Probiotics-A Promising Novel Therapeutic Approach in the Management of Chronic Liver Diseases.

An increased incidence of liver diseases has been observed in recent years and is associated with gut dysbiosis, which causes bacterial infection, intestinal permeability, and further leads to disease-related complications. Probiotics, active microbial strains, are gaining more clinical importance due to their beneficial effect in the management of many diseases, including liver diseases. Clinical scenarios show strong evidence that probiotics have efficacy in treating liver diseases due to their ability to improve epithelial barrier function, prevent bacterial translocation, and boost the immune system. Moreover, probiotics survive both bile and gastric acid to reach the gut and exert their health benefit. Evidence shows that probiotics are a promising approach to prevent several complications in clinical practice. Herein, we discuss the recent evidence, challenges, and appropriate use of probiotics in managing advanced liver diseases, which may have an impact on future therapeutic strategies. Furthermore, the superior effect of strain-specific probiotics and their efficacy and safety in managing liver diseases are discussed.

Effectiveness of different tools for malnutrition in the assessment of patients with cirrhosis.

BACKGROUND: We aimed to evaluate the prevalence of malnutrition using traditional measures of nutritional assessments like body mass index (BMI), mid-arm circumference (MAC), triceps skin fold thickness (TSF), mid-arm muscle circumference (MAMC), hand grip strength (HGS) and subjective global assessments (SGA) among cirrhotic patients referred for liver transplantation (LT). METHODS: The study was conducted among 215 cirrhotic patients referred for LT at a tertiary care hospital. Patients were enrolled between July 2021 and October 2022 to assess the prevalence of malnutrition. Patient's demographic details, clinical history, BMI using dry weight, MAMC, HGS, SGA score and disease severity were assessed. RESULTS: Chronic alcoholism was the main causative factor for cirrhosis, followed by viral infection. 58% of cirrhotic patients were moderately to severely malnourished based on SGA, 12% were undernourished based on BMI, 91% had low MAC, and 94% had low HGS/muscle strength indicating malnutrition. Low MAC (p = 0.048) and SGA (p = 0.000) were associated with CTP - B and C class, and low MAC (p = 0.046), low TSF (p = 0.005), and SGA (p = 0.000), were associated with MELD Na score >15. Low MAC (p = 0.011) and SGA (P = 0.000) were associated with mortality, although 78% of patients had MAC within the normal range. A strong association exists between malnutrition and complications, liver disease severity, and death. CONCLUSION: In patients with chronic liver diseases, SGA performed well as a good predictor of malnutrition, this might be because SGA analyses various domains which can be affected in chronic liver disease. Assessing malnutrition early may help in initiating appropriate medical nutritional therapy.

Congenital bilio-bronchial fistula in an adult: a review of literature and video demonstration of laparoscopic fistula tract excision.

This article presents a review of the literature on congenital bilio-bronchial fistula (BBF), a rare anomaly characterized by abnormal communication between the bile duct and respiratory tract. Congenital BBF often presents with bilioptysis in early neonates and infants; however, patients with no overt symptoms may occasionally present in adulthood. Our literature search in Medline from 1850 to 2023 revealed 42 reported cases of congenital BBF, primarily managed with thoracotomy and excision of the fistula tract. About one-third of these cases required multiple surgeries due to associated biliary anomalies. The review underscores the importance of diagnostic imaging, including bronchoscopy, in identifying and delineating the extent of the fistula. It also highlights the evolving surgical management, with recent cases showing the efficacy of minimally invasive approaches such as laparoscopy and thoracoscopy. In addition to the literature review, we report a young female patient with a history of recurrent respiratory infections presenting with bilioptysis and extensive left lung damage. Initial management included bronchoscopy-guided glue instillation, left thoracotomy, and pneumonectomy. Following the recurrence of symptoms, the patient was successfully treated with laparoscopic excision of the fistula tract. In recent times, minimally invasive approaches such as laparoscopy and thoracoscopy, with excision of the fistula tract are gaining popularity and have shown good results. We suggest biliary communication being the high-pressure end, tackling it transabdominal may prevent recurrent problems.

Early mobilization and delayed arterial ligation (EMDAL) as a surgical technique for splenectomy and shunt surgery in portal hypertension.

Backgrounds/Aims: Splenectomy is the most frequently performed procedure as definitive management or as part of shunt surgery or devascularization in portal hypertension. Splenectomy is technically challenging because of the frequent coexistence of multiple collateral varices, splenomegaly, poor liver function, and thrombocytopenia. Early arterial ligation and late mobilization (EALDEM) is the traditional method for splenectomy in portal hypertension. Early spleen mobilization offers good control of the hilum. We aim to compare the effect of the early mobilization and delayed arterial ligation (EMDAL) technique with that of the conventional splenectomy technique in patients with portal hypertension. Methods: During the study period from September 2011 to September 2022, 173 patients underwent surgical intervention for portal hypertension at our institution. Among these patients, 114 underwent the conventional method of splenectomy (early arterial ligation and late splenic mobilization) while 59 underwent splenectomy with the EMDAL technique. Demographics were compared between the two groups. Intraoperative and postoperative outcomes were analyzed using the Mann-Whitney test in each group. A minimum follow-up of 12 months was performed in each group. Results: Demographics and type of surgical procedure were comparable in the two surgical method groups. Median blood loss was higher in the conventional group than in the EMDAL method. The median duration of surgery was comparable in the two surgical procedures. Clavien-Dindo grade III/IV complications were reported more frequently in the conventional group. Conclusions: The splenic hilum can be controlled well and bleeding can be minimised with early mobilization and delayed arterial ligation.

Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma.

BACKGROUND: Angiogenesis contributes to hepatocellular carcinoma (HCC) progression by promoting tumor growth and metastasis. Netrin-4 (NTN4) is a secreted glycoprotein that has been reported to control angiogenesis and preserve endothelial homeostasis. Macrovascular invasion of the portal vein, referred to as portal vein invasion (PVI) is associated with poor prognosis in HCC patients. In this work, we sought to understand more about the systemic and hepatic level expression of NTN4 and its receptors in HCC patients with and without portal vein invasion. METHODS: A total of 154 patients with HCC, and 90 healthy volunteers were recruited in this case-control study. Patients with HCC were further subdivided into those with portal vein invasion (PVI) (n=68), and those without portal vein invasion (NPVI) (n=86). Clinical characteristics and liver function parameters were recorded among the study subjects PVI and NPVI. The serum levels of NTN4 (pg/ml) were estimated by ELISA. HCC tissues and normal non-tumorous liver tissues (controls) were collected for gene expression analysis of NTN4 and its receptors. RESULTS: ALT, ALP, and GGT levels were significantly elevated in the serum of HCC patients with PVI compared to NPVI and control subjects. Systemic NTN4 was significantly reduced in both PVI and NPVI patients compared to control subjects. At the tissue level, the hepatic NTN4 followed a similar trend with significantly lower mRNA expression in both patients with PVI and NPVI compared to control subjects. CONCLUSIONS: Systemic and hepatic NTN4 levels were reduced in both PVI and NPVI subjects. The hepatic expression of NTN4 receptors Neogenin and UNC5B were markedly elevated in patients with HCC with PVI compared to NPVI. Future experimental studies might shed the role of NTN4 and its receptors in the development of PVI in HCC.

Serum Levels of Netrin-4 and Its Association With Hepatocellular Carcinoma: Results From a Case-Control Study.

BACKGROUND: Angiogenesis plays a vital role in the progression of hepatocellular carcinoma (HCC) by contributing to tumor growth and metastasis. Netrin-4 (NTN4) is a secreted glycoprotein that regulates angiogenesis and maintains endothelial homeostasis. There were no studies found focusing on the value of NTN4 as a serum biomarker for the diagnosis and prognosis of HCC. In this study, we aimed to investigate the systemic expression of NTN4 in patients with HCC. We also explore the association of NTN4 with major clinicopathological and biochemical characteristics of HCC. METHODS: A total of 116 patients with HCC and 44 healthy volunteers were recruited in this case-control study. Clinical characteristics and liver function parameters were recorded among the study subjects. The levels of α-fetoprotein (AFP) were quantified in patients with HCC. The serum levels of NTN4 (pg/ml) were estimated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The median NTN4 levels were significantly decreased in patients with HCC when compared to control subjects (p < 0.0001). There was no difference between NTN4 levels in AFP-positive patients and AFP-negative patients (p = 0.39). Of note, NTN4 levels were significantly decreased in HCC patients with metastasis (p < 0.02) and portal vein invasion (p < 0.04). Further, NTN4 levels were significantly reduced in HCC patients with Child-Pugh C score (p < 0.05). The receiver operating characteristic curve for serum levels of NTN4 in the HCC group and control group was generated. At a cut-off of 30 pg/ml, the sensitivity and specificity for NTN4 were 80% and 82%, respectively, with an AUC of 0.894. CONCLUSIONS: Low levels of NTN4 were associated with increased tumor aggressiveness and metastasis in HCC. Estimation of circulating NTN4 has prognostic value as a minimally invasive biomarker in HCC. Future studies might shed the role of NTN4 in the development of HCC.

Effect of probiotics on nutritional status, biochemical parameters, and disease severity in cirrhotic patients referred for liver transplantation-A randomised double blind, placebo-controlled trial.

INTRODUCTION: Probiotics have been shown to be effective in many diseases. However, their effects on the nutritional status in patients with cirrhosis is uncertain. AIM: We aimed to study the effect of probiotics on nutritional status, biochemical parameters, and liver disease severity in patients with cirrhosis referred for liver transplantation. METHODS: A randomised, double-blind, placebo-controlled study was conducted from July 2021-October 2022. A total of 215 patients with cirrhosis referred for liver transplantation were enrolled and randomised to two groups to receive either probiotics (VSL#3, Sun Pharma, India, 112.5 billion colony-forming units (cfu) containing eight strains of bacteria) or placebo (corn starch filled capsules), two capsules/day for six weeks. Nutritional assessment was done, and biochemical parameters were measured before and after the intervention. RESULTS: Nutritional assessment parameters like body mass index (p = 0.001), triceps skin fold thickness (p = 0.011), muscle strength (p = 0.007) and subjective global assessment scores (p < 0.000) showed a positive trend in the probiotic group. Probiotic intake also significantly downregulated direct bilirubin levels (p = 0.043) and increased albumin levels compared to baseline, but other biochemical parameters remained unchanged. Child Turcotte Pugh score also decreased significantly compared to pre therapy (p = 0.0001). These changes were not observed in the placebo group. Moreover, probiotic VSL#3 supplementation was safe and well-tolerable without any adverse events in patients with cirrhosis. CONCLUSION: Probiotic VSL#3 supplementation improved the nutritional status, reduced the severity of liver disease and was safe and tolerable in patients with cirrhosis. TRIAL REGISTRATION: www.ctri.nic.in (CTRI/2021/07/034917).

Unconventional shunt surgery for non-cirrhotic portal hypertension in patients not suitable for proximal splenorenal shunt.

Backgrounds/Aims: Proximal splenorenal shunt (PSRS) is a commonly performed procedure to decompress portal hypertension, in patients with refractory variceal bleed, especially in non-cirrhotic portal hypertension (NCPH). If conventional methods are hindered by any technical or pathological factors, alternative surgical techniques may be required. This study analyzes the effectiveness of various unconventional shunt surgeries performed for NCPH. Methods: A retrospective analysis of NCPH patients who underwent unconventional shunt surgeries during the period July 2011 to June 2022 was conducted. All patients were followed up for a minimum of 12 months with doppler study of the shunt to assess shunt patency, and upper gastrointestinal endoscopy to evaluate the regression of varices. Results: During the study period, 130 patients underwent shunt surgery; among these, 31 underwent unconventional shunts (splenoadrenal shunt [SAS], 12; interposition mesocaval shunt [iMCS], 8; interposition PSRS [iPSRS], 6; jejunal vein-cava shunt [JCS], 3; left gastroepiploic-renal shunt [LGERS], 2). The main indications for unconventional shunts were left renal vein aberration (SAS, 8/12), splenic vein narrowing (iMCS, 5/8), portalhypertensive vascular changes (iPSRS, 6/6), and portomesenteric thrombosis (JCS, 3/3). The median fall in portal pressure was more in SAS (12.1 mm Hg), and operative time more in JCS, 8.4 hours (range, 5-9 hours). During a median follow-up of 36 months (6-54 months), shunt thrombosis had been reported in all cases of LGERS, and less in SAS (3/12). Variceal regression rate was high in SAS, and least in LGERS. Hypersplenism had reversed in all patients, and 6/31 patients had a recurrent bleed. Conclusions: Unconventional shunt surgery is effective in patients unsuited for other shunts, especially PSRS, and it achieves the desired effects in a significant proportion of patients.

Deep learning techniques in liver tumour diagnosis using CT and MR imaging - A systematic review.

Deep learning has become a thriving force in the computer aided diagnosis of liver cancer, as it solves extremely complicated challenges with high accuracy over time and facilitates medical experts in their diagnostic and treatment procedures. This paper presents a comprehensive systematic review on deep learning techniques applied for various applications pertaining to liver images, challenges faced by the clinicians in liver tumour diagnosis and how deep learning bridges the gap between clinical practice and technological solutions with an in-depth summary of 113 articles. Since, deep learning is an emerging revolutionary technology, recent state-of-the-art research implemented on liver images are reviewed with more focus on classification, segmentation and clinical applications in the management of liver diseases. Additionally, similar review articles in literature are reviewed and compared. The review is concluded by presenting the contemporary trends and unaddressed research issues in the field of liver tumour diagnosis, offering directions for future research in this field.

Effect of Immunonutrition on the Liver Function Status of End-Stage Liver Disease Patients Waiting/Referred for Liver Transplant: A Randomized Controlled Trial.

Background Malnutrition and liver dysfunction are commonly observed in patients with chronic liver disease. With the current surge in liver diseases, prompt nutritional planning will ensure the well-being of patients during the waiting period and will improve the clinical outcomes following liver transplantation (LT). We conducted this study to monitor the effect of immunonutrition on liver function parameters among end-stage liver disease (ESLD) patients referred for LT. Methodology In this randomized controlled trial, 144 ESLD patients who met the inclusion criteria were randomly enrolled into control (CON) and intervention (INT) groups after obtaining informed consent. Three patients were lost to follow-up due to the COVID-19 lockdown. The INT group (n = 69) was provided with 100 g of immunonutrient and the CON group (n = 72) was provided with supervised diet advice. Liver function test (LFT) parameters such as total protein, albumin, total bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and prothrombin time/international normalized ratio before and after therapy at one month were checked in both groups. Results The majority of patients with the disease were males (83.3% in the CON group vs 76.8% in the INT group), having alcoholism as the etiology in both groups with 45.8% in the CON group and 56.5% in the INT group. The comparison of LFT parameters among ESLD patients during pre and post-therapy between the control and immunonutrition groups did not show any statistically significant difference in the LFT parameters between the INT and CON groups both at baseline and at one month. Conclusions The impact of immunonutrition on ESLD patients awaiting LT compared to supervised diet advice did not significantly improve liver function. The liver disease itself profoundly affects the level of nutrition; hence, nutritional assessment and early nutritional interventions can be instituted to improve clinical outcomes.

Appraisal of gastric stump carcinoma and current state of affairs.

Gastric stump carcinoma, also known as remnant gastric carcinoma, is a malignancy arising in the remnant stomach following gastrectomy for a benign or malignant condition. Enterogastric reflux and preexisting risk factors in a patient with gastric cancer are the major contributors to the development of gastric stump carcinoma. The occurrence of gastric stump carcinoma is time-dependent and seen earlier in patients operated on for malignant rather than benign diseases. The tumor location is predominantly at the anastomotic site towards the stomach. However, it can occur anywhere in the remnant stomach. The pattern of lymph node involvement and the type of surgery required is distinctly different compared to primary gastric cancer. Gastric stump carcinoma is traditionally considered a malignancy with a dismal outcome. However, recent advances in diagnostic and therapeutic strategies have improved outcomes. Recent advances in molecular profiling of gastric stump carcinoma have identified distinct molecular subtypes, thereby providing novel therapeutic targets. Also, reports of gastric stump carcinoma following pancreatoduodenectomy and bariatric surgery highlight the need for more research to standardize the diagnosis, staging, and treatment of these tumors. The present review aims to provide an overview of gastric stump carcinoma highlighting the differences in clinicopathological profile and management compared to primary gastric carcinoma.

Role of 68 Ga-FAPI PET/CT in Assessing Hepatobiliary Malignancies : A Prospective Pilot Study.

INTRODUCTION AND AIM: Preliminary studies showed good expression of fibroblast activating protein inhibitor (FAPI) in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Our aims were to study the diagnostic performance of 68 Ga-FAPI PET/CT in diagnosing the primary hepatobiliary malignancies and to compare its performance with 18 F-FDG PET/CT. PATIENTS AND METHODS: Patients suspected to have HCC and CC were recruited prospectively. FDG and FAPI PET/CT studies were completed within 1 week. Final diagnosis of malignancy was achieved by tissue diagnosis (either histopathological examination or fine-needle aspiration cytology) and radiological correlation from conventional modalities. Results were compared with final diagnosis and expressed as sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. RESULTS: Forty-one patients were included. Thirty-one were positive for malignancy and 10 were negative. Fifteen were metastatic. Of 31, 18 were CC and 6 were HCC. For overall diagnosis of the primary disease, FAPI PET/CT performed exceptionally compared with FDG PET/CT with sensitivity, specificity, and accuracy of 96.77%, 90%, and 95.12%, respectively, versus 51.61%, 100%, and 63.41% for FDG PET/CT. FAPI PET/CT clearly outperformed FDG PET/CT for the evaluation of CC with sensitivity, specificity, and accuracy of 94.4%, 100%, and 95.24%, respectively, whereas for FDG PET/CT sensitivity, specificity, and accuracy were 50%, 100%, and 57.14%, respectively. Diagnostic accuracy of FAPI PET/CT was 61.54% for metastatic HCC compared with 84.62% for FDG PET/CT. CONCLUSIONS: Our study highlights the potential role of FAPI-PET/CT in evaluating CC. It also ascertains its usefulness in the cases of mucinous adenocarcinoma. Although it showed a higher lesion detection rate than FDG in primary HCC, its diagnostic performance in the metastatic setting is questionable.

CORRIGENDUM: Early experience with robot-assisted Frey's procedure surgical outcome and technique: Indian perspective.

[This corrects the article on p. 145 in vol. 25, PMID: 36601487.].

External pancreatic ductal stenting in minimally invasive pancreatoduodenectomy: How to do it?

It has been shown that external pancreatic ductal stenting (EPDS) can reduce the incidence of clinically relevant postoperative pancreatic fistula. Although studies have described EPDS in open pancreaticoduodenectomy (PD), EPDS in minimally invasive PD has not been reported yet. Thus, the objective of this study was to describe the technique of EPDS in minimally invasive PD. The procedure was performed either laparoscopically or using a robot. Once PD was completed, key steps included triple enterotomy, threading of silk-suture through all enterotomies and exteriorization, completing posterior layer of pancreaticojejunostomy (PJ), railroading stent through preplaced silk-suture, intubation of stent into the pancreatic duct, completion of PJ, followed by hepaticojejunostomy and parietalization of jejunum at the stent exit site. EPDS in PD through a minimally invasive approach can be performed safely in selected cases with either a small-sized pancreatic duct or a soft pancreas.

Risk factor analysis for duodenal margin positivity following gastrectomy for resectable gastric cancer.

BACKGROUND: Duodenal margin positivity is a poor prognostic factor following gastrectomy for resectable gastric cancer. Intraoperative frozen section (IFS) analysis allows radical resection to be achieved in a single operation but is time- and resource-consuming. Hence resection is usually performed based on surgeon's judgment and palpation. AIM OF STUDY: To determine risk factors for duodenal resection margin (RM) positivity following gastrectomy for resectable gastric cancer. MATERIALS AND METHODS: We retrospectively analyzed prospectively maintained data of 376 patients admitted with diagnosis of gastric cancer from August 2011 to January 2020 in JIPMER, a tertiary center in Puducherry, India. Of these, 146 patients underwent gastric resection with curative intent and were the subject of this study. RM status was assessed by definitive histopathology examination. The potential risk factors were compared between patients with positive margin on definitive histopathology examination and a control cohort of similar patients with negative margins. RESULTS: Of the 146 patients, 16 patients (10.9%), 11 men and 5 women, had positive duodenal margin. The mean age of study group was 59 years. None of the patient characteristics like age, sex, comorbidities, or addictions were statistically significant with regard to duodenal margin positivity. Among tumor characteristics, locally advanced tumors and pyloroantral tumors were found more frequently in the margin-positive group. High-risk features for duodenal margin positivity were extensive nodal disease, oligometastatic disease, lymphovascular invasion, and perineural invasion. Neoadjuvant chemotherapy and types of surgical access did not have significant impact on RM. Interestingly, both proximal and circumferential resection margin positivity had a linear association with distal margin positivity suggesting that tumor biology may have a significant role in margin positivity. However, none of these factors were statistically significant on multivariate analysis using logistic regression model. Among oligometastatic patients, survival was dependent on R0 resection and was not different from patients without metastases though our study was not powered for survival analysis (mean survival of 11.040 months) and expectedly, duodenal margin positive patients had lower overall survival compared to margin negative patients (mean survival of 5.188 vs. 11.763 months, p = 0.12). CONCLUSIONS: Locally advanced tumors and pyloroantral tumors are associated with an increased risk of duodenal margin positivity after gastrectomy for carcinoma stomach and may benefit from intraoperative frozen section analysis as survival is negatively affected by positive RM. Patients with high-risk features like extensive nodal and oligometastatic disease have a greater propensity for positive duodenal margin. A prospective study with a large sample size is needed to further validate these results.

Primary hyperparathyroidism presenting as acute pancreatitis: An institutional experience with review of the literature.

BACKGROUND: Acute pancreatitis (AP) presenting as an initial manifestation of primary hyperparathyroidism (PHPT) is uncommon, and its timely diagnosis is crucial in preventing recurrent attacks of pancreatitis. AIM: To determine the clinical, biochemical, and radiological profile of PHPT patients presenting as AP. METHODS: This is a retrospective observational study, 51 consecutive patients admitted with the diagnosis of PHPT during January 2010 and October 2021 at a tertiary care hospital in Puducherry, India was included. The diagnosis of AP was established in the presence of at least two of the three following features: abdominal pain, levels of serum amylase or lipase greater than three times the normal, and characteristic features at abdominal imaging. RESULTS: Out of the 51 consecutive patients with PHPT, twelve (23.52%) had pancreatitis [5 (9.80%) AP, seven (13.72%) chronic pancreatitis (CP)]. PHPT with AP (PHPT-AP) was more common among males with the presentation at a younger age (35.20 ± 16.11 vs 49.23 ± 14.80 years, P = 0.05) and lower plasma intact parathyroid hormone (iPTH) levels [125 (80.55-178.65) vs 519.80 (149-1649.55, P = 0.01)] compared to PHPT without pancreatitis (PHPT-NP). The mean serum calcium levels were similar in both PHPT-AP and PHPT-NP groups [(11.66 ± 1.15 mg/dL) vs (12.46 ± 1.71 mg/dL), P = 0.32]. PHPT-AP also presented with more gastrointestinal symptoms like abdominal pain, nausea, and vomiting with lesser skeletal and renal manifestations as compared to patients with PHPT-NP. CONCLUSION: AP can be the only presenting feature of PHPT. Normal or higher serum calcium levels during AP should always draw attention towards endocrine causes like PHPT.

Do preoperative pancreatic computed tomography attenuation index and enhancement ratio predict pancreatic fistula after pancreaticoduodenectomy?

BACKGROUND: The commonly used predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) have subjective assessment components and can be used only in the postoperative setting. Also, the available objective predictors based on preoperative cross-sectional imaging were not prospectively studied. AIM: To evaluate the accuracy of the pancreatic attenuation index (PAI) and pancreatic enhancement ratio (PER) for predicting CR-POPF following PD and its correlation with pancreatic fat fraction and fibrosis. METHODS: A prospective observational study included patients who underwent PD for benign and malignant pathology of the periampullary region or pancreatic head between February 2019 and February 2021. Patients undergoing extended or total pancreatectomy and those with severe atrophy of pancreatic tissue or extensive parenchymal calcifications in the pancreatic head and neck precluding calculation of PAI and PER were excluded from the study. Preoperatively PAI was measured in the neck of the pancreas by marking regions of interest (ROI) in the non-contrast computed tomography (CT), and PER was measured during the contrast phase of the CT abdomen. Also, the fibrosis score and fat fraction of the pancreatic neck were assessed during the histopathological examination. Demographic, clinical and preoperative radiological indices (PAI, PER) were evaluated to predict CR-POPF. Preoperative pancreatic neck CT indices were correlated with the histopathological assessment of fat fraction and fibrosis. RESULTS: Of the 70 patients who underwent PD, 61 patients fulfilling the inclusion criteria were included in the analysis. The incidence of CR-POPF was 29.5% (18/61). PAI had no association with the development of CR-POPF. Of the preoperative parameters, PER (mean ± standard deviation [SD]) was significantly lower in patients developing CR-POPF (0.58 ± 0.20 vs 0.81 ± 0.44, P = 0.006). The area under the curve for the PER was 0.661 (95%CI: 0.517-0.804), which was significant (P = 0.049). PER cut-off of 0.673 predicts CR-POPF with 77.8% sensitivity and 55.8% specificity. PAI and PER had a weak negative correlation (Strength-0.26, P = 0.037). Also, PER showed a moderately positive correlation with fibrosis (Strength 0.50, P < 0.001). Patients with CR-POPF had a significantly higher incidence of the intraabdominal abscess (50% vs 2.3%, P < 0.001), delayed gastric emptying (83.3% vs 30.2, P < 0.001), and prolonged mean (± SD) postoperative hospital stay (26.8 ± 13.9 vs 9.6 ± 3.6, P = 0.001). CONCLUSION: PER exhibited good accuracy in predicting the development of CR-POPF. PER additionally showed a good correlation with PAI and fibrosis scores and may be used as an objective preoperative surrogate for assessing pancreatic texture. However, ROI-based PAI did not show any association with CR-POPF and pancreatic fat fraction.

Modified binding pancreaticogastrostomy vs modified Blumgart pancreaticojejunostomy after laparoscopic pancreaticoduodenectomy for pancreatic or periampullary tumors.

BACKGROUND: Laparoscopic pancreaticoenteric anastomosis is one of the technically challenging steps of minimally invasive pancreaticoduodenectomy (PD), especially during the learning curve. Despite multiple randomized controlled trials and meta-analyses, the type of pancreatico-enteric anastomosis as a risk factor for post-pancreatectomy complications is debatable. Also, the ideal technique of pancreatic reconstruction during the learning curve of laparoscopic PD has not been well studied. AIM: To compare the short-term outcomes of modified binding pancreaticogastrostomy (PG) and Blumgart pancreaticojejunostomy (PJ) during learning curve of laparoscopic PD. METHODS: The first 25 patients with resectable pancreatic or periampullary tumors who underwent laparoscopic PD with modified binding PG or modified Blumgart PJ between January 2015 and May 2020 were retrospectively analyzed to compare perioperative outcomes during the same learning curve. A single layer of the full-thickness purse-string suture was placed around the posterior gastrotomy in the modified binding PG. In the modified Blumgart technique, only a single transpancreatic horizontal mattress suture was placed on either side of the pancreatic duct (total two sutures) to secure the pancreatic parenchyma to the jejunum. Also, on the ventral surface, the knot is tied on the jejunal wall without going through the pancreatic parenchyma. Post pancreatectomy complications are graded as per the International Study Group for Pancreatic Surgery criteria. RESULTS: During the study period, modified binding PG was performed in 27 patients and modified Blumgart PJ in 29 patients. The demographic and clinical parameters of the first 25 patients included in both groups were comparable. Lower end cholangiocarcinoma and ampullary adenocarcinoma were the primary indications for laparoscopic PD in both groups (32/50, 64%). The median operative time for pancreatic reconstruction was significantly lower in the binding PG group (42 vs 58 min, P = 0.01). The clinically relevant (Grade B/C) postoperative pancreatic fistula (POPF) was significantly more in the modified PJ group (28% vs 4%, P = 0.04). In contrast, intraluminal postpancreatectomy hemorrhage (PPH) was more in the binding PG group (32% vs 4%, P = 0.02). There was no significant difference in the incidence of delayed gastric emptying between the two groups. CONCLUSION: During the learning curve of laparoscopic PD, modified binding PG reduces POPF but is associated with increased intraluminal PPH compared to PJ using the modified Blumgart technique.

Clinicopathologic profile of gastroenteropancreatic neuroendocrine neoplasms in a referral center of South India.

BACKGROUND: The neuroendocrine system of the gastroenteropancreatic (GEP) region gives rise to unique, heterogeneous malignancies that need a high index of suspicion to make a diagnosis owing to their indolent course. AIMS: The present study aimed to find the incidence and the differences in the morphologic and immunohistochemical profile of gastroenteropancreatic neuroendocrine tumors (GEPNET) in a referral center of South India, JIPMER, Puducherry, India. METHODS: There were 55 gastroenteropancreatic region neuroendocrine neoplasms (NEN) assessed for demographic, clinical and radiological features. Gross morphological features, histopathological features, mitotic index, Ki67 proliferation index, and immunohistochemical positivity for synaptophysin, chromogranin-A, CD-56, NSE (Neuron Specific Enolase) and pan-cytokeratin (Pan-CK) were also assessed. RESULTS: The majority were nonfunctional tumors presenting with abdominal pain, gastrointestinal bleed, vomiting, jaundice, and loss of weight and appetite. The sites of involvement according to the order of frequency were duodenum, stomach, rectum, pancreas, ileum, appendix and jejunum. The endoscopic appearance of duodenal and jejunal tumors showed polypoidal, nodular and ulceroproliferative growth. These tumors were diagnosed by preoperative biopsy; 54% of them were grade-1 neuroendocrine tumors exhibiting nesting, trabecular, cord, and solid sheet patterns. All 55 cases were synaptophysin-positive with variable positivity for chromogranin, neuron-specific enolase, CD56, and Pan-CK. Mixed adenoneuroendocrine carcinomas (MANECs) involving the duodenum and stomach comprised 7.3% of all GEPNETs. Pancreatic neuroendocrine tumors constituted 9% of all tumors; one was multifocal. Lymph node metastasis was seen in 12/55 tumors; 6/12 showed liver metastasis also. All metastasizing tumors measured less than 4 cm in size. Statistical correlation of the tumor grade, mitotic count and Ki67 index as analysed by Spearman's correlation between the paired data denoted by rs in 55 tumors showed a strong correlation between mitotic count and Ki67 index; a moderate correlation was noted between the tumor grade and Ki67 index. CONCLUSION: The clinicopathologic profile of 55 GEPNET revealed a majority to be sporadic Grade 1 tumor. Tumors that showed lymph node and liver metastasis were less than 4 cm in size. MANECs were found in the duodenum and stomach.