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Phrenic nerves (PNs) play an important role in respiration; however, very few morphological studies have assessed them. This study aimed to provide control reference values, including the density of large and small myelinated PN fibers, for future pathological studies. We assessed a total of nine nerves from eight cases among consecutive autopsy cases registered to the Brain Bank for Aging Research between 2018 and 2019 (five men and three women, mean age 77.0 ± 7.0 years). The nerves were sampled distally, and their structures were analyzed using semi‐thin sections stained with toluidine blue. The mean and standard deviation of the density of each myelinated fiber of the PN was 6908 ± 1132 fibers/mm2 (total myelinated fiber), 4095 ± 586 fibers/mm2 (large diameter myelinated fiber; diameter ≥7 μm), and 2813 ± 629 fibers/mm2 (small diameter myelinated fiber; diameter <7 μm). There was no correlation between myelinated fiber density and age. This study provides the density measurement of the human PN myelinated fiber, and these findings can be used as reference values for the PN in elderly individuals. [ABSTRACT FROM AUTHOR]

The clinicopathological significance of carbohydrate antigen 19‐9 (CA19‐9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19‐9 in GC utilizing autopsy cases. We examined the expression of CA19‐9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19‐9 levels and clinicopathological variables or complications. We also investigated whether fucosyltransferases 2 and 3 (FUT2/3) allelic variants influence CA19‐9 expression in GC. Compared to GC cases with negative CA19‐9 expression (tCA19‐9‐N), those with positive CA19‐9 expression (tCA19‐9‐P) demonstrated significant differences in characteristic features such as lymph node and distant organ metastases, lymphatic and venous permeation, and higher Tumor, Node, Metastasis (TNM) stages. Moreover, compared to GC cases with low serum CA19‐9 levels (sCA19‐9‐L), those with high serum CA19‐9 levels (sCA19‐9‐H) were related to venous permeation, higher proportion of lymph node and distant organ metastases, and higher TNM stages. Both tCA19‐9‐P GC and sCA19‐9‐H GC cases were significantly associated with coagulation abnormalities. sCA19‐9‐H GC cases correlated significantly with MUC1 and MUC5AC expression. FUT2/3 genotypes were not associated with CA19‐9 expression in GC. These results suggest that CA19‐9 can predict the risk of lymph node and distant metastases as well as of coagulation abnormalities. [ABSTRACT FROM AUTHOR]

Aim: Neutrophil extracellular traps play key roles in the necrotizing vasculitis associated with anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV). However, the relationships between neutrophil extracellular traps formation and the distribution and phase of vasculitis are not well understood. In the present study, we clarified the clinicopathological characteristics of older AAV patients, as well as the expression of citrullinated histone H3 (citH3), a marker of neutrophil extracellular traps, in autopsied AAV patients. Methods: We reviewed autopsy cases that were carried out at Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, from 2001 to 2018. The expression of citH3 was determined by immunostaining. Results: AAV patients (six cases) were elderly (aged 73–94 years; three men and three women; myeloperoxidase anti‐neutrophil cytoplasmic antibody‐positive, five cases; proteinase‐3 anti‐neutrophil cytoplasmic antibody‐positive, one case; disease duration was 1.5–5.5 months; and patients were treated with steroids. All patients had necrotizing vasculitis in the medium‐to‐small‐sized vessels in various organs, and also severe vasculitis‐associated lesions including brain hemorrhage, alveolar bleeding, interstitial pneumonia, crescentic nephritis, acute pancreatitis and gastrointestinal bleeding. Expression of citH3 was associated with the activity of inflammation. Conclusions: We report severe clinicopathological characteristics of AAV in older patients. Expression of citH3 was a useful marker to evaluate vasculitis severity. Identification of these features might aid in the diagnosis of AAV. Geriatr Gerontol Int 2019; 19: 259–264. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We aimed to clarify the characteristics of malignancies in older adults focusing on distant metastasis in the whole body. Methods: We retrospectively evaluated 7710 cases of autopsies (4011 men, 3699 women, median age of 80 years), and analyzed the characteristics of metastasis of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma in each organ. Results: The total number of cases with adenocarcinoma, squamous cell carcinoma or urothelial carcinoma was 2856, and most of them were adenocarcinomas. Among them, 1604 had metastatic lesions, and patients with metastasis were younger than those without metastasis. The major primary organs of adenocarcinoma were the stomach, colon, lung, prostate, gallbladder and pancreas, whereas those for squamous cell carcinoma were the lung, esophagus and uterus. Urothelial carcinoma cases were found in the urinary bladder, kidney and ureter. Metastatic adenocarcinomas mainly originated from the stomach, colon, lung, pancreas and gallbladder. Metastatic squamous cell carcinomas were from the lung, esophagus and uterus, whereas the kidney, bladder and ureter were the primary origins of metastatic urothelial carcinomas. Squamous cell carcinoma showed the highest incidence of metastasis, suggestive of it being of an aggressive phenotype. Furthermore, metastatic ability and the preferred metastatic sites varied among primary organs. Conclusions: We revealed an accurate incidence and the characteristics of metastatic cancer in a large‐scale autopsy study of older Japanese patients from one institution. Identifying these features might prompt screening for malignancies, and consequently improve quality of life for older adults. Geriatr Gerontol Int 2018; 18: 211–215. [ABSTRACT FROM AUTHOR]

Aim To determine the incidence and endoscopic types of colorectal lesions diagnosed with colonoscopy in elderly patients. Methods Consecutive Japanese patients who underwent colonic endoscopy between 1994 and 2007 ( n = 5145; 2245 men and 2900 women, age 20-101 years) were examined retrospectively. Correlations between age, sex and number of lesions were analyzed. Results The incidence of advanced tumors was significantly correlated with increasing age in men ( P = 0.02), and tumors were detected mainly in the sigmoid colon and rectum in both sexes. Right-sided colon cancer was significantly more common in women compared with men ( P < 0.001). Polyps were detected throughout the colon, and their incidence was correlated significantly with increasing age in women ( P = 0.01). Diverticula were frequently detected in the ascending and sigmoid colon in both sexes. Left-sided diverticula were significantly more common in women compared with men ( P < 0.001). Lateral spreading tumors were detected mainly in the cecum in both sexes. Though the number of cases with angioectasia was small, angioectasia was slightly more common in the cecum and the ascending colon in women. Conclusions In the present study, the incidence of advanced tumors correlated with increasing age in men, and right-sided cases were significantly more common in women than in men. The incidence of polyps correlated with increasing age in women. Left-sided diverticula were significantly more common in women than in men. Geriatr Gerontol Int 2016; 16: 1319-1323. [ABSTRACT FROM AUTHOR]

A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three days after completing pulse steroid therapy, he suffered from a sudden disturbance of consciousness and died. On autopsy, the kidneys showed the most severe vasculitis with dense infiltration of citH3-positive neutrophils. The lungs showed intra-alveolar hemorrhage due to capillaritis. Severe brain hemorrhage was found in the left frontal lobe and putamen with uncal herniation. No vasculitis or thrombi was observed in the brain. The right dura mater was thickened due to fibrosis and inflammation. In conclusion, autopsy revealed systemic vasculitis with infiltration of abundant citH3-positive neutrophils, suggesting that the neutrophil extracellular trap formation and citH3 might play important roles in the early phases and development of microscopic polyangiitis. [ABSTRACT FROM AUTHOR]

As estrogens play an important role in maintaining physiological function in various organs, the estrogen decrease after menopause is thought to cause various diseases frequently observed in postmenopausal or elderly women. With the aging of society and a decrease in infectious or vascular diseases, neoplasms have now become the most frequent cause of death in Japan. Cancers of the colorectum, breast, and lung have been rapidly increasing both in incidence and death, especially among postmenopausal women. Interestingly, all three of these cancers are associated with estrogens. In premenopausal women, ovarian estrogens plays major roles in the female reproductive organs through the classic estrogen receptor, ER-α. In postmenopausal women, however, estrogens produced/activated by peripherally localized estrogen-metabolizing enzymes such as aromatase, which converts androgen into estrogens, are thought to play physiologically and pathobiologically important roles in various organs through second ER, namely ER-β, distributing systemically. In this article, the association of estrogens with these cancers in postmenopausal or elderly women are reviewed, especially focusing on the role of ER-β and peripheral estrogen metabolism. The possibility of prevention or treatment of these diseases through estrogenic control is also discussed. [ABSTRACT FROM AUTHOR]

Background: Assessment of the pathobiological determinants of atherosclerosis is crucial for a better understanding of cardiovascular events. Methods: The study was conducted in 178 autopsy cases of in-hospital death (104 men and 74 women; mean age, 81 years), for whom serum lipid values recorded during outpatient follow ups for chronic diseases were available. Severity of the atherosclerosis was semiquantitatively assessed in 10 arteries, and the correlations with age, sex, serum levels of total cholesterol and high-density lipoprotein cholesterol (HDL-C), and the history of hypertension, diabetes mellitus and/or smoking were evaluated. Results: The statistically significant risk factors differed between the genders and among the arterial systems. The effect of total cholesterol and HDL-C was more prominent in women than in men. The odds ratio of an elevated total cholesterol value (per 0.1 g/L) for coronary atherosclerosis was 1.56 (95% confidence interval, 1.25–1.95, P < 0.001) in women and 1.19 (1.07–1.33, P = 0.002) in men. Hypertension, but not serum lipid profiles, was significantly associated with cerebral atherosclerosis in both genders ( P < 0.05). Diabetes mellitus and smoking were associated with atherosclerosis in selected arteries. Conclusion: Dyslipidemia is a major determinant of atherosclerosis in the elderly, and control of dyslipidemia is still necessary in the elderly population. [ABSTRACT FROM AUTHOR]

Mucinous carcinoma and poorly differentiated adenocarcinoma of the large intestine have a high frequency of microsatellite instability, and their occurrence increases gradually with age. To elucidate the clinicopathological and immunohistochemical features of microsatellite-unstable mucinous carcinoma and compare the tumor with medullary type poorly differentiated adenocarcinoma, the clinicopathological status and expression of mucin core and hMLH1 proteins were studied in 15 microsatellite-unstable and 20 microsatellite-stable mucinous colorectal carcinomas occurring in elderly patients, and compared with 23 cases of medullary type poorly differentiated adenocarcinoma in which 21 cases were microsatellite-unstable. Thirteen (87%) of 15 microsatellite-unstable carcinomas exhibited absent hMLH1 expression compared with three (15%) of 20 microsatellite-stable carcinomas ( P < 0.01). The proportion (87%) of positive MUC5AC expression in microsatellite-unstable mucinous carcinoma was significantly higher than that (45%) in microsatellite-stable mucinous carcinoma ( P = 0.01). Compared with microsatellite-stable mucinous carcinoma, microsatellite-unstable mucinous carcinomas were significantly associated with a proximal location, intra- and peritumoral inflammatory cell infiltration, frequent MUC5AC expression, a low incidence of lymph node metastasis and absent hMLH1 protein expression, which is not different to medullary type poorly differentiated adenocarcinoma except for MUC2 expression and age-related occurrence. These results suggest that microsatellite-unstable mucinous carcinoma occurring in the elderly shares clinicopathological and molecular features with medullary type poorly differentiated adenocarcinoma and that microsatellite instability with absent hMLH1 expression plays an important role in the development of these two carcinomas. [ABSTRACT FROM AUTHOR]

Microsatellite instability (MSI) is present in approximately 15–20% of sporadic colorectal cancers. However, despite the increased prevalence of absent hMLH1 expression and MSI in colorectal cancer in the elderly, few attempts have been made to define it in detail. The aim of the present paper was to correlate age-related alterations in absent hMLH1 expression and MSI with various histological types of colorectal carcinoma. hMLH1 expression and microsatellite status were studied in 184 colorectal carcinomas (49 well-differentiated, 49 moderately differentiated, 49 poorly differentiated adenocarcinomas, and 37 mucinous carcinomas). The prevalence of absent hMLH1 expression was higher in poorly differentiated adenocarcinoma (63%) and mucinous carcinoma (43%) than in well- (8%) and moderately (12%) differentiated adenocarcinomas. MSI was found more frequently in poorly differentiated adenocarcinoma (69%) and mucinous carcinoma (41%) than in well- and moderately differentiated adenocarcinomas (8% and 6%, respectively). Age-related differences in absent hMLH1 expression and MSI were found only in poorly differentiated adenocarcinoma, in which the prevalence of medullary-type carcinoma increased with advancing age. These results indicate that an age-related increase of medullary-type tumors in poorly differentiated adenocarcinoma may play an important role in the increase of absent hMLH1 expression and MSI in colorectal carcinoma. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine standard organ weights among the elderly, because little has been reported on this subject. To analyze the human aging process in terms of organ weights, age-associated changes and correlations among organ weights and the contributions of age and nutrition to organ weights were also examined. The subjects included 1615 consecutive autopsy cases of patients aged 60–99 years who died between 1995 and 2003, and cases of 50 centenarians who died between 1973 and 2005. The weights of nine organs were measured before formalin fixation. If affected by serious diseases, such as cancer, the organs were excluded from the study. Values beyond 99% of the bilateral measurement limits were also excluded. In this manner the standard organ weights were obtained. The organ weights decreased significantly according to age in all organs except for the heart in men and the lungs in both genders. Undernutrition strongly contributed to organ weight except for the hypophysis, and was especially apparent in the heart and liver. In conclusion, the standard organ weights of elderly patients who died while hospitalized were determined. Undernutrition contributed significantly to a reduction in organ weights. [ABSTRACT FROM AUTHOR]

Background: In 1991, Kelly first reported the presence of red or brown mucosal protrusions or polyps associated with diverticular disease and described this syndrome as ‘polypoid prolapsing mucosal folds in diverticular disease.’ In 1994, Matake et al. independently reported several long mucosal intraluminal protrusions as ‘colonic muco-submucosal elongated polyps.’ The purpose of the present study is to address the relationship between the two syndromes. Methods: We performed a careful review of the published work on the clinicopathological features of these syndromes. Results: The clinical symptoms associated with these two syndromes do not differ notably. Because of the mucosal redundancy of the colonic mucosa, the excessive propulsive power of peristalsis may play an important role in generating both types of polyps. Neither ‘polypoid prolapsing mucosal folds in diverticular disease’ nor ‘colonic muco-submucosal elongated polyps’ fit into any of the conventional classifications, and their histological characteristics are similar. In addition, we describe the diagnosis and clinical management at our institution of an emergent case of polypoid prolapsing mucosal folds in diverticular disease. Conclusion: In light of their similar etiology and pathology, we propose that these conditions are different manifestations of the same entity. Unifying these two classifications into one makes the diagnosis of either type of polyp less onerous for clinicians, endoscopists and pathologists. As a consequence, it is likely that more cases will be diagnosed and reported. The accumulation of more cases will lead to deeper understanding and further clinicopathological characterization of diverticular polyps. [ABSTRACT FROM AUTHOR]

Aims/Background: The entire spectrum of persistent infection by hepatitis C virus (HCV) is still unknown Methods: A total of 37 autopsy cases, positive with second generation anti-HCV ELISA, were analyzed. The cases comprised 15 males and 22 females, the average ages being 76.5 in males and 81.1 in females. Twenty-one cases were found to be asymptomatic, while 16 were symptomatic. Results: Based on two pathological parameters of hepatic fibrosis and inflammation, the cases were divided into five groups; group A (non-inflammatory group without significant fibrosis; 11 cases), group B (inflammatory group without significant fibrosis; 9 cases), group C (non-inflammatory group with significant fibrosis; 1 case), group D (inflammatory group with significant fibrosis; 11 cases) and group E (undetermined inflammatory index; 5 cases). All cases in group A and seven cases in group B were asymptomatic. Group A included 6 cases with normal liver. All cases in groups C and D were symptomatic. All examined cases of the inflammatory groups were positive for serum HCV-RNA. Conclusion: Anti-HCV-positive elderly autopsy patients include many asymptomatic cases. The two pathological parameters of hepatic fibrosis and inflammation can be used to divide the cases into five groups with each group being well correlated with clinical and virological features. [ABSTRACT FROM AUTHOR]

Abstract: Introduction:: Studies examining the correlation between aortic pulse wave velocity (PWV) and atherosclerosis have reported conflicting results. The present paper verifies this correlation by conducting autopsy examination of elderly subjects. Methods:: A total of 3456 PWV examinations had been performed on 1538 elderly people, as a part of routine physical check-up. During long-term follow-up, many of these subjects died, and autopsy study could be conducted on 304 of these subjects. The average age at death of the subjects was 83 years and the male: female ratio was 6:5. The pathological atherosclerotic index (PAI) was defined as the average pathological degree of atherosclerosis in eight large arteries, including aorta. Results:: Significant positive correlations were observed between the age and PWV (γ =0.273, P &#60;0.001), and between the systolic blood pressure and PWV (γ =0.478, P &#60;0.001). There was a significantly positive correlation between the aortic atherosclerotic degree and mean PWV (ρ =0.239, P &#60;0.005), and between the PAI and mean PWV (γ =0.323, P &#60;0.001). The partial regression coefficient between the PAI and mean PWV was 0.209, after adjusting for the mean systolic blood pressure and age at death. Conclusion:: The present study proved a weak correlation between the PWV and the pathologically verified degree of the aortic and systemic atherosclerosis. [Copyright &y& Elsevier]