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Coronavirus disease (COVID-19) vaccine and its utility in solid organ transplantation (SOT) needs to be revised timely and updated. These guidelines have been formalized by the experts -the apex technical committee members of the National Organ and Tissue Transplant Organization (NOTTO), and the heads of transplant societies for the guidance of transplant communities. In our general recommendations, we recommend that all personnel involved in organ transplantation should get vaccinated as early as possible and continue COVID-19 appropriate behaviour, despite a full course of vaccination. For specific guidelines of recipients, we suggest completing the full schedule before transplantation whenever the clinical condition permits. We also suggest a single dose, rather than proceeding unvaccinated for transplant, in case a complete course is not feasible. In case, vaccination is planned before surgery, we recommend a gap of at least 2 weeks between the last dose of vaccine and surgery. For those not vaccinated prior to transplant, we suggest waiting for 4-12 weeks after transplant. For the potential living donors, we recommend the complete vaccination schedule before transplant. However, if not feasible, we suggest getting at least a single dose of vaccine, 2 weeks prior to donation. We suggest that suitable transplant patients and those on the waiting list should accept a third dose of the vaccine when one is offered to them. In the context of Vaccine-induced thrombotic thrombocytopenia (VITT), we recommend organs from a deceased donor with suspected/proven VITT should be notified and best avoided and are justified only in case of emergency situations with informed consent and counselling.

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 esophageal 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 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 is new cancer registrations and elective gastrointestinal cancer surgeries. Perioperative morbidity remained similar despite 7.1% perioperative Covid -19 exposure.

Differentiation of hepatocyte-like cells (HLCs) from human induced pluripotent stem cells (iPSCs) in vitro has great potential in regenerative medicine. Current protocol uses matrigel of animal origin as a substrate for the differentiation of iPSCs to HLCs. Use of an appropriate non-xenogenic substrate is very important for potential future clinical applications. Towards this goal, we used Cellulose Nanofibril (CNF) gel, a natural, non-toxic, biocompatible and biodegradable polymer in humans as a thin film substrate for the differentiation of iPSCs to HLCs. Here we demonstrated that CNF as a substrate film can efficiently differentiate human iPSCs to HLCs. We investigated the expression profile of the endoderm markers (SOX17 and CXCR4), hepatoblast markers (EpCAM and AFP) and mature hepatocyte marker (ASGPR1) by flow cytometry during the differentiation of iPSCs to HLCs on both CNF and matrigel substrates. We also tested the HLCs generated from both the substrates for the expression of hepatic markers such as A1AT, HNF4A, CYP450 isotypes by Real Time-PCR and its mature hepatocyte functions (lipid accumulation and albumin expression). Our results showed that the differentiated HLCs from both the substrates are comparable and expressed stage specific hepatocyte markers as well as functional maturity. We have demonstrated that CNF, a natural biomaterial, may be used in tissue engineering applications as a potential substrate for the differentiation of iPSCs to HLCs.

e16608 Background: Protein Induced by Vitamin K Absence-II (PIVKA-II) is a tumor marker specific for hepatocellular carcinoma (HCC). PIVKA-II levels correspond with HCC oncogenesis and disease progression. Portal vein tumor thrombus (PVTT) in patients with HCC is a significant factor that affect treatment and prognosis. In this study we assessed the predictive value of PIVKA-II and AFP for vascular invasion and BCLC stage in newly diagnosed HCC patients. Methods: We retrospectively reviewed records of newly diagnosed HCC patients at a tertiary hospital in India between January 2019 to December 2019. Clinical details, BCLC stage, radiological imaging records, serum levels of PIVKA-II and AFP at the time of diagnosis were obtained from medical records. Diagnostic accuracy and cut-off value of PIVKA-II in patients with portal invasion were calculated using receiver operator curve (ROC) analysis. Multiple pairwise comparisions between BCLC stage with PIVKA-II and AFP levels were analysed using Kruskal-Wallis test. Results: Out of 162 newly diagnosed HCC patients 42(25.9%) were detected with PVTT on imaging such as contrast-enhanced computed tomography or magnetic resonance imaging at the time of diagnosis.120(74.1%) patients without PVTT were taken as controls for the analysis. Serum level of PIVKA-II in HCC patients with PVTT was significantly higher than in HCC patients without PVTT (1152.57 mAU/ml vs 146.39 mAU/ml; p = 0.001). AUROC of PIVKA-II was 0.796 (95%CI 0.70-0.892, p = 0.000).The optimal cut-off value of PIVKA-II was 271.81 mAU/ml with a sensitivity of 78.6% and specificity of 52.4%, and the diagnostic accuracy was 59.98%. AUROC of AFP was 0.619 (95%CI 0.59-0.72, p = 0.001). Median PIVKA-II value increased from BCLC stage A to D. Kruskal-Wallis test showed a significant difference of PIVKA-II levels between all stages except stage A and B (p values for stage A-B (0.297), A-C (0.000), A-D(0.000),whereas for AFP results were significant only between stages A and C (p values for stage A-B (0.348), A-C (0.003), A-D(0.206). Conclusions: Serum PIVKA-II level appears as a good predictive marker for PVTT and BCLC stage when compared to AFP which may guide therapeutic strategy and assessment of prognosis in newly diagnosed HCC patients.

Deterioration of kidney function is the most worrisome long term complication following liver transplantation. This study was performed to identify the risk factors of renal dysfunction following living donor liver transplant and the effect of immunosuppressant dosage adjustment on the recovery of renal function. A retrospective observational study was conducted on 133 consecutive adult living donor liver transplant recipients over an 8 year period from 2006 onwards. An increase in serum creatinine of >1.4 mg/dl was taken as a marker for renal insufficiency. The incidence of post living donor liver transplant renal dysfunction was 35% and maximum incidence occurred at one year of liver transplantation. Male gender, pretransplant diabetes, hepatorenal syndrome, posttransplant hypertension, bilirubin >1.2 mg/dl, albumin 1.4 mg/dl and tacrolimus trough level >7mcg/l at 3rd month of liver transplantation were significant risk factors for the development of renal dysfunction. Reduction of tacrolimus dosage was the most effective intervention to restore renal function. This however resulted in abnormal liver function tests secondary to rejection and necessitated the addition of alternative non-nephrotoxic immunosuppressants. Two and four year survival rates were 98.9% and 96.6% for patients without renal dysfunction compared to 97.4% and 91.6% for those complicated by renal dysfunction after living donor liver transplant. Maintaining lower levels of tacrolimus along with addition of non-nephrotoxic immunosuppressants may be a worthwhile strategy to protect the kidneys and preserve long term graft function in patients at high risk of post living donor liver transplant renal dysfunction.

Objective: To assess azathioprine-induced bone marrow toxicity and its correlation with thiopurine methyltransferase (TPMT) mutation in liver transplant patients who develop myelosuppression while on azathioprine therapy.Methods: A prospective observational study was conducted from 1st September 2014 to 30thJune 2015 on 60 liver transplant patients who were tested for TPMT allele activity prior to receiving azathioprine. Haemoglobin levels, platelet counts and white blood cell counts of the patients were monitored for the occurrence of myelotoxicity. Patients who underwent liver transplant during the retrospective period from 1st September 2011 to 31st August 2014 and who developed myelosuppression while on azathioprine therapy were also tested for TPMT genotype.Results: A total of 76 liver transplant patients were tested for TPMT mutation. Prevalence of TPMT mutation in the study patients was 3.95%. The heterozygous TPMT*1/*3C genotype was traced in 2.63% of the patients while 1.32% of patients were homozygous for TPMT*3C allele. Interestingly 43.4% of patients with wild allele also showed azathioprine-induced myelosuppression. Azathioprine dose of 100 mg showed a higher degree of myelotoxicity than lower doses. Haematological indices of 42.1% of patients normalised on cessation of azathioprine therapy.Conclusion: Myelosuppression following the introduction of azathioprine was observed in patients with both ‘mutant’ and ‘wild-type’ alleles. Therefore a cautious approach has to be taken in pre-screening liver transplant recipients for TPMT allele determination in our population. The absence of TPMT mutation does not ensure freedom from myelosuppression. Hence regular monitoring of haematological indices of such patients receiving thiopurine therapy should be continued.

We describe a case of bacteraemia caused by Weissella confusa in a 48-year-old male who was operated on for adenocarcinoma of the gastro-oesophageal junction and maintained on total parenteral nutrition. Blood cultures were positive for a vancomycin-resistant streptococcus-like organism which was identified as W. confusa by 16S rRNA gene sequencing.

Congenital esophageal duplications represent about 15% of digestive tract duplications. We report a 38-year-old man who presented with longstanding heartburn and recent dysphagia. Endoscopy showed communicating tubular duplication of lower esophagus with ulceroproliferative growth at the gastric cardia extending into the lower esophagus. Histology of radical esophagogastrectomy specimen showed poorly differentiated adenocarcinoma of gastric cardia without evidence of Barrett's esophagus.

Many renal transplant centres are reluctant to use kidneys from non-heart-beating (NHB) donors because of the high incidence of primary non-function and delayed graft function reported in the literature. Here, we report our favourable experience of using kidneys from Maastricht category 3 donors (controlled NHB donors).From January 1996 to June 2002, 42 renal transplants using kidneys from 25 controlled NHB donors were undertaken at our centre. The rates of primary non-function, delayed graft function (DGF), rejection and long-term graft and patient survival were compared with those of 84 recipients of grafts from heart-beating (HB donors) transplanted contemporaneously.Primary non-function did not occur in recipients of grafts from NHB donors but was seen in two grafts from HB donors. DGF occurred in 21 of 42 (50%) kidneys from NHB donors and 14 of 84 (17%) kidneys from HBD donars (p0.001). The acute rejection rates in the two groups were similar (33% for grafts from NHB donors vs. 40% from HB donors). By 1 month after transplantation, there was no significant difference in serum creatinine concentration between the two groups. Over a median follow-up period of 32 months (range 2-75 months), the actuarial graft survival rates at 1, 3 and 5 yr after transplantation were 84, 80 and 74% for recipients of kidneys from NHB donors, compared with 89, 85 and 80% for kidneys from HB donors.Controlled NHB donors are a valuable and under-used source of kidneys for renal transplantation. The outcome for recipients of kidney allografts from category 3 NHB donors is similar to that seen in recipients of grafts from conventional HB cadaveric donors.