Masahito Kido

Prevalence of Prostate Cancer on Autopsy: Cross-Sectional Study on Unscreened Caucasian and Asian Men

BACKGROUND Substantial geographical differences in prostate cancer (PCa) incidence and mortality exist, being lower among Asian (ASI) men compared with Caucasian (CAU) men. We prospectively compared PCa prevalence in CAU and ASI men from specific populations with low penetrance of prostate-specific antigen screening. METHODS Prostate glands were prospectively obtained during autopsy from men who died from causes other than PCa in Moscow, Russia (CAU), and Tokyo, Japan (ASI). Prostates were removed en-block and analyzed in toto. We compared across the 2 populations PCa prevalence, number and Gleason score (GS) of tumour foci, pathological stage, spatial location, and tumor volume using χ(2), Mann-Whitney-Wilcoxon tests, and multiple logistic regression. All statistical tests were two-sided. RESULTS Three hundred twenty prostates were collected, 220 from CAU men and 100 from ASI mean. The mean age was 62.5 in CAU men and 68.5 years in ASI men (P < .001). PCa prevalences of 37.3% in CAU men and 35.0% in ASI men were observed (P = .70). Average tumor volume was 0.303cm(3). In men aged greater than 60 years, PCa was observed in more than 40% of prostates, reaching nearly 60% in men aged greater than 80 years. GS 7 or greater cancers accounted for 23.1% and 51.4% of all PCa in CAU and ASI men, respectively, (P = .003). When adjusted for age and prostate weight, ASI men still had a greater probability of having GS 7 or greater PCa (P = .03). CONCLUSIONS PCa is found on autopsy in a similar proportion of Russian and Japanese men. More than 50% of cancers in ASI and nearly 25% of cancers in CAU men have a GS of 7 or greater. Our results suggest that the definition of clinically insignificant PCa might be worth re-examining.

Genetic and functional analyses implicate the NUDT11, HNF1B, and SLC22A3 genes in prostate cancer pathogenesis

One of the central goals of human genetics is to discover the genes and pathways driving human traits. To date, most of the common risk alleles discovered through genome-wide association studies (GWAS) map to nonprotein-coding regions. Because of our relatively poorer understanding of this part of the genome, the functional consequences of trait-associated variants pose a considerable challenge. To identify the genes through which risk loci act, we hypothesized that the risk variants are regulatory elements. For each of 12 known risk polymorphisms, we evaluated the correlation between risk allele status and transcript abundance for all annotated protein-coding transcripts within a 1-Mb interval. A total of 103 transcripts were evaluated in 662 prostate tissue samples [normal (n = 407) and tumor (n = 255)] from 483 individuals [European Americans (n = 233), Japanese (n = 127), and African Americans (n = 123)]. In a pooled analysis, 4 of the 12 risk variants were strongly associated with five transcripts (NUDT11, MSMB, NCOA4, SLC22A3, and HNF1B) in histologically normal tissue (P ≤ 0.001). Although associations were also observed in tumor tissue, they tended to be more attenuated. Previously, we showed that MSMB and NCOA4 participate in prostate cancer pathogenesis. Suppressing the expression of NUDT11, SLC22A3, and HNF1B influences cellular phenotypes associated with tumor-related properties in prostate cancer cells. Taken together, the data suggest that these transcripts contribute to prostate cancer pathogenesis.

Prevalence of Inflammation and Benign Prostatic Hyperplasia on Autopsy in Asian and Caucasian Men

UNLABELLED Inflammation has been suggested to be involved in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the prevalence of inflammation and BPH in Asian and Caucasian men on prostate glands (n=320) obtained during autopsy in Moscow, Russia (Caucasian men, n=220), and Tokyo, Japan (Asian men, n=100). We correlated the presence and grade of acute inflammation (AI) or chronic inflammation (CI) and BPH. AI, CI, and histologic BPH were analyzed in a blinded fashion using a grading system (0-3). We used the Cochran-Armitage test for associations between the degree of BPH and clinical variables and proportional odds logistic regression models in multivariable analysis. Histologic BPH was observed in a similar proportion of Asian and Caucasian men (p=0.94). CI was found in>70% of men in both the Asian and Caucasian groups (p>0.05). Higher BPH scores were associated with more CI (p<0.001). In multivariate analyses, individuals with CI were 6.8 times more likely to have a higher BPH score than individuals without (p<0.0001). Men included in this study presented at the hospital and their symptomatic status was not known. The prevalence of CI and BPH on autopsy is similar in Asian and Caucasian men despite very different diet and lifestyle. CI is strongly associated in both groups with BPH. PATIENT SUMMARY In this study, we looked at the prevalence of inflammation and benign prostatic hyperplasia (BPH) on autopsy in Asian and Caucasian men. We found chronic inflammation in>70% of men on autopsy. More chronic inflammation was associated with more BPH.

Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial

BackgroundThe optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB) in intermediate-risk prostate cancer (PCa) patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT) with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS) provide no firm recommendations.Methods/DesignSeed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment.The primary endpoint is biochemical progression-free survival (BPFS). Secondary endpoints are overall survival (OS), clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS]), quality of life (QOL) evaluation, and adverse events. In the correlative study (SHIP36B), we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy.DiscussionThese two multicenter trials (SHIP0804 & SHIP36B) are expected to provide crucial data regarding the efficacy, acceptability and safety of adjuvant ADT. SHIP36B will also provide important information about the prognostic implications of PSA levels in intermediate-risk PCa patients treated with 125I-TPPB.Trial registrationNCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709

Salvage partial brachytherapy for prostate cancer recurrence after primary brachytherapy

To characterize local recurrence of prostate cancer and to assess the effect of salvage partial brachytherapy after primary 125‐iodine low‐dose rate brachytherapy with or without external beam radiotherapy in Japanese men.

Analysis of cervical injuries in persons with head injuries

To determine which clinical factors are useful for predicting concomitant injuries of the cervical spine and cervical spinal cord in persons with head injuries, we examined the nature and mechanisms of cervical injuries. For 109 forensic autopsies of persons with head injuries, the cause of injury, mechanism of cervical injury, survival time, and anatomic injury severity (1990 revision of the abbreviated injury scale [AIS] and injury severity score) were determined. Traffic accidents were the most common cause of injuries (41.3%), followed by slips and falls (24.8%), assaults (17.4%), and falls from height (9.2%). The mean maximum AIS scores and the AIS scores of the head or neck were similar in the 4 groups. Cervical spine injuries and epidural or subdural hemorrhages of the cervical spinal cord were more common in persons dying in traffic accidents and falls from height than in persons dying in slips and falls or assaults. Cervical injuries were significantly more common in persons sustaining frontal impacts than lateral or rear impacts. The most common cervical hyperextension injuries were atlanto-occipital and atlantoaxial dislocation and injuries of the 5th intervertebral disc. Our results suggest that persons with injuries of the head due to high-energy frontal impacts should be carefully examined for concomitant cervical injuries. These findings should be helpful for decreasing preventable deaths from undiagnosed cervical injuries in head-injured persons.

3. Sudden Death Due to Pulmonary Thromboembolism After Car Driving

An autopsy case of sudden death due to pulmonary thromboembolism after a car trip is reported. A 56-year-old Japanese man with hypertension and atrial fibrillation suddenly died immediately after having driven for two and a half hours. At autopsy, the pulmonary arteries were found to be filled with dark-red, coiling thrombi consisting of fibrin and red blood cells. In the dilated right popliteal vein, a thrombus consisting of fibroblasts, a large number of collagen fibres, and newly formed capillaries was attached to the vessel wall. The cause of death was determined to be pulmonary embolism due to the thrombus of the right popliteal vein. Two and a half hours of prolonged sitting while driving a car encouraged thrombus formation. We believe that this case, the first autopsy case of fatal pulmonary thromboembolism after a car trip to be reported, highlights the importance of predicting venous thrombosis of the leg or fatal venous thromboembolism after a car trip.

Mid-term outcome of permanent prostate iodine-125 brachytherapy in Japanese patients

To analyze mid‐term oncological outcomes of low‐dose rate brachytherapy in Japanese patients.

Safety of fondaparinux for prevention of postoperative venous thromboembolism in urological malignancy: A prospective randomized clinical trial.

To prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro‐oncological surgery.

Accidental strangulation of a mentally retarded patient by a clothing collar: a case report.

A 40-year-old mentally retarded woman died of accidental strangulation in a nursing home. She was found in a kneeling position with her hands on her knees and the collar of her clothing compressing the front and sides of the neck. Before the accident, a nurse had dressed the patient in one-piece overall-style pyjamas put on back to front so that she could not remove the garment herself. The post-mortem findings and reconstruction of the scene of death suggested that the patient had been strangled by the collar of her backward-facing clothing while in a kneeling position. Because patients with psychiatric illnesses may have a limited ability to recognize or communicate symptoms of physical danger, they must be closely monitored by knowledgeable medical and nursing staff. This case highlights the importance of preventing the accidental deaths of mentally retarded patients in nursing homes.