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.

Neuroendocrine neoplasms of the gallbladder: A single institute analysis of outcomes and prognostic factors.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are classified as neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine and nonneuroendocrine neoplasms (MiNENs) according to World Health Organization classification. We present our experience of NENs of the gallbladder (GB) from a high-volume cancer hospital. MATERIALS AND METHODS: The present study is a retrospective analysis of all patients with GB NENs who presented between January 2015 and June 2023. The patient details and treatment received with follow-up were noted. The primary endpoint was overall survival (OS). RESULTS: A total of 147 patients were included in the study. The median age was 52 (27-81) years. There was a female predominance (70.7%). NEC was the most common subtype (84.4%) followed by MiNEN (12.9%) and NET (2.7%). The most common stage at presentation was metastatic (70.7%) followed by locally advanced (21.8%), and early disease (7.5%). The median follow-up was 9.92 (1.77-76.06) months. Median OS was 6.14 (3.93-8.35) months. Median OS in patients who received multimodality treatment was 20.20 (17.99-22.41) months versus 4.00 (2.91-5.10) months in those who did not receive it. CONCLUSION: GB NENs are rare, but aggressive tumors with NEC being the most common type. Multimodality treatment yields favorable outcomes. However, the development of better systemic therapy is needed to help improve survival further.

Comparison of age-stratified survival outcomes of gallbladder cancers in an Indian population.

BACKGROUND: Gallbladder cancers (GBCs) occur a decade earlier in India in comparison to the global occurrence, limiting the applicability of existing literature on age adjusted outcomes. METHODS: Patients who underwent surgery between 01.01.2010 and 31.12.2020 for GBC were analyzed. Patients were divided into three age groups: group 1(≤40 years), group 2(41-60 years), group 3(>60 years) and their outcomes were compared. RESULTS: Total of 6190 patients were treated for suspected or diagnosed GBC with a median age of 57 years. Curative resection was performed in 749 (67.9%) patients, of whom 114 (16.2%), 471 (62.9%), and 164 (21.9%) patients were in groups 1, 2, and 3, respectively. 5-year disease-free survival (DFS) [46.8% vs. 58.5%, p = 0.031] and overall survival (OS)[53.5% vs. 66.6%, p = 0.05] of group 3 were significantly lower than group 1. Patient age (HR 1.021), AJCC stage (HR 6.413), pathologic residual disease in the gallbladder fossa (HR 2.44), and extranodal tumor deposits (HR 1.762) were identified as independent predictors of poor OS. CONCLUSIONS: Gallbladder cancers in the Indian population show poorer outcomes with advancing age. Higher proportion of males in the elderly group with a more advanced stage at presentation are plausible reasons for poorer outcomes.

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.

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.

Modified FOLFIRINOX compared to Gemcitabine & nab-Paclitaxel in advanced pancreatic ductal adenocarcinoma - results of a match-pair analysis.

Background & objectives: FOLFIRINOX and gemcitabine plus nab-paclitaxel (GN) are the most commonly used regimens in advanced pancreatic ductal adenocarcinomas (PDACs). As there is limited data on comparison of these two regimens, the present study was aimed to compare survivals and tolerance for both regimens through a match-pair analysis. Methods: The data of 350 patients with metastatic and locally advanced PDAC, treated between January 2013 and December 2019, were retrieved. A 1:1 matching, using age and performance status, without replacement was performed by using nearest neighbour matching method. Results: A total of 260 patients (130 modified FOLFIRINOX and 130 GN) were matched. The median overall survival (OS) was 12.98 months [95% confidence interval (CI) 7.257-8.776 months] in modifications of FOLFIRINOX (mFOLFIRINOX) cohort and 12.06 months (95% CI 6.690-8.88 months) in GN group (P=0.080). The incidence of grade 3 and 4 infections, diarrhoea, oral mucositis, and fatigue was higher with mFOLFIRINOX. Patients who received second line therapy had improved OS as compared to those who did not (14.06 vs. 9.07 months, P<0.001). Interpretation & conclusions: GN and mFOLFIRINOX appear to have similar survival outcomes in an unselected match paired patient population with advanced PDAC. A markedly increased incidence of non-myelosuppressive grade 3 and grade 4 side-effects and lack of survival improvements suggest a need for nuanced use of the mFOLFIRINOX regimen. Administration of second-line chemotherapy improves OS in patients with advanced PDAC.

Phase I Study Evaluating Dose De-escalation of Sorafenib with Metformin and Atorvastatin in Hepatocellular Carcinoma (SMASH).

BACKGROUND: This phase I dose de-escalation study aimed to assess the tolerability, safety, pharmacokinetics (PK), and efficacy of sequentially decreasing doses of sorafenib in combination (SAM) with atorvastatin (A, 10 mg) and metformin (M, 500 mg BD) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients were enrolled in 1 of 4 sequential cohorts (10 patients each) of sorafenib doses (800 mg, 600 mg. 400 mg, and 200 mg) with A and M. Progression from one level to the next was based on prespecified minimum disease stabilization (at least 4/10) and upper limits of specific grade 3-5 treatment-related adverse events (TRAE). RESULTS: The study was able to progress through all 4 dosing levels of sorafenib by the accrual of 40 patients. Thirty-eight (95%) patients had either main portal vein thrombosis or/and extra-hepatic disease. The most common grade 3-5 TRAEs were hand-foot-syndrome (grade 2 and grade 3) in 3 (8%) and transaminitis in 2 (5%) patients, respectively. The plasma concentrations of sorafenib peaked at 600 mg dose, and the concentration threshold of 2400 ng/mL was associated with higher odds of achieving time to exposure (TTE) concentrations >75% centile (odds ratio [OR] = 10.0 [1.67-44.93]; P = .01). The median overall survival for patients without early hepatic decompensation (n = 31) was 8.9 months (95% confidence interval [CI]: 3.2-14.5 months). CONCLUSION: The SAM combination in HCC patients with predominantly unfavorable baseline disease characteristics showed a marked reduction in sorafenib-related side effects. Studies using sorafenib 600 mg per day in this combination along with sorafenib drug level monitoring can be evaluated in further trials.(Trial ID: CTRI/2018/07/014865).

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.

Downstaging in Advanced Rectal Cancers: A Propensity-Matched Comparison Between Short-Course Radiotherapy Followed by Chemotherapy and Long-Course Chemoradiotherapy.

BACKGROUND: Short-course radiotherapy followed by chemotherapy has not been widely evaluated as an alternative to traditional long-course chemoradiotherapy in locally advanced rectal cancer. OBJECTIVE: This study compared the oncological and short-term outcomes between short-course radiotherapy + chemotherapy and long-course chemoradiotherapy in locally advanced rectal cancer. DESIGN: This is a retrospective propensity-matched study. SETTINGS: The study was conducted in a colorectal department at a tertiary care oncology center in India. PATIENTS: There were 173 patients. Group A had 47 patients and group B had 126 patients. A 1:2.7 matching was done for age, sex, distance of tumor from the anal verge, sphincter preservation surgeries, MRI-based pretreatment T stage, and circumferential resection margin. INTERVENTIONS: The interventions performed were short-course radiotherapy + chemotherapy (group A) and long-course chemoradiotherapy (group B) in locally advanced rectal cancer. MAIN OUTCOME MEASURES: The primary measures were pathological circumferential resection margin positivity, downstaging, tumor regression grade, and postoperative complications. RESULTS: Of the patients, 52% had a positive circumferential resection margin on MRI, 57% had low rectal tumors, and 20% had T4 tumors. Distribution of rectal surgeries was similar between the 2 groups. pT downstaging and tumor regression scores were significantly better in group B ( p = 0.028 and 0.026). Pathological circumferential resection margin, distal resection margin, and nodal yield were similar. On multivariate analysis, pretreatment N status was the only independent predictive factor for pathological circumferential resection margin status. Grade 3 to 4 Clavien-Dindo complications, anastomotic leak rates, and hospital stay were similar between the 2 groups. LIMITATIONS: This was a retrospective study. Although propensity matching was performed, selection bias cannot be eliminated completely, as seen in the difference in the surgical approaches between the 2 groups. CONCLUSIONS: In a cohort containing a significant portion of MRI circumferential resection margin-positive low rectal cancers, short-course radiotherapy + chemotherapy followed by delayed surgery resulted in lower T downstaging and lower tumor regression scores compared with long-course chemoradiotherapy, but pathological circumferential margin status, distal resection margin, nodal yield, and perioperative morbidity were similar between the 2 groups. This suggests that short-course radiotherapy + chemotherapy could be a viable alternative to long-course chemoradiotherapy in locally advanced rectal cancers. See Video Abstract at http://links.lww.com/DCR/B855 . REDUCCIN DEL ESTADIO EN LOS CNCERES RECTALES AVANZADOS UNA COMPARACIN DE PROPENSIN EQUIPARADA ENTRE LA RADIACIN DE CICLO CORTO SEGUIDA DE QUIMIOTERAPIA Y LA QUIMIO RADIACIN DE CICLO LARGO: ANTECEDENTES:La radioterapia de ciclo corto seguida de quimioterapia no ha sido evaluada ampliamente como una alternativa a la tradicional quimio radioterapia de ciclo largo en el cáncer de recto localmente avanzado.OBJETIVO:Estudio que compara los resultados oncológicos y a corto plazo entre la radioterapia de ciclo corto + quimioterapia y la quimio radioterapia de ciclo largo en el cáncer de recto localmente avanzado.DISEÑO:Estudio comparado de propensión de manera retrospectiva.AJUSTE:Departamento colorrectal en un centro de atención oncológica de tipo terciario en la India.PACIENTES:Hubo 173 pacientes. El grupo A tenía 47 y el grupo B tenía 126 pacientes. Se realizó una comparación de 1: 2,7 para edad, sexo, distancia del tumor desde el margen anal, cirugías de preservación del esfínter, estadio T previo al tratamiento basada en resonancia magnética y margen de resección circunferencial (CRM).INTERVENCIONES:Radioterapia de ciclo corto + quimioterapia (grupo A) y quimio radioterapia de ciclo largo (grupo B) en cáncer de recto localmente avanzado (LARC).PRINCIPALES MEDIDAS DE RESULTADO:Positividad histopatológica de CRM, reducción del estadio tumoral, grado de regresión tumoral, complicaciones posoperatorias.RESULTADOS:El 52% de los pacientes han tenido un margen de resección circunferencial positivo en la resonancia magnética, 57% de tumores rectales bajos, 20% de tumores T4. La distribución de cirugías rectales fue similar entre los 2 grupos. Las puntuaciones de regresión tumoral y de reducción del estadio de pT fueron significativamente mejores en el grupo B ( p = 0.028 y 0.026 respectivamente). El margen de resección circunferencial patológico, el margen de resección distal y los ganglios arrojados fueron similares. En el análisis multivariado, el estadio N previo al tratamiento fue el único factor predictivo independiente para el estadio de pCRM. Las complicaciones Clavien-Dindo de grado 3-4, las tasas de fuga anastomótica y la estancia hospitalaria fueron similares entre los dos grupos.LIMITACIONES:Retrospectiva; aunque la propensión coincide, existe potencial sesgo de selección.CONCLUSIONES:En una cohorte que contenía una porción significativa de cánceres rectales bajos con margen de resección circunferencial positivo por resonancia magnética, la radioterapia de ciclo corto + quimioterapia seguida de cirugía tardía dio como resultado una mayor reducción del estadio T y de regresión tumoral en comparación con la quimio radioterapia de ciclo largo. Pero el estatus histopatológico del margen circunferencial, el margen de resección distal, el rendimiento ganglionar y la morbilidad perioperatoria fueron similares entre los dos grupos. Esto sugiere que la radioterapia de ciclo corto + quimioterapia podría ser una alternativa viable a la quimio radioterapia de ciclo largo en cánceres rectales localmente avanzados. Consulte Video Resumen en http://links.lww.com/DCR/B855 . (Traducción-Dr. Osvaldo Gauto ).

Revision Surgery for Incidental Gallbladder Cancer-Challenging the Dogma: Ideal Timing and Real-World Applicability.

BACKGROUND: There is a lack of consensus on the ideal time interval and therapeutic value of revision surgery in patients with incidental gallbladder cancer (iGBC) in the context of multimodality management. PATIENTS AND METHODS: Retrospective analysis of an institutional database of patients with iGBC who underwent surgery from January 2010 to December 2019 was performed. Patients who underwent upfront surgery were divided into four time interval groups: A, B, C, and D (< 6 weeks, 6-10 weeks, 10-14 weeks, and > 14 weeks, respectively). RESULTS: A cohort of 517 patients planned for revision surgery was analyzed. Overall, 382 (73.9%) patients underwent upfront surgery while 135 (26.1%) were given neoadjuvant treatment. With median follow-up of 18 months, 2-year overall survival (OS) was 66% and disease-free survival (DFS) was 52.6%, with inferior survival outcomes observed with advancing stage and presence of residual disease on final histopathology. Propensity score-matched analysis after matching for pT stage of cholecystectomy specimen suggested a survival benefit for patients operated between 10 and 14 weeks in terms of OS (p = 0.049) and DFS (p = 0.006). Patients with locally advanced iGBC at presentation had superior OS when operated after neoadjuvant therapy [3-year estimated OS of 59.9% vs 32.3%, respectively (p = 0.001)]. CONCLUSIONS: Revision surgery is at best the most accurate staging procedure guiding timely initiation of systemic therapy. Patients with iGBC operated between 10 and 14 weeks after initial cholecystectomy tend to have favorable survival outcomes, although this depends on final disease stage. Revision surgery should also be offered to all patients presenting at any later point of time, if deemed operable.

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.

Long-term oncological outcomes of the sphincter preserving total mesorectal excision with varying distal resection margins.

INTRODUCTION: A subcentimeter distal resection margin (DRM) appears to be acceptable for most patients, however, long-term follow up and specific subsets where DRM would influence recurrences have not been adequately investigated. METHODS: A retrospective analysis of all sphincter-preserving resections for mid and low rectal cancers between July 2011 and May 2015 was performed. Extended total mesorectal excisions (TME) and patients with positive pathologic circumferential margins (CRM) were excluded. RESULTS: Two hundred and thirty-six patients fit the inclusion criteria. DRM > 20 mm was obtained in 117 patients (49.6%), between 10 and 20 mm in 78 (33%) and <10 mm in 41 (17.4%) patients. Pathological DRM was positive in 4 patients (1.7%). Sixty-five recurrences occurred at a median follow up of 78.5 months. DRM did not influence any of the oncological outcomes. In a subset analysis of patients with poor pathological response to neoadjuvant radiation, that is, tumor regression grade > 3, DRM influenced disease-free survival (DFS) but not overall survival with a hazard ratio of 4.4 (p = 0.02). This was confirmed on multivariate regression analysis in this subgroup as well where pathological nodal status and DRM < 10 mm were independent predictors of DFS. CONCLUSIONS: A subcentimeter DRM may be acceptable in most patients except those who have an inadequate response to neoadjuvant radiation.

Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum-Is TNT the solution?

INTRODUCTION: The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology. METHODS: A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS: CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS. CONCLUSIONS: SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.

Towards standardization of management of gallbladder carcinoma with obstructive jaundice: Analysis of 113 cases over 10 years at a single institution.

BACKGROUND: Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways. METHODS: Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS). RESULTS: Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%. CONCLUSION: Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.

Laparoscopic versus open resection in locally advanced rectal cancers: a propensity matched analysis of oncological and short-term outcomes.

AIM: The aim was to compare oncological and short-term outcomes between open and laparoscopic surgery in locally advanced rectal cancers. METHODS: It is a retrospective analysis conducted in a high volume tertiary centre. Matching was carried out for nine variables, including preoperative factors, neoadjuvant treatment and sphincter preservation. RESULTS: Both the open and laparoscopic surgery arms had 239 patients each. The distributions of pretreatment MRI T3, T4, circumferential resection margin (CRM) positive tumours, neoadjuvant long-course chemoradiation and sphincter preservation were 80.3%, 13.6%, 50%, 89% and 56.4% respectively. The mean number of nodes harvested (12.9 vs. 12.7, P = 0.716), pathological CRM positivity (6.3% in open vs. 5.4% in laparoscopic, P = 0.697) and distal resection margins were similar. The mean blood loss was higher in open surgeries (910 ml vs. 349 ml, P < 0.001). Anastomotic leaks and Clavien-Dindo Grade 3-4 complications were higher in the open arm than in the laparoscopy arm (5.9% vs. 1.7%, P = 0.024, and 12.5% vs. 6.7%, P = 0.015 respectively). The median postoperative hospital stay was significantly shorter in the laparoscopy arm (7 vs. 6, P = 0.015). In CRM positive and threatened cases, the measured outcomes were similar between the two groups except for blood loss which was significantly higher in the open surgery (872 vs. 379, P = 0.000). CONCLUSIONS: In high volume centres, in the hands of experienced colorectal surgeons, laparoscopic rectal surgery is oncologically safe in locally advanced rectal cancers and has lesser morbidity and shorter hospital stay than open surgery. In CRM positive and threatened cases the laparoscopic surgery showed less blood loss compared to open surgery, while other outcome measures were similar to open surgery.

Outcomes of radical surgical resections for nonmetastatic anorectal melanomas: Experience from a tertiary care centre.

AIM: The outcome of radical surgery in nonmetastatic anorectal melanoma (AM) patients is studied infrequently. Here, we aimed to explore the stage-wise outcomes and the impact of radical resections in these patients. METHODS: In this single-centre retrospective study, data of 154 eligible patients were recorded and analysed. Data were obtained from November 2010 to September 2019 with follow-up until November 2020. Overall survival (OS) and disease-free survival (DFS) was calculated by Kaplan Meir method and univariate analysis of prognostic factors by Cox regression. RESULTS: Of 154 patients, 110 were metastatic (stage III) and 44 were nonmetastatic (stage I:22, stage II:22) and underwent curative resections. Median follow-up was 48 months (14-119 months). A total of 39 patients underwent total mesorectal excisions (TME) and five transanal excision (TAE) were performed. Seven patients underwent extended resections. Stage I and II patients had 3- and 5-year OS of 40% and 36%; and DFS of 45% and 33.2%, respectively. Median OS and DFS were 31 and 24 months, respectively. Stage II (node-positive) patients had better median OS compared to stage III (21 vs. 4 months; p = 0.000), and 54.5% patients had recurrences, most commonly both systemic and nodal (45.83%). Median OS of patients without recurrence was 34 months. CONCLUSION: In this large surgical series of AMs, outcome in stage I and II patients was significantly better than stage III and patients with stage II disease can have acceptable oncological outcomes. Radical surgical resections with or without lymphadenectomy could be considered in these patients. The role of adjuvant systemic therapy and radiation needs to be explored as part of multimodality treatment.

Outcomes of exenteration in cT4 and fixed cT3 stage primary rectal adenocarcinoma: a subgroup analysis of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy.

PURPOSE: The aim was to evaluate the oncological outcomes and the prognostic factors following pelvic exenteration (PE) in cT4 and fixed cT3 stage primary rectal adenocarcinoma and to study the impact of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy (NACRT). METHODS: A retrospective analysis of a prospectively maintained database of PE from 2013 to 2018. RESULTS: Out of 2900 colorectal resections, there were 131 pelvic exenterations that were performed, and 100 of these patients had undergone exenteration for primary rectal adenocarcinoma. Of these 100 patients, there were 81 patients who had received NACRT followed by surgery, 50 of whom who had received consolidation chemotherapy and 31 who had undergone surgery without consolidation chemotherapy. R0 resection was achieved in 90% cases. At a median follow-up of 32 months, 2-year disease free survival was 61.8% and estimated 5-year overall survival was 62%. The incidence of distant metastases was 44% vs. 19% (p = 0.023), and the 2-year distant recurrence-free survival was 58% vs. 89% (p = 0.025), respectively, in the 'consolidation chemotherapy group' and the 'no chemotherapy group'. The poorly differentiated grade of tumours, presence of lympho-vascular-invasion, consolidation chemotherapy, and disease recurrence were all found to affect the survival. CONCLUSION: PE with R0 resection achieves excellent survival rates in cT4 and fixed cT3 stage primary rectal adenocarcinoma. The distant recurrence rate may not be altered by consolidation chemotherapy in the subset of high-risk patients. However, further research on consolidation chemotherapy following NACRT in cT4 and fixed cT3 stage primary rectal adenocarcinoma will give a definite answer in the future.

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.

Mustard oil consumption, cooking method, diet and gallbladder cancer risk in high- and low-risk regions of India.

The current study aimed to investigate the role of cooking with mustard oil and other dietary factors in relation to gallbladder cancer (GBC) in high- and low-incidence regions of India. A case-control study was conducted including 1,170 histologically confirmed cases and 2,525 group-matched visitor controls from the largest cancer hospital in India. Dietary data were collected through a food frequency questionnaire. For oil consumption, we enquired about monthly consumption of 11 different types of cooking oil per family and the number of individuals usually sharing the meal to estimate per-individual consumption of oil. Information about method of cooking was also requested. Odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association of GBC risk consumption of different types of oil, method of cooking, and dietary food items, were estimated using logistic regression models, after adjusting for potential confounders. High consumption of mustard oil was associated with GBC risk in both high- and low-risk regions (OR = 1.33, 95% CI = 0.99-1.78; OR = 3.01, 95% CI = 1.66-5.45), respectively. An increased risk of GBC was observed with deep frying of fresh fish in mustard oil (OR = 1.57, 95% CI = 0.99-2.47, p-value = 0.052). A protective association was observed with consumption of leafy vegetables, fruits, onion and garlic. No association was observed between consumption of meat, spicy food, turmeric, pulses or with any other oil as a cooking medium. The effect of high consumption of mustard oil on GBC risk, if confirmed, has implications for the primary prevention of GBC, via a reduced consumption.