Validation and Optimisation of the ISGPS Risk Classification for Postoperative Pancreatic Fistula after Pancreatoduodenectomy for Periampullary Tumours.

OBJECTIVES: To externally validate the International Study Group of Pancreatic Surgery (ISGPS) classification and test its performance for predicting clinically relevant pancreatic fistula (CRPF) for periampullary tumours (P-amps). BACKGROUND: The ISGPS is a simple two-factor, four-tier classification of pancreas-related risk for CRPF after a pancreatoduodenectomy (PD). External validation and performance of the classification specific to P-amps are lacking. P-amps have different disease biology, lesser need for neoadjuvant therapy, softer pancreas, and a higher rate of CRPF, underscoring the importance of site-specific prediction. METHODS: Validation was performed in a cohort of 1422 patients, with CRPF as the primary outcome. Model performance was tested by plotting the receiver operating curve and calibration plots. After analysing the factors predicting CRPF, the model was optimised for P-amps. RESULTS: CRPF rate was 22.2% (315/1422), for P-amps being 25.8%. The ISGPS model performed moderately (AUC=0.632, 95% CI 0.598-0.666, P<0.001), with worse performance for P-amps (AUC=0.605, 95% CI 0.566-0.645, P<0.001). On multivariate analysis, soft pancreas (OR 1.689, 95% CI 1.136-2.512, P=0.010), body mass index ≥23 kg/m2 (OR 2.112, 95% CI 1.464-3.046, P<0.001) and pancreatic duct ≤3 mm (OR 2.113 95% CI 1.457-3.064, P<0.001), emerged as independent predictors and the model was optimised. The adjusted ISGPS for P-amps showed improved discrimination (AUC=0.672, P<0.001, 95% CI 0.637-0.707), with adequate performance on internal validation. CONCLUSION: The adjusted ISPGS performs better than the original ISGPS in predicting CRPF for P-amps. Large-scale multicenter data is needed to generate and validate site-specific predictive models.

CA 19-9 Surveillance Detects Recurrences Early and Contributes to Improvement in Survival in Resected Ampullary Cancers: Analysis of 572 cases.

OBJECTIVE: To determine the clinical utility of serum CA 19-9 surveillance for detecting recurrences in resected ampullary carcinomas (ACs). INTRODUCTION: Although an established prognostic marker for pancreatic ductal adenocarcinoma, the value of CA 19-9 in resected ACs during follow-up is unknown. METHODS: Retrospective analysis of ACs undergoing pancreaticoduodenectomy at Tata Memorial Centre-Mumbai, from January 2012 to January 2020 was performed. Survival, recurrence patterns, factors associated with recurrences and the utility of CA 19-9 surveillance were assessed. RESULTS: The 5-year OS of 572 included patients with ACs, was 56.4%. There were 251(43.88%) recurrences, majority being distant (n=223). Higher 'T' & 'N' stage, margin involvement, perineural invasion, poor tumour differentiation and pancreatobiliary subtype were associated with poor outcomes. Optimal CA 19-9 level to predict recurrence was 77.85 U/mL (sensitivity-61.22%, specificity-76.67%, AUC-0.711); however, a serial rise was a more accurate predictor (sensitivity-71.05%, specificity-91.67%). The median duration between the first rise in CA 19-9 (>37 U/mL) and radiological evidence of recurrence was 4.04 months. The optimal level of relative rise in CA 19-9 in diagnosing a recurrence was established at 2.79x (sensitivity-46.26%, specificity-83.33%, AUC-0.614). A serial rise and absolute value of >200 U/mL was associated with recurrence in 87% & 92.9% of cases. Recurrence detection & treatment after serum CA 19-9 elevation was associated with superior median survival as compared to recurrence detection without elevation (12.8 mo vs. 7.6 mo, P=0.005). CONCLUSION: Serum CA 19-9 testing during follow-up evaluation detects recurrences early and improves survival in resected ACs, and therefore should be recommended as a routine surveillance test.

Interobserver Variability in the International Study Group for Pancreas Surgery (ISGPS)-Defined Complications After Pancreatoduodenectomy: An International Cross-Sectional Multicenter Study.

OBJECTIVE: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others. SUMMARY BACKGROUND DATA: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking. METHODS: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored six standardized case vignettes. This variability and the 'within centers' variability were calculated for twofold scoring (no complication/grade A vs grade B/C) and threefold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula (POPF), post-pancreatoduodenectomy hemorrhage (PPH), chyle leak (CL), bile leak (BL), and delayed gastric emptying (DGE). Interobserver variability is presented with Gwet's AC-1 measure for agreement. RESULTS: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for twofold scoring was 68% (95%-CI: 55%-81%, AC1 score: moderate agreement) and for threefold scoring 55% (49%-62%, AC1 score: fair agreement). The mean 'within centers' agreement for twofold scoring was 84% (80%-87%, AC1 score; substantial agreement). CONCLUSION: The interobserver variability for the ISGPS defined complications of pancreatoduodenectomy was too high even though the 'within centers' agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability.

Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.

OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Robotic Pancreaticoduodenectomy with 'SMA-First Approach (Posterior and Right Medial)' and 'Triangle Operation'.

BACKGROUND: Notable improvements in pancreatic cancer surgery have been due to utilization of the superior mesenteric artery (SMA)-first approach1 and triangle operation (clearance of triangle tissue between origin of SMA and celiac artery).2 The SMA-first approach was originally defined to assess resectability before taking the irreversible surgical steps. However, in the present era, resectability is judged by the preoperative radiology, and the benefit of the SMA-first approach is by improving the R0 resection rate and reducing blood loss. The basic principle is to identify the SMA at its origin and in the distal part, to guide the plane of uncinate dissection. This video demonstrates the combination of the posterior and right medial SMA-first approach along with triangle clearance during robotic pancreaticoduodenectomy (RPD). METHODS: The technique consisted of early dissection of SMA from the posterior aspect, by performing a Kocher maneuver using the 'posterior SMA-first approach'. The origin of the celiac artery, along with the SMA, was defined early in the surgery. During uncinate process dissection, the 'right/medial uncinate approach' was used to approach the SMA. 'Level 3 systematic mesopancreatic dissection' was performed along the SMA,3 culminating in the 'triangle operation'.2 RESULTS: The procedure was performed within 600 min, with a blood loss of 150 mL and no intraoperative or postoperative complications. The final histopathology report showed a moderately differentiated adenocarcinoma (pT2, pN2), with all resection margins free. CONCLUSION: The standardized technique of the SMA-first approach and triangle clearance during RPD is demonstrated in the video. Prospective studies should further evaluate the benefits of this procedure.

Prognostic Impact of Para-Aortic Lymph Node Metastasis in Resected Non-Pancreatic Periampullary Cancers.

BACKGROUND: Surgery remains debatable in para-aortic lymph node (PALN, station 16b1) metastasis in non-pancreatic periampullary cancer (NPPAC). This study examined the impact of PALN metastasis on outcomes following pancreaticoduodenectomy (PD) in NPPAC. METHODS: A retrospective analysis of patients with NPPAC who were explored for PD with PALN dissection was performed. Based on the extent of nodal involvement on final histopathology, they were stratified as node-negative (N0), regional node involved (N+) and metastatic PALN (N16+) and their outcomes were compared. RESULTS: Between 2011 and 2022, 153/887 PD patients underwent a PALN dissection, revealing N16+ in 42 patients (27.4%), of whom 32 patients underwent resection. The 3-years overall survival (OS) for patients with N16+ was 28% (95% confidence interval [CI] 13-60%), notably lower than the 67% (95% CI 53-83.5%; p = 0.007) for those without PALN metastasis. Stratified by nodal involvement, the median OS for N+ and N16+ patients was similar (28.4 months and 26.2 months, respectively). The N0 subgroup had a significantly longer 3-years OS of 87.5% (95% CI 79-96.7%; p = 0.0051). Interestingly, 10 patients not offered resection following N16+ identified on frozen section had a median survival of only 9 months. The perioperative morbidity and mortality in patients undergoing PD with PALN dissection were similar to standard resections. CONCLUSION: In a select group of patients with NPPAC, PD in isolated PALN metastasis was associated with improved OS. The survival in this group of patients was comparable with regional node-positive patients and significantly better than palliative treatment alone.

Central versus distal pancreatectomy for low-grade and benign pancreatic neck-body tumours.

PURPOSE: Central pancreatectomy (CP) offers parenchymal preservation compared to conventional distal pancreato-splenectomy for pancreatic neck and body tumours. However, it is associated with more morbidity. This study is aimed at evaluating the peri-operative and long-term functional outcomes, comparing central and distal pancreatectomies (DPs). METHODS: Retrospective analysis of patients undergoing pancreatic resections for low-grade malignant or benign tumours in pancreatic neck and body was performed (from January 2007 to December 2022). Preoperative imaging was reviewed for all cases, and only patients with uninvolved pancreatic tail, whereby a CP was feasible, were included. Peri-operative outcomes and long-term functional outcomes were compared between CP and DP. RESULTS: One hundred twenty-two (5.2%) patients, amongst the total of 2304 pancreatic resections, underwent central or distal pancreatectomy for low-grade malignant or benign tumours. CP was feasible in 55 cases, of which 23 (42%) actually underwent CP and the remaining 32 (58%) underwent DP. CP group had a significantly longer operative time [370 min (IQR 300-480) versus 300 min (IQR 240-360); p = 0.002]; however, the major morbidity (43.5% versus 37.5%; p = 0.655) and median hospital stay (10 versus 11 days; p = 0.312) were comparable. The long-term endocrine functional outcome was favourable for the CP group [endocrine insufficiency rate was 13.6% in central versus 42.8% in distal (p = 0.046)]. CONCLUSION: Central pancreatectomy offers better long-term endocrine function without any increased morbidity in low malignant potential or benign pancreatic tumours of neck and body region.

Differential impact of incrementally elevated CA 19-9 levels on prognosis of resected pancreatic ductal adenocarcinoma.

BACKGROUND: CA 19-9 is an extremely useful biomarker for pancreatic ductal adenocarcinomas (PDACs). However, the optimal cut-off and prognostic significance at higher cut-offs are yet to be determined. METHODS: Retrospective analysis included patients with PDAC who underwent curative resection from January 2010 to May 2020 at Tata Memorial Centre, Mumbai. The pretherapy CA 19-9 was dichotomized using various cut-off levels and analysed. RESULTS: In 244 included patients, the median overall survival (OS) for those with CA19-9 level (IU/ml) < or >78, 200, 500, 1000, and 2000 was 27, 24, 23, 22, 21 months versus 18, 16, 15, 14, 13 months; respectively, and was statistically significant (p-value- 0.002, 0.001, 0.002, 0.002 and 0.004, respectively). The number of recurrences and mortality had significant correlation with CA 19-9 cut-offs. On multivariate analysis, adjuvant treatment completion (p-0.004) and decreasing or stable CA19-9 after Neoadjuvant therapy (NAT) (p- 0.031) were associated with improved OS. CONCLUSION: The prognostic significance of CA 19-9 was observed at all the cut-off levels examined, beyond mere elevated value as per the standard cut-off level. In patients with high CA19-9 level, surgery should be offered if technically and conditionally feasible, only when a response in CA19-9 level to NAT is achieved.

Adjuvant therapy may improve overall survival in high-risk periampullary adenocarcinomas patients - A match-pair analysis from a multi-institutional cohort study (The MIPPAP study).

BACKGROUND: The role of adjuvant therapy in resected periampullary adenocarcinomas is equivocal due to contrasting data and limited prospective trials. METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP), included data from 8 institutions across India. Of the 1679 pancreatic resections, 736 patients with T3/T4 and/or Node positive adenocarcinomas (considered as high risk for recurrence) were included for analysis. Three (adjuvant): one (observation) matching, using T3/T4 T staging, nodal positivity and ampullary subtype was performed by using the nearest neighbour matching method. RESULTS: Of 736 patients eligible for inclusion, 621 patients were matched of which 458 patients received adjuvant therapy (AT) (predominantly gemcitabine-based) and 163 patients were observed (O). With a median follow-up of 42 months, there was a statistical difference in overall survival in favour of patients receiving AT as compared to those on observation [68.7 months vs. 61.1 months, Hazard ratio: 0.73 (95% CI: 0.54-0.97); p = 0.03]. Besides AT, presence of nodal involvement (median OS: 65.4 months vs not reached; p = 0.04) predicted for inferior OS. CONCLUSIONS: The results of the match-pair analysis suggest that adjuvant therapy improves overall survival in periampullary adenocarcinomas at high risk of recurrence with a greater benefit in T3/T4, node-positive and ampullary subtypes.

'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer.

BACKGROUND: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.

A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery.

OBJECTIVE: The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD). SUMMARY BACKGROUND DATA: Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking. METHODS: A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort. RESULTS: Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001). CONCLUSION: For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results.

Pancreaticoduodenectomy in the Portal Annular Pancreas-Mesopancreas Triangle Approach (with Video).

BACKGROUND: Portal Annular Pancreas (PAP) is a relatively uncommon entity with 4% reported incidence. Pancreaticoduodenectomy is challenging in cases with PAP and is associated with higher postoperative pancreatic fistula rate and overall morbidity. PAP is classified according to the pattern and location of fusion around the portal vein as-supra-splenic, infra-splenic & mixed fusion type. Also, the ductal anatomy can vary as pancreatic duct present only in the ante-portal portion or only in the retro-portal portion or ducts in both ante and retro-portal portion. At present, ideal surgical strategy is not defined as per the PAP types. METHODS: The case demonstrated in the video presented with a localized, large duodenal mass with type IIA PAP (supra-splenic fusion with both ante and retro-portal ducts) detected on the preoperative triphasic CT scan. To achieve a single pancreatic cut surface with a single pancreatic duct for anastomosis, an extended pancreatic resection was performed using meso-pancreas triangle approach. RESULTS: Patient had a smooth intraoperative course & the postoperative recovery was also uneventful. Pathology reported pT3 duodenal cancer with negative margins and uninvolved lymph nodes. CONCLUSION: A preoperative knowledge of PAP and its various types is extremely important in order to tailor intraoperative management, specially of the retro-portal portion. In patients with retro-portal duct or both ante and retro-portal ducts (as the case presented in the video), an extended resection is recommended to mitigate postoperative pancreatic fistula.

Big data and RCT's in surgical oncology: Impact on improving hepatopancreatobiliary cancer surgical care on the global stage.

Randomized controlled clinical trials (RCTs) are at the heart of "evidence-based" medicine. Conducting well-designed RCTs for surgical procedures is often challenged by inadequate recruitment accrual, blinding, or standardization of the surgical procedure, as well as lack of funding and evolution of the treatment strategy during the many years over which such trials are conducted. In addition, most clinical trials are performed in academic high-volume centers with highly selected patients, which may not necessarily reflect a "real-world" practice setting. Large databases provide easy and inexpensive access to data on a large and diverse patient population at a variety of treatment centers. Furthermore, large database studies provide the opportunity to answer questions that would be impossible or very arduous to answer using RCTs, including questions regarding health policy efficacy, trends in surgical practice, access to health care, the impact of hospital volume, and adherence to practice guidelines, as well as research questions regarding rare disease, infrequent surgical outcomes, and specific subpopulations. Prospective data registries may also allow for quality benchmarking and auditing. There are several high-quality RCTs providing evidence to support current practices in hepatopancreatobiliary (HPB) oncology. Evidence from big data bridges the gap in several instances where RCTs are lacking. In this article, we review the evidence from RCTs and big data in HPB oncology identify the existing lacunae, and discuss the future directions of research in HPB oncology.

Global Perceptions on ERAS® in Pancreatoduodenectomy.

BACKGROUND: Uptake of ERAS® pathways for pancreatic surgery have been slow and impacted by low compliance. OBJECTIVE: To explore global awareness, perceptions and practice of ERAS® peri-pancreatoduodenectomy (PD). METHODS: A structured, web-based survey (EPSILON) was administered through the ERAS® society and IHPBA membership. RESULTS: The 140 respondents included predominantly males (86.4%), from Europe (45%), practicing surgery (95%) at academic/teaching hospitals (63.6%) over a period of 10-20 years (38.6%). Most respondents identified themselves as general surgeons (68.6%) with 40.7% reporting an annual PD volume of 20-50 cases, practicing post-PD clinical pathways (37.9%), with 31.4% of respondents auditing their outcomes annually. Reduced medical complications, cost and hospital length of stay, and improved patient satisfaction were perceived benefits of compliance to enhancing-recovery. Multidisciplinary co-ordination was considered the most important factor in the implementation and sustainability of peri-PD ERAS® pathways, while reluctance to change among health care practitioners, difficulties in data collection and audit, lack of administrative support, and recruitment of an ERAS® dedicated nurse were reported to be important barriers. CONCLUSIONS: The EPSILON survey highlighted global clinician perceptions regarding the benefits of compliance to peri-PD ERAS®, the importance of individual components, perceived facilitators and barriers, to the implementation and sustainability of these pathways.

Prognostic predictors for recurrence following curative resection in grade I/II pancreatic neuroendocrine tumours.

INTRODUCTION: Pancreatic neuroendocrine tumours (pNETs) have an excellent long-term survival after resection, but are associated with a high recurrence rate. Identification of prognostic factors affecting recurrences would enable identifying subgroup of patients at higher risk of recurrences, who may benefit from more aggressive treatment. METHODS: A retrospective analysis of prospectively maintained database of patients undergoing pancreatectomy with curative intent for grade I and II pNETs between July 2007 and June 2021 was performed. Perioperative and long-term outcomes were analysed. RESULTS: A total of 68 resected patients of pNETs were included in this analysis. Fifty-two patients (76.47%) underwent pancreaticoduodenectomy, 10 (14.7%) patients had distal pancreatectomy, and 2 (2.9%) patients underwent median pancreatectomy, while enucleation was performed in 4 patients (5.8%). The overall major morbidity (Clavien-Dindo III/IV) and mortality rates were 33.82% and 2.94%, respectively. At a median follow-up period of 48 months, 22 (32.35%) patients had disease recurrence. The 5-year overall survival and 5-year recurrence-free survival (RFS) rates were 90.2% and 60.8%, respectively. While OS was unaffected by different prognostic factors, multivariate analysis showed that lymph node involvement, Ki-67 index ≥5%, and presence of perineural invasion (PNI) were independently associated with recurrence. CONCLUSIONS: While surgical resection gives excellent overall survival in grade I/II pNETs, lymph node positivity, higher Ki-67 index, and PNI are associated with a high risk for recurrence. Patients with these characteristics should be stratified as high risk and evaluated for more intensive follow-up and aggressive treatment strategies in future prospective studies.

Development of biotissue training models for anastomotic suturing in pancreatic surgery.

BACKGROUND: Anastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be trained outside the operating room. Realistic training models are therefore needed. METHODS: Models of the pancreas, small bowel, stomach, bile duct, and a realistic training torso were developed for training of anastomoses in pancreatic surgery. Pancreas models with soft and hard textures, small and large ducts were incrementally developed and evaluated. Experienced pancreatic surgeons (n = 44) evaluated haptic realism, rigidity, fragility of tissues, and realism of suturing and knot tying. RESULTS: In the iterative development process the pancreas models showed high haptic realism and highest realism in suturing (4.6 ± 0.7 and 4.9 ± 0.5 on 1-5 Likert scale, soft pancreas). The small bowel model showed highest haptic realism (4.8 ± 0.4) and optimal wall thickness (0.1 ± 0.4 on -2 to +2 Likert scale) and suturing behavior (0.1 ± 0.4). The bile duct models showed optimal wall thickness (0.3 ± 0.8 and 0.4 ± 0.8 on -2 to +2 Likert scale) and optimal tissue fragility (0 ± 0.9 and 0.3 ± 0.7). CONCLUSION: The biotissue training models showed high haptic realism and realistic suturing behavior. They are suitable for realistic training of anastomoses in pancreatic surgery which may improve patient outcomes.

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS).

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

Pathological N3 Stage (pN3/ypN3) Gastric Cancer: Outcomes, Prognostic Factors and Pattern of Recurrences After Curative Treatment.

BACKGROUND: pN3 or ypN3 stage gastric cancers (GCs) are known to have aggressive clinical behaviour. This study aimed to investigate factors affecting survival and pattern of recurrences of N3 stage GCs, treated with curative intent. METHODS: A total of 196 GC patients, operated on at the Tata Memorial Centre from 2003 to 2017 and reported as pN3 or ypN3 status on histopathology after D2 gastrectomy were included in this retrospective analysis. RESULTS: On multivariate analysis, use of NACT (neoadjuvant chemotherapy) and LN ratio (≤ 0.5/> 0.5) emerged as significant predictors for long-term survival. Patients who received NACT but were still harbouring N3 nodes (ypN3; n = 102) had a worse prognosis than those operated on upfront (pN3; n = 94), with a median survival of 19 months versus 24 months respectively (p = 0.003). The 5-year overall survival of the entire cohort was 16.3% (95% CI 12.8-19.8%), while 5-year disease-free survival (DFS) was 14.6% (95% CI 12.6-20%). Adjuvant chemoradiotherapy, though offered in a small number of patients (n = 38) resulted in improvement in DFS. Median DFS of adjuvant CT versus adjuvant CRT was 13 months versus 23 months (p = 0.020). The commonest site of relapse was the peritoneum (49.18%) and incidence of isolated loco-regional failure was 10.7%. CONCLUSION: In GCs with N3 stage determined after radical D2 gastrectomy, LN ratio of > 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.

Organ preserving pancreatic resections offer better long-term conservation of pancreatic function at the expense of high perioperative major morbidity: a fair trade-off for benign or low malignant potential pancreatic neoplasms-a single-center experience.

BACKGROUND: Standard pancreatic resections (SPRs) might have long-term deleterious effects on pancreatic function, without added oncological advantage in low malignant potential (LMP) or benign neoplasms. This study aimed to evaluate outcomes following organ-preserving pancreatic resections (OPPARs) and SPRs. METHOD: Post hoc analysis of patients undergoing OPPAR or SPR for benign or LMP pancreatic tumors from January 2011 to January 2020 at Tata Memorial Hospital, Mumbai. RESULTS: Thirty-six and 114 patients were identified in OPPAR and SPR groups respectively. The overall morbidity (58.3% vs 43.9%, p-0.129) was comparable. Major morbidity (41.7% vs 21.9%, p-0.020), post-operative pancreatic fistula (POPF) (63.9% vs 35.1%, p-0.002), and clinically relevant POPF (41.7% vs 20.2%, p-0.010) were significantly higher with OPPAR. Post-operative endocrine insufficiency (14.9% vs 11.1%, p-0.567), exocrine insufficiency (19.3% vs 0%, p-0.004), and requirement of long-term pancreatic enzyme replacement (17.5% vs 0%, p-0.007) were higher in SPRs. Comparing left-sided and right-sided resections in the entire cohort, incidence of endocrine insufficiency was 17.1% vs 11.2% (p-0.299) and that of exocrine insufficiency was 8.6% vs 20% (p-0.048) respectively. CONCLUSION: OPPAR is associated with high post-operative major morbidity and pancreatic fistula rate but offers long-term benefit due to better preservation of pancreatic function than SPR. The incidence of exocrine insufficiency is higher in right sided as compared to left-sided pancreatic resections.