Clinicopathological Significance and Prognostic Role of Her2neu Protein Expression in Patients with Carcinoma Stomach: A Prospective Study from Northern India.

Manas Kumar BeheraBackground and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease. Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done. Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61-3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan-Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression ( p = 0.001). Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.

Creep in nitroimidazole inhibitory concentration among the Entamoeba histolytica isolates causing amoebic liver abscess and screening of andrographolide as a repurposing drug.

Infections by Entamoeba histolytica (E. histolytica) lead to considerable morbidity and mortality worldwide and treatment is reliant on a single class of drugs, nitroimidazoles. Treatment failures and intermittent reports of relapse from different parts of world indicate towards development of clinical drug resistance. In the present study, susceptibility testing of clinical isolates of E. histolytica was carried against metronidazole and tinidazole. Additionally, anti-amoebic property of active compounds of Andrographis paniculata was also evaluated. Prevalence of metronidazole resistance gene (nim) in patients attending hospital was also done to get comprehensive insight of present situation of drug resistance in E. histolytica. Mean inhibitory concentration 50 (IC50) value of E. histolytica isolates against metronidazole and tinidazole was 20.01 and 16.1 µM respectively. Andrographolide showed minimum mean IC50 value (3.06 µM). Significant percentage inhibition of E. histolytica isolates by andrographolide was seen as compared to metronidazole (p = 0.0495). None of E. histolytica isolates showed presence of nim gene. However, in stool samples from hospital attending population, prevalence of nimE gene was found to be 76.6% (69/90) and 62.2% (56/90) in diarrheal and non-diarrheal samples respectively. Inhibitory concentration of commonly used nitroimidazoles against clinical isolates of E. histolytica are on rise. Percentage inhibition of E. histolytica isolates by andrographolide was significantly higher than control drug metronidazole.

Etiological spectrum of isolated ileo-cecal ulcers in patients with gastrointestinal symptoms.

Background: Isolated ileo-cecal region (ICR) ulcers may represent underlying Crohn's disease (CD), intestinal tuberculosis (ITB), bacterial infections (including typhoid), amoebiasis, eosinophilic enteritis, drug-induced sequelae, or neoplasm. Overlapping morphological and microscopic characteristics of many of these diseases make it challenging to unequivocally confirm a diagnosis. Aims: The aim of the study was to investigate the etiology and clinical outcomes of isolated ileo-cecal ulcers discovered during an ileocolonoscopy in patients with gastrointestinal symptoms. Methods: Patients with isolated ileo-cecal ulcers and symptoms within the age range of 10 - 80 years were included in the study (N = 100). Patients not giving consent (assent in case of a minor), with a prior diagnosis of tuberculosis or inflammatory bowel disease, with incomplete colonoscopy and associated colonic lesions other than ICR were excluded from the study. Demographics, clinical information, and relevant biochemical and serological tests were recorded. During the colonoscopy, multiple biopsies were taken from the ileo-cecal ulcers for histopathological examination. Repeat ileocolonoscopy was performed as needed in consenting patients. Results: The mean age and mean duration of symptoms were 36.0 ± 15.6 years and 18.8 ± 21.6 months, respectively. The majority of the patients presented with abdominal pain (59%), followed by diarrhea (47%), weight loss (20%), gastrointestinal bleeding (15%), and fever (11%). A history of taking nonsteroidal anti-inflammatory drugs was present in only 5% of the patients. Mean hemoglobin, C-reactive protein, and albumin levels were 11.6 ± 2.8 g/dL, 6.9 ± 9.5 mg/L, and 3.7 ± 0.8 g/dL, respectively. Based on clinical, colonoscopic, and histopathological findings, initial treatment was symptomatic/antibiotics in 55%, anti-tubercular treatment in 21%, 5-aminosalicylic acid/steroids for CD in 13%, oral budesonide in 10% of patients, and one patient was referred for management of malignancy. Final diagnoses after 8 - 24 weeks of follow-up were non-specific ileitis/colitis (45%), CD (20%), ITB (18%), infective (7%), eosinophilic ileitis/colitis (6%), non-steroidal anti-inflammatory drug-induced (2%), and amoebic and malignant in 1% of patients each. Conclusions: The majority of patients with ileo-cecal ulcers have specific etiologies. Non-specific ulcers at the ICR can be managed symptomatically; however, close follow-up is necessary as sometimes the ulcers may harbor an underlying specific disease. Relevance for Patients: Isolated ileo-cecal ulcers are common findings during colonoscopy in both symptomatic and asymptomatic patients. The majority of these ulcers harbor underlying significant diseases that can cause morbidity and mortality if left undiagnosed and untreated. Reaching a specific diagnosis in such cases is not straightforward, and patients are often subjected to repeat examinations.

Hypercalcemia - An enigmatic cause of acute pancreatitis.

Background: Acute pancreatitis (AP) continues to be one of the common abdominal emergencies encountered in tertiary care hospitals. The majority of AP is caused by gall stones and alcohol. Hypercalcemia though uncommon has been reported to cause AP, recurrent AP, and chronic pancreatitis (CP). Aim: The aim of this study was to describe hypercalcemia-induced AP in different settings. Materials and Methods: In total 100 patients with AP, admitted from January 2021 to December 2021 at our center, etiologies were biliary (36%), alcohol (19%), idiopathic (21%), alcohol plus Biliary (5%), post-endoscopic retrograde cholangiopancreaticography (7%), drug-induced (6%), hypercalcemia (3%), and dengue infection (3%). Overall mortality was 11%. Results: In three patients with hypercalcemia-induced pancreatitis, causes of hypercalcemia were multiple myeloma, parathyroid adenoma leading to hyperparathyroidism, and hypervitaminosis D in association with hyperthyroidism. Conclusion: Hypercalcemia-induced AP is not a rare phenomenon and should be actively investigated to prevent further attacks of AP and progression to CP. Relevance for Patients: Hypercalcemia is a potentially treatable cause of AP and its identification will not only help to treat and prevent further episodes of pancreatitis but also to manage underlying diseases leading to hypercalcemia.

Epidemiology of clinically relevant Entamoeba spp. (E. histolytica/dispar/moshkovskii/bangladeshi): A cross sectional study from North India.

BACKGROUND: Entamoeba infections have major impact on millions of the people worldwide. Entamoeba histolytica has long been accepted as the only pathogenic species. However, recent reports of other Entamoeba spp. in symptomatic cases have raised questions on their pathogenicity. METHODOLOGY/PRINCIPAL FINDINGS: Total 474 stool samples and 125 liver aspirates from patients with intestinal and extra intestinal manifestations and from community were included. Sewage samples from the hospital and the city were also included. Microscopic examination and molecular detection were performed to detect presence of E. histolytica/ dispar/ moshkovskii/ bangladeshi. The associated demographic and socioeconomic factors were statistically analyzed with the presence of Entamoeba. Microscopy detected Entamoeba spp. in 5.4% stool and 6.4% liver aspirate samples. Through nested multiplex PCR, prevalence of Entamoeba spp. in intestinal and extra-intestinal cases was 6.6% (20/301) and 86.4% (108/125) respectively and in asymptomatic population was 10.5% (13/123). Sewage samples did not show presence of any Entamoeba spp. Uneducated subjects, low economic conditions, untreated drinking water, consumption of raw vegetables and habit of not washing hands before meals were significantly associated with presence of Entamoeba spp. CONCLUSIONS: E. histolytica still remains the only Entamoeba spp. in invasive extra intestinal infections. E. dispar was detected in both asymptomatic and symptomatic intestinal infections. Routine identification of Entamoeba spp. should incorporate PCR based detection methods.

Idiopathic acute pancreatitis-A myth or reality? Role of endoscopic ultrasonography and magnetic resonance cholangiopancreatography in its diagnosis.

BACKGROUND: Around 10% to 30% patients with acute pancreatitis (AP) do not have a cause after the routine investigations, and are considered as having idiopathic acute pancreatitis (IAP). Establishing the etiology in such patients will prevent recurrences and evolution to chronic pancreatitis. Endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) characteristically are used to diagnose IAP when routine methods fail, but their exact role is not determined. METHODS: This prospective study was undertaken in a tertiary care hospital, in which patients admitted initially with diagnosis of IAP were evaluated. These patients underwent MRCP and EUS at least 4 weeks after an attack of AP. The results of EUS and MRCP were compared and analyzed with various clinical variables using suitable statistical tests. RESULTS: A total of 31 patients with IAP were included. EUS and/or MRCP was able to establish at least one etiology in 17 patients (54.8%). The diagnoses revealed were gallbladder (GB) microlithiasis, GB sludge, choledocholithiasis, pancreatobiliary ductal anomalies, pancreatic adenocarcinoma, and intraductal papillary mucinous neoplasm. Comparing the diagnostic accuracy of both the modalities, EUS (14/31) was able to diagnose more cases than MRCP (8/31). The diagnostic capability of EUS was lower in patients who had a cholecystectomy (12.5% vs. 56.5%; p = 0.03). CONCLUSIONS: EUS and MRCP are useful modalities in the etiological diagnosis of IAP and should be used in conjunction. EUS is better for establishing a possible biliary etiology and MRCP for an anatomical alteration in pancreatobiliary ducts.

Factors Associated with High Rates of Recurrence of Amebic Liver Abscess (ALA) in North India.

Recurrence of amebic liver abscess (ALA), once considered unusual, is increasingly being reported, despite proper management. Realizing the endemicity of ALA in the study setup, this 2-year follow-up study was conducted to investigate the recurrent cases and study the associated factors. A total of 101 confirmed cases of ALA were followed up for a period of 2 years. Recurrent cases were studied for associated bacterial flora, presence of resistance genes (nim), level of matrix metalloproteinase 3 and MMP-9, and genotypes of Entamoeba histolytica and statistically compared with the nonrecurrent cases as controls. Recurrence rates of 8.9% (nine patients) were detected. The presence of Prevotella along with an increased level of MMP-9 in abscess fluid and large size of abscesses (11 × 10.8 cm) was found to be significantly associated with recurrence in ALA. Among the nine cases, the presence of nimE gene was detected in two (22.2%) patients. The genotyping of E. histolytica strains showed that in seven (77.7%) cases, the genotype of E. histolytica was the same in the primary and recurrent samples. This study reports a high rate of recurrence in the cases of ALA, hinting toward the gradual development of clinical resistance toward the commonly used drug. The presence of nim gene and Prevotella in abscess fluid along with increased MMP-9 levels and large abscess size could be important predictors of recurrent ALA.

Prevalence of cases of amebic liver abscess in a tertiary care centre in India: A study on risk factors, associated microflora and strain variation of Entamoeba histolytica.

BACKGROUND: Amebiasis, caused by Entamoeba histolytica (E. histolytica), is a significant cause of morbidity and mortality in developing countries. Mortality due to amebiasis is mostly by extra intestinal infections, amebic liver abscess being the most common one. This study was conducted to determine the current epidemiological status, risk factors, associated microflora and strain variation of E. histolytica causing liver abscesses. METHODS/FINDINGS: A total of 115 liver abscess cases comprising of 107 (93%) males and 8 (6.9%) females were included in the study. Microscopic examination of pus samples from the abscesses and species discrimination using nested multiplex PCR showed the presence of E. histolytica in 101 (87.5%) cases. Data collected by face to face interviews using a pre tested questionnaire suggested intake of untreated drinking water (ORs: 6.4, p = 0.002), habit of alcohol consumption (ORs: 4.0, p = 0.019) and lack of urban services (ORs: 0.08, p = 0.017) to be major risk factors associated with E. histolytica infections. The study of associated bacterial flora through aerobic culture of liver aspirates and conventional PCR for detection of anaerobes revealed the presence of Fusobacterium (19, 25.5%), Peptococcus (19, 25.5%), Prevotella (18, 24.3%), Bacteroides (8, 10.8%), Staphylococcus aureus (3, 4%), Escherichia coli (2, 2.7%), Peptostreptococcus (2, 2.7%), Clostridium (2, 2.7%) and Klebsiella pneumoniae (1, 1.3%). Further to study the clonality, genotyping of E. histolytica targeting six tRNA-linked polymorphic STR loci (A-L, D-A, N-K, R-R, STGA -D and S-Q) was carried out which showed the presence of 89 different genotypes in the liver aspirate samples. CONCLUSION: The findings highlight the high prevalence of genetically diverse E. histolytica from the liver abscess cases in this geographical region. Low socio-economic status and habit of alcohol consumption were important predictors of amebic liver abscess.

Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India.

BACKGROUND & OBJECTIVES: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. METHODS: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon α-2a 180 µg per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). RESULTS: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). INTERPRETATION & CONCLUSIONS: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.

A preliminary evaluation of comparative effectiveness of riluzole in therapeutic regimen for irritable bowel syndrome.

OBJECTIVE: To develop agents that are specifically effective in controlling the key disturbance of visceral hyperalgesia besides abating of associated multiple symptoms, and evaluate comparative effectiveness for IBS symptom relief for standard regimen (antispasmodic and probiotic) and add-on amitriptyine or riluzole regimens following two weeks administration. METHODS: 108 patients with visceral hypersensitivity accompanying IBS, divided into three groups were studied. First group received standard treatment (mebeverine 200 mg twice daily and probiotic 200 mg twice daily). Second group received add-on amitriptyline 25 mg before bedtime, while the third group got add-on riluzole 50 mg twice daily. Overall gastrointestinal symptom rating scale improving symptoms and hospital anxiety depression scale improving associated psychological morbidity were employed as measures at induction and at two-week follow-up period. Individual symptom scores were also examined to define the outcome profiles. RESULTS: Riluzole regimen resulted in significant reduction of overall gastrointestinal symptom rating scale score, not the other two regimens. Pain relief was seen with both riluzole and amitriptyline regimens significantly superior to standard treatment regimen, but riluzole effect appeared specific and independent anxiolytic effect. Amitriptyline caused relief in diarrhea and did not benefit in constipation point to non-specific remedial role in IBS. CONCLUSIONS: Riluzole specifically relieves visceral hypersensitivity and is proved to be superior to current treatments in IBS patients. It appears a lead remedy based on glutamate transporter mechanisms in visceral hypersensititvity.