Proton beam therapy for hepatocellular carcinoma: a retrospective review of 162 patients.

PURPOSE: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy. EXPERIMENTAL DESIGN: We reviewed 162 patients having 192 HCCs treated from November 1985 to July 1998 by proton beam therapy with or without transarterial embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days. RESULTS: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments and a few late sequelae during and after the treatments. CONCLUSIONS: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent diseases.     

Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat.

Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to 4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56 was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continuous exposure to DBA. The sperm membrane proteome was altered in a dose-related manner with SP22, and one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.     

Maternal death reviews at a rural hospital in Malawi

ObjectiveTo analyze maternal deaths at Nkhoma Church of Central Africa Presbyterian (CCAP) Hospital and identify factors causing delays in care.MethodsMaternal death audits are performed after every maternal death at Nkhoma CCAP Hospital. Information regarding the care provided at the health facility, the referral process, and any delays in the community was collected by an audit team using a structured approach. Data from August 2007 to September 2011 were analyzed retrospectively.ResultsIn total, 61 maternal deaths occurred during the study period, of which 58 were analyzed. Most deaths were categorized as indirect (n = 34 [58.6%]). Non-pregnancy-related infections were the leading cause of indirect death (n = 22), with meningitis the most common (n = 13). Most patients experienced a delay in seeking care (n = 37 [63.8%]), a transport delay (n = 43 [74.1%]), or a delay in receiving adequate care (n = 34 [58.6%]).ConclusionMost maternal deaths had indirect causes and were associated with delays in all phases. An audit makes clear which part of the referral chain needs to be strengthened. Nkhoma CCAP Hospital has taken steps to address all phases of delay.     

Parental loss of family members within two years of offspring birth predicts elevated absorption scores in college

Liotti proposed that interactions during infancy with a parent suffering unresolved loss could lead to vulnerabilities to altered states of consciousness. Hesse and van IJzendoorn provided initial support for Liotti’s hypothesis, finding elevated scores on Tellegen’s Absorption Scale - a normative form of dissociation - for undergraduates reporting that their parents had experienced the loss of family members within two years of their birth. Here, we replicated the above findings in a large undergraduate sample (N = 927). Additionally, we investigated mother’s and father’s losses separately. Perinatal losses, including miscarriage, were also considered. Participants reporting that the mother or both parents had experienced loss within two years of their birth scored significantly higher on absorption than those reporting only perinatal, only father, or no losses. While not applicable to the assessment of individuals, the brief loss questionnaire utilized here could provide a useful addition to selected large-scale studies.     

Epstein–Barr virus positivity among surgically resected intramucosal gastric cancer

Epstein–Barr virus‐associated gastric cancer (EBV‐GC) accounts for approximately 8% of gastric cancers. However, little is known regarding intramucosal EBV‐GC. The present study aimed to evaluate endoscopic and clinicopathological characteristics of intramucosal EBV‐GC. Pathological data of 172 patients with 173 intramucosal gastric cancers who received gastrectomy with lymph node dissection were obtained for review. EBV‐encoded small RNA in situ hybridization (EBER‐ISH) was carried out using a tissue microarray block. Eight intramucosal early gastric cancers (4.6%) were EBER‐ISH positive in which no cases had any lymph node metastasis. Macroscopic types were either depressed or flat, dominant histology was mixed type of moderate and poorly differentiated adenocarcinoma. In detail, histological features of “lace pattern” or “lymphocyte infiltration into the stroma or cancer nests” were observed.     

A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to rats in their drinking water for 52 weeks. DPAA was administered to groups 1–4 at concentrations of 0, 5, 10, and 20 ppm in their drinking water for 52 weeks. There were no significant differences in the final body weights between the control groups and the treatment groups in male or female rats. In serum biochemistry, in females 20 ppm DPAA significantly increased alkaline phosphatase and γ-glitamyl transferase compared to controls, and 10 and 20 ppm DPAA significantly increased total cholesterol compared to controls. Absolute and relative liver weights were significantly increased in females treated with 20 ppm DPAA compared to the control group. Dilation of the common bile duct outside the papilla of Vater and stenosis of the papilla of Vater was observed in all male and female rats administered 20 ppm DPAA. The incidence of intrahepatic bile duct hyperplasia was significantly increased in male and female rats treated with 20 ppm DPAA compared to the control groups. These results suggest that DPAA is toxic to the bile duct epithelium in rats. The no-observed adverse effect levels of DPAA were estimated to be 10 ppm (0.48 mg/kg b.w./day) for males and 5 ppm (0.35 mg/kg b.w./day) for females under the conditions of this study.     

Maternal education level and low birth weight: a meta-analysis

ObjectiveTo assess the association between maternal education level and birth weight, considering the circumstances in which the excess use of technology in healthcare, as well as the scarcity of these resources, may result in similar outcomes.MethodsA meta-analysis of cohort and cross-sectional studies was performed; the studies were selected by systematic review in the MEDLINE database using the following Key**words socioeconomic factors, infant, low birth weight, cohort studies, cross-sectional studies. The summary measures of effect were obtained by random effect model, and its results were obtained through forest plot graphs. The publication bias was assessed by Egger's test, and the Newcastle-Ottawa scale was used to assess study quality.ResultsThe initial search found 729 articles. Of these, 594 were excluded after reading the title and abstract; 21, after consensus meetings among the three reviewers; 102, after reading the full text; and three for not having the proper outcome. Of the nine final articles, 88.8% had quality ≥ six stars (Newcastle-Ottawa Scale), showing good quality studies. The heterogeneity of the articles was considered moderate. High maternal education showed a 33% protective effect against low birth weight, whereas medium degree of education showed no significant protection when compared to low maternal education.ConclusionsThe hypothesis of similarity between the extreme degrees of social distribution, translated by maternal education level in relation to the proportion of low birth weight, was not confirmed.     

CHRNB3 is more strongly associated with Fagerström Test for Cigarette Dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results

AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.