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.

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.

1657 Resected Gastric Adenocarcinomas at a Single Institution: Outcomes and Trends over 17 Years.

BACKGROUND: Outside of clinical trials, real-world data of advanced gastric cancers (AGCs) managed with perioperative or adjuvant chemotherapy with a backbone of D2 lymphadenectomy is limited. PATIENTS AND METHODS: Curative resections for gastric adenocarcinoma between January 2003 and January 2020 at the Tata Memorial Centre were analyzed, comparing three time periods marking major increments in annual gastric resections (GRs). RESULTS: 1657 radical gastric resections were performed with a morbidity and mortality rate of 34.9% and 1.4%, respectively. Over three consecutive periods, the number of annual GRs increased from 56/year to 97/year to 156/year (P < 0.001) with a significant escalation in surgical magnitude and complexity. Improvement in surgical quality indicators (median lymph node yield from 15 to 25, P < 0.001 and margin negativity from 8.2 to 5.5%, P = 0.002) was observed with no corresponding increase in severe complications (6.9%) or mortality (1.4%). The proportion of distal and signet ring cancers was found to decrease over time, with an increase in proximal cancers and younger age at presentation. Overall, 90% of GRs were for AGCs with a median overall survival (OS) of 4.4 years (± 6 months), and 5-year OS rate of 47.6% (± 1.9%). CONCLUSIONS: Change in pattern of tumor characteristics was observed. Aggressive treatment options for AGC were employed progressively with excellent survival. With increase in volumes, improvements in surgical quality indicators, and a relative improvement in postoperative mortality was observed. These results provide a roadmap for developing dedicated gastric cancer centers.

Outcomes of incidental versus non-incidental T2 gallbladder cancer: A single-institute experience of 425 cases.

BACKGROUND: Up to 60% of incidentally detected gallbladder cancers (GBCs) have a primary stage of pathologic T2 stage (pT2), defined by invasion of the peri-adventitial tissue by the tumour, a plane breached during a simple cholecystectomy. This study assesses the impact of incidental detection of pT2 GBCs on survival outcomes. METHODS: Retrospective analysis of pT2 GBCs undergoing a curative resection was performed. Patients who received neoadjuvant chemotherapy before an upfront radical resection were excluded. Outcomes of patients undergoing upfront surgery (uGBC) and incidentally detected tumours (iGBC) were compared. RESULTS: From a total of 1356 patients, 425 patients with pT2 GBCs were included. Of these, 118 (27.7%) and 307 (72.23%) patients were in the uGBC and iGBC groups, respectively. Patients with iGBC had significantly higher locoregional, (62 [19.8%] vs. 11 [9.3%]; p = 0.009), liver, (36 [11.5%] vs. 4 [3.4%]; p = 0.01), and abdominal wall recurrences (23 [7.4%] vs. 1 [0.8%]; p = 0.009). Five-year disease free survival rates were 68.7% and 49.2% in the uGBC and iGBC groups, respectively (p = 0.013). Five-year overall survival rates were 71.7% and 64.6% in the uGBC and iGBC groups, respectively (p = 0.317). CONCLUSIONS: Incidentally detected pT2 GBCs have significantly poorer outcomes compared to similarly staged patients undergoing an upfront radical cholecystectomy.

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.

International Hepato-Pancreato-Billiary Association (IHPBA) registry study on COVID-19 infections in HPB surgery patients.

BACKGROUND: In response to the pandemic, the International Hepato-Pancreato-Biliary Association (IHPBA) developed the IHPBA-COVID Registry to capture data on HPB surgery outcomes in COVID-positive patients prior to mass vaccination programs. The aim was to provide a tool to help members gain a better understanding of the impact of COVID-19 on patient outcomes following HPB surgery worldwide. METHODS: An online registry updated in real time was disseminated to all IHPBA, E-AHPBA, A-HPBA and A-PHPBA members to assess the effects of the pandemic on the outcomes of HPB procedures, perioperative COVID-19 management and other aspects of surgical care. RESULTS: One hundred twenty-five patients from 35 centres in 18 countries were included. Seventy-three (58%) patients were diagnosed with COVID-19 preoperatively. Operative mortality after pancreaticoduodenectomy and major hepatectomy was 28% and 15%, respectively, and 2.5% after cholecystectomy. Postoperative complication rates of pancreatic procedures, hepatic interventions and biliary interventions were respectively 80%, 50% and 37%. Respiratory complication rates were 37%, 31% and 10%, respectively. CONCLUSION: This study reveals a high risk of mortality and complication after HPB surgeries in patient infected with COVID-19. The more extensive the procedure, the higher the risk. Nonetheless, an increased risk was observed across all types of interventions, suggesting that elective HPB surgery should be avoided in COVID positive patients, delaying it at distance from the viral infection.

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.

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.

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.

Utility and limitations of intraoperative frozen section diagnosis to determine optimal surgical strategy in suspected gallbladder malignancy.

BACKGROUND: Preoperative diagnosis of gallbladder cancer (GBC) remains a challenge. Unwarranted extensive surgery for benign disease and undertreatment for GBC pose challenges. We aimed to analyze the utility, diagnostic accuracy, and limitations of intraoperative frozen section (FS), for primary diagnosis of suspected gallbladder malignancy. METHODS: Patients with suspected GBC underwent a cystic-plate cholecystectomy and FS for primary diagnosis. The procedure was considered adequate if FS suggested a benign pathology. A radical cholecystectomy was performed if FS favoured GBC, or in patients with high intra-operative suspicion of malignancy. All FS records were compared with final histopathology. RESULTS: FS guided the surgical strategy in 491 of 575 resections (85.4%). FS had a sensitivity of 88.3%, specificity of 99.6%, a positive predictive value of 99.4% and a negative predictive value of 92.7%. The diagnostic accuracy of FS was 95.1%. With routine use of intraoperative FS, only 10 out of 491 patients (2%) required a revised surgical strategy. CONCLUSIONS: For radiologically suspected GBC it is prudent to confirm the histological diagnosis by use of intraoperative FS before undertaking radical resections. This study emphasizes the safety and accuracy of FS as an adjunct for directing optimal surgical strategy in suspected GBC.

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.

Surgical Site Infections in patients undergoing major oncological surgery during the COVID-19 paNdemic (SCION): A propensity-matched analysis.

BACKGROUND AND OBJECTIVES: There are reports of outcomes of elective major cancer surgery during the COVID-19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. METHODS: Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre-COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. RESULTS: There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID-19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61-0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45-4.17; p < 0.001), duration of surgery >4 h (OR = 2.17; 95%CI = 1.55-3.05; p < 0.001) and clean contaminated wounds (OR = 2.50; 95% CI = 1.09-2.18; p = 0.012) were significantly associated with SSI. CONCLUSION: Increased compliance with hand hygiene, near-universal mask usage, and social distancing during the COVID-19 pandemic possibly led to a 23% decreased odds of SSI in major oncologic resections. Extending these low-cost interventions in the post-pandemic era can decrease morbidity associated with SSI in cancer surgery.

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.

Impact of Covid-19 on gastrointestinal cancer surgery: A National Survey.

PURPOSE: To understand the actual impact of the Covid-19 pandemic and frame the future strategies, we conducted a pan India survey to study the impact on the surgical management of gastrointestinal cancers. METHODS: A national multicentre survey in the form of a questionnaire from 16 tertiary care gastrointestinal oncology centres across India was conducted from January 2019 to June 2021 that was divided into a 15-month pre-Covid era and a similar period of active Covid pandemic era. RESULTS: There was significant disruption of services; 13 (81%) centres worked as dedicated Covid care centres and 43% reported suspension of essential care for more than 6 months. In active Covid phase, there was a 14.5% decrease in registrations and proportion of decrease was highest in the centres from South zone (22%). There was decrease in resections across all organ systems; maximum reduction was noted in hepatic resections (33%) followed by oesophageal and gastric resections (31 and 25% respectively). There was minimal decrease in colorectal resections (5%). A total of 584 (7.1%) patients had either active Covid-19 infection or developed infection in the post-operative period or had recovered from Covid-19 infection. Only 3 (18%) centres reported higher morbidity, while the rest of the centres reported similar or lower morbidity rates when compared to pre-Covid phase; however, 6 (37%) centres reported slightly higher mortality in the active Covid phase. CONCLUSION: Covid-19 pandemic resulted in significant reduction in new cancer registrations and elective gastrointestinal cancer surgeries. Perioperative morbidity remained similar despite 7.1% perioperative Covid 19 exposure.

Long-term outcome of "Sandwich" chemo-PRRT: a novel treatment strategy for metastatic neuroendocrine tumors with both FDG- and SSTR-avid aggressive disease.

OBJECTIVE: The primary aims of this study were to evaluate the long-term outcome of a "sandwich chemo-PRRT (SCPRRT)" regimen with regard to therapeutic response rate, progression-free survival (PFS), and overall survival (OS) rates in metastatic neuroendocrine tumors (NETs) with both somatostatin receptor (SSTR)- and fluorodeoxyglucose (FDG)-avid aggressive disease. Additionally, health-related quality of life (HRQoL) scales, clinical toxicity, and association of PFS and disease control rate (DCR) with various variables were also evaluated. MATERIALS AND METHODS: A total of 38 patients of the aforementioned cohort, who received SCPRRT (at least 2 cycles of each PRRT and chemotherapy) at our institute between January 2012 and December 2018, were included and analyzed in this retrospective study. Between two cycles of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT), two cycles of oral capecitabine and temozolomide (CAPTEM) were sandwiched. Therapeutic responses following SCPRRT were assessed by using pre-defined criteria. PFS and OS after first SCPRRT were determined. Eastern Cooperative Oncology Group (ECOG) and Karnofsky score were used for evaluation of HRQoL before and after SCPPRT in all 38 patients. Any adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) of the National Cancer Institute. Associations of PFS and DCR with various variables were evaluated. RESULTS: Response (complete response and partial response) to SCPRRT was seen in 28 patients (73%), 15 patients (39%), and 16 patients (42%) on symptomatic, biochemical, and molecular imaging response evaluation criteria respectively. A total of 17 patients (45%) had anatomical imaging response with DCR of 84% based upon the RECIST 1.1 criteria. Pre-therapy mean ECOG and KPS was 2.0 and 68, which changed to 1.0 and 75 respectively following SCPRRT. Long-term follow-up data was available and ranged from 12 to 65 months after the first SCPRRT. Median PFS and OS were not reached at a median follow-up of 36 months. An estimated PFS rate of 72.5% and OS rate of 80.4% was found at 36 months. Longer PFS was dependent upon high SSTR uptake and number of CAPTEM cycle (≥ 7 cycles), absence of skeletal metastasis, and no previous external beam radiotherapy (EBRT) exposure with significant P value. Higher DCR was dependent upon absence of skeletal metastasis with significant P value. SCPRRT was tolerated well with none developing grade 4 hematotoxicity and nephrotoxicity of any grade. Anemia (grade 3), thrombocytopenia (grade 3), and leukopenia (grade 3) were noticed in 1 patient (2.5%), 2 patients (5%), and 1 patient (2.5%) respectively in this study. CONCLUSION: Thus, favorable response rates with effective control of symptoms and longer PFS and OS without high-grade or life-threatening toxicities were important observations in the present study following SCPRRT in NET patients with aggressive, both FDG- and SSTR-avid, metastatic progressive disease. The study results indicate the potential role of "sandwich chemo-PRRT" in future therapeutic algorithms of aggressive, both SSTR- and FDG-positive subset of neuroendocrine tumors.