%) than other groups (vs. LV2 (21%), P < .0001; vs. LV3 (34%), P < .0001; LV2 vs. LV3, P = 0.20), most cases of diarrhea were well controlled. Adjuvant chemotherapy was introduced similarly among groups (LV2, 76%; LV3, 81%; E-LV3, 88%, P = 0.29). The 3- and 5-year overall survival rates in the LV2/3/E-LV3 groups were 42/33/42% and 27/22/26%, respectively, showing no significant difference among groups.Our tailored dissection and preemptive use of opioid antidiarrheal effectively prevents intractable diarrhea, increasing the success of adjuvant chemotherapy.

Mesopancreas dissection (MPD) level 3 in combined robotic/open pancreatoduodenectomy (CR/OPD) is technique-demanding. This study aims to clarify the feasibility and justification of MPD level 3.

In pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), Prophylactic right-half dissection of the superior mesenteric artery (SMA) nerve plexus has been attempted in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In this study, we evaluated the significance of prophylactic right-half dissection of the SMA nerve plexus by extending the observation period to 5 years.From April 2014 to June 2018, 74 patients with PDAC in the pancreatic head were randomly assigned to either the dissection group, in which the right half of the nerve plexus of the SMA was dissected (n = 37) or the preservation group, in which the nerve plexus of the SMA was completely preserved (n = 37). The 5-year relapse-free survival (RFS), overall survival (OS), and incidence of diarrhea were prospectively compared between groups.The median RFS (20 vs. 16 months, P = 0.503) and OS (37.0 vs. 30.0 months, P = 0.582) did not differ significantly between the dissection and preservation groups. There was no significant difference in locoregional recurrence (27.0% vs. 37.8%, P = 0.320) or distant metastasis (64.9% vs. 83.0%, P = 0.451). Postoperative diarrhea occurred in 64.9% and 62.2% of the cases in the dissection and preservation groups, respectively (P = 0.809).Prophylactic right half dissection of the SMA nerve plexus did not improve the RFS or OS.© 2025. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.

BACKGROUND

Pancreatic ductal carcinoma (PDAC) is the fourth most frequent cause of cancer-related death in the Western world, and its incidence is rising. In patients that undergo curative resection, local recurrence (LR) is frequent. A recently described surgical technique of extended pancreatoduodenectomy (PD) termed the TRIANGLE operation has been proposed as a promising approach to reduce LR and improve disease-free survival in PDAC patients.The TRIANGLE trial is a multicentre confirmatory randomised controlled superiority trial with two parallel study groups. A total of 270 patients with suspected or histologically confirmed pancreatic head cancer scheduled for PD will be included in the trial and randomly assigned to the intervention group (extended PD defined as Inoue level 3 dissection along the superior mesenteric and celiac artery as well as removal of all soft tissue in the so-called triangle between the celiac artery, the SMA and the mesenterico-portal axis) or the control group (conventional PD with lymphadenectomy and removal of soft tissue according to current guidelines). The primary endpoint of the trial will be the disease-free survival of patients. Other perioperative outcomes as well as oncological parameters and patient-reported outcomes will be analysed as secondary outcomes.Despite multimodal treatment, LR remains high and disease-free survival is limited following PD for PDAC. The TRIANGLE operation could address these shortcomings of conventional PD as indicated in several retrospective studies. However, this technique could be associated with more adverse events for patients including intractable diarrhoea. The TRIANGLE trial will close the evidence gap as well as offer a risk-benefit assessment of this more radical approach to PD.German Clinical Trials Register DRKS00030576 (UTN U1111-1243-4412) 19th December 2022.© 2023. The Author(s).

Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a "Triangle Volume" (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute (< 90 days) toxicity after IORT measured by Clavien-Dindo classification. Secondary objectives include late (> 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival.If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach. Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513.© 2022. The Author(s).

To systematically evaluate the efficacy and safety of radical antegrade modular pancreatosplenectomy (RAMPS) versus conventional distal pancreatectomy (CDP) for left-sided pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Radical surgical resection offers the only potential cure. There is increasing agreement that radical antegrade modular pancreatosplenectomy (RAMPS) may benefit patients with tumors in the body and tail of the pancreas. To address this, the Chinese Study Group for Pancreatic Cancer (CSPAC)-3 trial is proposed to compare the effect of RAMPS and standard retrograde pancreatosplenectomy (SRPS) on patient survival and preoperative safety