Birt‐Hogg‐Dubé syndrome‐associated renal cell carcinoma: Histopathological features and diagnostic conundrum

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed.     

Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.     

Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.     

N-terminal pro-brain natriuretic peptide predicts hospitalization for ischemic stroke in Japanese hemodialysis patients

Clinical and Experimental Nephrology - The association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and stroke in Japanese hemodialysis (HD) outpatients is unclear. Therefore, in...     

Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

Who Is Responsible? A Man With Dementia Wanders From Home,Is Hit by a Train,and Dies

The impact of dementia and Alzheimer's disease extends far beyond the healthcare needs of the person with dementia. As the disease progresses, individuals with dementia often require ongoing formal or informal care for their basic daily routine because of behavior changes and continuing loss of cognitive function. Most of the care for people with dementia takes place at home, and the unpaid, informal caregivers are often spouses or other relatives. Providing long-term informal care at home for someone with dementia is psychologically, physically, and financially draining. The tragedy described in this case elucidates the far-reaching societal impact of dementia care and the implicit health policy considerations.In 2007, a 91-year-old Japanese man with dementia was in the care of his wife when he wandered from home, was hit by a train, and died, immediately affecting the Central Japan Railway Company operations and, subsequently, legal practice as well as Japanese elder care policy. The railway sued the man's wife and son for negligence and lost revenue, winning both trials at the local and district courts. This ruling shocked families and caregivers in Japan, where care for elderly parents traditionally falls on the oldest son, and brought attention to the complex issues related to dementia care. A decade later, we revisit this case to provoke a renewed dialogue about the matrix of responsibilities and liabilities associated with caregiving; to illuminate the unmet needs of the person with dementia, as well as his or her informal caregivers; and the financial implications related to long-term care policy. We close with 2 practical suggestions which preserve the dignity of the individual and provide reassurance for caregivers.     

Relationship between oral Candida species and risk factors with reference to drugs with xerostomic side effects among institutionalised elderly in Aichi Pref., Japan

OBJECTIVE: To clarify the relationship between Candida carriage and drugs which have reported xerostomic side effects in the elderly. DESIGN: Cross-sectional study. Setting Two long-term care facilities in Aichi Pref., Japan. PARTICIPANTS: Eight men and 63 women with a mean age of 86 years (range 62 to 95 years) with at least some of their natural teeth. METHOD: Oral examination by dentists, microbiological test by microbiologists, questionnaire interviews, and data obtained from medical files. The Candida species (CFU) was adopted as an objective variable with risk indicators being age, number of teeth, saliva flow rate, denture wearing, xerostomic drugs, activities of daily living (ADL), frequency of brushing and type of meals. RESULTS: Bivariate analysis confirmed that participants with a higher number of Candida species (CFU) fell into the following categories: denture wearing (p < 0.05), older age (p < 0.05), xerostomic drugs (p < 0.10), more teeth, poor ADL, soft/liquid meals, and brushing once a day. This was in contrast to the categories of no denture wearing, younger age, no xerostomic drugs, fewer teeth, good ADL, normal meals, and brushing two or more times a day, in that order of significant probability on an ascending scale. A multiple logistics regression model confirmed that the variables of older age (80 years and over) and more teeth (six or more) had statistically significant (p < 0.05) effects on the number of Candida species present (CFU). Xerostomic drugs and the other variables had no significant effect. CONCLUSION: Older age and more teeth had a significant effect on the number of oral Candida species in the elderly. The results of this study did not support a role of those drugs as a risk indicator for oral Candida carriage. Larger trials are needed to assess the effect of drugs on the presence of oral Candida.