[Statistical investigation on cases associated with medical implication in administrative autopsy within the 23 wards of Tokyo: the role of the medical examiner system in investigation of cases associated with medical implication].

Actual circumstances of administrative autopsies which proved connections between medical implication and death had not been very clear in the past. Therefore, using the records of administrative autopsies performed from 2003 to 2005 at Tokyo Medical Examiner's Office, this study looked into the cases in which a certain level of connection between medical implication and death was proved or suspected. This study dealt with 877 cases. The largest age group among the male was the one between 65 and 74, and the number of female cases increased as the age increased. The percentage of the studied cases among all the administrative autopsy cases has become larger after 2004. As regarding medical departments for implication, "internal medicine" had the largest number of the cases, and "unknown", "psychiatry", and "emergency" followed in order. 30 percent were being hospitalized during the final medical consultations, and the percentage went up to just over 60 when the deaths during and on the day after the final consultations were added to the figure. Regarding the causes of death, the great majority was natural death, and the other causes were 'unknown', 'fall', and 'asphyxia'. Also, about 80 percent of the natural deaths were caused by circulatory, gastroenteric and respiratory diseases. Contradictions between clinical and forensic diagnoses were found in approximately 10 percent of the cases. In any case, medical examiners are to diagnose the causes of deaths by autopsy, not to evaluate the quality and safety of medical treatment. But if the quality and safety of medical treatment could be improved through the diagnoses of administrative autopsy, the medical examiner system would function practically as a part of administration for health and welfare. However, as it handles not only deaths by medical treatment but also all the other types of unnatural deaths, the system can also deal with other social problems, for which the correct causes of death must be diagnosed initially. It is socially very unhealthy to focus only on death associated with medical implication, as other types of unnatural death could be seen as relatively less important. Therefore, it is considered that the medical examiner system is effective for investigation of a variety of unnatural death as well as cases associated with medical implication.

Ruptured Syphilitic Aneurysm: A Cause of Sudden Death in a Man with Human Immunodeficiency Coinfection.

Syphilis, a sexually transmitted infection caused by the bacterium Treponema palladium, is experiencing a worldwide resurgence. The risk of syphilis infection is particularly high in men who have sex with men (MSM), especially those who are human immunodeficiency virus (HIV)-positive. Untreated syphilis can lead to rare but severe late-stage complications, including syphilitic aortitis. Herein, we present an autopsy case of a ruptured thoracic aneurysm that resulted from an undetected case of syphilitic aortitis in an HIV-positive Japanese MSM with undiagnosed syphilis. Although no syphilitic skin lesions were observed on the body, anatomical changes consistent with a syphilitic etiology were present at the site of the rupture, including medial aortic scarring with "tree-bark"-like atherosclerotic plaque. In addition, heart blood was positive for T. palladium in a latex agglutination test. This case highlights for forensic pathologists the importance of recognizing syphilis as a possible underlying cause of sudden death among HIV-positive MSM.

An autopsy case of pulmonary artery intimal sarcoma: detailed observation of tumor and its related lesions in pulmonary arteries.

We report an autopsy-proven case of a 33-year-old man who died of intimal sarcoma of the pulmonary artery. A large mass (5×4 cm) occluded the main and bilateral pulmonary arteries. Tumor cell morphology was consistent with that of undifferentiated pleomorphic sarcoma. Comprehensive histological observation of 18 pulmonary arteries from proximal to distal revealed continuous extension of the tumor from the main to the subsegmental arteries along the intima, forming an arteriosclerosis-like intimal thickening. Distal small arteries were also affected by eccentric intimal thickening or recanalization. Lung parenchyma was not involved, although there were two wedge-shaped small pulmonary infarctions caused by tumorous obstruction of the associated arteries. Histological results indicated that the intimal sarcoma in the pulmonary artery, which appeared occlusive with growth limited to the proximal artery, had in fact already spread more peripherally than expected. Both the proximal lesions and the distal small arteries were affected by peripheral tumor emboli or by pulmonary hypertension induced by the proximal tumor. However, as seen in this case, most of the occlusive tumor was located locally and intraluminally, in the proximal artery, and removing the proximal tumor by pulmonary endarterectomy was considered effective for symptomatic improvement.

Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma.

We evaluated the efficacy of anti-human VEGF antibody (bevacizumab) with or without irinotecan (CPT-11) against lung metastases in which neovascularization was already induced, as a postoperative adjuvant therapy using orthotopically implanted colon cancer in rat. The high VEGF productive KM12SM human colon cancer cells were injected into the cecal wall. At 5 weeks after the injection, the cecum was removed including the tumor. Then, 5 mg/kg of bevacizumab and 40 mg/kg of CPT-11 were administered, alone or in combination, intravenously once a week for 3 weeks, from day 15 after the cecal removal. The results show that the incidences of macroscopic and/or microscopic lung metastases in the bevacizumab-alone group (B) and in the combination group (C) were significantly lower (B, p=0.001 and C, p=0.037) than that in the control group at day 35 after the cecal removal. The number of lung metastases in B was 0.8+/-0.8 (p=0.024) and in C 2.4+/-1.8 (p=0.060), each value lower than the 12.4+/-4.2 of the control group. The growth of a subcutaneously implanted tumor was significantly inhibited in the combination group compared to either the CPT-alone (p=0.003) or the bevacizumab-alone groups (p=0.027). Apoptosis was significantly (p<0.001) induced in the combination group. In conclusion, a beneficial effect of bevacizumab against postoperative lung metastases may be expected even after the establishment of neovascularization in metastatic foci in nude rat. The results from the present subcutaneously implanted tumor model suggested that a higher efficacy may be expected when bevacizumab is combined with the cytotoxic agent CPT-11, compared to bevacizumab alone, against tumors with a variety of VEGF production levels in clinical situations.

Long-Term Outcomes of Pancreatic Function Following Pancreatic Trauma.

The objective of this study is to retrospectively assess long-term outcomes and late complications of pancreatic trauma. We studied 14 patients with pancreatic trauma who were treated at the Advanced Emergency Medical Service Center, Kurume University Hospital, between 1981 and 2012 and discharged alive. Relevant data were extracted from patient records and a retrospective patient questionnaire and blood test were completed to evaluate pancreatic function. The median patient age at the time of the survey was 49 years; the median post-injury period was 23 years and 5 months. The comorbidity rates for pancreatic endocrine and exocrine dysfunctions were 35.7% and 33.3%, respectively. No new-onset diabetes mellitus (DM) was seen within 3 years of trauma, except in 1 patient who underwent pancreaticoduodenectomy. DM developed >15 years after trauma in 2 patients each in the pancreatectomy and non-pancreatectomy groups. Diarrhea exacerbated by fat intake was seen in 3 and 1 patient in the pancreatectomy and non-pancreatectomy groups, respectively. Both complications were more common in the pancreatectomy group, but without statistical significance. Although post-surgical pancreatic dysfunction may be absent at discharge, treatment for pancreatic trauma should take into account the possibility that pancreatectomy may accelerate DM onset.

Dosage escalation study of S-1 and irinotecan in metronomic chemotherapy against advanced colorectal cancer.

The anti-angiogenic efficacy of chemotherapy would seem to be optimized by administering comparatively lower doses of drugs on a more frequent (daily, several times a week, or weekly) or continuous schedule, with no extended interruptions - sometimes referred to as 'metronomic' chemotherapy. This phase I study was performed to determine the recommended dosage (RD) of metronomic chemotherapy using oral fluoropyrimidine S-1 plus weekly irinotecan (CPT-11) in patients with previously untreated advanced or recurrent colorectal cancer. Patients received first-line chemotherapy consisting of 80 mg/m(2) of S-1 given on days 3 to 7, 10 to 14, and 17 to 21 with escalating dosages of CPT-11 (from 40 mg/m(2)) administered intravenously on day 1, 8, and 15 of a 28-day cycle. Standard patient eligibility criteria were used. Based on the concept of metronomic chemotherapy, dose limiting toxicity (DLT) was defined any toxicity that resulted in skipping of CPT-11 administration, or more than 5 days suspension in S-1 administration, in addition to the conventional criteria. If the maximum tolerated dosage (MTD) was defined as the maximum dosage at which no suspension of CPT-11 or S-1 administration occurred, the RD was considered to be the dosage one rank lower than the MTD. On the other hand, in the present study the MTD was defined as the dosage at which at least one suspension of CPT-11 or S-1 administration occurred, the MTD was considered to be the RD. Two of the first 3 patients at level 4 received 60 mg/m(2) of CPT-11 and 80 mg/m(2) of S-1 experienced a suspension in CPT-11 administration, thus level 4 was defined as the MTD and RD. Sixty mg/m(2) of CPT-11 and 80 mg/m(2) of S-1 were the indicated RD for the following phase II study of metronomic chemotherapy.