Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.

The Intake of Kiwifruits Improve the Potential Antioxidant Capacity in Male Middle- and Long-Distance Runners Routinely Exposed to Oxidative Stress in Japan.

Oxidation damages cells and muscles, and thus, causes injuries and fatigue, which negatively affect the conditioning of athletes. Thus, in this study, we aimed to investigate the effects of high-antioxidant fruits (kiwifruit) intake on oxidative stress level (d-ROMs) and antioxidant activity (BAP) in male middle- and long-distance runners routinely exposed to oxidative stress. This study was performed from May to July 2017 (Study 1) and October to December 2018 (Study 2). The subjects in Study 1 were 30 male runners, of which 15 consumed two yellow kiwifruits (Zespri® SunGold Kiwifruit) per day for one month of the survey period (Intake group). The subjects of Study 2 were 20 male runners who had high d-ROMs from preliminary testing. These runners consumed two yellow kiwifruits (Zespri® SunGold Kiwifruit) per day for two months. d-ROMs and BAP were measured using a free radical analyzer. In study 1, the d-ROMs decreased while the potential antioxidant capacity (BAP/d-ROMs ratio) increased in the Intake group. In study 2, BAP/d-ROMs ratio was higher after one and two months compared to that at pre-intervention. Study findings suggested that consumption of kiwifruits may reduce oxidative stress levels and increase antioxidant activity, resulting in improved potential antioxidant capacity.

Attempt to Determine the Cut-Off Value of Serum Ferritin for Iron Deficiency in Male College Student Runners.

For the evaluation of iron nutrition status, the measurement of serum ferritin levels is the most convenient and widely used technique for estimating stored iron. However, the cut-off value of serum ferritin for iron deficiency in athletes has not yet established. This study aimed to determine the cut-off value of serum ferritin to define iron deficiency in male college student runners. This study included 37-43 Japanese male college student runners for each month. Anthropometric measurements and blood collection were conducted from March to December 2018. In all months except May, significant negative correlations were observed between serum ferritin and transferrin levels, total iron binding capacity (TIBC), and unsaturated iron binding capacity. Furthermore, a significant association between serum ferritin levels and TIBC was observed by nonlinear regression analysis. The curvature radius and curvature were calculated using the data from 9 mo, and serum ferritin levels with the smallest curvature radius and the highest curvature in each month were identified. The serum ferritin levels were as follows: 35.0 ng/mL in March, 45.0 ng/mL in April, 40.0 ng/mL in June, 35.0 ng/mL in July, 35.0 ng/mL in August, 35.0 ng/mL in September, 35.0 ng/mL in October, 35.0 ng/mL in November, and 40.0 ng/mL in December. The average value was 37.2 ng/mL. In conclusion, the cut-off value of serum ferritin for defining iron deficiency in runners was determined to be 40.0 ng/mL in this study. This value (40.0 ng/mL) may be useful for iron deficiency screening in runners.

Clinical characteristics and short-term outcomes in patients with acute cholecystitis over aged >80 years.

AIM: We investigated the clinical characteristics and short-term outcomes in acute cholecystitis (AC) patients aged ≥80 years. We therefore sought to determine the ideal treatment for elderly patients with AC. METHODS: We retrospectively evaluated 253 patients with AC. The patients were divided into two groups according to their age: elderly group (n = 77, aged ≥80 years) and non-elderly group (n = 176, aged <80 years). We compared the clinical characteristics, in-hospital mortality and recurrence of cholecystitis within 6 months between the two groups. The predictive factors for in-hospital mortality were also assessed. RESULTS: The elderly group had more severe comorbidities (P = 0.0055), higher severity grade of AC (P = 0.00071) and higher in-hospital mortality (P = 0.029) than the non-elderly group. The multivariate analysis showed that the serum creatinine level (hazard ratio 12.43; P = 0.002) was independently associated with the in-hospital mortality. The elderly group (20.8%) underwent subsequent cholecystectomy less frequently than the non-elderly group (63.2%; P < 0.0001). The recurrence rate of AC was comparable between the two groups (P = 0.89). The proportion of patients in the elderly group who received percutaneous drainage in the latter period (64.3%) was significantly higher than in the former period (33.3%; P = 0.015). CONCLUSIONS: More attention should be paid to AC patients with chronic renal disease after treatment. Percutaneous drainage might serve as a definitive treatment without subsequent cholecystectomy in elderly AC patients with various comorbidities. Geriatr Gerontol Int 2019; 19: 208-212.

[A Case of Advanced Gastric Cancer with Bladder Metastasis].

A 61-year-old man was referred to the urology department in our hospital with gross hematuria and hydro nephrosis. Cystoscopy revealed a smooth mass lesion in his bladder, and a transurethral biopsy was performed. Signet ring cell carcinoma was found in the submucosa. Upper gastrointestinal endoscopy revealed an ulcerated lesion in his gastric body. Biopsy specimens obtained from the ulcerated lesion showed signet ring cell carcinoma. No other primary lesions were detected using colonoscopy, gallium scintigraphy, or computed tomography of the chest. He was ultimately diagnosed with advanced gastric cancer with bladder metastasis. He was prescribed combination chemotherapy of cisplatin and tegafur, gimeracil, oteracil potassium, and trastuzumab. After 2 courses of chemotherapy, there was a decrease in the size of both the gastric and bladder lesions. There was also a significant decrease in the tumor marker levels. He is currently alive after 7 courses of chemotherapy.

Inflammation-based prognostic scores predict disease severity in patients with acute cholecystitis.

BACKGROUND: Although several investigators have reported that inflammation-based prognostic scores can predict disease severity in patients with various inflammatory diseases, whether or not these scores are associated with disease severity in patients with acute cholecystitis (AC) has not yet been fully clarified. PATIENTS AND METHODS: Two hundred and sixty-two patients with AC were reviewed retrospectively. We evaluated the correlations between demographic or clinical variables, including the neutrophil-to-lymphocyte ratio (NLR), the Glasgow Prognostic Score (GPS), the modified Glasgow Prognostic Score (mGPS), and the C-reactive protein/albumin (CRP/Alb) ratio, as well as the disease severity grade on the basis of the revised Tokyo guidelines. Multivariate analyses were carried out to identify the clinical parameters associated with disease severity grade. RESULTS: The NLR (P<0.0001), GPS (P<0.0001), mGPS (P<0.0001), and CRP/Alb ratio (P<0.0001) were all elevated according to the severity grade. Multivariate analyses showed that the NLR [odds ratio (OR)=3.41-4.77; P<0.005], GPS (OR=2.49; P=0.012), mGPS (OR=2.79; P=0.005), and the CRP/Alb ratio (OR=12.53; P<0.0001) were associated independently with grade II/III AC. The value of the area under the curve of the CRP/Alb ratio (continuous 0.759) or NLR (continuous 0.753) was higher than that of other inflammation-based prognostic scores for diagnosing ≥grade II AC, grade III AC, respectively. CONCLUSION: Inflammation-based prognostic scores could predict the severity grade independently in patients with AC. These scores may play a complementary role in predicting disease severity in patients with AC in conjunction with the Tokyo guidelines severity grade.

Endoscopic submucosal dissection in a patient with esophageal adenoid cystic carcinoma.

We report the first use of endoscopic submucosal dissection (ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus (EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution, and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor, primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion, an 8 mm submucosal tumor. Immunohistologically, tumor cells differentiating into ductal epithelium and myoepithelium were observed, and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall, vertical stump or horizontal margin invasion with pT1b-SM2 staining (1800 µm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC.

Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids.

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.

A case of adenosquamous cell carcinoma of the gallbladder with markedly elevated PTHrP and G-CSF levels.

A 76-year-old woman was referred to our hospital with anorexia. Computed tomography revealed a tumor lesion measuring 110mm in the liver at S4/5 with calcification and swelling of a paraaortic lymph node. The gallbladder was not visualized. Histological examination of a biopsy specimen from the liver tumor revealed squamous cell and undifferentiated carcinomas, and several tumor markers were elevated. Therefore, we diagnosed the patient with gallbladder adenosquamous cell carcinoma T3N2M0 stage III. Because the serum parathyroid hormone-related protein (PTHrP) and granulocyte-colony stimulating factor (G-CSF) levels were significantly elevated, we suspected that PTHrP and G-CSF production occurred because of adenosquamous cell carcinoma in the gallbladder. We initiated chemotherapy with S-1.

Clinical characteristics and survival outcomes of super-elderly hepatocellular carcinoma patients not indicated for surgical resection.

AIM: Considering the dramatic increase in average life expectancy during the 20th century throughout the world, the management of elderly patients with cancer has become a global issue. We herein investigated the clinical characteristics and outcomes of super-elderly hepatocellular carcinoma (HCC) patients over 80 years old not indicated for surgical resection. METHODS: We retrospectively evaluated 206 newly diagnosed HCC patients. The patients were divided into two groups according to their age at inclusion; a super-elderly group (n = 37, ≥80 years) and a younger group (n = 169, <80 years). We compared the clinical characteristics, overall survival (OS) and disease-specific survival (DSS) rates among the two groups. Both univariate and multivariate analyses were performed to identify the factors associated with the OS and DSS. RESULTS: The proportion of women was higher in the super-elderly group than in the younger group (P = 0.017). There were no significant differences in the OS (P = 0.171) or DSS (P = 0.176) between the two groups. The multivariate analysis revealed that only the Cancer Liver Italian Program score (hazard ratio [HR], 2.972; P < 0.0001; HR, 3.694; P < 0.0001) was independently associated with the OS and DSS. Age was not found to be associated with the OS or DSS according to either the univariate or multivariate analysis. CONCLUSION: There were no significant differences in the OS and DSS rates among the super-elderly HCC patients and younger HCC patients not indicated for surgical resection. An advanced age itself does not restrict the therapeutic approach, even in super-elderly HCC patients not indicated for surgical resection.

C-Reactive Protein as a Prognostic Marker in Patients with Hepatocellular Carcinoma.

C-reactive protein (CRP) is an acute phase reactant synthesized by hepatocytes that is regulated by pro-inflammatory cytokines, particulary interleukin-6 (IL-6). Over the last decade, CRP has been reported to be associated with a poor prognosis in patients with various types of cancer. Although the mechanisms by which the systemic inflammatory response reflected by an elevated serum CRP level influences survival in patients with cancer have not been fully elucidated, several possibilities involving the activation of IL-6, thereby elevating the CRP level, in cancer patients have been proposed. With regard to hepatocellular carcinoma (HCC), since Hashimoto et al. first demonstrated that the preoperative serum CRP level is an independent and significant factor predictive of a poor prognosis in patients undergoing surgical resection, several investigators have identified an elevated serum CRP level to be an indicator of poor outcomes in HCC patients undergoing transplantation, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection and best supportive care. Recently, the CRP level has been reported to be clinically applicable as a marker of treatment outcomes in HCC patients. However, large-scale, prospective validation studies are needed to confirm these results.

The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma.

BACKGROUND: The C-reactive protein/albumin (CRP/Alb) ratio is associated with outcomes in septic patients. We investigated the prognostic value of the CRP/Alb ratio in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated 186 newly diagnosed HCC patients and investigated the correlations among the pretreatment CRP/Alb ratio, clinicopathological parameters, and overall survival (OS). Multivariate analyses were performed to identify the clinicopathological parameters associated with OS. Subsequently, we evaluated the prognostic value of the CRP/Alb ratio compared with other inflammation-based prognostic scores [Glasgow Prognostic Score (GPS), modified GPS (mGPS), and neutrophil lymphocyte ratio (NLR)] using the area under the curve (AUC). RESULTS: The optimal cutoff level for the CRP/Alb ratio was 0.037. An elevated CRP/Alb ratio (≥0.037) was associated with tumor progression and reduced liver functional reserve. In the multivariate analysis, the CRP/Alb ratio [hazard ratio (HR) 3.394; p < 0.0001], Cancer Liver Italian Program score (HR 2.686; 95% CI 2.122-3.401; p < 0.0001), and vascular invasion (HR 3.376; 95% CI 1.594-7.151; p = 0.001) were independently associated with OS (HR 3.394; p < 0.0001). The CRP/Alb ratio had higher AUC values at 6 months (0.844), 12 months (0.863), and 24 months (0.82) compared with the GPS, mGPS, and NLR. CONCLUSION: The CRP/Alb ratio might be an independent prognostic marker in patients with HCC, and may have comparable prognostic ability to other established inflammation-based prognostic scores. The prognostic value of this novel inflammation-based prognostic score needs to be verified in patients with other types of cancer.

The addition of C-reactive protein to validated staging systems improves their prognostic ability in patients with hepatocellular carcinoma.

OBJECTIVES: C-reactive protein (CRP) is a practical prognostic marker in patients with hepatocellular carcinoma (HCC). We investigated the prognostic value of adding the CRP level to other validated staging systems (Cancer Liver Italian Program, Japan Integrated Staging, Barcelona Clinic Liver Cancer classification system, Tokyo score and tumor node metastasis classification) in HCC patients. METHODS: One hundred and eighty-six newly diagnosed HCC patients were retrospectively evaluated. A multivariate analysis identified the clinicopathological variables associated with overall survival; the variables identified were then added to each staging system and compared to those without the additional variable. RESULTS: In multivariate analysis, an elevated serum CRP level was independently associated with a poor prognosis (hazard ratio 3.792, p < 0.0001). The addition of the CRP level to each of the established staging systems provided a higher linear χ(2) value and a lower -2 log likelihood than those without the addition of the term. Moreover, the area under the receiver-operating characteristic curve (AUC) analysis showed that the addition of CRP improved the AUC of each staging system. CONCLUSIONS: This study demonstrates that an elevated serum CRP level is independently associated with a poor prognosis in HCC patients, and the addition of the CRP level to the validated staging systems could improve the prognostic ability of each staging system.

Elevated plasma fibrinogen levels are associated with a poor prognosis in patients with hepatocellular carcinoma.

OBJECTIVES: Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in cancer patients. We investigated the prognostic value of pretreatment plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and thirteen patients with newly diagnosed HCC were retrospectively evaluated. We investigated the correlation between pretreatment plasma fibrinogen levels, clinicopathological parameters and overall survival. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with overall survival. RESULTS: The median value of the pretreatment plasma fibrinogen level was 279 mg/dl. Elevated plasma fibrinogen levels were associated with larger tumor size, the presence of vascular invasion and higher Cancer Liver Italian Program scores. Lower plasma fibrinogen levels were associated with higher Child-Pugh grades. The overall survival rates in patients with pretreatment plasma fibrinogen levels ≥ 315 mg/dl were significantly lower than those with a pretreatment plasma fibrinogen level <315 mg/dl (p = 0.016). On multivariate analysis, the plasma fibrinogen levels (per 100 mg/dl) were found to be independently associated with overall survival (hazard ratio 1.236; p = 0.046). CONCLUSIONS: This study demonstrates that elevated pretreatment plasma fibrinogen levels are associated with tumor progression and are independently associated with a poor prognosis in patients with HCC.

The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma.

BACKGROUND: Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. METHODS: One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. RESULTS: Elevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. CONCLUSIONS: Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status.

Pretreatment serum C-reactive protein level predicts poor prognosis in patients with hepatocellular carcinoma.

C-reactive protein (CRP) is known to be associated with poor prognosis in patients with various malignancies. We investigated the relationship between the pretreatment serum CRP level and survival in patients with hepatocellular carcinoma (HCC) in various stages of the disease. A cohort of 133 patients with newly diagnosed HCC was prospectively evaluated. The patients were divided into two groups: high-CRP group (n=27) with the pretreatment serum CRP level≧1.0 mg/dl and low-CRP group (n=106) with the CRP level<1.0 mg/dl. They were followed 22 months in average (1-69 months) and clinicopathological variables, and overall survivals between the two groups were compared at the end of the follow-up period. There was a significant difference between the two groups in aspartate aminotransferase, alanine aminotransferase, total serum bilirubin, albumin, α-fetoprotein level, maximal tumor diameter, frequency of vascular invasion and extrahepatic metastases. Patients in the high-CRP group had higher Child-Pugh scores, higher Cancer of the Liver Italian Program scores and higher Japan Integrated Staging scores than patients in the low-CRP group. The overall survival rates in the high-CRP group were significantly lower than those in the low-CRP group. Survival rates were similar in tumor stage and liver function-matched patients. On multivariate analysis, pretreatment serum CRP level was independently associated with overall survival. Our results demonstrate that the pretreatment serum CRP level is associated with tumor progression and reduced liver function and is an independent poor prognostic marker in patients with HCC.

Psychosocial factors that aggravate the symptoms of sick house syndrome in Japan.

Over the last 30 years in Japan, there has been a 10% increase in the number of people suffering from sick house syndrome due to toxic chemicals released from construction materials and wallpaper. This syndrome can develop into the more complex and disabling, chemical sensitivity syndrome, so preventing early exposure to toxins at home is critical in reducing the likelihood of health problems in the community. A qualitative study was undertaken using ethnographic methods to identify the psychosocial aggravating factors of sick house syndrome. As a result, the participants identified three aggravating factors that extended the period of exposure of the participant to toxic chemicals: a lack of knowledge about the disorder; the difficulty in establishing a diagnosis; and the difficulty of taking radical measures to improve the home environment. Public awareness of sick house syndrome and the dangers of toxicity from construction materials is vital to eliminate these aggravating factors and to prevent illness.

Induction of apoptosis by rhapontin having stilbene moiety, a component of rhubarb (Rheum officinale Baillon) in human stomach cancer KATO III cells.

We have investigated the effects of rhapontin on proliferation and DNA of human stomach cancer KATO III cells. Growth inhibition and induction of apoptosis by rhapontin were observed in the KATO III cells. Morphological change showing apoptotic bodies was observed in the KATO III cells treated with rhapontin. The fragmentation of DNA by rhapontin to oligonucleosomal-sized fragments that is a characteristic of apoptosis was observed to be concentration- and time-dependent in the KATO III cells. N-acetyl-L-cysteine, an antioxidant, suppressed the DNA fragmentation caused by rhapontin. On the other hand, it was found that resveratrol having stilbene moiety as well as rhapontin induced apoptosis in the KATO III cells. So, it is considered that stilbene moiety in the molecule is essential for the induction of apoptosis. The data of the present study show that the suppression of KATO III cell-growth by rhapontin results from the induction of apoptosis by the compound, and that active oxygen is involved in the inductions of apoptosis caused by rhapontin in the KATO III cells.