The role of SARS-CoV-2 genomic surveillance and innovative analytical platforms for informing public health preparedness in Bengaluru, India.

A comprehensive SARS-CoV-2 genomic surveillance programme that integrates logistics, laboratory work, bioinformatics, analytics, and timely reporting was deployed through a public-private partnership in the city of Bengaluru, Karnataka in India. As a result, 12461 samples have been sequenced and reported to the Karnataka State public health officials as time-sensitive, decision support during the last one year and uploaded in global public databases in a timely manner. This programme has developed an analytics platform for studying SARS-CoV-2 sequences and their epidemiological context. Continuous sequencing effort enabled timely detection of emergence of Omicron variant in India and the subsequent spread of the same and its sub-lineages with more logistic growth (BA.10, BA.12 and BA.5) in Bengaluru. Our data also helped to provide timely information on variants to determine which of the Variants of Concern tracked globally, were observed in Bengaluru, ensuring targeted efforts and reducing unwarranted fear. This effort highlights the importance of, and the urgent need to, increase genomic surveillance to support the states with limited sequencing and bioinformatics capacity. We describe the development and deployment of this end-to-end solution for genomic surveillance of SARS-CoV-2 in the city of Bengaluru.

The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

Resection for hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) continues to present major challenges in management, which is further complicated by the presence of associated chronic liver disease. Key issues in surgical resection of HCC include the site, size, and number of lesions, the severity of the chronic liver disease, and the size of the functional liver remnant. De novo HCC in the absence of chronic liver disease can be treated by major liver resection with little risk of postoperative liver failure. Liver resection can also be used a bridge to liver transplantation as it affords the possibility of determining the pathologic grade of the tumortumor and its invasiveness, and thereby the prognosis. This review summarizes the current treatment approaches to surgical resection for HCC.

A 51-week, open-label clinical trial in India to assess the efficacy and safety of pancreatin 40000 enteric-coated minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis.

BACKGROUND/OBJECTIVES: To assess the efficacy and safety of pancreatin (pancrelipase) enteric-coated minimicrospheres (MMS) over a one-year period in patients with pancreatic exocrine insufficiency (PEI) due to chronic pancreatitis (CP). METHODS: This was a 51-week, open-label extension (OLE) of a one-week, multicenter, double-blind, randomized, placebo-controlled trial in India that enrolled patients ≥18 years of age with confirmed PEI due to CP. Patients received pancreatin (Creon(®) 40000 MMS™) at a dose of 80,000 Ph. Eur. lipase units with each of three main meals/day and 40,000 with each of up to three snacks/day. RESULTS: Of 61 patients entering the OLE, 48 completed treatment (nine were lost to follow up, two withdrew consent, one discontinued due to adverse event [acute exacerbation of CP], one protocol violation). There were significant improvements from baseline to end of OLE in mean ± SD coefficient of fat absorption (CFA: 22.7 ± 12.2%), coefficient of nitrogen absorption (CNA: 6.5 ± 7.9%), body weight (4.9 ± 4.9 kg), BMI (1.9 ± 1.9 kg/m(2)), and most nutritional laboratory parameters tested (p ≤ 0.001). Mean daily stool frequency was reduced from 2.8 to 1.6 (p < 0.001). Improvements in clinical symptoms, clinical global impression of disease symptoms, and quality of life were also observed. Treatment-emergent adverse events (TEAEs) were observed in 64% of patients overall. Only 13% of patients experienced TEAEs judged treatment related. CONCLUSIONS: In patients with PEI due to CP, treatment with pancreatin for one year was associated with significant improvements in fat absorption, nitrogen absorption, and nutritional parameters, improvements in clinical symptoms, and a favorable safety and tolerability profile.

Stellate cell activation in tropical calcific pancreatitis compared to alcoholic pancreatitis, adenocarcinoma of pancreas and normal pancreas.

CONTEXT: Pancreatic stellate cell (PSC) is known to be the source of fibrosis in pancreatic pathology of various etiologies. However, there is no published data on activation of PSCs in tropical calcific pancreatitis. OBJECTIVES: The present study was undertaken to estimate the proportion of activated stellate cells, in a semi-quantitative manner, in normal pancreas and pancreatic fibrosis due to, tropical calcific pancreatitis, alcoholic chronic pancreatitis and pancreatic adenocarcinoma. PATIENTS: Surgically resected specimen from patients with tropical calcific pancreatitis (n=22), alcoholic chronic pancreatitis (n=16), adenocarcinoma of pancreas (n=20) and normal pancreas (n=20) were included. MAIN OUTCOME MEASURES: Expression of CD34, and alpha-smooth muscle actin (α-SMA) was assessed by immunohistochemistry. Morphometry was performed by a point counting procedure and CD34 positive areas were excluded from α-SMA positive areas for estimating activated PSCs. STATISTICS: The one-way ANOVA and the Tukey multiple comparison test were used to compare the proportion of activated stellate cells among the four categories. RESULTS: In all the disease conditions studied, namely, tropical calcific pancreatitis (16.7±14.5%, mean±SD), alcoholic chronic pancreatitis (13.6±12.4%) and pancreatic adenocarcinoma (22.8±14.4%), there was highly significant (P<0.001) increased percentage of activated PSCs compared to normal pancreas (-0.9±6.4%). Proportion of activated PSCs in tropical calcific pancreatitis was similar to that in cases of alcoholic chronic pancreatitis and pancreatic adenocarcinoma. Such activation is documented for the first time in tropical calcific pancreatitis while it is known for the other causes. CONCLUSIONS: The present study suggests that a final common pathway of PSC activation leads to fibrogenesis in tropical calcific pancreatitis just as in other pancreatic pathologies.

Progressive familial intrahepatic cholestasis: A case with improvement in liver tests and growth following partial external biliary diversion.

A 2(1/2)-year-old boy presented with pruritus and jaundice of 2 weeks duration. On investigation, serum total bilirubin was 23.4 mg/dL and gamma glutamyl transpeptidase was normal. Liver biopsy was consistent with progressive familial intrahepatic cholestasis (PFIC). A partial external biliary diversion (PEBD) was done. Pruritus disappeared, growth improved and serum total bilirubin became normal, 2 months after surgery. This is the first report from India, of PFIC treated with PEBD and suggests that PEBD should be considered in patients with PFIC even if bridging fibrosis is present.

Peri-operative outcomes for pancreatoduodenectomy in India: a multi-centric study.

BACKGROUND: There have been an increasing number of reports world-wide relating improved outcomes after pancreatic resections to high volumes thereby supporting the idea of centralization of pancreatic resectional surgery. To date there has been no collective attempt from India at addressing this issue. This cohort study analysed peri-operative outcomes after pancreatoduodenectomy (PD) at seven major Indian centres. MATERIALS AND METHODS: Between January 2005 and December 2007, retrospective data on PDs, including intra-operative and post-operative factors, were obtained from seven major centres for pancreatic surgery in India. RESULTS: Between January 2005 and December 2007, a total of 718 PDs were performed in India at the seven centres. The median number of PDs performed per year was 34 (range 9-54). The median number of PDs per surgeon per year was 16 (range 7-38). Ninety-four per cent of surgeries were performed for suspected malignancy in the pancreatic head and periampullary region. The median mortality rate per centre was four (range 2-5%). Wound infections were the commonest complication with a median incidence per centre of 18% (range 9.3-32.2%), and the median post-operative duration of hospital stay was 16 days (range 4-100 days). CONCLUSIONS: This is the first multi-centric report of peri-operative outcomes of PD from India. The results from these specialist centers are very acceptable, and appear to support the thrust towards centralization.

Chronic pancreatitis. A prospective nationwide study of 1,086 subjects from India.

CONTEXT: Chronic pancreatitis is common in India. However, its risk factors are not clear. There is sparse data on the current prevalence of tropical pancreatitis in India. OBJECTIVE: To undertake a prospective nationwide study of the risk factors and clinical profile of chronic pancreatitis. SETTING: Thirty-two major centers from different regions of India contributed data on 1,086 patients to a common online website (www.ipans.org). MAIN OUTCOME MEASURES: Risk factors, clinical features complications and treatment of chronic pancreatitis. RESULTS: Of the 1,086 subjects, complete data on risk factors were available for 1,033 subjects. Idiopathic pancreatitis was the most common form of pancreatitis (n=622; 60.2%) and alcoholic chronic pancreatitis accounted for about a third of the cases (n=400; 38.7%); the rest (n=11; 1.1%) had rare risk factors. Smoking and cassava intake were documented in 292 (28.3%) and 189 (18.3%) subjects, respectively. Using well-defined criteria, only 39 (3.8%)cases could be labeled as 'tropical pancreatitis'. Pain occurred in 971 patients (94.0%). Four hundred and eighteen (40.5%) subjects had diabetes mellitus. Of alcohol consumers, alcoholism and female gender were independent risk factors for diabetes in subjects with chronic pancreatitis (OR=1.48, P=0.003; and OR=1.75, P<0.001, respectively). The most common complications were pseudocysts (15.8%) and biliary obstruction (8.2%). Pancreatic cancer occurred in 42 subjects (4.1%). Ultrasound detected calculi in 69.7%, ductal dilatation in 63.4% and atrophy in 27.3%. The majority of patients were on medical therapy (n=849; 82.2%); endotherapy and surgery accounted for the rest. About 50% percent of the patients with diabetes required insulin (198/418). CONCLUSIONS: In this first nationwide prospective survey of chronic pancreatitis in India, idiopathic pancreatitis was the most common form, followed by alcoholic pancreatitis. The classical form of tropical chronic pancreatitis is becoming less common.

Cefoperazone-sulbactam for treatment of intra-abdominal infections: results from a randomized, parallel group study in India.

BACKGROUND: Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option. METHODS: This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India. RESULTS: Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%). CONCLUSION: Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.

Surgery for hilar cholangiocarcinoma: feasibility and results of parenchyma-conserving liver resection.

BACKGROUND/AIM: Major liver resection has improved the resectability rate of hilar cholangiocarcinomas, but morbidity and mortality may be significant. The aim of this study was to assess the value of parenchyma-conserving liver resection (resection of bile duct with liver segments I and IVb; PCLR) in hilar cholangiocarcinoma. METHODS: Retrospective analysis of prospectively collected data. Factors influencing survival following three types of operations were studied by univariate and multivariate analyses. The three types of operations were: (1) local resection of the bile duct alone (LR); (2) major liver resection (resection of three or more segments, hepatic resection; HR), and (3) PCLR. RESULTS: Forty-six patients (21 males, 25 females; age range 35-77 years, mean age 57, median age 57 years) underwent surgery. There were 11 LR, 12 HR, and 23 PCLR procedures. There were 3 deaths (mortality 6.5%). The mortality was higher following HR (3 out of 12; 25%) than following LR or PCLR (0 out of 34; p = 0.01). Survival was longer following curative resection (median 27 months) than after palliative resection (median 15 months; p = 0.001). Lymph nodal and perineural involvement were adverse factors on univariate, but not on multivariate analysis. PCLR produced better survival (median 29 months) as compared with LR (median 15 months) or HR (median 22.5 months; p < 0.01). CONCLUSIONS: PCLR is applicable to selected patients with Bismuth-Corlette type III disease without major vascular involvement and produces survival rates comparable to those of LR and HR. PCLR may help avoid major liver resections in some patients with hilar cholangiocarcinoma.

Ductal drainage with head coring in chronic pancreatitis with small-duct disease.

PURPOSE: To assess prospectively the feasibility of drainage procedures in patients with chronic pancreatitis and small ducts. METHODS: Forty-five patients with chronic pancreatitis and main pancreatic ductal diameters less than 5 mm (group 1) underwent lateral pancreaticojejunostomy with varying degrees of head coring. Their outcomes were recorded and compared with 212 patients who had large ducts (diameter >7 mm; group 2). Patients in the two groups were comparable in age, etiology, presence of jaundice, diabetes, steatorrhea, head mass, pseudocysts, and biliary obstruction. RESULTS: Mortality and complication rates were similar in the two groups. Drainage procedures relieved pain in 94% (43/45 cases) in small-duct disease, and 91% (193/212) of cases with large-duct disease over a median follow-up greater than 30 months. Functional results were also comparable. CONCLUSION: In the light of these results, drainage procedures merit wider application for small-duct disease.

Biliary access loops for intrahepatic stones: results of jejunoduodenal anastomosis.

BACKGROUND: Patients with intrahepatic calculi require multiple interventions following successful surgical stone clearance for recurrent stones and cholangitis. The present paper describes the results of a technique of in-continuity side-to-side jejunoduodenal anastomosis (JDA) that provides endoscopic access to the hepaticojejunostomy and intrahepatic ducts. This operation is compared to other techniques in a critical appraisal of various biliary access procedures described for long-term management of intrahepatic -calculi. METHODS: A retrospective analysis of clinical data of 13 patients who underwent biliary drainage procedures with access loops for intrahepatic calculi during the period March 1990 to December 2000 was performed. The postoperative course of patients and the feasibility of postoperative endoscopic access to the hepaticojejunostomy and intrahepatic ductal system in treatment of recurrent cholangitis were assessed. Nine patients underwent JDA, two underwent permanent-access hepaticojejunostomy (PAH) and two others underwent an interposition hepaticojejunoduodenostomy (IHJ). RESULTS: The analysis revealed no major procedure-related complications or mortality. Endoscopic access (using forward-viewing gastroscope) was possible in 100% of cases following JDA, and with difficulty in both cases after PAH. Endoscopic access in the two patients with IHJ failed because of technical reasons. Recurrent cholangitis was seen in seven patients (54%) - two out of two patients in the PAH group, one out of two in the IHJ group and four out of nine in the JDA group. This required 12 endotherapy sessions (mean: 1.5 procedures per patient). CONCLUSION: In-continuity side-to-side JDA allows easy access of conventional gastroduodenoscopes to the biliary tree for removal of recurrent/residual intrahepatic stones. The technique has advantages over other access loop procedures in the long term management of recurrent intrahepatic stones.