Helicobacter pylori, chronic atrophic gastritis, inactive aldehyde dehydrogenase-2, macrocytosis and multiple upper aerodigestive tract cancers and the risk for gastric cancer in alcoholic Japanese men

BACKGROUND: Gastric carcinoma occurs at a high rate in alcoholic Japanese men. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/2*2) and macrocytosis (mean corpuscular volume [MCV] > or = 106 fl) enhance the risk for esophageal carcinoma, which frequently occurs with gastric carcinoma in this population. Whether alcoholism affects Helicobacter pylori-induced chronic atrophic gastritis (CAG) is unknown. METHODS: This study of Japanese alcoholic men with (n = 45) and without (n = 281) gastric carcinoma included assessment of H. pylori IgG antibody, serum pepsinogen-confirmed CAG, MCV, and ALDH2 genotype. RESULTS: The gastric carcinoma cases had a significantly higher age-adjusted prevalence of H. pylori-positivity (78%vs 57%), CAG (78%vs 42%), ALDH2*1/2*2 (36%vs 14%), MCV > or =106 fl (38%vs 20%), and concurrent esophageal/oropharyngolaryngeal carcinoma (18%vs 5%) than controls. Among gastric cancer-free controls, the prevalence of CAG was higher than generally reported in Japan, regardless of H. pylori status (H. pylori-positive, 56%vs 35-36% for Japanese general population; H. pylori-negative, 8%vs 1-3%). Alcoholism may accelerate the progression of CAG. Each of these factors increased the risk of gastric carcinoma (OR(s) = 3.7 for H. pylori-positive, 2.7 for non-severe CAG, 8.7 for severe CAG, 3.5 for ALDH2*1/2*2, 2.5 for MCV > or =106 fl, and 3.7 for concurrent carcinoma). A multivariate analysis showed that CAG and ALDH2*1/2*2 were independently related to the risk of gastric carcinoma. Combinations of CAG and ALDH2*1/2*2 showed greater risks of gastric carcinoma (OR(s) = 4.0 for non-severe CAG alone, 17.6 for severe CAG alone, 9.7 for ALDH2*1/2*2 alone, 17.1 for non-severe CAG plus ALDH2*1/2*2, and 39.2 for severe CAG plus ALDH2*1/2*2). CONCLUSIONS: Combining blood tests for H. pylori, CAG, MCV and ALDH2 genotype could offer a new means of predicting risk of gastric carcinoma in Japanese alcoholic men.     

Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C

Background We have previously demonstrated that in patients with chronic hepatitis C (CHC), iron depletion improves serum alanine aminotransferase (ALT) levels as well as hepatic oxidative DNA damage. However, it has not been determined whether continuation of iron depletion therapy for CHC favorably influences its progression to hepatocellular carcinoma (HCC). Methods We conducted a cohort study on biopsy-proven CHC patients with moderate or severe liver fibrosis who failed to respond to previous interferon (IFN) therapy or had conditions for which IFN is contradicted. Patients were divided into two groups: subjects in group A (n = 35) underwent weekly phlebotomy (200 g) until they reached a state of mild iron deficiency, followed by monthly maintenance phlebotomy for 44–144 months (median, 107 months), and they were advised to consume a low-iron diet (5–7 mg iron/day); group B (n = 40) comprised CHC patients who declined to receive iron depletion therapy. Results In group A, during the maintenance phase, serum ALT levels decreased to less than 60 IU/l in all patients and normalized (<40 IU/l) in 24 patients (69%), whereas in group B no spontaneous decrease in serum ALT occurred. Hepatocarcinogenesis rates in groups A and B were 5.7% and 17.5% at the end of the fifth year, and 8.6% and 39% in the tenth year, respectively. Multivariate analysis revealed that iron depletion therapy significantly lowered the risk of HCC (odds ratio, 0.57) compared with that of untreated patients (P = 0.0337). Conclusions Long-term iron depletion for CHC patients is a promising modality for lowering the risk of progression to HCC.     

Pericarditis causing congestive heart failure as an initial manifestation of systemic lupus erythematosus

Pericarditis is a common complication in systemic lupus erythematosus (SLE) patients, however, that causing congestive heart failure (CHF) is a rare initial manifestation of SLE. We treated a patient whose initial manifestation of SLE was pericardial effusion causing CHF, which improved following prednisolone therapy that led to a dramatic decrease in pericardial effusion and improvement in left ventricular diastolic dysfunction as shown in Doppler echocardiography findings. Further, the plasma brain natriuretic peptide level became normalized.     

Significance of preserving vagus nerve in ileocolon interposition after total gastrectomy

BACKGROUND/AIMS: We have performed ileocolon interposition for reconstruction (IR) after total gastrectomy in order to reduce postoperative symptoms such as heartburn, reflux esophagitis and nutritional disturbance. After IR, however, the frequency of diarrhea increased in the postoperative period. We therefore investigated whether post-IR diarrhea could be prevented by preserving the vagus nerve. METHODOLOGY: The vagus nerve was not preserved in 46 (non-PV group) stage I and II gastric cancer patients treated with the IR method, and preserved in 28 for stage IA (PV group). By means of a mailed and interviewed questionnaire, we surveyed the patients at six months postoperatively to examine how diarrhea had occurred in either group. RESULTS: The frequency of diarrhea of the PV group was as low as 26% (7/27) which was significantly lower than 76% (35/46) of the non-PV group. CONCLUSIONS: Preservation of the vagus nerve during reconstruction using ileocolon interposition after total gastrectomy for stage IA is a superior approach for the prevention of postoperative diarrhea.     

Protein C deficiency in a family with thromboembolism and identified gene mutations

Protein C is the central component of the major anti-thrombotic regulatory system, and individuals with hereditary protein C deficiency tend to have an increased risk of thromboembolism. During the last several years, mutations causing protein C deficiency have been identified. In the present study, we report familial cases with three nucleotide substitutions: One is a missense mutation Arg169Trp, which was previously reported. The other two are C-154T promoter polymorphism (rs1799808 on dbSNP database), the function of which is unknown and Ser99Ser synonymous polymorphism (rs5936). All three mutations were found in a 24-year-old patient with pulmonary thromboembolism and his 54-year-old father who also had pulmonary thromboembolism. C-154T promoter polymorphism (rs1799808 on dbSNP database) and Ser99Ser synonymous polymorphism (rs5936) were found in the patient's mother.     

Forensic aspects of complications resulting from cardiopulmonary resuscitation

While cardiopulmonary resuscitation (CPR) can save lives, it can also injure patients. As a result, forensic pathologists often see CPR-related injuries during autopsies that are unrelated to the patients' primary cause of death. Therefore, pathologists must be able to distinguish between CPR-related injuries and those caused by other factors, such as assaults or accidental violence. This distinction is complicated because even therapeutically unimportant injuries can have forensic significance. For example, resuscitative injuries are observed frequently in the neck and the chest. This article focuses mainly on complications due to ventilation and chest compression during CPR. The following iatrogenic complications are described: bruising and abrasions in the face and neck, fractures of the hyoid bone and thyroid cartilage, air way injuries, vomitus aspiration, positional error of the tube for intra-tracheal intubation, petechiae, retinal hemorrhages, subarachnoid hemorrhages, rib and sternum fractures, bone marrow embolism, cardiac injuries including myocardial hemorrhages and frothy heart blood, and injuries to the abdominal organs such as liver and spleen.     

Nuclear cyclin B1 in human breast carcinoma as a potent prognostic factor

Cyclin B1 is translocated to the nucleus from the cytoplasm, and plays an essential role in cell proliferation through promotion of mitosis. Although overexpression of cyclin B1 was previously reported in breast carcinomas, the biological significance of the intracellular localization of cyclin B1 remains unclear. Therefore, in this study, we examined cyclin B1 immunoreactivity in 109 breast carcinomas, according to the intracellular localization, that is, nucleus, cytoplasm or total (nucleus or cytoplasm). Total cyclin B1 was detected in carcinoma cells in 42% of breast carcinomas examined, whereas nuclear and cytoplasmic cyclin B1 were positive in 17 and 35% of the cases, respectively. Total or cytoplasmic cyclin B1 were positively associated with histological grade, mitosis, Ki-67, p53, c-myc or 14-3-3sigma, and inversely correlated with estrogen or progesterone receptor. Nuclear cyclin B1 was significantly associated with tumor size, lymph node metastasis, histological grade, mitosis, Ki-67 or polo-like kinase 1. Only nuclear cyclin B1 was significantly associated with adverse clinical outcome of the patients, and multivariate analyses of disease-free and overall survival demonstrated nuclear cyclin B1 as the independent marker. A similar tendency was detected in the patients receiving adjuvant therapy after surgery. These results suggest that an onocogenic role of overexpressed cyclin B1 is mainly mediated in nuclei of breast carcinoma cells, and the nuclear translocation is regulated by polo-like kinase 1 and 14-3-3sigma. Nuclear cyclin B1-positive breast carcinoma is resistant to adjuvant therapy, and nuclear cyclin B1 immunoreactivity is a potent prognostic factor in breast carcinoma patients.