1.Case Reports on Black Fungus of the Gastrointestinal Tract: A New Complication in COVID-19 Patients
Sachin ARORA ; Ashish SINGH ; Pallavi PRASAD ; Rahul ; Rajneesh SINGH
The Korean Journal of Gastroenterology 2023;81(5):221-225
Gastrointestinal mucormycosis is a rare disease with a significant mortality rate, even when promptly diagnosed and treated. An unusual complication was observed in India during the second wave of coronavirus disease 2019 (COVID-19). Two incidences of gastric mucormycosis were found. A 53-year-old male patient with a history of COVID-19 one month earlier came into the intensive care unit. After admission, the patient developed hematemesis, which was initially treated with blood transfusions and digital subtraction angiography embolization. Esophagogastroduodenoscopy (EGD) revealed a large ulcer with a clot in the stomach. During an exploratory laparotomy, the proximal stomach was necrotic. Histopathological examination confirmed mucormycosis. The patient was started on antifungals, but despite rigorous therapy, the patient died on the tenth postoperative day. Another patient, an 82-year-old male with a history of COVID-19, arrived with hematemesis two weeks earlier and was treated conservatively. EGD revealed a large white-based ulcer with abundant slough along the larger curvature of the body. Mucormycosis was verified by biopsy.He was treated with amphotericin B and isavuconazole. He was discharged after two weeks in a stable condition. Despite quick detection and aggressive treatment, the prognosis is poor. In the second case, prompt diagnosis and treatment saved the patient’s life.
2.Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing
Niraj KUMARI ; Rajneesh K. SINGH ; Shravan K. MISHRA ; Narendra KRISHNANI ; Samir MOHINDRA ; Raghvendra L.
Journal of Pathology and Translational Medicine 2021;55(3):192-201
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.
3.Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing
Niraj KUMARI ; Rajneesh K. SINGH ; Shravan K. MISHRA ; Narendra KRISHNANI ; Samir MOHINDRA ; Raghvendra L.
Journal of Pathology and Translational Medicine 2021;55(3):192-201
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.
4.Mirizzi's syndrome: lessons learnt from 169 patients at a single center.
Ashok KUMAR ; Ganesan SENTHIL ; Anand PRAKASH ; Anu BEHARI ; Rajneesh Kumar SINGH ; Vinay Kumar KAPOOR ; Rajan SAXENA
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2016;20(1):17-22
BACKGROUNDS/AIMS: Mirizzi's syndrome (MS) poses great diagnostic and management challenge to the treating physician. We presented our experience of MS cases with respect to clinical presentation, diagnostic difficulties, surgical procedures and outcome. METHODS: Prospectively maintained data of all surgically treated MS patients were analyzed. RESULTS: A total of 169 MS patients were surgically managed between 1989 and 2011. Presenting symptoms were jaundice (84%), pain (75%) and cholangitis (56%). Median symptom duration s was 8 months (range, <1 to 240 months). Preoperative diagnosis was possible only in 32% (54/169) of patients based on imaging study. Csendes Type II was the most common diagnosis (57%). Fistulization to the surrounding organs (bilio-enteric fistulization) were found in 14% of patients (24/169) during surgery. Gall bladder histopathology revealed xanthogranulomatous cholecystitis in 33% of patients (55/169). No significant difference in perioperative morbidity was found between choledochoplasty (use of gallbladder patch) (15/89, 17%) and bilio-enteric anastomosis (4/28, 14%) (p=0.748). Bile leak was more common with choledochoplasty (5/89, 5.6%) than bilio-enteric anastomosis (1/28, 3.5%), without statistical significance (p=0.669). CONCLUSIONS: Preoperative diagnosis of MS was possible in only one-third of patients in our series. Significant number of patients had associated fistulae to the surrounding organs, making the surgical procedure more complicated. Awareness of this entity is important for intraoperative diagnosis and consequently, for optimal surgical strategy and good outcome.
Bile
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Bile Duct Diseases
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Cholangitis
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Cholecystitis
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Cholestasis
;
Diagnosis
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Fistula
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Gallbladder
;
Humans
;
Jaundice
;
Mirizzi Syndrome*
;
Prospective Studies
;
Urinary Bladder
5.Risk Factors for Development of Biliary Stricture in Patients Presenting with Bile Leak after Cholecystectomy.
Hosur Mayanna LOKESH ; Biju POTTAKKAT ; Anand PRAKASH ; Rajneesh Kumar SINGH ; Anu BEHARI ; Ashok KUMAR ; Vinay Kumar KAPOOR ; Rajan SAXENA
Gut and Liver 2013;7(3):352-356
BACKGROUND/AIMS: This study was aimed at determining the factors associated with the development of benign biliary stricture (BBS) in patients who had sustained a bile duct injury (BDI) at cholecystectomy and developed bile leaks. METHODS: A retrospective analysis of 214 patients with BDI who were referred to our center between January 1989 and December 2009 was done. RESULTS: One hundred fifty-three (71%) patients developed BBS (group I), and 61 (29%) were normal (group II). By univariate analysis, female gender (p=0.02), open cholecystectomy as the index operation (p=0.0001), delay in the referral from identification of injury (p=0.04), persistence of an external biliary fistula (EBF) beyond 4 weeks (p=0.0001), EBF output >400 mL (p=0.01), presence of jaundice (p=0.0001), raised serum total bilirubin level (p=0.0001), raised serum alkaline phosphatase level (p=0.0001), and complete BDI (p=0.0001) were associated with the development of BBS. Furthermore, open cholecystectomy as the index operation (p=0.04), delayed referral (p=0.02), persistent EBF (p=0.03), and complete BDI (p=0.001) were found to predict patient outcome in the multivariate analysis. CONCLUSIONS: For the majority of patients with BDI, the risk of developing BBS could have been predicted at the initial presentation.
Alkaline Phosphatase
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Bile
;
Bile Ducts
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Biliary Fistula
;
Bilirubin
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Cholecystectomy
;
Constriction, Pathologic
;
Female
;
Humans
;
Jaundice
;
Referral and Consultation
;
Retrospective Studies
;
Risk Factors