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.

Evolution and improved outcomes in the era of multimodality treatment for extended pancreatectomy.

BACKGROUND: The evolution and outcomes of extended pancreatectomies at a single institute over 15 years are presented in this study. METHODS: A retrospective analysis of the institutional database was performed from 2015 to 2022 (period B). Patients undergoing extended pancreatic resections, as defined by the International Study Group for Pancreatic Surgery, were included. Perioperative and survival outcomes were compared with data from 2007-2015 (period A). Regression analyses were used to identify factors affecting postoperative and long-term survival outcomes. RESULTS: A total of 197 (16.1%) patients underwent an extended resection in period B compared to 63 (9.2%) in period A. Higher proportions of borderline resectable (5 (18.5%) versus 51 (47.7%), P = 0.011) and locally advanced tumours (1 (3.7%) versus 24 (22.4%), P < 0.001) were resected in period B with more frequent use of neoadjuvant therapy (6 (22.2%) versus 79 (73.8%), P < 0.001). Perioperative mortality (4 (6.0%) versus 12 (6.1%), P = 0.81) and morbidity (23 (36.5%) versus 83 (42.1%), P = 0.57) rates were comparable. The overall survival for patients with pancreatic adenocarcinoma was similar in both periods (17.5 (95% c.i. 6.77 to 28.22) versus 18.3 (95% c.i. 7.91 to 28.68) months, P = 0.958). Resectable, node-positive tumours had a longer disease-free survival (DFS) in period B (5.81 (95% c.i. 1.73 to 9.89) versus 14.03 (95% c.i. 5.7 to 22.35) months, P = 0.018). CONCLUSION: Increasingly complex pancreatic resections were performed with consistent perioperative outcomes and improved DFS compared to the earlier period. A graduated approach to escalating surgical complexity, multimodality treatment, and judicious patient selection enables the resection of advanced pancreatic tumours.

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.

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.

Factors Predicting Prognosis in Metastatic Grade 1 Gastro-entero-pancreatic Neuroendocrine Tumors.

INTRODUCTION: The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) has steadily increased. These tumors are considered relatively indolent even when metastatic. What determines survival outcomes in such situations is understudied. MATERIALS AND METHODS: Retrospective analysis of a prospectively maintained NET clinic database, to include patients of metastatic grade 1 GEP-NET, from January 2018 to December 2021, to assess factors affecting progression-free survival (PFS). RESULTS: Of the 589 patients of GEP-NET treated during the study period, 100 were grade 1, with radiological evidence of distant metastasis. The median age was 50 years, with 67% being men. Of these, 15 patients were observed, while 85 patients received treatment in the form of surgery (n = 32), peptide receptor radionuclide therapy (n = 50), octreotide LAR (n = 22), and/or chemotherapy (n = 4), either as a single modality or multi-modality treatment. The median (PFS) was 54.5 months. The estimated 3-year PFS and 3-year overall survival rates were 72.3% (SE 0.048) and 93.4% (SE 0.026), respectively. On Cox regression, a high liver tumor burden was the only independent predictor of PFS (OR 3.443, p = 0.014). The 5-year OS of patients with concomitant extra-hepatic disease was significantly lower than that of patients with liver-limited disease (70.7% vs. 100%, p = 0.017). CONCLUSION: A higher burden of liver disease is associated with shorter PFS in patients with metastatic grade I GEP-NETs. The OS is significantly lower in patients with associated extrahepatic involvement. These parameters may justify a more aggressive treatment approach in metastatic grade 1 GEP-NETs.

Neuroendocrine Tumours of Extrahepatic Biliary Tract: Report of Four Cases with Literature Review.

Neuroendocrine tumours (NETs) originating from extrahepatic bile duct are an extremely rare entity. They are typically slow growing tumours with malignant potential. Commonly presenting as obstructive jaundice, preoperative clinico-radiologic differentiation between extrahepatic biliary tract neuroendocrine tumours and cholangiocarcinoma is difficult and the final diagnosis is usually established after surgical histopathology and immunohistochemistry examination. R0 resection offers the only curative option with good long-term outcomes for well-differentiated NETs (grade1, grade2, and grade3) while the aggressive poorly differentiated neuroendocrine carcinoma (NEC) needs multimodality approach. We present our experience of management of four cases including three cases of grade II NET and one case of NEC undergoing surgical resection at a single centre with a short review of available literature.

Impact of pCR after neoadjuvant chemotherapy and radical D2 dissection in locally advanced gastric cancers: Analysis of 1001 cases.

BACKGROUND: Advances in perioperative chemotherapy have improved outcomes in patients with gastric cancers (GC). This strategy leads to tumour downstaging and may result in a pathologic complete response (pCR). The study aimed to evaluate the predictors of pCR and determine the impact of pCR on long-term survival. METHODS: At the Department of Gastrointestinal and HPB Oncology at the Tata Memorial Centre, Mumbai, 1001 consecutive patients with locally advanced GCs undergoing radical resection following neoadjuvant chemotherapy from January 2005 to June 2022 were included. RESULTS: At a median follow-up of 61 months, the median OS was 53 months with a 5-year OS of 46.8 %. Ninety-five patients (9.49 %) realized pCR. Non-signet and well-differentiated histology were associated with pCR. pCR was significantly associated with improved OS, 5-year OS 79.2 % vs 43.2 % (HR 0.30, p < 0.001). On multivariable analysis, the realization of pCR and completion of adjuvant chemotherapy had superior OS. Whereas, signet-ring histology, linitis-like tumours, and high lymph node ratio had adverse outcomes. CONCLUSION: Tumour grade and signet-ring histology predict achievement of pCR in locally advanced GCs after neoadjuvant chemotherapy. Patients with pCR have significantly improved survival. Future neoadjuvant strategies should focus on enhancing pCR rates to improve overall outcomes.

Primary Pancreatic GIST - A-Single Centre Case Series and Systematic Review of Literature.

PURPOSE: GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs. We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature. METHODS: A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. After literature search for all studies published before February 2023, 51 articles including 57 patients were identified. Their clinicopathological data and survival analysis were assessed. RESULTS: The median age of patients treated at our centre was 53 years with a female predominance. The most common epicentre was pancreatic head with abdominal pain as the most common presenting symptom. All 57 patients documented in literature belonged to a similar age group with similar gender predilection. The factors impacting DFS were histologic type, mitotic index, NIH risk category and adjuvant therapy. The median DFS was 74 months with a 5-year DFS being 71.9%, while the 5-year OS was 90.4%. CONCLUSION: Pancreatic GIST is a rare entity. Due to limited evidence and evolving literature, results cannot be generalised to a larger population. Larger case series with longer follow-up data are required to further understand the disease biology and long-term outcomes of pancreatic GIST.

Gastric salvage after venous congestion during major pancreatic resections: A series of three cases.

Pancreatic resections, depending on the location of the tumor, usually require division of the vasculature of either the distal or proximal part of the stomach. In certain situations, such as total pancreatectomy and/or with splenic vein occlusion, viability of the stomach may be threatened due to inadequate venous drainage. We discuss three cases of complex pancreatic surgeries performed for carcinoma of the pancreas at a tertiary care center in India, wherein the stomach was salvaged by reimplanting the veins in two patients and preserving the only draining collateral in one case after the gastric venous drainage was compromised. The perioperative and postoperative course in these patients and the complications were analyzed. None of these 3 patients developed any complication related to gastric venous congestion, and additional gastrectomy was avoided in all these patients. Re-establishment of the Gastric venous outflow after extensive pancreatic resections helps to avoid additional gastric resection secondary to venous congestive changes.

Hepatocellular carcinoma (HCC) masquerading as hilar cholangiocarcinoma: An unusual presentation of jaundice.

Jaundice usually occurs in the late stages of hepatocellular carcinoma (HCC). Obstructive jaundice is rarely seen as an initial presentation of HCC, as opposed to cholangiocarcinoma. Various causes of obstructive jaundice in these cases also known as "Icteric HCC" have been described such as tumour thrombi, compression, infiltration or tumours arising from native hepatocytes in the bile duct. We present a case of 74-year-old gentleman with "Icteric HCC" that clinically and radiologically mimicked cholangiocarcinoma for which the patient underwent left hepatectomy with Roux-en-Y hepaticojejunostomy. Histopathology revealed dilated large duct with polygonal sheets of cells of hepatoid morphology which stained diffusely positive for both glypican 3 and Hep-par 1. The epicentre was in the left hepatic duct with no discernible liver lesion and the tumour probably originated from the ectopic hepatocytes within the biliary duct The patient was disease free at 1.5 years of follow up. In conclusion, HCC should be a differential for obstructive jaundice. Patients with such "Icteric HCC" benefit from surgical resection with favourable outcomes. The prognosis in such patients is better than in patients of HCC with jaundice due to hepatic insufficiency.

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.

Multimodality liver directed treatment for colorectal liver metastasis: Array of complementary options can improve outcomes - A single centre experience from India.

AIM: Complimentary use of Liver directed therapies (LDTs) with systemic chemotherapy has improved oncologic outcomes in colorectal liver metastasis (CRLM). We analysed institutional results of multimodality management. Methods: Retrospective analysis of prospectively maintained database of CRLM patients managed with LDT including surgical resection, Ablation, Transarterial chemoembolization (TACE) or Transarterial radioembolization (TARE) between November 2011 to March 2020. Management plan was decided in multidisciplinary meeting. Resectable tumours underwent surgical resection or ablation or both in some cases. Borderline resectable or unresectable disease was treated with down staging chemotherapy or TACE/TARE followed by resection or ablation. All patients received adjuvant chemotherapy. Factors influencing survival were analysed. Results: Out of total 375 patients, surgery alone was done in 191 (50.93%) patients while surgery with other LDT in 26 patients (6.93%). Ablation alone was done in 100 (26.66%) whereas TACE/TARE were done as standalone treatment in 21 (5.6%) and 7 (1.86%) patients respectively. TACE + ablation was done in 28 (7.46%) and TARE + ablation was done in 2(0.53%) patients.5-year Overall Survival(OS) was 49.8% while Event free survival(EFS) was 21.4%. The median OS and EFS for surgical group was significantly better than non-surgical group (78 V/s 39 months; p<0.05 and 20 V/s 15 months p <0.005). The resectable (78 months) group had better median OS as compared to borderline resectable and Unresectable group (39 months and 29 months). Male gender, resectable disease and surgical intervention were associated with improved OS. Conclusion: Although surgery remains the mainstay of treatment, complementary use of non-surgical LDT with systemic therapy offers possibility of good outcomes in advanced liver limited disease. Our experience highlights the impact of multidisciplinary care in optimizing CRLM treatment.

Oxaliplatin-Induced Sinusoidal Obstruction Syndrome Masquerading as Colorectal Liver Metastasis: A Case Report.

INTRODUCTION: Oxaliplatin-based chemotherapy is commonly used in adjuvant treatment of colon cancer as well as in neoadjuvant setting in patients with liver metastases. However oxaliplatin can cause damage to non-tumor bearing liver which presents as sinusoidal obstructive syndrome (SOS). These changes are difficult to differentiate from metastasis clinic-radiologically and manifests as sinusoidal dilatation, peliosis and nodular regenerative hyperplasia. CASE: The present study reports the case of a patient with oxaliplatin-induced SOS which mimicked colo-rectal liver metastasis on follow up imaging studies after receiving neoadjuvant oxaliplatin based chemotherapy. After multidisciplinary discussion, patient was planned for simultaneous resection of rectal primary and right hepatectomy for metastasis. Final histopathology revealed no tumour in liver but the liver lesions seen radiologically were actually changes of oxaliplatin induced focal SOS and mimicked metastatic nodules. CONCLUSION: In patients with colo-rectal cancer having received oxaliplatin-based chemotherapy, SOS may be considered as one of the causes of newly developed liver lesions, and should be subjected to additional radio-pathologic evaluation to prevent overtreatment and avoiding potentially morbid surgeries.

SMA syndrome: management perspective with laparoscopic duodenojejunostomy and long-term results.

BACKGROUND: Superior mesentery artery syndrome (SMAS) is a rare vasculo-anatomic occlusive pathologic entity for which a period of conservative medical management is advocated with surgery reserved for nonresponsive cases. We present our management plan that entails a single admission approach and complete rendering of medical and surgical treatment to the patient on a background of the socioeconomic and cultural trends prevalent in this geographic region. METHODS: A retrospective analysis of 22 cases of SMAS admitted in our health care system who underwent a period of preoperative conditioning followed by laparoscopic duodenojejunostomy from September 2009 to June 2019 was performed. Patients were followed up at regular intervals. RESULTS: The mean follow-up of the cohort was 41.2 months (2-108 months). The median length of stay was 6 days. The mean postoperative stay was 4.13 days. A subgroup of six patients who had severe physiological depletion required a period of preoperative optimisation. Five of the 22 (22.7%) patients suffered from postoperative complications in the form of delayed return of bowel functions. None of the patients had complications more than Clavien-Dindo grade 2 with no mortality. Long-term data are available for 19 patients (86.3%) which showed no symptom recurrence. CONCLUSION: Management of SMAS that entails an antecedent medical therapy followed by surgery can be accomplished in a single admission with good to excellent results in the intermediate and long-term follow-up. Physiologically depleted patients do require a period of intensive preconditioning but on long-term follow-up, they have excellent results.