Methylation study of tumor suppressor genes in human aberrant crypt foci, colorectal carcinomas, and normal colon.

BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.

Clinical significance of Notch pathway-associated microRNA-107 in pancreatic ductal adenocarcinoma.

Background & aim: MicroRNAs associated with the Notch pathway play a critical role in the progression of pancreatic carcinoma. Our aim was to study the clinical significance of miR-107 and NOTCH2 in pancreatic ductal adenocarcinoma (PDAC). Methods: The circulating miR-107 levels in PDAC and controls were determined by qPCR. NOTCH2 protein (target) expression in tissue of PDAC, periampullary carcinoma, chronic pancreatitis and normal pancreatic tissue was assessed by immunohistochemistry. Results: The circulating miR-107 levels were found to be significantly reduced in PDAC as compared with controls. Additionally, NOTCH2 protein expression was higher in PDAC tissue as compared with controls and was clinically associated with metastasis. Conclusion: Our findings demonstrate the utility of circulating miR-107 as a potential differentiating marker in PDAC.

Hemorrhage and Rupture of an Unusual Benign Liver Lesion in Pregnancy: A Case Report.

Liver rupture in pregnancy is an acute condition with significant risk to the mother and fetus. It is known to occur with tumors such as hepatic adenoma, infective causes such as abscess, granulomatous diseases, and parasitic infections, and rarely spontaneously. Most of these conditions have overlapping clinicoradiological findings, almost always requiring histopathological confirmation. We report a case of a ruptured hepatic lesion, with an unusual diagnosis of Bartonella henselae infection causing cat-scratch disease, in a 24-year-old pregnant lady.

Sepsis Following Liver Biopsy in a Liver Transplant Recipient: Case Report and Review of Literature.

Percutaneous liver biopsy is a relatively safe procedure with low complication rates. Infections following liver biopsy are uncommon and can lead to a poor outcome. There are limited data on liver biopsy-related infections among liver transplant (LT) recipients. Also, there is a paucity of data regarding the use of prophylactic antibiotics in LT patients undergoing percutaneous liver biopsy. We report a case of systemic sepsis following percutaneous liver biopsy in a LT recipient with choledochojejunal anastomosis. This was followed by severe rejection and deterioration of liver function and recurrence of primary sclerosing cholangitis (PSC) to the extent that he has been listed for retransplantation. This case report emphasizes the potential risk of sepsis in LT recipients with bilioenteric anastomosis undergoing percutaneous liver biopsy. This increased risk may warrant periprocedural broad spectrum antibiotic prophylaxis, in this subgroup of patients.

Altered respiratory microbiota composition and functionality associated with asthma early in life.

BACKGROUND: The microbiota of the respiratory tract has an important role in maintaining respiratory health. However, little is known on the respiratory microbiota in asthmatic patients among Middle Eastern populations. This study investigated the respiratory microbiota composition and functionality associated with asthma in Emirati subjects. METHODS: We performed 16S rRNA and ITS2-gene based microbial profiling of 40 expectorated sputum samples from adult and pediatric Emirati individuals averaging 52 and 7 years of age, respectively with or without asthma. RESULTS: We report bacterial difference belonging to Bacteroidetes, Firmicutes, Fusobacteria and Proteobacteria phyla between asthmatic and non-asthmatic controls. Similarly, fungal difference belonging to Ascomycota, Basidiomycota phyla and other unclassified fungi. Differential abundance testing among asthmatic individuals with relation to Asthma Control Test show a significant depletion of Penicillium aethiopicum and Alternaria spp., among poorly controlled asthmatics. Moreover, data suggest a significant expansion of Malassezia spp. and other unclassified fungi in the airways of those receiving steroids and leukotriene receptor antagonists' combination therapy, in contrast to those receiving steroids alone. Functional profiling from 16S data showed marked differences between pediatric asthmatic and non-asthmatic controls, with pediatric asthmatic patients showing an increase in amino acid (p-value < 5.03 × 10- 7), carbohydrate (p-value < 4.76 × 10- 7), and fatty acid degradation (p-value < 6.65 × 10- 7) pathways, whereas non-asthmatic controls are associated with increase in amino acid (p-value < 8.34 × 10- 7), carbohydrate (p-value < 3.65 × 10- 7), and fatty acid (p-value < 2.18 × 10- 6) biosynthesis pathways in concordance with enterotype composition. CONCLUSIONS: These differences provide an insight into respiratory microbiota composition in Emirati population and its possible role in the development of asthma early in life. This study provides important information that may eventually lead to the development of screening biomarkers to predict early asthma development and novel therapeutic approaches.

Specific Tumor Characteristics Predict Upstaging in Early-Stage Esophageal Cancer.

BACKGROUND: Early-stage esophageal cancer (stages 0-1) has been shown to have relatively good outcomes after local endoscopic or surgical resection. For this reason, neoadjuvant chemoradiation usually is reserved for higher-stage disease. Some early tumors, however, are found after resection to be more advanced than predicted based on initial clinical staging, termed pathologic upstaging. Such tumors may have benefited from alternate treatment models had their true stage been known preoperatively. This study aimed to identify high-risk features in early esophageal cancers that might predict tumor upstaging and guide more individualized treatment algorithms. METHODS: Through retrospective review of a single-institution foregut disease registry, we evaluated patients who underwent esophagectomy for high-grade dysplasia (Tis) or stage 1 esophageal cancer, searching for factors associated with pathologic upstaging. RESULTS: The review included 110 patients (88% male, median age at diagnosis, 64.5 years) treated between January 2000 and June 2016. Upstaging occurred for 20.9% of the patients, and was more common for patients with angiolymphatic invasion (odds ratio [OR], 11.07; 95% confidence interval [CI], 2.96-41.44; P < 0.001) or signet-ring features (OR, 23.9; 95% CI, 2.6-216.8; P = 0.005). In the absence of other predictors, upstaging was associated with decreased overall survival (P = 0.006). CONCLUSIONS: Approximately 20% of patients with early-stage esophageal cancer may be upstaged at resection. Angiolymphatic invasion and signet-ring features may predict tumors likely to be upstaged, resulting in decreased overall survival.

Topographic, histological and molecular study of aberrant crypt foci identified in human colon in different clinical groups.

BACKGROUND/AIMS: Aberrant crypt foci (ACF) are early microscopic lesions of the colonic mucosa, which can be detected by magnified chromoendoscopy. Herein, we have investigated whether ACF identified in different clinical groups can be differentiated based on their characteristics. METHODS: Macroscopically unremarkable mucosal flaps were collected from 270 fresh colectomies and divided into 3 clinical groups: colorectal carcinoma (group A), disease controls having known pre-neoplastic potential (group Bc), and disease controls without risk of carcinoma development (group Bn). Topographic and histologic analysis, immunohistochemistry, and molecular studies (high-resolution melt curve analysis, real-time polymerase chain reaction, and Sanger sequencing) were conducted for certain neoplasia-associated markers. RESULTS: ACF were seen in 107 cases, out of which 72 were left colonic ACF and 35 right colonic ACF (67.2% vs. 32.7%, P=0.02). The overall density of left colonic ACF was 0.97/cm, which was greater than the right colonic ACF density of 0.81/cm. Hypercrinia was present in 41 out of 72 left colonic ACF and in 14 out of 35 right colonic ACF (P=0.01). Immunohistochemical expression of p53 was also greater in left colonic ACF than in right colonic ACF (60.5% vs. 38.2%, P=0.03). However, ACF identified among the 3 clinical groups did not show any distinguishing topographic, histological, or genetic changes. CONCLUSIONS: Left colonic ACF appear to be high-risk based on their morphological and prototypic tumor marker signature. ACF identified in different clinical groups do not show significant genotypic or topographic differences. Further detailed genetic studies are required to elucidate them further.

Pancreaticojejunostomy: Does the technique matter? A randomized trial.

BACKGROUND: Despite a large number of studies, the ideal technique of pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD) remains debatable. We compared the two most common techniques of PJ (duct-to-mucosa and dunking) in a randomized trial. METHODS: This open-label randomized trial was done at a tertiary care center from January 2009 to October 2015. Patients with resectable periampullary tumours with a pancreatic duct diameter ≥2 mm, requiring PD were randomly assigned to one of the two techniques using computer generated random numbers. The primary outcome was postoperative pancreatic fistula (POPF) rate and secondary outcomes were frequency of other postoperative complications. RESULTS: A total of 193 patients were randomized and analyzed (intention-to-treat analysis), 97 in duct-to-mucosa and 96 in dunking group. Both groups were comparable for baseline demographic and clinical profiles. The incidence of POPF in the entire study group was 23.8%. There was no statistically significant difference between the two groups (24.7% vs 22.9%, P = 0.71). Similarly, the incidence of grades B and C (clinically significant) POPF was comparable (16.5% vs 13.5%, P = 0.57). Both groups were comparable with respect to the secondary outcomes. DISCUSSION: The duct-to-mucosa technique of PJ after PD is not superior to the dunking technique with respect to POPF rate. (CTRI/2010/091/000531).

Pancreatic heterotropia in wall of extra-hepatic choledochal cysts: A retrospective analysis of thirteen of such cases from north India.

INTRODUCTION: Heterotopic pancreas (HP) has rarely been identified in the wall of choledochal cyst (CC). METHODS: Retrospectively we screened 200 excised specimens of CC received at our Institute over a period of last eight years and looked for presence of HP rests in them. All the specimens were processed in their entirety. RESULT: HP was identified in the wall of 13 (6.5%) CCs, out of which 11 were Heinrich Type 2, and two were Heinrich Type 1. In half of the cases peribiliary mucous glands were observed intermingled with the HP rests. Features of chronic fibrosing pancreatitis were identified in these rests, with ulceration of overlying cyst lining. CONCLUSIONS: HP rests in the wall of CC though rare; their coexistence with peribiliary glands may possibly indicate their common embryonic origin. As a common site of inflammation, HP rest may be one of the common causes of CC.

Left-sided colitis and extensive colitis have similar colectomy rates after index episode of acute severe colitis: A long-term follow-up study.

BACKGROUND AND AIM: The extent of disease of ulcerative colitis (UC) has been found to be a predictor of acute severe colitis (ASC), but it is unclear whether the extent of disease at the index episode of ASC is a predictor of long-term outcome. METHODS: Hospitalized patients satisfying Truelove and Witts' criteria under follow-up at a single center from January 2003 to December 2016 were included. The extent of disease at index ASC was classified according to the Montreal classification as left-sided or extensive colitis. Extent was used to predict the long-term risk of colectomy or steroid dependence following an index episode of ASC. RESULTS: Of 2076 patients with ulcerative colitis, 241 (12%) had an index episode of ASC. In total, 34 (14%) patients underwent a colectomy at index admission and 53 (26%) over a median follow-up of 48(1-172) months. Left-sided colitis and extensive colitis did not differ in the rate of colectomy at index admission (12% vs 15%, P = 0.4) and colectomy in follow-up (31% vs 23%, P = 0.17). Readmission due to ASC was also similar between the two groups (28% vs 32%, P = 0.6). CONCLUSION: Extent of disease at index ASC does not predict colectomy at admission and over the long term.

Spectrum of hepatobiliary cystic lesions: A 7-year experience at a tertiary care referral center in North India and review of literature.

CONTEXT: Cysts arising from the hepatobiliary tree are a group of heterogeneous lesions with regard to pathogenesis, clinical presentation, and radiological finding. They can be intrahepatic or extrahepatic, developmental, secondary to infective/inflammatory etiologies, as well as neoplastic. This study was conducted to determine the spectrum of hepatobiliary cysts in surgically intervened cases, with regard to their prevalence, histological spectrum, and clinicoradiological correlation, wherever possible. METHODS: In this retrospective observational study, hematoxylin and eosin stained slides of all cases of hepatobiliary cystic lesions, operated between 2009 and 2016 were reviewed. Special stains as reticulin, Masson's trichrome, and periodic acid Schiff were done wherever necessary. Overall prevalence, age-sex distribution, clinical presentation and histopathological patterns were studied. Relevant imaging findings were correlated wherever possible. RESULTS: A total of 312 cases of hepatobiliary cysts were identified, the majority in females. Choledochal cysts (CCs) were the most common type (n = 198,63.5%), followed by hydatid cysts (n = 73,23.3%), simple hepatic cysts (n = 10,3.2%), congenital hepatic fibrosis (n = 10,3.2%), biliary cystadenomas (n = 4,1.2%) hepatic mesenchymal hamartomas (n = 7,2.2%), and cavernous hemangiomas (n = 3,0.9%). Fibropolycystic liver disease (n = 2,0.6%), Caroli's disease (n = 1, 0.3%), liver abscess (n = 2, 0.6%), infantile hemangioendothelioma (n = 1,0.3%), and biliary cystadenocarcinomas (n = 1,0.3%) were rare. Lesions noted mostly in 1st decade of life were: CCs, fibrocystic liver disease, Caroli's syndrome, cystic mesenchymal hamartoma, and infantile hemangioendotheliomas. CONCLUSION: In our cohort of surgically intervened cases of hepatobiliary cystic lesions from a tertiary care hospital in North India, the CCs, followed by hydatid cyst were the most common lesions. Histology can play vital role in characterization, as often clinical findings and radiology can overlap.

Delayed Severe Hemobilia Due to Bilio-venous Fistula After Percutaneous Transhepatic Biliary Drainage: Treatment With Covered Stent Placement.

Biliovenous fistula occurs due to development of a communication between hepatic duct and portal vein branches and is a rare complication of percutaneous transhepatic biliary drainage (PTBD). Most of them are self-limiting and only occasionally they need interventional management. Placement of biliary stent graft is a viable option. We present here a case of a 56-year-old male with carcinoma of gall bladder presenting with hemodynamic shock due to severe hemobilia after PTBD and treated successfully by biliary covered stent placement.

Why are we Poor Organ Donors: A Survey Focusing on Attitudes of the Lay Public From Northern India.

BACKGROUND: Knowledge, sociocultural views, and awareness about organ donation in the general population are important for the success of deceased organ donation. There is an urgent need to gather this information in order to find out the reasons for poor organ donation rates in India. METHODS: A 30-item questionnaire was designed in the English and Hindi language and was administered to the lay people in order to assess their knowledge, views, and attitude regarding brain death and organ donation. RESULTS: Three hundred and fifty-two people (male:female = 202:150; mean age = 30.6 ± 13.9 years) completed the questionnaire. Only 70% of the people were aware that the organs can be donated after brain death and only 44% thought that they understood the meaning of brain death. Media and Internet were the preferred sources for seeking information on brain death and organ donation. The majority of people (81.2%) were willing to donate organs after brain death but only 1.4% had registered for organ donation. Lack of awareness (80.1%), religious beliefs and superstitions (63.4%), and lack of faith in the healthcare system (40.3%) were believed to be the most important reasons for poor deceased organ donation rates in India. The survey also highlighted the importance of the opinion of family members and the religious leaders in making the decision for organ donation. Educational qualification above matriculation was significantly associated with the knowledge of brain death and the willingness for organ donation. CONCLUSION: Lack of awareness appears to be the most important factor for low donation rates in India. Educating people by using media and Internet and conducting awareness programs may help in improving the donation rates.

Hepatic resection for predominantly large size hepatocellular carcinoma: Early and long-term results from a tertiary care center in India.

BACKGROUND AND AIM: There are no large series on hepatic resection for hepatocellular carcinoma (HCC) from India. We present the results of consecutive patients of HCC treated with hepatic resection at a tertiary care center in India. METHODS: The records of all patients who underwent hepatic resection for HCC in the Department of Gastrointestinal Surgery, All India Institute of Medical Sciences (New Delhi), were reviewed. The relevant perioperative and follow up data were extracted from a prospectively maintained database. RESULTS: Between January 1987 and December 2013, 81 patients [71 males; mean age: 49.2 ± 15.6 years] underwent hepatic resection for HCC. Of these, 23 (28 %) were cirrhotic and 36 (49 %) had hepatitis B. Hepatitis B was significantly more common in cirrhotic (77 % vs. 37 %; p = 0.001). Most patients had locally advanced disease at presentation [tumor size ≥10 cm in 61 (75 %); vascular tumor thrombus in 10 (12 %)]. Anatomical resection was done in 61 (75 %) including 56 major hepatic resections (≥3 segments). Overall in-hospital mortality was 13 (16 %) [cirrhotic 5 (22 %) vs. noncirrhotic 8 (14 %), p = 0.503]. Grade III-V complications (modified Clavien-Dindo classification) occurred in 25 (31 %) patients (cirrhotic 48 % vs. noncirrhotic 24 %; p = 0.037). Follow up information was available for 51 (75 %) patients. The median time to recurrence was 12 months, and most (86 %) occurred within 1 year. The recurrence-free survival at 1, 3, and 5 years was 48 %, 40 %, and 36 %, respectively. Positive resection margin and vascular invasion were significantly associated with very poor prognosis. CONCLUSION: Majority of Indian HCC patients present with locally advanced disease. Despite this, surgical resection provides a chance for long-term recurrence-free survival in a third of them.

Alveolar Echinococcosis of the Liver: A Diagnostic Problem in a Nonendemic Area.

Alveolar echinococcosis is a parasitic disease primarily invading the liver. Owing to its aggressive nature, it invades the adjacent structures and can even metastasize to distant organs. The appearance of hepatic involvement on computed tomographic scan is characteristic, but not specific, with areas of calcification seen within a hypoenhancing mass. Although magnetic resonance imaging may better define the extent of the disease, it often misleads the radiologist, especially if the lesion is devoid of cystic component(s) and if it occurs in nonendemic areas. Knowledge of the imaging appearance may prompt serological evaluation and aid in making an early diagnosis and planning appropriate treatment of this uncommon fatal disease, especially in nonendemic areas.

Endovascular Embolization of Visceral Artery Pseudoaneurysms Using Modified Injection Technique with N-Butyl Cyanoacrylate Glue.

PURPOSE: To evaluate the indications, feasibility, safety, and effectiveness of N-butyl cyanoacrylate (NBCA) with modified injection technique in embolization of visceral artery pseudoaneurysms (PSAs). MATERIALS AND METHODS: A retrospective evaluation was performed of 31 patients (26 men, 5 women; mean age, 32.6 y) with visceral artery PSAs that were treated with embolization using NBCA with modified sequential injection and flushing technique. The most common indication for using NBCA was preservation of a major feeding artery (n = 18), followed by difficult catheterization secondary to arterial tortuosity (n = 5), failed previous coil embolization (n = 4), and short landing zone for coils (n = 4). NBCA alone was used in 25 patients, and NBCA with coils was used in 6 patients. The patients were followed clinically until discharge and 1 and 3 months after discharge. RESULTS: The mean amount of NBCA-ethiodized oil (Lipiodol; Guerbet LLC, Villepinte, France) mixture injected was 0.24 mL (range, 0.1-1.1 mL). Embolization with NBCA was technically successful in all (100%) patients. Recurrence was seen in 3 (9.7%; 2--splenic artery; 1--left gastric artery) patients after a mean time of 16.3 days (range, 10-27 d) of initial embolization resulting in clinical success of 90.3%. All 3 patients underwent successful repeat embolization with secondary technical success rate of 100%. Minor (pain) and major (nontarget embolization in 2; microcatheter adhesion and fracture in 1) complications were seen in 3 patients each. CONCLUSIONS: NBCA is a safe and effective embolization agent when injected with modified technique in treatment of visceral artery PSAs.

Transarterial chemoembolization for liver metastases from solid pseudopapillary epithelial neoplasm of pancreas: A case report.

Solid pseudo-papillary epithelial neoplasm (SPEN) is a rare epithelial tumor of pancreas with a low malignant potential occurs most commonly in young females. We report a case of 40 years old woman presented with extensive liver metastasis from SPEN of pancreatic body for which she was operated four years ago. Due to the extensive nature of metastatic disease she was offered Transarterial chemoembolisation (TACE) using gemcitabine as chemotherapeutic agent. Short term follow up after a month of TACE with multiphase computed tomography showed > 90% resolution in the viable tumor with significant clinical improvement. TACE ensures targeted delivery of chemotherapeutic drugs in higher doses with least systemic toxicity and is more effective and safe than systemic chemotherapy. TACE with gemcitabine was found to be very effective in our patient with numerous liver metastasis.