Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease.

Background & objectives: The cytokines, adipokines, and oxidative stress have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, such data remain scarce in India. The present study evaluated pro-inflammatory cytokines, adipokines, and markers of oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD), and their association with degree of adiposity, insulin resistance and markers of disease severity. Methods: The present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD, 22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters studied were adiponectin, leptin, tumour necrosis factor α (TNFα), interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress. Results: The mean body mass index (kg/m2) in NAFLD patients, CHB, and HC were 26.4±3.7, 21.3±2.3, and 22.3±2.7, respectively. The median serum levels of all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD compared to control groups. Compared to HC, levels of adiponectin and leptin were significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked and selective increase only in NAFLD patients. The levels of IL-6 were significantly (P<0.02) higher in NAFLD patients with advanced histology grade and correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress were significantly higher, and that of antioxidant potential were significantly lower among NAFLD patients compared to control subjects. Interpretation & conclusions: Patients with NAFLD revealed significantly elevated levels of pro-inflammatory cytokines, increased oxidative stress, and a significant association of IL-6 with IR and advanced histopathology.

Surgical outcome in relation to duct size at the porta hepatis and the use of cholagogues in patients with biliary atresia.

Background : Small ductules communicating with the bile ducts have been described at the porta hepatis in extrahepatic biliary atresia (EHBA) and these form the basis for hepatic portoenterostomy. The use of cholagogues like dehydrocholic acid (DHC) and ursodeoxycholic acid (UDCA) to enhance bile flow postoperatively has been reported. Aims : This communication describes our experience with the use of cholagogues following surgery in EHBA and attempts to correlate the outcomes with the diameter of the ductules. Material and methods : Fifty five EHBA patients treated by the Kasai procedure form the basis of this study; 35 patients treated during 1979-1986 and administered DHC (3-5mg/kg) postoperatively and 20 patients treated during 1999-2002 and administered UDCA (15mg/kg) postoperatively. The diameter of ductules was measured using an optical micrometer on 5μm serial sections; the ducts were classified as type I (no demonstrable ducts, n=14), type II (<50μm, n=22) and type III (>50μm, n=19). The clinical outcome was categorized as 1 (jaundice free survival at 5 years follow-up, n=7), 2 (initial good response but deteriorated after one year, n=27) and 3 (expired within one year following surgery, n=21). The response to surgery was monitored using biochemical liver function tests (LFT), hepatobiliary scintigraphy (HIDA scan) and occurrence of cholangitis. Results : Age did not affect the size of ducts in both DHC and UDCA groups but patients in the DHC group were older than those treated with UDCA (mean age DHC: 105.22+33.53 days, UDCA: 74.68+23.73 days; p=0.009). There was no statistically significant difference between duct size and postoperative LFT in both groups (DHC p=0.1, UDCA p=0.5). Bile excretion on HIDA scan was significantly better with larger ducts (DHC p=0.003, UDCA p=0.025); overall UDCA showed significantly better bile excretion (p=0.003) but this was not reflected in the surgical outcome. There was no significant difference in the surgical outcome of those treated with DHC or UDCA but a significantly higher incidence of cholangitis was seen with smaller ducts in the UDCA group (p=0.02). Conclusions : There was no correlation between duct diameter and postoperative LFT but type III ducts were associated with better bile flow on HIDA scan. Cholangitis was seen more often with type I and II ducts in both DHC and UDCA groups. UDCA administration seemed to be beneficial in patients with type III ducts in increasing bile flow and reducing cholangitis.

Effect of preoperative short course famotidine on TILs and survival in breast cancer.

BACKGROUND: Histamine receptor antagonists have been shown to induce tumor-infiltrating lymphocytes (TILs) in colonic cancers and improve survival. The role of histamine receptor anatagonists in breast cancer is unclarified. AIM: To evaluate the role of histamine receptor antagonists in inducing (TILs) in breast cancer. METHOD: Forty-five patients with operable breast cancers (25 cases who received preoperative famotidine and 20 controls) were studied for the effect of famotidine in inducing TILs and survival in breast cancer. RESULTS: Significant TILs were seen in 75% (18/24) of cases as opposed to 35% (7/20) controls. In logistic regression analysis the only variable found to be predictive of TILs was famotidine, odds ratio 7.324 (1.693-31.686) P=0.008. In Cox's regression presence of TILs was favorably associated with improved disease free survival at a median follow up of 35.56 months. The hazard ratio for disease relapse was 3.327 (1.174-9.426) P=0.024 in TIL negative as compared to TIL positive patients. Famotidine use alone was not significant in the original model, however, on incorporation of quadrant of involvement in addition to other established prognostic factors in the above multivariate model, it assumed borderline significance with a hazard ratio for disease free survival 3.404 (1.005-11.531, P=0.049). CONCLUSIONS: Preoperative short course famotidine induces TILs in breast cancer. Patients with TILs demonstrable in tumor specimens had an improved disease free survival. Famotidine may improve disease free survival in breast cancer and these findings need validation in larger population subsets.

Lymphangioleiomyomatosis: a rare cause of breathlessness.

A 24-year-old female presented with complaints of cough with scanty expectoration, breathlessness on exertion and chest pain for the last three years. These symptoms had appeared during the 12th week of her third pregnancy. She was given anti-tuberculosis treatment at another hospital for nine months without any improvement in symptoms. Four years ago she had been diagnosed to have leprosy of borderline variety for which she had received treatment. On examination, she was tachypnoeic with a respiratory rate of 33 breaths per minute. She had clubbing and small, discrete and firm lymph nodes in the anterior cervical region. Chest examination revealed wheezing with bibasilar end-inspiratory crepitations.

Pulmonary hyalinizing granuloma presenting with dysphagia.

We describe a middle aged, non-smoking female who presented with dysphagia and underwent repeated endoscopies and oesophageal dilatation for a period of six months without any response. On imaging she was found to be having a lobulated mass with a radiological differential diagnosis of malignancy, lymphoma or a rare inflammatory lesion. After an inconclusive CT guided biopsy the patient underwent thoracoscopy on which an unresectable mass was found. The biopsy from the mass revealed pulmonary hyalinizing granuloma (PHG). To best of our knowledge this is the first case of PHG presenting as dysphagia reported in the English Literature. Literature on this rare entity is reviewed.