Fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma (FLM) is a rare tumour that typically presents in young adults. It occurs in non-cirrhotic liver and is usually associated with normal serum alpha-fetoprotein. It is defined by a triad of morphological features: polygonal tumour cells with eosinophilic cytoplasm, prominent macronucleoli and lamellar fibrosis. A central scar can be present. The principal differential diagnosis is conventional hepatocellular carcinoma (HCC), especially the scirrhous variant. Acinar differentiation and focal mucin production are common and can be confused with adenocarcinoma. Focal neuroendocrine differentiation can occur and can be mistaken for neuroendocrine tumours. FLM also shows distinctive features at the molecular level; many of the commonly observed abnormalities in conventional HCC like p53 and β-catenin mutations are not observed in FLM. The extent of cytogenetic changes and CpG island methylation is low in FLM compared to conventional HCC. FLM is an aggressive neoplasm with 5-year survival of around 50%. Although the outcome in FLM has been considered more favourable compared to conventional HCC, this is likely to be related to absence of cirrhosis rather than unique morphological features of the tumour.     

Transcatheter closure of perimembranous ventricular septal defect with amplatzer membranous occluder

BACKGROUND: Use of trancatheter device closure for membranous ventricular septal defect is still in evolving phase. We report the early and mid-term results of our experience with the new asymmetric Amplatzer membranous ventricular septal defect occluder. METHODS AND RESULTS: We attempted, transcatheter closure of perimembranous ventricular septal defect using asymmetric Amplatzer occluder in 26 patients. The patients were selected on the basis of transthoracic and transesophageal echocardiographic assessment of the ventricular septal defect. The procedure was successful in 21 (81%) patients. The age ranged from 3 to 23 years, weight from 10 to 59 kg and defect size ranged from 3 to 9 mm (mean: 5 +/- 1.8 mm). One patient had situs inversus with dextrocardia: 11 had aneurysmal tissue partly occluding the defect and the device was deployed either across (n=6) or within the aneurysmal sac (n=5). Three patients developed high degree atrioventricular block on attempts to cross the defect with the sheath and the procedure was discontinued. In two patients it was not possible to place the sheath in left ventricle despite repeated attempts. There was a residual flow in 4 (19%) patients at 24 hours. Two patients developed bundle branch block and none had complete heart block. At follow-up (1-9 months, n=20), residual flow was seen in two patients. None developed late conduction defect, aortic regurgitation, infective endocarditis or hemolysis. CONCLUSIONS: Transcatheter closure of perimembranous ventricular septal defect can be performed safely and effectively with the new asymmetric Amplatzer occluder device in selected patients with good short- and midterm results. These devices can be deployed safely in and across and the aneurysmal sacs. In selected cases, this procedure is a satisfactory alternative to surgery.     

Investigation of an outbreak of scrub typhus in the himalayan region of India

In Indira Gandhi Medical College, Himachal Pradesh, India, during autumn of 2003 (September-November), more than 100 cases of fever of unknown origin (FUO) were reported with 15 ensuing deaths. In addition to all routine investigations and cultures, the Weil-Felix test was incorporated for the investigation of these cases. Antigen was procured from the Central Research Institute, Kasauli. Forty-six percent (45/96) of the cases demonstrated a > or =1:80 titer of agglutinins against OXK antigen. A team from the National Institute of Communicable Diseases, New Delhi, confirmed the antibodies for scrub typhus in some of the serum samples tested for leptospirosis, dengue fever, and rickettsial infections. Twelve blood samples positive for OXK antigen were sent to the Defense Research Development Establishment, Gwalior, for polymerase chain reaction studies, but none of the samples were positive, as all of the patients were already on broad-spectrum antibiotics and had reported to our hospital after 7-10 days of fever. At our institute, the Weil-Felix test has now been rountinely introduced for the investigation of cases of FUO, and the results until April 2004 (150 cases) revealed the presence of other rickettsial infections prevalent in the region. To evaluate the epidemiology and magnitude of the problem, further prospective studies are required.     

A Randomized Controlled Trial of β-Blockers Versus Endoscopic Band Ligation for Primary Prophylaxis: A Large Sample Size is Required to Show a Difference in Bleeding Rates

Primary prophylaxis with nonselective -blockers in high-risk subjects has been shown to be effective in reducing both esophageal variceal bleeding and mortality. Recently it has been suggested that band ligation may be a better option for primary prophylaxis. We compared nonselective -blockers with band ligation in patients with large varices (F2, F3) and elevated hepatic venous wedge pressure gradient (HVWPG, 12 mm Hg). All patients were prospectively followed for variceal bleeding, mortality, and treatment-related complications. Based on previous published studies, we estimated that 90 patients in each arm would be required to show a difference in bleeding rate. The study was prematurely terminated when we realized that our estimated sample size was inadequate to show a difference based on the observed bleeding rate. At the time of termination, 31 patients (Child A, 11; B, 14; C, 6), with a mean HVWPG of 19 ± 9.1 mm Hg, were randomized to either band ligation (group A; n = 16) or -blockers (group B; n = 15). Baseline demographics of both groups were similar and the mean follow-up period was 27.4 ± 12.9 months. During the follow-up, two patients in group A and one patient in group B had bleeding. Nine patients (29%; group A, six; group B, three; P = ns) died due to non-bleeding-related causes and five (16%) patients (group A, three; group B, two) underwent liver transplantation. Treatment-related complication were minimal in both groups. Despite the selection of high-risk patients, the observed bleeding rate was much lower than anticipated. Based on our observed bleeding rates, 424 patients would be required in each arm to show a difference between band ligation and -blocker therapy.     

Association of HLA phenotype with primary non-response to recombinant hepatitis B vaccine: a study from north India.

The hepatitis B vaccine is considered to be highly immunogenic and has a good safety profile. In adults, it has a primary non-response rate of 5%-10%. Causes of nonresponse to hepatitis B vaccine include age, sex, obesity smoking. Certain human leucocyte antigen (HLA) phenotypes have been known to be associated with responsiveness to the vaccine, and found to be different in different ethnic groups, such as Caucasians and Orientals. The study was designed to identify the HLA phenotypes that are associated with non-responsiveness to hepatitis B virus (HBV) vaccination amongst a cohort of Indian subjects who agreed to participate in the vaccination programme. The study was offered to 107 volunteers, of whom 102 were found to be negative for HBV markers (hepatitis B surface antigen [HBsAg], anti-HBc, anti-HBe, anti-HBs, hepatitis Be antigen [HBeAg]) . All 102 volunteers were offered recombinant hepatitis B vaccine (20 microg) at 0, 1, and 6 months. Anti-HBs antibody titres were tested on days 90 and 210 of the first vaccine dose. HLA typing was done using standard microlymphotoxicity tests. The seroconversion rate of the hepatitis B vaccine was 86.3% (88/102). Fifteen nonresponders (15/102) and 15 of the 88 responders were randomly selected after age and sex matching for the purpose of studying the HLA phenotypes. HLA subtypes A1, B15, B40, A10 and DQ2 were found to be increased among nonresponders while HLA- A11, C3, DR10, DR51 (p>0.05) were the most common phenotypes amongst the responders. Further studies are needed to characterize the HLA phenotypes amongst the responders in different ethnic groups in India with respect to HBV vaccination.     

How Do Hospitalized Patients Feel About Resident Work Hours,Fatigue, and Discontinuity of Care?

BACKGROUND: Patient-centered care requires that physicians understand patients' perspectives. Since the resident work hour rules were instituted, little information is available about how patients perceive these issues. Our objectives were to explore patients' knowledge, concerns, and attitudes about resident work hours, fatigue, and continuity of inpatient care and to evaluate the association between patients' trust and satisfaction with these concerns and attitudes. METHODS: We conducted a cross-sectional survey of 134 internal medicine inpatients at 3 institutions including a tertiary care academic health center, a Veterans Affairs medical center, and a private community teaching hospital. RESULTS: Mean age was 59 (range, 24-90), with 60% men and 70% white. Most patients agreed (50%) or felt neutral (38%) toward resident work hours being limited. Patients estimated that residents worked 60 h per week but thought that they should work no more than 51 h per week (p < .01 for the difference). Twenty-seven percent of patients had some concern about fatigue in the residents, and 28% reported concern about how often hand-offs of care occurred. Factor analysis yielded 3 factors: "worried about discontinuity/fatigue," "attitude toward resident/nurse work hours," and "perceived resident/nurse fatigue." In multivariable analyses, the "worried about fatigue/discontinuity" factor significantly predicted trust and satisfaction, and the "perceived resident/nurse fatigue" factor also predicted satisfaction. CONCLUSIONS: Some inpatients are concerned about both fatigue in resident physicians and discontinuity of care. This may play a role in trust and satisfaction for patients. Taking steps to design systems to minimize fatigue and discontinuity would be ideal.     

Electrocardiographic patterns of superior right ventricular outflow tract tachycardias: distinguishing septal and free-wall sites of origin

INTRODUCTION: The superior right ventricular outflow tract (RVOT) septum and free wall are common locations of origin for outflow tract ventricular tachycardias (VT). We hypothesized that (1) unique ECG morphologies of pace maps from septal and free-wall sites in the superior RVOT could be identified using magnetic electroanatomic mapping for accurate anatomical localization; and (2) this ECG information could help facilitate pace mapping and accurate VT localization. METHODS AND RESULTS: In 14 patients with structurally normal hearts who were undergoing ablation for outflow tract VT, a detailed magnetic electroanatomic map of RVOT was constructed in sinus rhythm, then pace mapping was performed from anterior, mid, and posterior sites along the septum and free wall of the superior RVOT. Pace maps were analyzed for ECG morphologies in limb leads and transition patterns in precordial leads. Monophasic R waves in inferior leads for septal sites were taller (1.7 +/- 0.4 mV vs 1.1 +/- 0.3 mV; P < 0.01) and narrower (158 +/- 21 msec vs 168 +/- 15 msec; P < 0.01) compared with free-wall sites; lacked "notching" (28.6% vs 95.2%; P < 0.05); and showed early precordial transition (by lead V4; 78.6% vs 4.8%; P < 0.05). A positive R wave in lead I also distinguished posterior from anterior septal and free-wall sites. Based on QRS morphology in limb leads and precordial transition pattern (early vs late), in a retrospective analysis, a blinded reviewer was able to accurately localize the site of origin of clinical arrhythmia (the successful ablation site on the magnetic electroanatomic map) in 25 of 28 patients (90%) with superior RVOT VT. CONCLUSION: Pace maps in the superior RVOT region manifest site-dependent ECG morphologies that can help in differentiating free-wall from septal locations and posterior from anterior locations. Despite overlap in QRS amplitude and duration, in the majority of patients a combination of ECG features can serve as a useful template in predicting accurately the site of origin of clinical arrhythmias arising from this region.