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.

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.

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.

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.

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.

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.

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.

Localized gastric mesothelioma with nodal metastasis-an exceptionally rare entity.

Localized mesothelioma is a rare disease with very few reports of presentation in visceral organs. We report a case of localized gastric mesothelioma with lymph node metastasis in a 32-year-old man without asbestos exposure. A failed attempt at resection was made before presentation at another center. He was given perioperative chemotherapy that was followed by a D2 radical subtotal gastrectomy and hyperthermic intraperitoneal chemotherapy. Histopathology showed epithelioid mesothelioma with nodal metastasis but without visceral peritoneal involvement. Cytoreductive surgery and regional chemotherapy are standard in diffuse mesothelioma. Management of localized mesothelioma is anecdotal; however aggressive surgery plays a central role with selective use of perioperative chemotherapy.

Role of prophylactic HIPEC in non-metastatic, serosa-invasive gastric cancer: a literature review.

The role of prophylactic hyperthermic intraperitoneal chemotherapy (p-HIPEC) in serosa invasive gastric cancers without gross or microscopic peritoneal disease, to reduce the rate of peritoneal relapse is an area of ongoing research. Although p-HIPEC is effective in reducing the rate of peritoneal relapse and improving disease free and overall survival with or without adjuvant chemotherapy, when added to curative surgery in locally advanced, non-metastatic gastric cancers, the available literature is at best, heterogeneous, centre-specific and skewed. Apart from that, variations in the systemic therapy used, and the presence of the associated nodal disease further complicate this picture. To evaluate the role of p-HIPEC the PubMed, Cochrane central register of clinical trials, and the American Society of Clinical Oncology (ASCO) meeting library were searched with the search terms, "gastric", "cancer", "hyperthermic", "intraperitoneal", "chemotherapy", prophylactic", "HIPEC" in various combinations, and a critical review of the available evidence was done. Although p-HIPEC is a promising therapy in the management of locally advanced gastric cancers, the current evidence is insufficient to recommend its inclusion into routine clinical practice. Future research should be directed towards identification of the appropriate patient subset and towards redefining its role with current peri-operative systemic therapies.

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.

Minimally invasive surgery for pancreatic cancer-are we there yet?-a narrative review.

OBJECTIVE: The aim of this review article is to evaluate the current status of minimally invasive pancreatic resections (MIPR) for pancreatic ductal adenocarcinoma (PDAC), in light of the present evidence. BACKGROUND: Published data, largely in the form of retrospective studies and a few prospective/randomized controlled trials have confirmed feasibility, safety, and equivalent short-term outcomes of MIPR in experienced hands. Hence, several recent evidence-based international consensus guidelines have stated MIPR to be at par with the open approach, when these surgeries are performed at high-volume centers. However, longer operative duration, high conversion rates, inferior oncological outcomes, and increased mortality reported in low-volume centers, especially during minimally invasive pancreaticoduodenectomy remains a matter of concern, questioning its broad applicability. Hence, distal pancreatic resections are adopted more widely with a minimally invasive approach as compared to pancreatic head resections. Also, MIPR for PDAC in particular, remains controversial due to lack of high quality data evaluating long-term outcomes of MIPR for PDAC alone. Considering the ongoing impact of neoadjuvant treatment on pancreatic cancer surgery and the corresponding increase in vascular resections and arterial divestment procedures, applicability of MIPR in this setting remains questionable. METHODS: Medline, PubMed, Embase, Cochrane Library, and various international evidence-based guidelines were searched for the current status of minimally invasive resections for pancreatic cancer (PDAC). CONCLUSIONS: The available evidence establishes the feasibility and safety of MIPR, however for PDAC the widespread application remains controversial owing to a dearth of literature evaluating the long-term outcomes. Apart from the outcomes, establishing the exact indications, appropriate patient selection, enhanced cost, and learning curve issues need further studies.

"Mitigation strategies for post-operative pancreatic fistula after pancreaticoduodenectomy in high-risk pancreas: an evidence-based algorithmic approach"-a narrative review.

BACKGROUND AND OBJECTIVE: Postoperative pancreatic fistula (POPF) is associated with a mortality of up to 25% apart from significant morbid sequelae related to abdominal sepsis and post pancreatectomy hemorrhage. Numerous strategies to curtail the risk of POPF and associated morbidity have been largely unsuccessful. The pancreaticoenteric anastomosis post pancreaticoduodenectomy in a high-risk pancreas represents a significant surgical and clinical challenge. In this narrative review, we present the strategies for early identification and comprehensive management of the high-risk pancreas as per the available literature and present a stepwise algorithmic approach of different fistula mitigation strategies in patients undergoing pancreaticoduodenectomy. METHODS: Medline, PubMed, Embase, Cochrane Library, and various center-specific guidelines were searched for the pancreas, pancreatic cancer, pancreatectomy, pancreatoduodenectomy, Whipple's operation, postoperative, complications, fistula, High-risk pancreas, risk assessment, different predictors, and scoring systems for the high-risk pancreas, current and emerging concepts in the development of POPF and mitigation strategies management and treatment in various combinations. KEY CONTENT AND FINDINGS: Over the years, literature has mainly addressed the technical aspects of pancreatico-enteric anastomosis; however, the impact of different technical modifications has been at the most elusive. Recent literature has focused on other aspects like remnant ischemia, locoregional inflammation, and postoperative acute pancreatitis among others, defining their evolving role in pathophysiology of POPF. Although many pre-operative risk prediction models are available; their intra-operative implications are not clear. Furthermore, the evidence available on the mitigation strategies is limited, heterogeneous, and center specific. Fistula prediction includes numerous potentiating factors in addition to the factors described in various Fistula Risk Scores. Early identification of these high-risk scenarios allows the algorithmic application of mitigation strategies. Management of the high-risk pancreas starts in the pre-operative period by early identifications of the risk factors and then continues into the intra-operative period with strategies to decrease intraoperative blood loss, precise anastomosis, and external stenting wherever feasible; goal-directed fluid therapy as well as total pancreatectomy (TP) in certain highly selected scenarios followed by early identification of complications in the postoperative period and appropriate and early management of the same. The coherent application of these mitigation strategies provides the opportunity for the best possible outcome in this complicated scenario. CONCLUSIONS: At present, the zero post-operative pancreatic fistulae seem unattainable, and time has come to study the strategies outside the operation theatre. Till preventive strategies become mainstream, a strategic personalized algorithmic approach may yield best outcomes.

Does Preoperative Serum Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Lymphocyte to Monocyte Ratio (LMR) Predict Prognosis Following Radical Surgery for Pancreatic Adenocarcinomas? Results of a Retrospective Study.

BACKGROUND: Pretherapy serum neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have been shown to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the published literature is conflicting; hence, we aimed to evaluate their role in predicting survival outcomes in operated patients of PDAC. METHODS: A retrospective analysis was performed in all operated cases of PDAC who underwent curative resection between 2011 and 2018. The pretherapy NLR, PLR, and LMR were calculated and analyzed with respect to pathological and survival outcomes RESULTS: One hundred thirty-four operated patients were included. The median overall survival for NLR of less than 2, 2.7, and 5 was 30.8, 27.2, and 27.5 months and for NLR of more than 2, 2.7, and 5 was 22.9, 21.6, and 21.5 months, respectively, and was statistically insignificant (p-value-0.32, 0.91, 0.34, respectively). Similarly, the PLR was not significant for a cutoff of 150 (p-value-0.27), and LMR was not significant for a cutoff of 2.8 (p-value-0.13) and 4.8 (p-value-0.11). On univariate analysis age, CA 19-9 levels, perineural invasion, margin positivity, lymph node positivity, and TNM stage were found to have a significant correlation with overall survival. However, on multivariate analysis, only TNM stage was found to be significant. CONCLUSION: The NLR, PLR, and LMR do not correlate with overall survival in operated patients with PDAC in this study. A combination of inflammatory markers or their dynamic testing might probably achieve prognostic significance.

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.

Radical D2 gastrectomy with adjuvant chemotherapy for stage IB/II/III distal gastric cancers in the era of perioperative chemotherapy: A propensity matched comparison.

AIM: This study aimed to assess the impact of treatment sequencing on long-term survival, in distal gastric cancers (GCs) (stage IB/II/III). METHODS: This retrospective study included patients with distal GC undergoing D2 resection. Outcomes were compared between group 1 (surgery with adjuvant chemotherapy) and group 2 (perioperative chemotherapy with surgery). 1:1 matching for baseline characteristics (age, cT, and cN stage) was performed for outcome comparison. RESULTS: At a median follow-up of 47.5 months in the included 342 patients, the 5-year overall survival (OS) was 61.1% and disease-free survival (DFS) was 50.5%. OS was comparable in the unmatched (group 1, n = 118; group 2, n = 224) (HR 0.905, 95%CI 0.64-1.33, P = 0.615) and matched groups (group 1, n = 97; group 2, n = 97) (HR 0.77, 95% CI 0.48-1.26, P = 0.3). CONCLUSION: D2 resection followed by adjuvant chemotherapy provides similar long-term outcomes as compared to perioperative chemotherapy approach for stage IB/II/III distal GCs.