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.

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.

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.

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.

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.

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.

Incidence of SARS-CoV-2 infection among asymptomatic patients undergoing preoperative COVID testing prior to cancer surgery: ASPECT study.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic, with high rate of asymptomatic infections and increased perioperative complications, prompted widespread adoption of screening methods. We analyzed the incidence of asymptomatic infection and perioperative outcomes in patients undergoing cancer surgery. We also studied the impact on subsequent cancer treatment in those with COVID-19. METHODS: All patients who underwent elective and emergency cancer surgery from April to September 2020 were included. After screening for symptoms, a preoperative test was performed from nasopharyngeal and oropharyngeal swabs before the procedure. Patients were followed up for 30 days postoperatively and complications were noted. RESULTS: 2108 asymptomatic patients were tested, of which 200 (9.5%) tested positive. Of those who tested positive, 140 (70%) underwent the planned surgery at a median of 30 days from testing positive, and 20 (14.3%) had ≥ Grade III complications. Forty (20%) patients did not receive the intended treatment; 110 patients were retested in the Postoperative period, and 41 (37.3%) tested positive and 9(22%) patients died of COVID-related complications. CONCLUSION: Routine preoperative testing for COVID-19 helps to segregate patients with asymptomatic infection. Higher complications occur in those who develop COVID-19 in postoperative period. Prolonged delay in surgery after COVID infection may influence planned treatment.

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.

Capecitabine-Temozolomide in Advanced Grade 2 and Grade 3 Neuroendocrine Neoplasms: Benefits of Chemotherapy in Neuroendocrine Neoplasms with Significant 18FDG Uptake.

INTRODUCTION: Capecitabine-temozolomide (CAPTEM) chemotherapy, alone or with concurrent peptide receptor radionuclide therapy (PRRT), has activity in advanced WHO grade 2 and grade 3 neuroendocrine neoplasms (NENs). The objective of this study was to evaluate the activity of the CAPTEM in patients with grade 2 and grade 3 NENs and identify prognostic factors. MATERIALS AND METHODS: A retrospective analysis of patients with metastatic grade 2 and grade 3 NENs, who were having baseline significant dual uptake on 68Ga-DOTATATE/18F-fluorodeoxyglucose (FDG)-PET-CT scan and treated with CAPTEM chemotherapy between January 2014 and December 2019 at Tata Memorial Hospital, was conducted. The clinical variables and survival data were collected. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS: A total of 68 patients received the CAPTEM regimen, of whom 29 patients (43%) received CAPTEM alone and 39 patients (57%) received concurrent PRRT. The primary sites were pancreas in 32 (47%) and small intestine in 12 (18%) patients. Mean Ki-67 index was 12.6% (range: 3-50). Forty-five patients (65%) were treatment naïve. There were no significant differences in baseline clinical variables between patients treated with CAPTEM alone or with CAPTEM-PRRT. Both regimens were well tolerated. With a median follow-up of 22.1 months, the median PFS for the entire cohort was 27.5 months. There was no statistical difference in the median PFS between patients receiving CAPTEM alone or CAPTEM-PRRT (33.7 vs. 22 months; p = 0.199). A Ki-67 index of >5% predicted for inferior PFS on multivariate analysis (24 versus 73.8 months; p = 0.04; hazard ratio -3.77; 95% confidence interval: 1.07-13.26). CONCLUSION: CAPTEM, alone or concurrent with PRRT, has a significant activity in grade 2 and grade 3 NENs with dual SSTR and 18FDG expression. A Ki-67 index >5% predicts strongly for inferior outcomes and should be further explored as a prognostic cutoff in grade 2 NENs. Early initiation of CAPTEM should be considered in this group of tumors with significant baseline 18FDG expression.

Preoperative Albumin-Globulin Ratio and Its Association with Perioperative and Long-Term Outcomes in Patients Undergoing Pancreatoduodenectomy.

BACKGROUND: Systemic inflammatory response is involved in natural progression of cancers by different pathways. Albumin-globulin ratio (AGR) has been reported to have impact on prognosis in various solid tumors. OBJECTIVE: To study the significance of AGR on perioperative and long-term outcomes in patients undergoing PD. METHODS: This is a post hoc analysis of the pancreatic surgery database from January 2012 to March 2017. Cutoff value for AGR was calculated by using the receiver operating curve, and the study cohort was divided into group I (AGR ≥1) and group II (AGR <1). Two groups were compared for perioperative and long-term survival outcomes. RESULTS: Two groups were comparable with respect to clinicodemographic variables. Groups I and II had similar perioperative outcomes (p > 0.05) like median hospital stay (14 vs. 15 days), clinically relevant postoperative pancreatic fistula (16.6 vs. 15.7%), hemorrhage (3.1 vs. 2.6%), bile leak (1.4 vs. 0.65%), overall morbidity (30.1 vs. 28.9%), and postoperative mortality (2.7 vs. 3.9%). With a median follow-up of 3 years, median survival, overall survival, and disease-free survival were similar in both groups. CONCLUSION: AGR at the cutoff value of ≥1 was not associated with adverse perioperative and long-term oncological outcomes after PD.

Curative resection for adenocarcinoma of the gastro-esophageal junction following neo-adjuvant chemotherapy-thoraco-abdominal vs. trans-abdominal approach.

PURPOSE: This study compares the short- and long-term outcomes between the left thoraco-abdominal and trans-abdominal approaches for radical resection of adenocarcinoma of the gastro-esophageal junction (GEJ) (Siewert types II and III) following neo-adjuvant chemotherapy. METHODS: A retrospective analysis of a prospectively maintained database of patients from May 2008 to December 2016. Demographic variables, perioperative outcomes, and survival were compared between two approaches. RESULTS: Of the 792 patients, who underwent total/proximal gastrectomy during the specified time interval, 162 had Siewert's type II/III lesions, of which 147 received neoadjuvant chemotherapy and were included in the study. Ninety-two and 55 patients underwent definitive surgery through trans-abdominal and left thoraco-abdominal approach respectively. On baseline endoscopy, 81.8% of patients in the left thoraco-abdominal group had lower esophageal mucosal infiltration as compared to 41.3% in the trans-abdominal group (p < 0.001). Both groups were comparable in terms of duration of surgery, blood loss, complications, severity of complications (Clavien-Dindo grade), duration of hospital stay, R0 resection rate, length of proximal margin, and lymph node yield. At a median follow-up of 24 months, there was no difference in recurrence rate and survival between the groups. CONCLUSION: Both left thoraco-abdominal and trans-abdominal are comparable surgical approaches for tumors involving the GEJ in terms of morbidity, perioperative, and long-term oncological outcomes. In patients with lower esophageal involvement, the left thoraco-abdominal approach is a feasible alternative with no added overall morbidity or mortality and can be preferred especially in cases, where a safe proximal margin and anastomosis is deemed technically challenging.

Peri-operative, long-term, and quality of life outcomes after pancreaticoduodenectomy in the elderly: greater justification for periampullary cancer compared to pancreatic head cancer.

BACKGROUND: Pancreaticoduodenectomy (PD) is more challenging in the elderly. METHODS: Data of patients undergoing PD above 70 years of age was analysed to study short and long-term outcomes along with the quality of life parameters (QOL). RESULTS: Out of 1271 PDs performed, 94 (7%) patients were 70 years or more. American Society of Anaesthesiology (ASA) scores were higher in comparison to patients below 70 years (ASA 1;20% vs. 54% and ASA 2&3;80% vs. 46%, p < 0.001). The postoperative 90-day mortality rate of 5.3% and morbidity (Clavein Grade III and IV of 27%) was higher but non-significant compared to 3.9% (p = 0.50) and 20% (p = 0.11) in patients less than 70 years. The median survival of 40 months was significantly better for periampullary carcinoma when compared to 15 months in pancreatic ductal adenocarcinoma (PDAC) (p < 0.0001). Patients, less than 70 years had significantly better 3-year survival; 64% vs 43% with periampullary etiology (p < 0.01) and 29% vs 0% with PDAC (p < 0.0001). QLQ-PAN 26 questionnaire responses were suggestive of good long term QOL in these patients. CONCLUSION: Although PD is safe and feasible in the elderly population with good long-term QOL, postoperative morbidity and mortality can be slightly higher and long-term survival significantly lower.