Intraductal papillary neoplasm of the bile duct with metachronous development in the downstream bile duct after radical resection.

We report a case of intraductal papillary neoplasms of the bile duct (IPNB) that metachronously developed twice in the downstream bile duct after radical resection. The first lesion was located in the left intrahepatic bile duct, the second lesion in the perihilar bile duct, and the third lesion in the distal bile duct. All lesions were IPNBs with associated invasive carcinoma (pancreatobiliary type). The depth of invasion was to the Glisson's capsule in the first lesion, to the subserosa in the second lesion, and to the fibromuscular layer in the third lesion, without lympho-vascular/perineural invasion and lymph-node metastasis. These were resected radically and had no biliary intraepithelial neoplasia and hyperplasia in the surrounding mucosa. In immunohistochemical examination, each lesion showed a different pattern. Although the downstream occurrence suggests intrabiliary dissemination, the mechanism of these metachronous developments may be multicentric. A literature review revealed that most metachronous cholangiocarcinomas have a grossly papillary appearance and tend to arise downstream. Our findings suggest that IPNB may develop metachronously in the residual bile duct after radical surgery, which may assist in early detection.

Ultrasonographic Features of Nonneoplastic Protrusions in Pancreatic Cysts by Contrast-Enhanced Endoscopic Ultrasound.

OBJECTIVES: Most of the pancreatic cyst protrusions detected by B-mode endoscopic ultrasound (BM-EUS) are nonneoplastic and are not enhanced by contrast-enhanced EUS (CE-EUS) using ultrasound contrast agent (USCA). This study aimed to identify useful findings for distinguishing between neoplastic and nonneoplastic pancreatic cyst protrusions on BM-EUS to facilitate efficient USCA use. MATERIALS AND METHODS: A total of 151 pancreatic cyst protrusions in 119 consecutive patients who underwent CE-EUS were analyzed. We focused on the echo level (hyperechoic/isoechoic/hypoechoic/anechoic), base type (sessile without a basal waist/sessile with a basal waist/pedunculated), surface type (smooth/irregular), and the presence/absence of a hyperechoic surface layer. Enhanced and unenhanced protrusions on CE-EUS were interpreted as neoplastic and nonneoplastic, respectively. RESULTS: Forty-five and 106 protrusions were enhanced and unenhanced, respectively, on CE-EUS performed using USCA. In univariable analysis of predictors of nonneoplastic protrusion on BM-EUS, the following factors were found to be significant: echo level (hypoechoic/anechoic), base type (sessile with a basal waist/pedunculated), a smooth surface, and a hyperechoic surface layer. Of these, only a hyperechoic surface layer remained significant in the multivariable analysis ( P < 0.0001; odds ratio, 40.74; 95% confidence interval, 7.07-387.49). CONCLUSIONS: Pancreatic cyst protrusions with a hyperechoic surface layer on BM-EUS are suggestive of nonneoplastic disease.

Can the measurement of Locomo Age improve motivation for exercise in fitness club users?

AIM: In 2022, the Japanese Orthopaedic Association developed "Locomo Age," which can be used to measure mobility. The potential effects of measuring Locomo Age on motivation to exercise are yet to be explored. This study aimed to determine whether the measurement of Locomo Age improved motivation for exercise. METHODS: In total, 90 fitness club users (17 men and 73 women) were enrolled in the study. The participants performed the locomotive syndrome risk test. These results were entered on a smartphone website, and their Locomo Age was automatically calculated. Questionnaires about impressions of Locomo Age and changes in motivation for exercise after measuring Locomo Age were surveyed. RESULTS: The mean Locomo Age of the participants was 84.4 ± 8.5 years, which was significantly higher than their actual age (75.9 ± 7.2 years, P < 0.001). Questionnaires showed that 55 participants (61.1%) felt that their Locomo Age was higher than expected; 42 participants (46.7%) had increased motivation for exercise, and only two participants (2.2%) had decreased motivation. The rate of improvement in motivation for exercise was higher in the group of participants who reported having an older Locomo Age than they expected compared with that of the group with a Locomo Age that was the same as they expected (P < 0.05). CONCLUSIONS: The measurement of Locomo Age improved the motivation for exercise. This result remained true even when the Locomo Age was higher than expected, as it did not decrease the participants' motivation. Locomo Age allows for the comprehension of participants' mobility without medical knowledge. Geriatr Gerontol Int 2023; 23: 589-594.

Prognostic Significance of C-Reactive Protein in Lenvatinib-Treated Unresectable Hepatocellular Carcinoma: A Multi-Institutional Study.

BACKGROUND: Serum C-reactive protein (CRP) is an established biomarker for acute inflammation and has been identified as a prognostic indicator for hepatocellular carcinoma (HCC). However, the significance of the serum CRP level, specifically in HCC patients treated with lenvatinib, remains unclear. METHODS: We retrospectively analyzed 125 HCC patients who received lenvatinib treatment at six centers. Clinical characteristics were assessed to identify clinical associations between serum CRP and HCC prognosis. RESULTS: The median overall serum CRP level was 0.29 mg/dL. The cohort was divided into two groups: the low-CRP group with a serum CRP < 0.5 mg/dL and the high-CRP group with a serum CRP ≥ 0.5 mg/dL. The low-CRP group exhibited significantly longer overall survival (OS) than the high-CRP group (22.9 vs. 7.8 months, p < 0.001). No significant difference was observed for progression-free survival (PFS) between the high- and low-CRP groups (9.8 vs. 8.4 months, p = 0.411), while time-to-treatment failure (TTF) was significantly longer in the low-CRP group (8.5 vs. 4.4 months, p = 0.007). The discontinuation rate due to poor performance status was significantly higher in the high-CRP group (p < 0.001). CONCLUSION: A baseline serum CRP level exceeding 0.5 mg/dL was identified as an unfavorable prognostic factor in HCC patients receiving lenvatinib treatment.

[Three elderly patients in which systemic edema developed with subsequent large amounts of exudate excretion from the whole body].

AIM: Systemic edema is often observed at the terminal stages of cardiac or renal failure, with some cases showing a large amount of exudate excretion from the whole body. We investigated 3 such cases by comparison with those excreting less exudate. METHODS: We examined the data of 3 male inpatients (age, 81, 89 and 97 years) with cardiac or renal failure who had systemic edema, with excretions of a large amount of exudate (more than 3,000 ml/day) and who subsequently died of malnutrition, oliguria or anuria. We used a control group (20 inpatients, 10 men and 10 women, mean age, 82) with excretions of less than 1,000 ml/day of exudate for comparison. Blood test values and the number of remaining days of life after the onset of oliguria/anuria were compared between the 2 groups. Moreover, the laboratory test findings of exudade and serum were compared within the subject group. RESULTS: The subject group had a higher mean serum BUN level than the control group (138 mg/dl vs. 81 mg/dl). There were no significant differences in any other blood test values between the 2 groups. Remarkably, the number of remaining days of life after the onset of oliguria or anuria in the subject group was greater than that in the control group (mean, 14 days vs. 7 days). The laboratory data of the subject group showed that total protein, lipids, AST, ALT, γ-GTP, Ca and CRP levels were lower in the exudate than in the serum, whereas BUN, creatinine, UA, K and Cl levels showed no significant differences. CONCLUSIONS: It is suggested that a production of large amount of exudate is caused by a complex of various factors which increase vascular permeability. However, in the present study, BUN, UA and K levels in the exudate of patients were similar to those in the serum of the subject group. The longer survival observed after oliguria or anuria in the subject group may be explained by an increased excretion of K which occurs with a large amount of exudate. Further investigation is necessary for elucidation of the etiology of large amounts of exudate.

[Treatment of early rectal carcinoma by transanal resection-a case report].

A 55-year-old female was admitted to Ogikubo Hospital for severe anemia and prolapse of a tumor from the anus, which had developed over 2 years. Rectal examination revealed a giant soft tumor. Endoscopic study revealed a lobulated giant tumor with a granular surface. Gastrografin-enema study showed a giant tumor, which was full of the rectum. Pathological examination showed a well differentiated carcinoma. No other prominent metastatic lesions were demonstrated. The transanal diagnostic resection of rectal cancer was performed in October 2010. This correct diagnosis showed both well differentiated adenocarcinoma and intramucosal carcinoma. We therefore recommend that a tumor of the lower rectum should undergo a diagnostic excision by means of either a local excision, ESD or TEM.

A resected case of focal autoimmune pancreatitis with pancreatic duct wall thickening representing periductal lymphoplasmacytic infiltrate.

This case revealed that branch pancreatic duct wall thickening by endoscopic ultrasonography represented periductal lymphoplasmacytic infiltrate as a characteristic histopathological finding of autoimmune pancreatitis, which may help in the diagnosis of autoimmune pancreatitis. An 80-year-old man was referred because fluorodeoxyglucose-positron emission tomography for lung cancer indicated abnormal uptake in the pancreatic head. Computed tomography showed an enhanced mass with cystic structures in the pancreatic head. Magnetic resonance cholangiopancreatography revealed mild dilatation of the main pancreatic duct in the pancreatic body with no strictures. Endoscopic ultrasonography demonstrated a lobulated heterogeneous hypoechoic mass in the pancreatic head. A branch pancreatic duct with wall thickening connected the mass to the main pancreatic duct. An intraductal neoplasm filling and spreading into the branch pancreatic duct was considered, and surgery was performed. Histopathologically, the mass consisted of marked inflammatory cell infiltration, storiform fibrosis, and obliterative phlebitis. The branch pancreatic duct with wall thickening revealed a band-like inflammatory cell infiltration with mainly lymphocytes and plasma cells beneath the normal pancreatic duct epithelium. Immunohistological staining revealed abundant IgG4-positive plasma cells (> 10 cells/HPF) in the inflammatory cell infiltration. The definite diagnosis was type 1 focal autoimmune pancreatitis.

[A case of advanced gastric cancer resistant to S-1 successfully treated with weekly administration of paclitaxel].

A 62-year-old female was diagnosed with type 2 advanced gastric cancer in May 2003. Pathological examination showed a poorly differentiated carcinoma. Computed tomography (CT) revealed paraaortic lymph node metastasis, duodenal metastasis and ascites due to peritoneal dissemination. Chemotherapy with CDDP+S-1 was started and continued. After the chemotherapy, there were progressive diseases. Therefore, paclitaxel (PTX) was administered at a dose of 80 mg/m2/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and CT scan revealed metastatic lymph nodes were reduced after 4 cycles. After 13 cycles, MRI revealed a solitary brain mass was detected. She was resected for a right temporal-occipital brain metastatic tumor, and local cerebral irradiation was performed. After this operation, she was diagnosed with brain metastasis from advanced gastric cancer. The procedure was interrupted for about 6 months. After rehabilitation, PTX treatment was restarted as 14th cycle. She has survived without recurrence more than 30 cycles after the resection. A weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1 resistant recurrent gastric cancer.

Long-term outcome of branched-chain amino acid treatment in patients with liver cirrhosis.

Clinical impact of protein-energy malnutrition (PEM) on the outcome of liver cirrhosis is well documented. As a candidate interventional modality to improve PEM in cirrhosis, effects of branched-chain amino acid (BCAA) supplementation on event-free survival and quality of life (QOL) was first reported by Yoshida et al. in 1989. Although critical arguments still continue regarding the effects of BCAA, several randomized trials in the last 5 years have brought positive results, and seem to have settled the discussion in a favorable direction for the efficacy of BCAA in liver cirrhosis. Actually, The European Society for Clinical Nutrition and Metabolism (ESPEN) upgraded the recommendation of BCAA supplementation in decompensated liver cirrhosis in the latest revision of its guidelines in 2006, by referring to the literatures from Italy and Japan. Particularly in these two long-term randomized studies with 1-2 years-supplementation, event-free survival was estimated by employing composite endpoints such as aggravation of hepatic failure (ascites, peripheral edema, hepatic encephalopathy, and jaundice), rupture of esophageal or gastric varices, development of liver cancer, and death from any cause. Both trials agreed on the effect of BCAA to reduce the incidence of hepatic failure, thus contributing to the rise in the event-free survival. Quality of life is another essential marker of outcome survey. Marchesini, Muto, and Nakaya reported the improved QOL in cirrhotics with BCAA supplementation. In particular, quantitative analysis of QOL measured by Short Form 36 (SF-36) questionnaire demonstrated a significant recovery of general heath perception score in BCAA supplemented patients in a randomized trial. In this article, the long-term outcome of BCAA treatment in liver cirrhosis will be reviewed with its action mechanisms. In addition, the effects of BCAA treatment on the incidence of liver cancer in obese patients with type C liver cirrhosis, significance of obesity as a risk factor for type C liver cancer, and a possible role of Body Mass Index to estimate the histological grade of fat deposition in the liver will be briefly discussed.

Oral branched-chain amino acid supplementation improves the oxidized/reduced albumin ratio in patients with liver cirrhosis.

AIM: Branched-chain amino acid (BCAA) supplementation improves hypoalbuminemia in decompensated cirrhotics. Recently, it was clarified that the ratio of oxidized albumin within total albumin rises with progression of liver cirrhosis. We conducted a feasibility study to investigate whether BCAA supplementation might improve this ratio. METHODS: Seven cirrhotic patients (age: 70 +/-> 6 years; M/F = 4/3; etiology: hepatitis C in six and non-B/non-C hepatitis virus in one; Child-Pugh classification: A in six and B in one) were enrolled consecutively in this study in October 2004 to March 2005. Patients were given 4 g BCAA after each meal for 8 weeks. Serum total, oxidized and reduced albumin, plasma amino acids, glutathione, zinc, selenium, and lipid peroxide concentrations were measured every 2 weeks. RESULTS: Low total albumin, high oxidized albumin, and low reduced albumin levels were observed at entry. After 8 weeksBCAA supplementation, the ratio of oxidized albumin within total albumin decreased significantly and that of reduced albumin increased significantly (P < 0.05, respectively). Total albumin tended to rise and lipid peroxide concentrations tended to fall, but not significantly. CONCLUSION: BCAA supplementation improved the oxidized/reduced state of serum albumin. This intervention is effective to maintain the quality of serum albumin in cirrhotic patients.

Nutritional screening with Subjective Global Assessment predicts hospital stay in patients with digestive diseases.

OBJECTIVE: Nutritional status is an important factor that determines hospital stay, and the Subjective Global Assessment (SGA) is a candidate tool for nutritional screening on admission. However, the significance of the SGA has not been evaluated well in the ward for digestive diseases. We conducted the present study to test whether the SGA predicts hospital stay of these patients. METHODS: Two hundred sixty-two patients with digestive diseases were consecutively enrolled between July 2004 and April 2005. They consisted of 145 males and 117 females and included 110 patients with cancer. Disease category was gastrointestinal in 94, hepatic in 111, and biliary/pancreatic in 57. The SGA was performed by a certified dietician. Effects of SGA and other nutritional parameters on hospital stay were examined by simple and multiple regression analysis. RESULTS: Among tested variables, simple regression analysis identified the SGA, disease category, presence of malignancy, serum albumin level, percent triceps skinfold thickness, and percent arm muscle circumference as significant predictive parameters for hospital stay. Multiple regression analysis revealed that the SGA had the best predictive power, followed by the presence of malignancy and disease category. CONCLUSION: The SGA is a simple and reliable predictor for hospital stay in patients with digestive diseases.

Relationship between serum albumin level and aging in community-dwelling self-supported elderly population.

While lower serum albumin concentration is often found in the elderly, a relation between serum albumin and age has not been fully elucidated. We conducted population-based cross-sectional and 5-y longitudinal study to examine the relation. A total of 22,705 male and 40,149 female, aged 65 y and older, living in Gifu, participated in the health check service conducted by Gifu City Medical Association. They were self-supported in the activity of daily living and 3,438 of them were followed up every year from 1999 to 2003. Serum albumin levels decreased with age in both men and women. In the cross-sectional study, median value declined from 4.3 g/dL in males aged 65-69 y to 3.9 g/dL in 90< or = y, and 4.3 g/dL to 4.0 g/dL in females. Incidence of hypoalbuminemia (serum albumin < or =3.5 g/dL) increased in parallel with age from 1.2% (65-69 y) to 6.6% (85-89) in males, and 0.6% to 4.1% in females. In the longitudinal study, regression analysis showed a significant decline in serum albumin of 0.015 g/dL per year (r= -0.716) in males, and 0.012 g/ dL per year (r= -0.794) in females. Relative reduction of serum albumin in 5 y was larger in advanced age; 1.2% in females aged 65-69 y and 3.1% in 85-89 y (p<0.05), but not in males. In conclusion, a fall in serum albumin concentration in community-dwelling, self-supported elderly persons was associated significantly with aging.

Prevalence of diabetes and incidence of angiopathy in patients with chronic viral liver disease.

Patients with chronic liver disease (CLD) often develops glucose intolerance. We explored the prevalence of diabetes mellitus in viral CLD, and analyzed factors profoundly affecting the diabetic angiopathies. 229 CLD patients (124 chronic hepatitis and 105 liver cirrhosis) entered the study. The diagnosis of diabetes was made with the criteria by World Health Organization. Laboratory investigation included serum asparate aminotransferase, alanine aminotransferase, albumin, fasting blood sugar, hemoglobin A1c (HbA1c), fasting immunoreactive insulin, and HOMA-R (FBS*IRI/405). The incidence of macro- and microangiopathy were also examined. Forty (17.5%) CLD patients were diagnosed diabetes, giving a significantly higher incidence than that of general cohort (5.3%) (p<0.001). Among them, 12 (30%) had the triopathy, significantly lower than that in a matched group of diabetic patients without CLD (65%) (p<0.001). Significantly increased levels of HbA1c and HOMA-R were observed in diabetic CLD with angiopathy compared with diabetic CLD without. Incidence of diabetes was increased in viral CLD patients. The rate of diabetic angiopathies in CLD, however, was relatively low, this could be explained by low coagulability in these patients. Poor control of hyperglycemia, partly due to insulin resistance, might explain the onset of angiopathy in diabetic CLD.

Effects of electrical stimulation therapy on the blood flow in chronic critical limb ischemia patients following regenerative therapy.

OBJECTIVES: We investigated the effects of electrical stimulation therapy on cutaneous and muscle blood flow in critical limb ischemia patients following regenerative therapy. METHODS: Three groups were studied: 10 healthy young subjects, 10 elderly subjects, and 7 critical limb ischemia patients after regenerative therapy. After 5 min rest, electrical stimulation was applied at 5 Hz on the tibialis anterior muscle for 10 min. We estimated the relative changes in oxyhemoglobin and total hemoglobin compared to the basal values at rest (Δ[HbO2], Δ[Hbtot]), which reflected the blood flow in the skin and muscle layer, and we simultaneously measured the tissue O2 saturation (StO2) throughout the electrical stimulation and recovery phase by near-infrared spectroscopy. RESULTS: The Δ[HbO2] and Δ[Hbtot] values of the muscle layer in critical limb ischemia patients increased gradually and remained significantly higher at the 5-min and 10-min recovery periods after the electrical stimulation without reducing the StO2, but there is no significant change in the other two groups. Skin blood flow was not influenced by electrical stimulation in three groups. CONCLUSION: This improvement of the peripheral circulation by electrical stimulation would be beneficial as the adjunctive therapy after regenerative cell therapy.

Erectile dysfunction in patients with chronic viral liver disease: its relevance to protein malnutrition.

BACKGROUND: In patients with chronic liver disease (CLD), quality of life is generally accepted as poor, especially for physical function. However, sufficient data regarding erectile function has not been shown in patients with CLD. The international index of erectile function (IIEF) is widely used to assess erectile function, and a short form of the IIEF was recently developed (IIEF-5). Using this questionnaire, we evaluated erectile dysfunction (ED) in patients with CLD. METHODS: A total of 117 Japanese patients (64 with chronic hepatitis [CH] and 53 with liver cirrhosis [LC]) were analyzed. The etiologies were hepatitis B virus (HBV) in 21, HCV in 94, and non-B non-C in 2. The IIEF-5 and Medical Outcomes Study Short Form 36 (SF-36) were administered to the patients, and biochemical analyses for items serum albumin, prothrombin time, bilirubin, and ammonia were also performed. RESULTS: The incidence of ED was 85% in the total cohort with CLD, 78% in those with CH, and 92% in those with LC (P < 0.05 between CH and LC). ED was found in 50% of CLD patients under age 50 years, in 79% aged 50-59, and in 100% aged over 60 (P, overall <0.001). The scores for ED severity correlated with increasing grades of a modified Child-Pugh classification (P < 0.05). Simple regression analysis showed age (P < 0.01), physical function (P < 0.001), role physical (P < 0.001), and social functioning (P < 0.05) on the SF-36, and serum albumin (P < 0.001) as significant determinants of ED. Multiple regression analysis identified age (P < 0.001) and serum albumin (P < 0.001) as independent significant factors that determined ED. CONCLUSIONS: These data clearly demonstrate that liver disease is the cause of ED in patients with CLD, and serum protein status could be relevant to this condition in these patients.

Nocturnal branched-chain amino acid administration improves protein metabolism in patients with liver cirrhosis: comparison with daytime administration.

BACKGROUND: In an attempt to optimize oral branched-chain amino acid (BCAA) administration to improve serum albumin in cirrhotic patients, we compared the effects of nocturnal and daytime BCAA administration on protein metabolism in cirrhotic patients. METHODS: Twelve cirrhotic patients were enrolled in a short-term study. Patients were administered either conventional daytime BCAA granule or nocturnal BCAA for a week, and metabolic analyses were performed, followed by a crossover study in the next week. Another 12 patients, who showed no improvement of serum albumin level with previous daytime BCAA administration, were randomly assigned to either a nocturnal or a daytime BCAA administration group in a long-term study. RESULTS: Low Fischer's ratio, reduced respiratory quotient, and low serum albumin were observed at entry in cirrhotic patients. Whereas daytime BCAA administration improved nitrogen balance and Fischer's ratio, these 2 were further significantly improved after nocturnal BCAA administration. There were no changes in parameters of energy metabolism throughout the study. In the 3-month follow-up, a significant increase in serum albumin was observed in patients administered nocturnal BCAA but not in those administered daytime BCAA. CONCLUSIONS: Nocturnal BCAA administration improved serum albumin in cirrhotic patients who showed no improvement in serum albumin level with daytime BCAA administration. This effect could be partly caused by the improved protein sparing with this administration method.