The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?

BACKGROUND/AIMS: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). METHODS: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. RESULTS: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.     

The risk of advanced heart block in surgical patients with right bundle branch block and left axis deviation

The risk of advanced atrioventricular block during anesthesia was studied prosepctively in 44 patients with right bundle branch block and left axis deviation who underwent a total of 52 operations over a 14 month period. All patients had continuous electrocardiographic monitoring throughout anesthesia induction, operation, and surgical recovery. Of the 52 operative procedures, 24 were done under general anesthesia, 11 under spinal, and 17 under local. The preoperative cardiac rhythms were atrial fibrillation in two patients, atrial tachycardia with block in one patient, atrial flutter in one patient, and sinus rhythm in the remaining patients. Temporary pacemakers were inserted preoperatively in six patients, usually because of PR interval prolongation on the preoperative electrocardiogram. There was only one episode of transient complete heart block in 51 of the 52 operative procedures. In two of the six patients with temporary pacemakers, significant pacer-related ventricular irritability occurred. This study indicates that temporary pacemaker insertion is rarely required in patients with chronic right bundle branch block and left axis deviation who require noncardiac surgery.     

Malaria infection among pregnant women attending antenatal clinics in six Rwandan districts

OBJECTIVES: The aim of the study was to assess the knowledge, attitude and practices of pregnant women towards malaria and their association with malaria morbidity. METHODS: Cross-sectional malaria survey of 1432 pregnant women attending six health centres, each of them situated in a specific health district in Rwanda from September to October 2002. RESULTS: The overall prevalence of malaria infection was 13.6% and all infections but two were caused by Plasmodium falciparum. The six health districts were significantly different in terms of malaria prevalence, which varied between 11.5% and 15.4% in four and was <5% in the other two districts. The prevalence of anaemia and splenomegaly mirrored that of malaria infection. In three districts, the prevalence of infection was significantly higher in primigravidae than in secundigravidae and multigravidae (P = 0.01), while in two others it did not vary with parity. Bed net use was low - only 13.1% of the women had at least one bed net at home and 8.3% of them slept under it - and significantly different between districts. Most women knew that malaria might have serious consequences for their pregnancy and that insecticide-treated bed nets are useful for malaria prevention. However, the bed net market price [1525 Rwandan Francs (RFr), approximately 1.6] was much higher than that considered as affordable and acceptable (389 RFr, approximately 0.3). CONCLUSION: Malaria in pregnancy is a major problem in Rwanda, even in the districts of low transmission. Bed net use among pregnant women is low. The option of providing free insecticide-treated bed nets to pregnant women should be explored and possibly implemented; it could rapidly increase bed net use and earlier attendance to antenatal clinics with clear benefits for the women's health.     

Screening for Anti-Human T-Lymphotropic Virus Antibody in Blood Donors and Polytransfused Patients in Apulia (Italy)

A stringent procedure for the diagnosis of human T-lymphotropic virus (HTLV) infection was applied to 1,732 volunteer blood donors, 401 patients with various hematological disorders and 78 individuals at high risk for HIV infection. It consisted of a viral lysate-based screening assay (Abbott Laboratories, North Chicago, Ill., USA), and two confirmatory assays (Western blot and radioimmunoprecipitation assay). A confirmed positive sample had to react with at least two different HTLV gene products. Evidence of HTLV infection was not found in either blood donors or patients with hematological disorders. In fact, HTLV infection was only observed in 10 intravenous drug abusers or their sexual partners. Contrary to previous reports that claimed HTLV seroprevalences of between 0.3 and 8% in blood donors from Apulia (Italy), our data suggest that infection with this virus is principally restricted to intravenous drug abusers.     

The epidemiology of hepatitis delta infection in Italy. Promoting Group.

The epidemiology of HDV infection in Italy was assessed in a retrospective study involving 1556 HBsAg chronic carriers on their first presentation at one of the 35 Liver Units in 1987. Total anti-HD was detected in 23.4% of HBsAg carriers and was significantly more frequent in southern than in northern Italy (26.6% vs. 19.1%, p less than 0.01). Age distribution showed that 73% of the anti-HD-positive subjects, but only 56% of the anti-HD-negative subjects, were under 40 years of age (p less than 0.01). Anti-HD prevalence increased with the severity of the liver disease from 3.8% in healthy carriers to 42.5% in cirrhosis. No geographical statistical difference was found among HBsAg healthy carriers or subjects with chronic persistent hepatitis (CPH), while among patients with chronic active hepatitis (CAH) or cirrhosis anti-HD prevalence was much higher in the south (p less than 0.01). The various potential risk factors were evaluated by multiple logistic regression analysis. HDV infection was independently related to young age, residence in the south, i.v. drug abuse, a large family and household contact with an anti-HD-positive carrier. No association was found with blood transfusion or male homosexuality. These findings confirm that HDV infection is endemic in Italy, particularly in some southern areas, where intrafamily contact probably at a young age may favour the spread of the infection.     

Analysis of microsatellite instability in chronic lymphoproliferative disorders

Microsatellite instability (MSI) represents one specific pattern of genomic instability and is one of the genetic lesions most frequently detected in human neoplasia. Although MSI has been found to be associated with a wide variety of solid cancers, its involvement in lymphoid malignancies is virtually unexplored. In this study, we have investigated the presence of MSI in chronic lymphoproliferative disorders by comparing the pattern of nine microsatellite repeats (two tetranucleotides, two trinucleotides, and five dinucleotides) on autologous germline and tumor DNA of 23 patients, including 17 with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL), four with hairy cell leukemia, one with lymphoplasmacytoid lymphoma, and one with T-cell chronic lymphocytic leukemia. All samples at diagnosis displayed a germline pattern of the microsatellites examined, thus suggesting that MSI is not involved in the pathogenesis of these lymphoproliferations. Also, no microsatellite alterations were observed in consecutive samples of B-CLL/SLL obtained from the same patient at various stages of the disease both before and after chemotherapy. Conversely, alterations in 3/9 microsatellite repeats were detected in one case of Richter's syndrome which had evolved from a pre-existent B-CLL/SLL phase. Overall, the low frequency of MSI among chronic lymphoproliferative disorders adds further weight to the common view that the mechanisms and patterns of genomic instability in lymphoid neoplasia differ markedly from those commonly observed in solid cancers.     

Lithium-associated hyperparathyroidism and hypercalcaemia: A case-control cross-sectional study

Background

Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium.

Methods

112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8±74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels.

Results

PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels.

Limitations

Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism.

Conclusions

Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.