Endoscopic Ultrasound-Guided Antegrade Stent Placement in Patients with Failed ERCP as a Modality of Preoperative and Palliative Biliary Drainage.

BACKGROUND: No large studies have addressed the role of endoscopic-ultrasound biliary drainage (EUS-BD) as preoperative biliary drainage (PBD) for malignant extrahepatic biliary obstruction (MEBO). We aimed to discuss the outcomes of EUS antegrade stent placement (EUS-AG) in the preoperative and palliative setting. METHODS: Retrospective review of patients who underwent EUS-AG for MEBO between December 2019 and December 2021 was done. Primary outcome measures were technical success and clinical success. Secondary outcome measures were number of days of hospitalization postprocedure, adverse events related to EUS-AG procedure, morbidity related to surgery, and 3-month mortality after surgery. RESULTS: 54 patients underwent attempt for EUS-AG (mean age 54.8 ± 12.1 years; female 44.4%). Most common primary cancer was pancreatic cancer in 42.1% (23/54) patients. Indication was palliative in 34 (62.9%) patients and PBD in 20 (37%) patients. Level of block was distal in 35 (64.8%) and proximal in 19 (35.1%) patients. Technical success of EUS-AG was 88.7% (47/53). Clinical success was seen in 95.7% (45/47) patients. Median number of days of hospitalization postprocedure was 1 day. No procedure-related severe adverse events were seen. Of 20 patients who underwent EUS-AG as PBD, 19 had technical success (95%) with clinical success in 94.5% (18/19). Surgery was performed in 11 patients, of whom 10 patients underwent successful PPPD (one intraoperative liver metastasis). Two patients had Clavein-Dindo III/IV complication post-PPPD, with one mortality within 30 days of surgery. CONCLUSION: EUS-AG is safe and effective after failed ERCP in both preoperative and palliative setting.

EUS-guided biliary drainage in patients with moderate-severe cholangitis is safe and effective: a multi-center experience.

BACKGROUND: Patients with moderate-severe cholangitis require urgent/early biliary drainage and failed endoscopic retrograde cholangiopancreatography (ERCP) warrants use of percutaneous drainage. While endoscopic ultrasound-guided biliary drainage (EUS-BD) has evolved as an effective salvage modality but its safety and efficacy data in moderate-severe cholangitis are limited. PATIENTS AND METHODS: All consecutive moderate-severe cholangitis patients, with failed/technically non-feasible ERCP requiring EUS-BD in two tertiary care centers were included. Baseline laboratory and demographic parameters were documented. Technical and clinical success were primary outcome measures. Additionally, effective biliary drainage, adverse events due to procedure, hospital stay, ICU stay, and mortality were noted. RESULTS: Of the 49 patients (23 male; 46.9%) presenting with moderate/severe cholangitis, 23 (46.9%) had severe cholangitis. The median Charleston comorbidity index was 7.0 (IQR 2.0). Majority had malignant disease (87.8%) and 25 (51.0%) had inaccessible papilla. Technical success was achieved in 48 cases (98.0%), while clinical success with improvement of cholangitis was noted in 44 of 48 cases (91.7%). Effective biliary drainage was noted in 85.4% (41/48) cases. Adverse events in the form of mostly bleeding and bile leak were noted in 5 cases (10.2%) but managed conservatively. Distal obstruction exhibited significantly better clinical success (100% vs. 78.9%; p = 0.02) than hilar obstruction. Severe cholangitis had significantly lower clinical success (81.8% vs. 100%; p = 0.04) than moderate cholangitis. CONCLUSION: EUS-BD can be a safe and effective alternative option for patients with moderate to severe cholangitis, even with significant pre-morbid conditions, with acceptable adverse events rate.

Prognostic Nutritional Index Prior to Rectal Cancer Resection Predicts Overall Survival.

Prognostic nutritional index (PNI) correlates with postoperative complications and survival in colorectal cancers. Separate studies for rectal cancers are not available where the majority have preoperative radiation, operated by minimally invasive approaches and have diverting ostomies.Consecutive rectal resections between October 2014 and December 2017 from a single center were included. PNI was calculated as 10 x (serum Albumin) + 0.005 x TLC (per mm3) before operation. Multivariate cox regression was used with overall survival (OS) as the dependent variable. Interaction terms of PNI with neoadjuvant therapy, surgical approach and postoperative complications were used to assess specific subgroups.Three-hundred forty elective rectal resections were included with a mean PNI of 46.711 (SD - 6.692), and a median follow up of 44 mo. In multivariable regression, PNI predicted OS (HR - 0.943; p-0.001). Interaction of PNI with preoperative radiation or surgical approach (open, laparoscopic, or robotic) did not change its influence on survival. PNI predicted survival with similar hazard even in patients without major postoperative complicationsDespite routine diversion after rectal resections, PNI predicted OS with an absolute survival benefit of 1.2% at 3-year for every unit increase in PNI irrespective of preoperative therapy or surgical approach.

Laparoscopic ovarian transposition in teenage and young women with locally advanced rectal cancer: Respite amidst cancer chaos.

AIM: Ovarian transposition is an established surgical technique to salvage ovaries in premenopausal women requiring pelvic radiation. The success rate of ovarian transposition varies widely depending on the route, technique of surgery, type of cancer and treatment. Here, we aimed to analyse the effectiveness of laparoscopic ovarian transposition (LOT) in teenage and young women prior to pelvic radiation in locally advanced rectal cancers (LARC). METHODS: Patients who underwent LOT for rectal cancers were retrieved from a prospectively maintained database from June 2013-September 2019. Disease characteristics, return of menstrual function and oncological outcomes were analysed. RESULTS: A total of 46 women with a mean age of 25.2 years who underwent LOT at the cancer centre were included in the study. Seventy percent were nulliparous. All patients were fit for discharge by 24 h. Mean time to start radiation was 19.6 days (range 3-47 days). Median follow-up of patients was 42 months. A total of 41 patients were assessable for ovarian function, 65.5% had resumption of menses. Median ovarian survival was 79 months and 5-year ovarian survival was 54%. Median overall survival from rectal cancer was 51 months. CONCLUSION: Laparoscopic ovarian transposition is a safe and effective technique of ovarian protection from the gonadotoxic effects of pelvic radiation in LARC. It does not delay primary treatment and does not compromise oncological outcomes. Long-term follow-up is required to evaluate fertility and quality of life.

Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer.

Lipocalin 2 is a siderophore-binding protein that regulates iron homeostasis. Lipocalin 2 expression is elevated in multiple tumor types; however, the mechanisms that drive tumor progression upon Lipocalin 2 expression remain unclear. When Lipocalin 2 is over-expressed, it leads to resistance to 5-fluorouracil in colon cancer cell lines in vitro and in vivo by inhibiting ferroptosis. Lipocalin 2 inhibits ferroptosis by decreasing intracellular iron levels and stimulating the expression of glutathione peroxidase4 and a component of the cysteine glutamate antiporter, xCT. The increase in xCT levels is dependent on increased levels of ETS1 in Lipocalin 2 over-expressing cells. Inhibiting Lipocalin 2 function with a monoclonal antibody leads to a decrease in chemo-resistance and transformation in vitro, and a decrease in tumor progression and chemo-resistance in xenograft mouse models. Lipocalin 2 and xCT levels exhibit a positive correlation in human tumor samples suggesting that the pathway we have identified in cell lines is operative in human tumor samples. These results indicate that Lipocalin 2 is a potential therapeutic target and that the monoclonal antibody described in our study can serve as the basis for a potential therapeutic in patients who do not respond to chemotherapy.

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.

Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer.

BACKGROUND & OBJECTIVES: : There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy. METHODS: : Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity. RESULTS: : Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III-IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was ₹ 50,625 (1,125-303,750). INTERPRETATION & CONCLUSIONS: : In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.

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.

A survey of clinical practices among oncologists regarding hepatitis B screening in patients with cancer.

Background & objectives: Screening for hepatitis B prior to the initiation of chemotherapy in patients with cancer is recommended by all major hepatology and oncology societies. This study was aimed to determine the screening practices for hepatitis B among oncologists from India and their experience with hepatitis B reactivation. Methods: A questionnaire-based survey was conducted among oncologists attending the Evidence-Based Medicine Conference at Tata Memorial Centre, Mumbai, India. The questionnaire was developed in keeping with the recent guidelines for hepatitis B reactivation on chemotherapy, with questions regarding demographics, years in practice and hepatitis B screening practices and management. There was 78 per cent response rate to the questionnaire. Results: Most respondents were <35 yr of age (69%), with < five years of experience (39%), practicing in an academic institution (81%). Seventy four per cent respondents always screened their patients with cancer for hepatitis prior to chemotherapy, whereas 19 per cent in special settings and seven per cent never screened; 96 per cent respondents used hepatitis B surface antigen (HBsAg) as a screening test, while 17 per cent also used antibody to hepatitis B core antigen. Sixty one per cent respondents used entecavir or tenofovir for prophylaxis; 70 per cent continued prophylaxis till 6-12 months after completion of chemotherapy, while 21 per cent continued only till the end of chemotherapy. Interpretation & conclusions: More than 25 per cent of the oncologists were not screening their patients with cancer for viral hepatitis prior to cancer-directed therapy, and only 17 per cent of the oncologists used the recommended tests for screening. Better training of oncologists regarding viral hepatitis screening and management is needed.

Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae-induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation.

Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4-knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4-knockout mice showed diminished differentiation potential compared with wild-type mice. Fibroblasts from asthmatic lung exhibited increased TRPV4 activity and enhanced differentiation potential compared with normal human lung fibroblasts. Of interest, TGF-ß1 treatment enhanced TRPV4 activation in a PI3K-dependent manner in normal human lung fibroblasts in vitro Mechanistically, TRPV4 modulated matrix remodeling in the lung via 2 distinct but dependent pathways: one enhances matrix deposition by fibrotic gene activation, whereas the other slows down matrix degradation by increased plasminogen activator inhibitor 1. Of importance, both pathways are regulated by Rho/myocardin-related transcription factor-A and contribute to fibroblast differentiation and matrix remodeling in the lung. Thus, our results support a unique role for TRPV4 in D. farinae-induced airway remodeling and warrant further studies in humans for it to be used as a novel therapeutic target in the treatment of asthma.-Gombedza, F., Kondeti, V., Al-Azzam, N., Koppes, S., Duah, E., Patil, P., Hexter, M., Phillips, D., Thodeti, C. K., Paruchuri, S. Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae-induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation.

Pulmonary metastasectomy of colorectal cancer origin: Evaluating process and outcomes.

BACKGROUND: This study was undertaken to evaluate the effect of change in policy of computed tomography (CT) scan of the thorax in staging and follow-up of colorectal cancer (CRC). Another objective was to review the outcomes following pulmonary metastasectomies (Pmets) and to determine the prognostic factors affecting outcomes. METHODS: This is a retrospective analysis from a prospective cohort database of patients, who underwent Pmet for CRC origin from August 2004 to February 2016. The outcome measures were number of Pmets per year, overall survival (OS), disease-free survival (DFS), and prognostic factors affecting survival. RESULTS: Of 71 patients, 38% (n = 27) underwent Pmet before 2013 and 62% ( n = 44) had surgery after 2013. The 2-year DFS after Pmet was 49.3% and estimated 5-year OS was 51.4% at a median follow-up of 28 months. There was a significant increase in number of Pmets/year ( P = 0.0015), increased detection of synchronous pulmonary metastasis (PM) ( P = 0.005), increased diagnosis of extra-pulmonary metastases (EPM) ( P = 0.005), and improved OS ( P = 0.026) after introduction of CT scan as staging tool. Site of primary tumor (colon) ( P = 0.045), primary nodal stage ( P = 0.009), and the presence of EPM ( P = 0.01) were independent important prognostic factors affecting survival. CONCLUSION: The CT scan of thorax as a baseline tool for staging and follow-up in CRC increases referral for pulmonary metastasectomy. Surgery achieves excellent prognosis and long-term survival outcomes in CRC with isolated PM and carefully selected patients with solitary liver metastasis.

Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study.

BACKGROUND: Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer. METHODS: In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20-80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015. We only included patients who had been diagnosed less than 1 year before the date of enrolment and excluded patients with any other malignancies. We recruited visitor controls aged 20-80 years with no history of cancer visiting all departments or units of Tata Memorial Hospital during the same time period and frequency matched them to cases on the basis of age, sex, and current region of residence. We estimated association using logistic regression, adjusting for age, sex, and five eigenvectors. We recruited samples for a replication cohort from patients visiting Tata Memorial Hospital between Aug 4, 2015, and May 17, 2016, and patients visiting the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, between July, 2010, and May, 2015. We used the same inclusion and exclusion criteria for the replication set. We examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association. FINDINGS: The discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls and the replication cohort contained 428 gallbladder cancer cases and 420 controls. We observed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harbouring both the ABCB1 and ABCB4 genes, with the most notable SNPs after replication and meta-analysis being rs1558375 (GWAS p=3·8 × 10-9; replication p=0·01; combined p=2·3 × 10-10); rs17209837 (GWAS p=2·0 × 10-8; replication p=0·02; combined p=2·3 × 10-9), and rs4148808 (GWAS p=2·4 × 10-8; replication p=0·008; combined p=2·7 × 10-9). Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30-1·66; p=2·31 × 10-10) for rs1558375, 1·61 (1·38-1·89; p=2·26 × 10-9) for rs17209837, and 1·57 (1·35-1·82; p=2·71 × 10-9) for rs4148808. GWAS heritability analysis suggested that common variants are associated with substantial variation in risk of gallbladder cancer (sibling relative risk 3·15 [95% CI 1·80-5·49]). INTERPRETATION: To our knowledge, this study is the first report of common genetic variation conferring gallbladder cancer risk at genome-wide significance. This finding, along with in-silico and biological evidence indicating the potential functional significance of ABCB1 and ABCB4, underlines the likely importance of these hepatobiliary phospholipid transporter genes in the pathology of gallbladder cancer. FUNDING: The Tata Memorial Centre and Department of Biotechnology.

Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm.

PURPOSE: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors. PATIENTS AND METHODS: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks). RESULTS: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions. CONCLUSION: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival.

Redefining HCC Surveillance in India: A Call for Innovative and Inclusive Strategies.

Hepatocellular carcinoma (HCC) is one of the top ten leading causes of cancer-related death in India, with recent reports suggesting a rising incidence. Chronic HBV infection is still the commonest cause of HCC in India but the recent surge of MASLD and better control of viral hepatitis is already changing the epidemiology. Most HCC in India are diagnosed at an advanced stage where cure is impossible, and prognosis is poor. These factors force us to rethink strategies for surveillance and diagnosis of early stage HCC in India. Current guidelines including from INASL, suggest six-monthly surveillance using abdominal ultrasound (USG) with or without Alpha Fetoprotein (AFP) testing. This strategy has several limitations, especially in patients with MASLD. Also, HCC surveillance is neither well-organized nor universally practiced in India. The current screening approach, therefore needs a radical change. The Japanese guidelines provide a template for a successful model for increasing the diagnosis of early HCC. Tumor markers like PIVKA II, and newer algorithms like the GALAD and the GAAD scores could refine the surveillance strategies in the coming years, as shown by emerging data from Thailand and China. Moving away from hospital-based imaging towards community-based use of blood markers and digital technology may be a potential solution to help reach at-risk populations. Healthcare economics and logistics will play a big part in implementation of a radical new strategy, and a nationwide chronic liver disease and HCC registry is needed to evaluate current practices, define populations at risk, and identify the best beneficiaries of surveillance in a resource-constrained setting like India. We also concurrently need to identify, upgrade or develop statewide centers of excellence to provide state-of-the-art integrated multidisciplinary care to patients who get diagnosed through surveillance pathways to actually improve patient outcomes.

Outcomes of underwater endoscopic mucosal resection for colorectal polyps-Insights from western India.

INTRODUCTION: Underwater endoscopic mucosal resection (uEMR) represents an alternative to conventional EMR for resection of sessile colorectal polyps. We aimed at assessing the efficacy and safety of uEMR for sessile colorectal polyps. METHODS: A retrospective analysis of endoscopy database was done for patients who underwent uEMR for sessile colorectal polyps more than 10 mm in size without any features of sub-mucosal invasion from two tertiary care centres in western India between January 2021 and June 2023. Exclusion criteria were other modes of endoscopic resection. Primary outcome was rate of en bloc resection. Secondary outcomes were complete resection rate, adverse events and recurrence rate. RESULTS: During the study period, 159 patients with 261 lesions met the study inclusion. Mean lesion size was 1.935 ± 0.71 cm with most lesion located in the rectum (75, 28.73%) followed by sigmoid colon (69, 26.43%). Most lesions had a Paris 0-Is morphology (192, 73.56%). Japan NBI Expert Team (JNET) IIa pattern was seen on narrow band imaging (NBI) in 221 (84.67%) lesions. Complete resection was achieved in 98.46% lesions (257/261). En bloc resection was achieved in 91.82% (236/257) lesions. Complications were seen in 6.8%, all of which were managed endoscopically. Recurrence was seen in 3.1% of polyps on follow-up. CONCLUSION: uEMR is a safe and efficacious technique for endoscopic resection for sessile colorectal polyps with high rates of en bloc resection for polyps more than 10 mm size.

Non-operative management in low-lying rectal cancers undergoing chemoradiation.

PURPOSE: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. MATERIALS AND METHODS: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR, respectively) post-NACTRT and wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). RESULTS: Sixty-one consecutive patients post-NACTRT achieving cCR[44 (72%)] and nCR[17 (28%)], respectively, were identified. All patients received pelvic radiotherapy at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.