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.

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.

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.

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.

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.

Alveolar echinococcosis of liver: a diagnostic problem in a nonendemic area.

Alveolar echinococcosis is a parasitic disease primarily invading the liver. Due 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.

Palliative stenting for relief of dysphagia in patients with inoperable esophageal cancer: impact on quality of life.

The aim of palliation in patients with inoperable esophageal cancer is to relieve dysphagia with minimal morbidity and mortality, and thus improve quality of life (QOL). The use of a self-expanding metal stent (SEMS) is a well-established modality for palliation of dysphagia in such patients. We assessed the QOL after palliative stenting in patients with inoperable esophageal cancer. Thirty-three patients with dysphagia due to inoperable esophageal cancer underwent SEMS insertion between October 2004 and December 2006. All patients had grade III/IV dysphagia and locally advanced unresectable cancer (n = 13), distant metastasis (n = 14), or comorbid conditions/poor general health status precluding a major surgical procedure (n = 6). Patients with grade I/II dysphagia and those with carcinoma of the cervical esophagus were excluded. The QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3) and EORTC QLQ-Esophagus (OES) 18 questionnaire (a QOL scale specifically designed for esophageal diseases) before and at 1, 4, and 8 weeks after placement of the stent. The mean age of the patients was 56 (range 34-78) years, and 22 were men. A covered SEMS was used in all patients. The most common site of malignancy was the lower third of the esophagus (n = 18, 55%). In 23 (77%) patients, the stent crossed the gastroesophageal junction. Seven patients required a reintervention for stent block (n = 5) and stent migration (n = 2). Dysphagia improved significantly immediately after stenting, and this improvement persisted until 8 weeks (16.5 vs. 90.6; P < 0.01). The global health status (5.8 vs. 71.7; P < 0.01) and all functional scores improved significantly after stenting from baseline until 8 weeks. Except pain (14.1 vs. 17.7; P = 0.67), there was significant improvement in deglutition (22.7 vs. 2.0; P < 0.01), eating (48 vs. 12.6; P < 0.01), and other symptom scales (19.7 vs. 12.1; P = 0.04) following stenting. The median survival was 4 months (3-7 months). Palliative stenting using SEMS resulted in significant improvement in all scales of QOL without any mortality and acceptable morbidity.