Portal Vein Reconstruction-trans Jugular Intrahepatic Portosystemic Shunt and Portal Vein Stenting in Patients With Extrahepatic Portal Vein Obstruction.

Extrahepatic portal vein thrombosis (EHPVO) is an uncommon cause of portal hypertension. In the long term, patients may develop portal cavernoma cholangiopathy (PCC). Up to 30%-40% of patients with EHPVO may not have shuntable veins and are often difficult to manage surgically. Interventional treatment including portal vein recanalisation-trans jugular intrahepatic portosystemic shunt (PVRecan-TIPS) has been used for patients with EHPVO. However, PV reconstruction-trans jugular intrahepatic portosystemic shunt (PVRecon-TIPS) and portal vein stenting are novel techniques for managing such patients with EHPVO with non-shuntable venous anatomy. In contrast to PVRecan-TIPS, PV reconstruction-TIPS (PVRecon-TIPS) is performed through intrahepatic collaterals. Here we present six cases of PCC who presented with recurrent acute variceal bleeding (AVB) and or refractory biliary stricture. They did not have any shuntable veins. PVRecon-TIPS was performed for five patients whilst PV stenting was done in one. Amongst the six patients, one died of sepsis whilst one who developed hyponatremia and hepatic encephalopathy was salvaged with conservative management. Following the procedure, they were started on anti-coagulation. Decompression of cavernoma was documented in all other patients. Biliary changes improved completely in 40% of patients.

Current Utility of Transgastric Percutaneous Drainage for the Management of Pancreatitis-Related Retrogastric Walled-Off Necrotic Collections: A Prospective Observational Study.

Introduction Pancreatic fluid collection (PFC) is one of the most frequent complications associated with acute pancreatitis. The route of drainage is guided by the size and site of collection. The present study aims to assess the clinical and technical success of transgastric percutaneous drainage (PCD) for managing retrogastric walled-off pancreatic necrosis (WOPN). Materials and methods A total of 44 patients with acute pancreatitis diagnosed with WOPN who underwent transgastric PCD with ultrasound or CT guidance as part of standard clinical management were included in the study. Patients were observed for improvement in clinical parameters, and treatment outcomes were noted in terms of technical success, clinical success, adverse events, need for additional procedures, hospital stay, and duration of placement of all drains. Data for the internalization of transgastric PCD was also observed in the study. Results Technical success during the drain placement was observed in 93% (n=41) of patients.Internalization of the transgastric drain was attempted in 12 patients and successful in 11 (91%). The median duration of hospital stay from the time of placement of the first PCD until discharge and the median duration of all PCDs placed were higher in patients where the transgastric drain was not internalized as compared to patients where the transgastric drain was internalized. Conclusion In WOPN, transgastric drain placement and successful internalization in any form help in the early resolution of peripancreatic and abdominal collections. It also reduces the time to percutaneous catheter removal, which in turn reduces the morbidity and decreases the need for additional interventions or surgery.

Implications of Gender on the Outcome in Patients With Autoimmune Hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is uncommon and predominantly affects females. Data on AIH from India are scanty. We retrospectively analyzed the spectrum and outcome of adults with AIH and compared it between male and female patients. METHODS: AIH was diagnosed using a simplified AIH score. For suspected seronegative AIH, the revised score was used. Standard therapies for AIH and portal hypertension were administered and response was assessed at six months. Relapse rates and five-year mortality were also evaluated. RESULTS: Of the 157 patients with AIH, 85 (male: female 25: 60) were included in the study. The median age at diagnosis was 46 (interquartile range (IQR) 32-55.5) years in males vs 45 (IQR 34.2-54) years in females (p=0.91). A similar proportion of male and female patients presented with cirrhosis, acute severe AIH, or AIH-related acute on chronic liver failure (ACLF); Extra-hepatic autoimmune diseases were less common in male patients (16% vs 35.5% p=0.02). Other laboratory and histological features were comparable in both groups. During the median follow-up period of 51 months (IQR 45-67 months). The biochemical and clinical response at six months were seen in 64% of male patients and 63.3% of female patients (p= 0.57). Of patients, 75% relapsed in the male AIH group (12 of 16 patients) after initial remission compared to 42% in the female group (p=0.02). Five-year mortality was 14.1%, and no patient developed hepatocellular carcinoma. CONCLUSION: Male and female patients with AIH have similar clinical, biochemical, and histological profiles. More male patients relapsed after an initial response to therapy.

PD-L1 Expression in Ampullary Adenocarcinoma.

INTRODUCTION: Ampullary adenocarcinoma is a rare neoplasm often treated by the complex Whipple's procedure. Several histological factors predict poor prognosis including pancreatobiliary morphology, presence of lymphovascular, perineural invasion and local or distant metastasis. Systemic therapy with gemcitabine, 5-fluorouracil regimens are given with variable benefits. Immunotherapy checkpoint inhibitors have shown beneficial anti-tumor effects in several carcinomas, the most remarkable being in non-small cell lung cancer. Administration of these novel drugs is based on immunohistochemical expression (which may or may not be indicative of response to therapy) along with meticulous decision making by the multidisciplinary team. Immunohistochemistry (IHC) is an effective means of immune marker demonstration and has been used in various tumor types for predictive and prognostic purposes. METHODS: PD-L1 IHC (clone E1L3N) was applied in 101 cases of ampullary adenocarcinoma. Tumor infiltrating lymphocytes were also evaluated. The immunoreactivity was assessed and categorized into following staining thresholds: <1%, <5%, <10% and ≥10% for tumor cells (membranous and/or cytoplasmic staining pattern), and 5% and 10% cut-offs for immune cells. RESULTS: We found that at a 10% cut-off, 73.3% (74/101) patients were men (P = .006) older than 50 years of age (P < .001) presenting with a tumor measuring <3 cm (P = .001). It was significantly associated with intestinal differentiation (P = .004) and grade 1 tumors (P = .001). Twelve patients presented with recurrence as well (P = .03). CONCLUSION: In the context of ampullary adenocarcinoma, this study highlights the positivity observed with the PD-L1 IHC clone E1L3N at different thresholds, with the particularly stronger associations being evident at a 10% cut-off.

Endoscopic Band Ligation in Blue Rubber Bleb Nevus Syndrome: A Report of Two Children.

Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital disorder presenting with multifocal venous malformations of the skin, soft tissues, and gastrointestinal (GI) tract. Patients usually present with chronic anemia resulting from occult GI bleeding and sometimes with massive GI bleeding. We report 2 children with blue rubber bleb nevus syndrome with GI bleeding: 1 with obscure GI bleeding and the other with overt GI bleeding. In both cases, the presence of cutaneous lesions provided useful clues toward diagnosis. Colonoscopy and upper GI endoscopy revealed bluish polypoidal lesions in the GI tract. Capsule endoscopy helped in disease mapping. Both of them were successfully treated with endoscopic band ligation and nonselective beta-blockers, which resulted in an improvement in their hemoglobin levels. Our cases highlight the successful use of endoscopic band ligation of GI lesions as a therapeutic modality. It is important for gastroenterologists to be aware of this rare condition for current diagnosis.

PHPT with Pancreatitis: Atypical Presentation of PHPT.

Background: Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study aimed to assess the prevalence and disease characteristics of pancreatitis in PHPT. Materials and Methods: This study is a clinicopathological analysis of the medical records of patients who were diagnosed with PHPT with pancreatitis between 1989 and 2021 in the Endocrine Surgery department, SGPGI, Lucknow. Results: Out of 548 PHPT cases, 44 (8.03%) were found to be associated with pancreatitis. The mean age was 33.57 years (15-65 years); 5 were ≤20 years, while 26 were ≤30 years of age. There were 27 males and 17 females. Twenty-one cases were of acute (11 acute, nine recurrent acute, one acute on chronic), whereas 23 were of chronic pancreatitis (six chronic calcific pancreatitis). The major clinical presentation of PHPT with pancreatitis was abdominal pain (65.91%). The mean number of attacks per patient in recurrent acute pancreatitis was two. Mean PTH levels were 68.19 pmol/L. The mean tumor size (in the largest dimension) was 2.79 ± 1.4 cm while the mean tumor weight was 4.91 g. Nephrolithiasis was associated with 25 cases. An association with multiple endocrine neoplasia type 1 syndrome was seen in one case. The final histopathological diagnosis was parathyroid carcinoma in two, hyperplasia in three, and parathyroid adenoma in 39 cases. Normocalcemia was seen in 27.2%, hypercalcemic crisis in 15.9%, and 25% of patients required semi-emergency parathyroidectomy. The outcome was favorable in all, as none had any further attacks of pancreatitis. Conclusion: In our study, the prevalence of pancreatitis in PHPT cases was 8.03%. The majority of patients were young. Normocalcemia was seen in 12 patients, so even if calcium levels are normal, PHPT should be suspected in young patients with pancreatitis. Parathyroidectomy resulted in the complete resolution of symptoms of pancreatitis in all 44 patients.

Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing.

Ampulla is a complex region located at the confluence of pancreatic and common bile duct and intestinal epithelium. Tumors arising in this region are anatomically and morphologically heterogenous, however they show unique as well as overlapping molecular features. Cancers of both these anatomic sites share morphological as well as genetic profile despite having few unique differences. Targeted therapies are currently emerging as one of the demanding approaches for treatment in most cancer types especially for malignant epithelial tumors and therefore genetic profiling of cancers is the key for identification of potentially therapeutic targetable mutations to know their prevalence and prognostic impact. We studied 97 resected cases of formalin fixed paraffin-embedded AC by deep targeted sequencing using Ampliseq cancer hotspot panel comprising of 50 oncogenes and tumor suppressor genes. Potentially therapeutic targetable mutations were observed in 58/83 (70%) cases. Fourteen patients did not show any pathogenic mutation. TP53 (48.1%), KRAS (37.3%), APC (25.3%), SMAD4 (22.8%), MET (16.8%), CTNNB1 (15.6%) and PIK3CA (10.8%) were the major mutated potential therapeutic targets. KRAS mutation (43.2 Vs. 32.6%) was more prevalent in pancreatobiliary subtype, while TP53 (58.6 Vs 35.1), APC (36.9 Vs 10.8), SMAD4 (28.2 Vs 16.2), MET (21.7 Vs 10.8) and CTNNB1 (19.5 Vs 10.8) were more prevalent in intestinal subtype. WNT signaling pathway was the major altered pathway in intestinal subtype. These mutated genes and pathways may be targeted with currently available drugs and may be explored for future development of targetable agents to improve the disease course in patients of AC.

Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing.

BACKGROUND: The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. METHODS: We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. RESULTS: There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2-257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1-31/case), while PB showed variations in 51 genes (1-29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). CONCLUSIONS: The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.

Diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of tubercular lymphadenitis using combination of cytology and Gene Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) genes.

Diagnostic yield of an automated molecular test, Gene Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF), was evaluated in this study to simultaneously detect the MTB gene and resistance to rifampicin (RIF) on cytology samples acquired via endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNAC) in suspected tubercular lymphadenitis. Microscopy, cytology, Gene Xpert MTB/RIF assay data on Acid-fast bacillus (AFB), and traditional culture of lymph nodes were retrospectively analyzed. Thirty-one patients (median age 33.5 years, inter-quartile range [IQR] 21-66, 18, 58% female) presented with fever (28, 90%), dysphagia (2, 7%), and recurrent subacute intestinal obstruction (1, 3%). Gene Xpert showed higher sensitivity (30, 97%) compared to the other tests: cytology (23, 77%; odds ratio [OR] 8.8, 95% confidence interval [CI] 1.0-76.9; p = 0.05), AFB smears (12, 39%; OR 50, 95% CI 5.9-420.4; p = 0.00001), and conventional culture (4, 13%; OR 188.5, 95% CI 19.7-1796.3; p = 0.0000). We conclude that Gene Xpert MTB/RIF test on EUS-guided FNAC samples is very useful to diagnose tubercular lymphadenitis.

Prevalence and spectrum of pathogenic germline variants in intestinal and pancreatobiliary type of ampullary cancer.

BACKGROUND: Ampullary cancer may occur as a component of hereditary cancer syndromes. Mutations in inherited cancer susceptibility genes play a therapeutic role and its knowledge in ampullary cancer is lacking. METHODS: Thirty-seven cases of ampullary carcinoma were subjected to tumor-normal whole exome sequencing with mean coverage of 100X (blood) and 200X (tumor). Data were analyzed and correlated with intestinal and pancreatobiliary differentiation. RESULTS: There were 22 intestinal, 13 pancreatobiliary and 2 cases of mixed differentiation. One hundred and forty-three germline variations with at least >1 pathogenic germline variants (PGVs) across 83 genes were found in 36 of 37 patients. Twelve genes (14.5 %) showed >3, 20 genes (24.1 %) showed two and 51 genes (61.4 %) showed one PGVs. Intestinal differentiation showed higher PGVs (117 variants, 73 genes) than pancreatobiliary differentiation (85 variants, 62 genes). PGVs in ERCC5, MEN1, MSH3, CHEK1, TP53, APC, FANCA, ERBB2, BRCA1, BRCA2, RTEL1, HNF1A and PTCH1 were seen in >50 % of cases. Nine genes harbored somatic second hits in 14 cases. PGVs in DNA damage-repair, homologous recombination repair, TP53 transcriptional regulation, DNA double stranded breaks, cell cycle and nucleotide excision repair genes were seen in all cases of intestinal and pancreatobiliary differentiation, while DNA mismatch repair genes were found in 81.8 % of intestinal and 84.6 % of pancreatobiliary cancers. Functional pathway analysis showed that DNA damage-repair, double stranded break repair, mismatch repair, homologous recombination repair and TP53 transcriptional regulation genes were altered in both while nucleotide-excision repair was significantly mutated in intestinal type and cell-cycle genes in pancreatobiliary type (p < 0.05). CONCLUSION: This study reports spectrum of PGVs in intestinal and pancreatobiliary differentiation of ampullary carcinoma at higher frequency through whole exome sequencing. PGVs were most frequently found in DNA repair genes. Detecting PGVs through tumor-normal sequencing may identify therapeutically actionable and double-hit mutations that can guide towards appropriate management.

Investigation of LOY in Prostate, Pancreatic, and Colorectal Cancers in males: A case-control study.

Background: LOY is associated with ageing and increase the incidence of cancers. Aims: To elucidate the role of LOY in various cancer types, namely, prostate (PRT), pancreatic (PC), and colorectal (CRC) cancers in males. Material and Methods: Fifty CRC patients [mean age = 44.58±11.2 years], fifty PRT [mean age= 60.48± 17.07 years] and fifty PC [mean age = 48.74 ±16.45 years] along with 100 healthy controls [mean age= 54.06 ±15.04 years] were recruited. DNA was isolated from peripheral blood and was subjected to multiplex QF-PCR. The Y/X ratio was calculated from the peak height. Results: The mean Y/X ratio was lower in all patients with cancers (0.875333± 0.086; p value˂ 0.0001) than in controls (1.11 ± 0.071), as well as, in CRC (0.926±0.192; p value˂0.0001), PC (0.85 ± 0.0311; p value˂0.0001) and PRT (0.85±0.122; p value˂0.0001) when calculated separately. Multivariate logistic regression analysis was used to analyze the strength of the presence of cancer prediction using the percentage of LOY and age showed that LOY (p= 0.001) is a better predictor of cancer presence than age (p= 0.359). Conclusion: LOY in blood could be a predictive biomarker in the carcinogenesis of males.

Dual Airway and Esophageal Stenting in Advanced Esophageal Cancer With Lesions Near Carina.

BACKGROUND: Tracheobronchial stenting either alone or with esophageal stenting is often required for symptom palliation in obstructive or fistulous lesions of the airway due to esophageal cancer. There is limited evidence regarding dual stenting for lesions near the carina due to esophageal cancer. Hence, this study aims to evaluate the technical feasibility, outcomes, and complications of preplanned dual stenting in these patients. METHODS: This is a prospective observational study carried out over a period of 4 years (January 2015 to July 2019). All patients undergoing dual stenting in the airway and esophagus with obstructive or fistulous lesions near the carina were included. The esophageal stent was placed within 24 hours. Prestenting and poststenting symptoms were compared using a symptom-based visual analog scale, Hugh Jones dyspnea scale and dysphagia scale. RESULTS: Twenty-nine patients (20 males; mean±SD age, 55.3±12.2 y) underwent dual stenting. Twenty-four patients had central airway obstruction due to: infiltration in 20 (69%) and external compression in 4 (13.7%), respectively. Five (17.3%) patients had tracheoesophageal fistula with no airway obstruction. In 80% of the patients (n=23), silicone stents were placed. There was significant improvement in both dyspnea and dysphagia after dual stenting (P<0.001). Mucus plugging, lower respiratory infection, and granulation tissue were the main complications. Median survival after dual stent was 97 days (range, 17 to 297 d). CONCLUSION: Dual stenting within the airway and the esophagus is a safe and viable option for palliative relief of symptoms in patients with advanced esophageal cancer.

Childhood pancreatic trauma: Clinical presentation, natural history and outcome.

OBJECTIVES: To study the presentation, management strategies and long-term natural history of children with pancreatic trauma. METHODS: Children admitted with pancreatic trauma were analyzed for their presentation, management and outcome. Management included nasojejunal feeds, total parenteral nutrition (TPN), octreotide, drainage (radiological and endoscopic), endoscopic retrograde cholangiopancreatography (ERCP) and surgery. Patients were assessed in follow-up for development of chronic pancreatitis (CP). RESULTS: 36 children [29 boys, age 144 (13-194) months] presented at 30 (3-210) days after trauma. Most common cause of trauma was bicycle handle bar injury [n = 18,50%]. Presenting features were abdominal pain [n = 26,72%], lump [n = 16, 44.4%], ascites [n = 13,36%], pleural effusion [n = 9,25%] and anasarca [n = 3,8.3%]. All presented with sequelae of ductal disruption with pseudocyst, ascites or pleural effusion. Fifteen (41.6%) patients each had Grade III and IV injury, 4 (11%) had grade V, and grading was unavailable in 2. Other organs were injured in 4 (11%) cases. Management consisted of various combinations of nasojejunal feeds [n = 17,47.2%], TPN [n = 5,13.8%], octreotide [n = 13,36%], pseudocyst drainage [radiological (n = 18,50%), endoscopic (n = 3,8.3%)] and ERCP [n = 12,33.3%]. Surgical intervention was done in 2 (5.5%) cases [cystojejunostomy and peritoneal lavage in 1 each]. Two (5.5%) patients died due to sepsis. Of the 32 cases in follow-up, 19 (59.3%) recovered and 13 (40.6%) developed CP, with half (6/13) of them being symptomatic with recurrent pain. CONCLUSION: Multi-disciplinary non-operative management is effective for managing pancreatic trauma in 94.4% of children, with 75% requiring radiological or endoscopic intervention. 40% developed structural changes later but only half were symptomatic.

Palliation of malignant gastroduodenal obstruction with self-expandable metal stent using side- and forward-viewing endoscope: Feasibility and outcome.

BACKGROUND: The endoscopic placement of a self-expandable metal stent (SEMS), an alternative to surgical bypass for the palliation of malignant gastric outlet obstruction (GOO), is commonly performed using a forward-viewing endoscope with a wide therapeutic channel; however, due to limited availability, most Indian centers use a side-viewing duodenoscope. We studied the feasibility and outcome of SEMS placement using side- and forward-viewing endoscopes. METHOD: Data of patients undergoing SEMS placement using side- and forward-viewing endoscopes with a therapeutic channel for the palliation of malignant GOO presenting during a 5-year period were analyzed retrospectively. Follow-up data were obtained from records and telephonic interviews, and technical and clinical success, complications, and survival were evaluated. RESULTS: Of 114 patients (age 56.5 ± 11.6 years, 59 [52%] female), 90 (79%) and 24 (21%) underwent SEMS placement using side- and forward-viewing endoscopes, respectively. Technical (89, 98.9% vs. 24, 100%, P = ns) and clinical success (84, 93.3% vs. 23, 95.8%, P = ns) and complication rate (3, 3.3% vs. 0, P = ns) between side- and forward-viewing endoscopes were comparable. However, SEMS could be placed in a shorter time using a forward- rather than side-viewing endoscope (21 min [inter-quartile range 19.5-35] vs. 34 min [25-45], P = < 0.001). SEMS could be deployed successfully with a forward-viewing endoscope in two patients in whom an initial attempt using side-viewing endoscope failed. Gastric outlet obstruction scoring system (GOOSS) improved following stent placement (median 0, range 0-2 vs. 2, 0-3, P = 0.0001). The survival of patients undergoing SEMS placement using side- and forward-viewing endoscopes was comparable. CONCLUSION: Although side- and forward-viewing endoscopes are equally effective for antroduodenal SEMS placement, the procedure can be performed faster using the latter.

Perforation following pneumatic dilation of achalasia cardia in a university hospital in northern India: A two-decade experience.

Pneumatic dilation (PD) is a cost-effective first-line treatment for achalasia. The most feared complication of PD is esophageal perforation (EP). As data on EP after PD for achalasia are not widely reported, we present the frequency, risk factors, and treatment-outcome of EP. Records of patients undergoing PD for achalasia (January 1995 to September 2015) were retrospectively reviewed. Of 433 patients (age 38 years, 13-88, 57% male), and 521 dilations, 12 were complicated by EP (2.7% of patients and 2.3% of PD). EP occurred in 7 (3.4%), 4 (1.7%), and 1 (4.1%) with use of balloon diameters 30, 35, and 40 mm, respectively. In most (11/12, 92%), EP occurred during the first PD. No risk factor for EP was identified (p = 0.65 for the first dilation vs. > 1 dilation, and 0.75 for balloon size of 30 mm vs. > 30 mm). Seven patients with contrast leak on esophagogram and/or computed tomography scan underwent surgery. One other with contrast leak was successfully treated with a fully covered self-expandable metal stent (FC-SEMS); the remaining four with small leak/pneumomediastinum were managed conservatively. The median duration of hospital stay following perforation was 13 days (7-26) and 8 days (6-10) in surgery and conservative groups, respectively. No mortality was observed in either group. The frequency of EP with PD was 2.3%. Though most EP (92%) occurred during the first dilation, neither the balloon size nor repeated dilations were identified as risk factors. Both surgical and conservative approaches had a favorable outcome in appropriate settings.