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An 83-year-old man with hepatocellular carcinoma developed muscle weakness, ptosis, and dyspnea 3 weeks after receiving atezolizumab. Soon after, mechanical ventilation was initiated, which was followed by marked blood pressure spikes. The levels of creatine kinase and troponin-I were significantly elevated, and acetylcholine receptor antibodies were positive. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced myositis, myasthenia gravis (MG), myocarditis, and suspected autoimmune autonomic ganglionopathy (AAG). After immunotherapy, the serum markers and blood pressure normalized, and he was weaned from the ventilator after five months. To our knowledge, this is the first reported case of AAG secondary to ICI-induced myositis, MG, and myocarditis.

Background: Extracellular adenosine 5'-triphosphate (ATP) acts as a signaling molecule in the peripheral nerves, regulating myelination after nerve injury. The present study examined whether the cerebrospinal fluid (CSF) ATP levels in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are related to disease severity., Methods: CSF ATP levels in 13 patients with GBS and 18 patients with CIDP were compared with those in a control group of 16 patients with other neurological diseases (ONDs). In patients with CIDP, CSF ATP levels were compared before and after treatment. The correlations between CSF ATP levels and other factors, including clinical data and CSF protein levels, were also evaluated., Results: Median CSF ATP levels were significantly higher in patients with GBS and CIDP than in those with ONDs. When patients with CIDP were classified into two groups depending on their responsiveness to immunotherapy, median CSF ATP levels were significantly higher in good responders than in ONDs. CSF ATP levels tended to decrease after treatment in patients with CIDP. In patients with CIDP, there is a negative correlation between CSF ATP and CSF protein levels., Conclusions: CSF ATP levels were increased in patients with GBS and CIDP. In particular, CSF ATP levels tended to decrease following treatment in patients with CIDP. CSF ATP levels may be useful biomarkers for the diagnosis or monitoring of therapeutic effects in patients with GBS and CIDP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Takamasa Nukui et al.)

Background: Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs., Objective: To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS., Materials and Methods: We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD., Results: Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID., Conclusions: We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.

A 68-year-old man with small-cell lung cancer developed anti-collapsin response-mediator protein (CRMP)-5 antibody-related paraneoplastic neurological syndrome (PNS) presenting with ataxia and chorea during treatment with durvalumab. As a result of steroid therapy, anti-CRMP-5 antibodies became negative, hyperintense lesions on brain magnetic resonance imaging disappeared, and neurological symptoms improved. After resuming durvalumab, he became unable to walk due to neurological adverse events (nAEs). There have been no reported cases manifesting PNSs and nAEs as a result of the same immune checkpoint inhibitors (ICIs) administered at different times. Resuming ICIs in patients diagnosed with PNSs should be performed with prudence.

Background: Presarcopenia is a common complication of chronic liver disease. However, the relationship between serum zinc concentration and presarcopenia in patients with chronic liver disease remains unclear. Herein, we examined whether serum zinc concentration could predict presarcopenia in patients with chronic liver disease., Methods: Between October 2015 and December 2019, 278 patients with chronic liver disease (median age, 68 years; women/men, 133/145; hepatitis B virus/hepatitis C virus/negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody, 55/124/99) who underwent abdominal computed tomography (CT) and simultaneous measurement of serum zinc concentration were included. Zinc deficiency and subclinical zinc deficiency were classified using serum zinc concentration cutoff values of <60 and <80 μg/dL [based on the Japanese Society of Clinical Nutrition (JSCN) guidelines], respectively. Additionally, presarcopenia was evaluated based on the skeletal muscle mass as per the Japan Society of Hepatology (JSH)'s sarcopenia criteria., Results: Univariate analysis revealed that the following factors were significantly associated with the presence of presarcopenia in patients with chronic liver disease: age (P<0.001), male sex (P<0.001), body mass index (BMI) (P<0.001), serum zinc concentration (P=0.005), fibrosis-4 index (P<0.001), and serum albumin concentration (P=0.03). Additionally, the median L3 skeletal muscle indices were as follows: men, non-presarcopenia group/presarcopenia group, 47.56/37.91 cm 2 /m 2 (P<0.001); women, non-presarcopenia group/presarcopenia group, 41.64/32.88 cm 2 /m 2 (P<0.001). Multivariate analysis using logistic regression analysis revealed that male sex [odds ratio (OR), 0.194; 95% confidence interval (CI): 0.089-0.419; P<0.001], BMI (OR, 0.666; 95% CI: 0.582-0.761; P<0.001), and serum zinc concentration <60 μg/dL (OR, 5.930; 95% CI: 1.480-23.80; P=0.01) were factors associated with presarcopenia. The OR for serum zinc concentration between 60 and 80 μg/dL was 1.910 (95% CI: 0.824-4.420; P=0.13)., Conclusions: Low serum zinc levels may be an independent predictor of presarcopenia in patients with chronic liver disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-77/coif). The authors have no conflicts of interest to declare., (2024 Translational Gastroenterology and Hepatology. All rights reserved.)

Background: Microwave ablation (MWA) is a standard percutaneous local therapy for hepatocellular carcinoma (HCC). Next-generation MWA is reported to create a more spherical ablation zone than radiofrequency ablation (RFA). We compared the ablation zone and aspect ratio of two 2.45 GHz MWA ablation probes; Emprint ® (13G) and Mimapro ® (17G). We compared the ablation zone to the applied energy after MWA in patients with hepatocellular carcinoma (HCC). Furthermore, we investigated local recurrence., Materials and Methods: We included 20 patients with HCC, with an average tumour diameter of 33.2 ± 12.2 mm, who underwent MWA using Emprint ® , and 9 patients who underwent MWA using Mimapro ® with an average tumour diameter of 31.1 ± 10.5 mm. Both groups underwent the same ablation protocol using the same power settings. The images obtained after MWA showed the treatment ablation zone and aspect ratio, which were measured and compared using three-dimensional image analysis software., Results: The aspect ratios in the Emprint ® and Mimapro ® groups were 0.786 ± 0.105 and 0.808 ± 0.122, respectively, with no significant difference (p = 0.604). The ablation time was significantly shorter in the Mimapro ® group than in the Emprint ® group, and there was no significant difference in the frequency of popping or the ablation volume. There were no significant differences in local recurrence between the two groups., Conclusion: There was no significant difference in the aspect ratios of the ablation diameter, and the ablation zone was almost spherical in both cases. Mimapro ® at 17G was less invasive than Emprint ® at 13G., Competing Interests: The authors have no conflicts of interest to declare in relation to this study., (© 2023 Ishikawa et al.)

Background/aim: Ablating a spherical area during hepatocellular carcinoma ablation therapy is a very important issue. We aimed to determine the ablation area of bovine liver using various radiofrequency ablation (RFA) protocols., Materials and Methods: Bovine liver (1-2 kg) was placed in an aluminum tray, which was punctured with STARmed VIVA 2.0 17-gauge (G) and 15-G electrodes using a current-carrying tip. Under the step-up or linear method, with an ablation time up to one break and RFA output stop, the size of the color change area (representing the thermally coagulated area) of the bovine liver was measured along the vertical and horizontal axes, and the ablated volume and total heat generated were calculated., Results: 5-W per minute increases protocol resulted in greater horizontal and vertical diameters of the ablated area than 10-W per minute increases protocol under the step-up method. For 5-W and 10-W per minute increases under the step-up method, the aspect ratio was 0.81 and 0.67 with a 17-G electrode, and 0.73 and 0.69 with a 15-G electrode, respectively. For 5-W and 10-W increases under the linear method, the aspect ratio was 0.89 and 0.82, respectively. Sufficient ablation was obtained, with vertical and horizontal diameters of 50 mm and 43.50 mm, respectively. Although the ablation time was long, the watt output value at the break and average watt value were low., Conclusion: Gradual increase in output (5 W) using the step-up method yielded a more spherical ablation area, and longer ablation time in the linear method with a 15-G electrode could result in a more spherical ablation area in real clinical practice in humans. Future studies should examine concerns regarding long ablation times., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Lenvatinib is available as a molecular target agent for hepatocellular carcinoma (HCC). In this study, we investigated the popping phenomena in patients with HCC who underwent radiofrequency ablation (RFA) after taking lenvatinib., Patients and Methods: Fifty-nine patients with HCC between 21-30 mm in diameter and no history of systemic treatment were enrolled in the study. The patients underwent RFA using a VIVA RFA SYSTEM with an ablation tip of 30 mm in length. For the initial lenvatinib administration, 16 patients had an adequate course of treatment and were treated with RFA as add-on therapy (combination group). The other 43 patients were treated by RFA monotherapy (monotherapy group). The popping frequency during RFA was recorded and compared., Results: Popping frequency in the combination group (RFA combined with lenvatinib) was significantly higher than that in the monotherapy group. There was no significant difference between the combination group and the monotherapy group in ablation time, maximum output level, tumour temperature after ablation, or initial resistance value., Conclusion: Popping frequency was significantly higher in the combination group. It is possible that the intra-tumour temperature increased rapidly during RFA in the combination group due to the inhibitory effect of lenvatinib on tumour angiogenesis, leading to the occurrence of popping. Further studies are needed to investigate popping after RFA, and precise protocols need to be developed., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 47-year-old woman was admitted to our hospital for scrutiny of limb weakness and orthostatic hypotension that had progressed from childhood. She had been treated for alacrima and esophageal achalasia from childhood. On admission, she had hyperreflexia of upper and lower extremities, distal predominant muscle atrophy in the lower extremities, decreased sensation of the distal extremities, and autonomic neuropathy. Her blood test results ruled out adrenal insufficiency, but Schirmer's test was positive. Given the lacrimation symptoms, esophageal achalasia, and neuropathy, the patient was diagnosed with triple A syndrome in whom a c.463C>T mutation (p.R155C) was found in the AAAS gene by genetic testing. Triple A syndrome is an autosomal recessive inherited disease caused by mutations in the AAAS gene. Genetic testing of the AAAS gene should be considered in patients with one or two of main symptoms of triple A syndrome.

In this retrospective cohort study, we evaluated the efficacy of baricitinib in the treatment of coronavirus disease 2019 (COVID-19). Among 404 adult patients with COVID-19 who were admitted to our hospital between October 23, 2020, and July 31, 2021, 229 patients with respiratory failure were included. Among these, 41 patients in the baricitinib group and 41 patients in the control group were selected by propensity score matching to adjust for background factors. We compared the survival rates of the two groups at 30 and 60 days after admission. The 30-day survival rate was significantly higher in the baricitinib group than in the control group. However, there was no significant difference in 60-day survival in the two groups. Baricitinib may improve the early prognosis of patients with respiratory failure associated with COVID-19. However, efforts should be made to improve the long-term prognosis., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: We report a case of bilateral pachychoroid disease with type 3 uveal effusion syndrome (UES) in one eye and central serous chorioretinopathy (CSC) in the contralateral eye., Case Presentation: A 65-year-old man presented to our department because of decreased vision. Visual acuity was 16/20 in the right eye and 2/20 in the left eye, with normal axial lengths. The left eye was diagnosed with CSC and underwent photocoagulation 8 years ago. The right eye showed inferior non-rhegmatogenous retinal detachment and peripheral choroidal detachment. Macular optical coherence tomography showed submacular fluid in the right eye, pachychoroid in both eyes, and choroidal thickness of 565 μm in the right and 545 μm in the left eye. In both eyes, fluorescence angiography showed window defects and mild fluorescence leakage, and indocyanine green angiography showed dilated choroidal vessels, mild choroidal hyperpermeability, and mild dye leakage. The left eye was diagnosed with chronic CSC. Initially, chronic CSC was also suspected in the right eye. However, photodynamic therapy failed, with worsened retinal detachment and visual acuity. Pachychoroid in the peripheral fundus (choroidal thickness 820 μm) was observed only in the right eye. Based on these findings, UES was diagnosed in the right eye. Sclerectomies were performed. The absence of scleral thickening and glycosaminoglycan deposition led to a final diagnosis of type 3 UES. The procedure was not effective, due to connective tissue regeneration at the sclerectomy sites. In the revision surgery, mitomycin-C was used with sclerectomies. One month after surgery, retinal and choroidal detachment disappeared, visual acuity recovered to 8/20, pachychoroid in the macula and peripheral fundus decreased, and choroidal thickness decreased to 352 μm in the macula and 554 μm in inferior peripheral fundus., Conclusions: Pachychoroid in the posterior pole was the common finding in type 3 UES and CSC, although extensive pachychoroid in the peripheral fundus may have caused retinal and choroidal detachment in the eye with type 3 UES. Full-thickness sclerectomies with mitomycin-C improved pachychoroid in the peripheral fundus and resolved retinal and choroidal detachment, clearly indicating that the sclera was the main cause of type 3 UES., (© 2022. The Author(s).)

Previous studies have reported that transcranial direct current stimulation (tDCS) of the frontal polar area (FPA) ameliorated motor disability in patients with Parkinson's disease (PD). Here we report changes in neuromelanin (NM) imaging of dopaminergic neurons before and after rehabilitation combined with anodal tDCS over the FPA for 2 weeks in a PD patient. After the intervention, the patient showed clinically meaningful improvements while the NM-sensitive area in the SN increased by 18.8%. This case study is the first report of NM imaging of the SN in a PD patient who received tDCS. Abbreviations FPA: front polar area; PD: Parkinson's disease; NM: neuromelanin; DCI: DOPA decarboxylase inhibitor; STEF: simple test for evaluating hand function; TUG: timed up and go test; TMT: trail-making test; SN: substantia nigra; NM-MRI: neuromelanin magnetic resonance imaging; MCID: the minimal clinically important difference; SNpc: substantia nigra pars compacta; VTA: ventral tegmental area; LC: locus coeruleus; PFC: prefrontal cortex; M1: primary motor cortex; MDS: Movement Disorder Society; MIBG: 123 I-metaiodobenzylguanidine; SBR: specific binding ratio; SPECT: single-photon emission computed tomography; DAT: dopamine transporter; NIBS: noninvasive brain stimulation; tDCS: transcranial direct current stimulation; MAOB: monoamine oxidase B; DCI: decarboxylase inhibitor; repetitive transcranial magnetic stimulation: rTMS; diffusion tensor imaging: DTI; arterial spin labeling: ASL.

Although dual-energy X-ray absorptiometry (DXA) and body impedance analysis are commonly used to measure skeletal muscle mass (SMM), a computed tomography (CT) scan is preferred in clinical practice. We aimed to propose the cut-off values of skeletal muscle mass index (SMI) calculated using CT scans, using DXA as the reference method. We retrospectively assessed 589 patients with chronic liver disease. The SMI was assessed using appendicular SMM by DXA and total muscle area at the level of the third lumbar vertebra (L3) calculated by CT. The cut-off value was determined with reference to the Asian Working Group for Sarcopenia criteria. DXA identified 251 (42.6%) patients as having presarcopenia. In men, the cut-off value of SMI for presarcopenia was determined to be 45.471 cm 2 /m 2 , with an area under the curve (AUC) of 0.863 (95% confidence interval (CI): 0.823 to 0.903), and in women, this value was determined to be 35.170 cm 2 /m 2 , with an AUC of 0.846 (95% CI: 0.800 to 0.892). Cohen's kappa coefficient was 0.575 (95% CI: 0.485-0.665) in men and 0.539 (95% CI: 0.438-0.639) in women.

L-carnitine administration was reported to improve sarcopenia in patients with cirrhosis. However, the amount of evidence from previous studies is not sufficient. The present study aimed to clarify the effect of levocarnitine (L-carnitine) administration on body composition in patients with chronic liver disease (CLD). In the present study, 85 patients with L-carnitine administration and 87 control patients were enrolled and divided them into two groups, the L-carnitine administration group (LAG, n=44) and the without L-carnitine administration (controls, n=44) group, by using propensity score matching for age, sex, body mass index (BMI) and serum albumin. Δ skeletal muscle mass index (SMI)/year, Δ intramuscular adipose tissue content (IMAC)/year and Δ bone mineral density (BMD)/year were examined during L-carnitine administration. Each parameter was measured by computed tomography (CT) or dual-energy X-ray absorptiometry. The median age overall was 69 years (IQR, 64.0, 75.0); 36 were men and 52 were women. The median SMI was 37.4 cm 2 /m 2 (IQR, 34.01, 44.34). The initial CT scans showed similar median values of SMI for the two groups [37.74 (34.17, 43.58) and 37.16 (33.83, 44.34), P=0.67]. However, the median ΔSMI/year for the LAG and controls were 0.95% (-3.07, 6.10) and -2.34% (-5.34, 0.53), respectively (P=0.003). The median Δ whole body BMD/year for the LAG and controls were -0.24% (-1.20, 0.91) and -1.04% (-2.16, 0.47), respectively (P=0.038). The median ΔIMAC/year and Δ lumbar spine BMD were not significantly different between the LAG and controls. L-carnitine administration may prevent the loss of skeletal muscle mass and BMD; therefore, it may be used as a new treatment option for osteoporosis and sarcopenia in patients with CLD., (Copyright: © Ohashi et al.)

Aim: This study aimed to clarify the relationship between pre-sarcopenia (PS) and quality of life (QOL) in patients with chronic liver disease (CLD)., Patients and Methods: This cross-sectional study evaluated 335 patients with CLD. PS was diagnosed on the basis of the assessment criteria by the Japan Society of Hepatology. QOL was evaluated using the short form-36., Results: Patients' mean age was 69.52 ± 10.17 years, and 169 (50.4%) participants were men. The prevalence of PS was 53.7%. Patients were divided into the PS and non-pre-sarcopenia (NPS) groups. Patients in the PS group were older (71.84 ± 9.78 vs. 66.81 ± 9.97, P < 0.01) and mostly women (65.2 vs. 37.8%, P < 0.01) compared with those in the NPS group. QOL, physical function (38.30 ± 17.63 vs. 44.02 ± 14.76, P < 0.01), physical role functioning (RP) (40.63 ± 15.38 vs. 44.88 ± 13.89, P < 0.01), and bodily pain (BP) (48.42 ± 11.45 vs. 51.24 ± 10.19, P = 0.02) were significantly lower in the PS group than in the NPS group. Logistic regression analyses identified that the independent predictive factors for PS were female sex (odds ratio: 3.16, 95% confidence interval: 2.01-4.98; P < 0.01) and RP (odds ratio: 1.97, 95% confidence interval: 1.24-3.12; P < 0.01)., Conclusion: QOL characteristics of PS patients with CLD were low physical function, RP, and BP in short form-36. In addition, social role functioning was low in the PS patients aged 65-74 years, whereas RP and BP were low in those aged at least 75 years. Female sex and RP were independent predictors of PS according to the multivariate analysis. Maintaining and increasing muscle mass in patients with CLD may contribute toward improving physical QOL.

Background: Sarcopenia is a prognostic factor for patients with liver cirrhosis and hepatocellular carcinoma, and it affects the onset of hepatic encephalopathy. Therefore, the prevention of sarcopenia contributes to the improvement of the prognosis of patients with chronic liver disease (CLD). We focused on changes of hand grip strength (HGS), one of the indicators of sarcopenia. However, there are little data investigating the impact of physical activity (PA) on HGS in patients with CLD. This study aimed to clarify whether PA contributes to the prevention of muscle weakness in patients with CLD., Methods: This was a prospective observational study. We examined the effect of PA on changes in HGS from the baseline to the endpoint in each group. Metabolic equivalents-hour/week (METs-h/w) was used to evaluate PA. In total, 183 outpatients with CLD were analyzed. We divided participants into four groups (low PA in younger patients (n = 20), high PA in younger patients (n = 33), low PA in elderly patients (n = 47), and high PA in elderly patients (n = 83))., Results: Fifty-eight percent of patients were men, and the median (interquartile range) age was 69.0 (63.0, 75.0) years. The most common etiology of liver disease was hepatitis C (38%). The frequency of living alone and low exercise habit was significantly high, and sarcopenia was more obvious in elderly patients with low PA than in those with high PA. Additionally, the elderly with low PA showed significantly reduced HGS compared to that of the elderly with high PA (-1.00 (-2.27, 0.55) kg vs. 0.10 (-1.40, 1.10) kg, P < 0.05). However, changes in HGS in younger patients were not significant (-0.02 (1.83, 1.47) kg vs. 0.25 (-2.45, 2.05) kg, P = 0.96). Logistic regression analyses identified PA as the independent factor for prevention of decrease in HGS (odds ratio: 1.91, 95% confidence interval: 1.00 - 3.62, P = 0.049)., Conclusions: Young patients with low PA were characterized by a long sedentary time; however, there was no loss of HGS. In contrast, elderly patients with CLD and low PA had significantly reduced HGS compared to that in elderly patients with CLD and high PA., Competing Interests: All authors have no conflict of interest to declare., (Copyright 2019, Ohashi et al.)

Interferon-free direct acting antiviral agent regimens for chronic hepatitis C (CHC) have been developed. These regimens have shown a high rate of sustained virologic response (SVR), and a reduction in side effects during treatment is also anticipated. However, the impact of the regimens on health-related quality of life (HRQOL) and side effects during treatment is not fully understood. The purpose of the present study was to evaluate HRQOL in the clinical course of patients with CHC receiving daclatasvir/asunaprevir (DCV/ASV) therapy using the Short Form-36 (SF-36) method. Twenty-eight patients with CHC receiving DCV/ASV therapy were analyzed in the present study, and HRQOL was measured by SF-36. Patients were asked to fill out the SF-36 prior to therapy (baseline), following 12 weeks of therapy, at the end of treatment and at SVR week 24 (SVR24) to evaluate HRQOL. Laboratory data were also investigated during the same period, and associations between these results and SF-36 were investigated. Aspartate aminotransferase, alanine aminotransferase, serum albumin, α-fetoprotein, platelet counts and Fibrosis (Fib)-4 index were all significantly improved at each time point when compared with baseline. With regard to alterations in HRQOL during therapy, the ≥70-year-old group displayed a significantly greater improvement in physical functioning during the period between baseline and 12 weeks when compared with the <70-year-old group. In the analysis of the SF-36 differences within each group, general health improved significantly in the ≥70-year-old group, as well as albumin levels. In addition, Fib-4-index significantly improved at all time points (12 and 24 weeks, and SVR24) when compared with baseline in the ≥70-year-old group. Therefore, DCV/ASV therapy may improve HRQOL and hepatic functional reserve, particularly in elderly patients.

The rate of sustained virologic response (SVR) has increased in patients with chronic hepatitis C (CHC; genotype 1) since triple treatment with pegylated interferon (PEG-IFN), ribavirin (RBV) and telaprevir (TVR) was included in Japanese health insurance. However, side effects such as high-grade anemia and skin disorders means it is important to investigate the extent to which quality of life (QOL) is maintained during treatment. The impact on health-related (HR) QOL, as a result of TVR-based triple treatment was investigated long-term (48 weeks) in 34 patients (18 men, 16 women) following TVR-based triple treatment, using the 36-item short form health survey (SF-36). While scores for physical health were significantly lower during treatment, an improvement was seen in patients who showed complete response to treatment from 12 weeks following treatment (P<0.05). HRQOL improved significantly following completion of TVR-based triple treatment in these complete-responders, with higher scores compared with those prior to treatment. Anemia and skin symptoms appeared frequently during treatment and scores for physical health dropped. Particular care needs to be taken in regards to the management of side effects during TVR treatment. Further evaluations using the SF-36 may help in controlling doses to achieve SVR.

Metastases to the gastrointestinal tract rarely occur in breast cancer except in invasive lobular carcinoma. The present study reports a rare case of metastatic gastric cancer from invasive ductal carcinoma (IDC) of the breast mimicking primary gastric linitis plastica. A 51-year-old premenopausal female, who had a history of partial mastectomy for right breast cancer at the age of 40, was referred to Toyama City Hospital (Toyoma, Japan) for an endoscopic diagnosis of gastric linitis plastica. Abdominal computed tomography (CT) revealed left hydronephrosis, while peritoneal metastasis and malignant ascites were not detected. Chest CT detected a left lung tumor, which had invaded the left upper bronchus. Biopsy specimens were obtained and the histopathological findings on both the gastric tumor and lung tumor demonstrated poorly differentiated adenocarcinoma, whereas the histology of the original breast cancer was IDC with a solid-tubular type. Immunohistochemistry revealed that the biopsied specimens of the gastric and lung tumors were positive for estrogen receptor (ER), progesterone receptor (PgR) and negative for human epithelial growth factor receptor-2 (HER2). These molecular characteristics indicated the case was metastatic gastric carcinoma from the breast cancer with lung metastasis, since the statuses of ER, PgR and HER2 were concordant with those of the original breast cancer. However, the possibility of primary gastric cancer could not be completely ruled out. Therefore, a total gastrectomy was performed for the purpose of both diagnosis and treatment. Pathological examination of the resected specimen provided a definite diagnosis of multiple metastatic gastric carcinomas from the breast. To the best of our knowledge, metastatic gastric cancer derived from the breast presenting as linitis plastica 11 years following the surgical removal of IDC has not been described previously.

Background: Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images., Case Presentation: A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum., Conclusion: The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.

Introduction: Currarino syndrome (Currarino triad) was described in 1981 as a triad syndrome with a common embryogenesis in infants and with three characteristics: anorectal stenosis, a defect in the sacral bone, and a presacral mass. We describe here an unusual case of Currarino syndrome in an adult presenting with a presacral abscess but no meningitis., Case Presentation: A 32-year-old Japanese man presented with fever, arthralgia and buttock pain. A digital rectal examination showed mild rectal stenosis with local warmth and tenderness in the posterior wall of his rectum. Computed tomography showed a scimitar-shaped deformity of his sacrum and an 8cm presacral mass, which continued to a pedicle of his deformed sacrum. This was diagnosed as Currarino syndrome with a presacral abscess. The abscess was drained by a perianal approach with our patient treated with antibiotics. His symptoms soon disappeared. After three months, an excision was performed through a posterior sagittal approach. His postoperative course was uneventful and he was discharged 10 days after surgery. A histopathological examination revealed an infected epidermoid cyst. He has been free from recurrence as of four years and six months after surgery., Conclusions: We report a case of Currarino syndrome in an adult who presented with a presacral abscess but no meningitis. Abscess drainage followed by radical surgery resulted in a successful outcome.

Background: We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1., Methods: Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases., Results: Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life"., Conclusions: Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative to inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients, we administered a QOL questionnaire, The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD) to 8 older adult patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating activity, physical condition, psychological condition, social relationship, psychological condition and face scale were analyzed. No significant decrease in each factor was observed in this study.

A 77-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and hemoptysis. Chest X-ray film and computed tomography (CT) scan showed right-sided pleural effusion with lung tumor. Succeeding upper gastro-intestinal fiberscopy and cystoscopy revealed poorly-differentiated adenocarcinoma of the stomach and urothelial carcinoma of the bladder. Repeated treatment with 100 mg/body of S-1 on day 1 followed by 60 mg/m(2) of cisplatin on day 8 was effective in this patient.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients,we used a QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD) for 8 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating "activity," "physical condition," "psychological condition," "social relationship" and "face scale" were analyzed. Significant improvements in the factors indicating "psychological condition" were observed in this study.

A denitrification system for saline wastewater utilizing halophilic denitrifying bacteria has not been developed so far. In this study, denitrification performance and microbial community under various saline conditions were investigated using denitrifying sludge acclimated under low-salinity condition for a few years as seed sludge. A continuous denitrification experiment showed that denitrification performance and microbial community at 10% salinity was higher than that at 1% salinity. The microbial community in the denitrification sludge that was acclimated under low salinity was monitored by terminal-restriction fragment length polymorphism (T-RFLP) analysis during acclimation to high-salinity condition. T-RFLP profiles and clone analysis based on 16S rRNA-encoding genes in the sludge of the denitrification system with 10% salinity indicated that the gamma-Proteobacteria, particularly Halomonas spp., were predominant species, suggesting that these bacterial members were possibly responsible for a high denitrification activity under high-salinity conditions. Furthermore, the investigation of denitrification performance under various saline conditions revealed that 4-10% salinity results in the highest denitrification rate, indicating that this salinity was optimal for predominant bacterial species to exhibit denitrification activity. These results indicate the possibility that an appropriate denitrification system for saline wastewater can be designed using acclimated sludge with a halophilic community.

Aims: Denitrification efficiency at 10% salinity was compared with that at 2% salinity. The characteristics of bacterial strains isolated from the denitrification system, where an improvement of denitrification efficiency was observed at a high salinity were investigated., Methods and Results: Two continuous feeding denitrification systems for saline solutions of 2% and 10% salinity, were operated. Denitrification efficiency at 10% salinity was higher than that at 2% salinity. The bacterial strains were isolated using the trypticase soy agar (TSA) medium at 30 degrees C. The phylogenetic analysis of 16S rRNA gene sequences of isolates indicated that halophilic species were predominant at 10% salinity., Conclusions: The improvement of denitrification efficiency at a high salinity was demonstrated. The strains isolated from the denitrifying system with 10% salinity were halophilic bacteria, Halomonas sp. and Marinobacter sp., suggesting that these bacteria show a high denitrifying activity at 10% salinity., Significance and Impact of the Study: The long-term acclimated sludge used in this study resulted in high denitrification performance at a high salinity, indicating that the design of a high-performance denitrification system for saline wastewater will be possible.

We have experienced a case of advanced esophageal carcinoma successfully treated with chemoradiation therapy together with low-dose cisplatin and 5-fluorouracil, having only minor toxicity. A 55-year-old man was admitted to our hospital because of dysphagia. Cervical esophageal carcinoma was found to have invaded the larynx through endoscopy, and invasion to thyroid gland and trachea was suspected from a cervical CT. We diagnosed the condition as advanced esophageal carcinoma (A2N(-)M0Pl0 Stage III). We then treated the patient by chemoradiation therapy. After the treatment, the carcinoma could not be detected by CT and endoscopy, and endoscopic biopsy revealed there were no active carcinoma cells. The side effects of the therapy were very mild, therefore the patient could be discharged after a short time. No evidence of a tumor relapse was found 5 months after the therapy. We treated 4 patients with esophageal carcinoma using the same regimen, and the results of the therapy were 2 CR, 1 PR, and 1 PD, with an overall response rate of 75%.

We have previously reported a constitutively activated form of the Flt-1 kinase (BCR-FLTm) molecularly engineered based on the structural backbone of the activated tyrosine kinase BCR-ABL. Here we show that it can induce not only growth stimulation but also tubulogenic differentiation of non-tubulogenic NP31 (non parenchymal) sinusoidal endothelial cells of rat liver in basement membrane matrix. Tubules formed in vitro were accompanied by fenestration structures and allowed circulation when transplanted into syngeneic animals. This biological response was not observed in other activated forms of kinases constructed in a similar fashion, which include Trk (BCR-TRK), KDR (BCR-KDR), and the parental BCR-ABL. Interestingly, formation of fine tubules was accomplished with lower but not higher expression levels of BCR-FLTm. Compared to NP cells in primary culture NP31 is deficient in expression of alpha1 integrin subunit, which was restored by expression of BCR-FLTm that had tubulogenic ability. Matrix-induced tyrosine phosphorylation of an adaptor protein Shc with recruitment of Grb-2 was observed even when tubulogenesis was nearly completed at G1 stage of the cell cycle in 2-3 weeks. Activation of matrix metalloproteinase 2 (MMP-2) and expression of urokinase type plasminogen activator (uPA) was observed with cellular invasion into matrix at the depth of 200-300 microm. Inhibitors for MAP kinase activator MEK1 and for serine proteases showed deleterious effects on the tubulogenesis. We suppose that matrix ligand-induced integrin signals cooperate with a low level of Flt-1 kinase activity to promote tubulogenic behaviors of endothelial cells in this system.

High angular resolution images of extragalactic radio sources are being made with the Highly Advanced Laboratory for Communications and Astronomy (HALCA) satellite and ground-based radio telescopes as part of the Very Long Baseline Interferometry (VLBI) Space Observatory Programme (VSOP). VSOP observations at 1.6 and 5 gigahertz of the milli-arc-second-scale structure of radio quasars enable the quasar core size and the corresponding brightness temperature to be determined, and they enable the motions of jet components that are close to the core to be studied. Here, VSOP images of the gamma-ray source 1156+295, the quasar 1548+056, the ultraluminous quasar 0014+813, and the superluminal quasar 0212+735 are presented and discussed.

A case of gastric cancer with liver metastasis who responded well to low-dose PMUE (CDDP, MMC, UFT, etoposide) therapy is reported. A 65-year-old man underwent distal partial gastrectomy with D2 lymph node dissection under the diagnosis of type 5 gastric cancer with multiple liver metastases. Pathological findings revealed papillary adenocarcinoma in the primary lesion and metastatic lymph nodes (No. 8a). Low-dose PMUE therapy after resection of primary lesion was effective for the liver metastases. Exacerbation was suspected, so the lesions of metastases were resected again after 2 years and 11 months postoperative course. All 4 resected lesions of metastases became old fibrous tissue with hyalinization, and 2 of 4 lesions were necrotic and surrounded by fibrous connective tissue. None of these 4 lesions included viable cancer cells. The patient has now been followed with no evidence of exacerbation. It was suggested that low-dose PMUE therapy was effective for liver metastasis of gastric cancer, especially the differentiated type.

A case of macrocystic serous cystadenoma of the pancreas is presented, and literature is reviewed. A 35-yr-old woman presented with mild upper abdominal pain. Abdominal ultrasonography and an abdominal computed tomography revealed a multiloculated and calcified cyst in the body of the pancreas. A T1-weighted image, using magnetic resonance imaging, revealed a low-intensity multiloculated, pancreatic mass. In contrast, T2-imaging of the tumor showed a high-intensity mass. Endoscopic retrograde cholangiopancreatography showed no contact between the main pancreatic duct and the tumor. The preoperative diagnosis was a mucinous cystic neoplasm. Tumor enucleation was performed. Subsequent microscopic examination of this tumor suggested the diagnosis of a macrocystic serous cystadenoma of the pancreas.

We report 12 patients who ate raw firefly squid, Watasenia scintillans. The patients experienced abdominal pain one or two days after eating them. Ileus was suspected by abdominal X-ray, but abdominal muscle guarding was not recognized. No specific findings was revealed on laboratory data. Patients were recovered two or three days after admission by only drip infusion. Recently, type X larva of the suborder Spirurina is recognized in 3.3% of firefly squid viscus. Indirect fluorescent antibody test using antigen of the type X larva was evaluated for the sera of the 8 ileus patients who were admitted in 1993. The antibody titers were positive in 5 patients and were negative in 3 patients. These results suggested that the ileus like symptom we reported here was attributed to the type X larva of the suborder Spirurina.

A 62-year-old male patient with progressive gastric cancer and multiple liver metastases (H3, P0, ss gamma, n4) underwent total gastrectomy (R1). After 2 years and 2 months, he was re-hospitalized with epigastric tumor caused by re-manifestation of liver metastasis as well as inappetence. Since a large focus of liver metastasis and intraportal tumor embolism was identified, a continuous intraarterial infusion tube utilizing Infuse-A-Port was inserted in the hepatic artery. After conducting 2 cycles of PMUE intra-arterial chemotherapy, the tumor size was reduced by 84% (PR); and CEA, which had been high upon rehospitalization, recovered to the normal level. After discharge, the patient has been receiving 5-FU arterial infusion as an outpatient and undergoing UFT oral chemotherapy. The efficacy has continued and he has been well for 3 years since operation. Often operations for gastric cancer accompanied with multiple liver metastasis meet with little success, and almost no case of prolonged survival has been reported. In this case, the effectiveness of PMUE arterial infusion chemotherapy was clear, the patient has been well for 3 years since operation, and is an interesting example with seemingly good prospects for long-survival.

We studied the clinical efficacy of cefdinir (CFDN), a new oral cephalosporin, in 18 children with ages 2 years and 4 months to 11 years and 4 months with pediatric infections. The diagnoses consisted of respiratory tract infections in 15 cases, impetigo in 2 and balanoposthitis in 1. Clinical efficacies were excellent in 11 patients and good in 7, with an efficacy rate of 100%. Bacteriologically, 9 (64.3%) of the 14 strains of clinical isolates were eradicated. No side effects nor abnormal laboratory findings were observed. We have concluded that CFDN is a useful antibiotic for the treatment of mild to moderate pediatric infections.

Cefpodoxime proxetil (CS-807, CPDX-PR), a new cephalosporin antibiotic, was investigated for its usefulness in pediatrics. 1. The total number of patients treated were 21 with their ages ranging from 3 months to 9 years and 1 month, consisting of 5 male and 16 female infants. 2. Single dosages of the drug ranged between 4.4 mg and 5.8 mg/kg with oral administration for 3 times daily in fasting. A total aggregated dosage was between 46.4 mg/kg and 200.0 mg/kg. The length of administration was 3 to 12 days. 3. The breakdown of symptoms were 9 cases of acute pharyngitis, 5 cases of acute tonsillitis, 3 cases of acute bronchitis, and 1 case each of impetigo + purulent rhinitis, cervical lymphadenitis, scarlet fever, and urinary tract infection. 4. The clinical efficacy rate was 100% with 18 excellent responses and 3 good responses. 5. The bacteriological efficacy rate was 90.9% in eradication rate, based on results on 17 strains of suspected causative microorganism among which 10 strains were eradicated, 1 strain was decreased, and 6 strains were unknown. 6. There was no side effect during the treatment and after the discontinuation, while, in clinical laboratory tests, GOT and GPT were elevated in 1 case which was judged as abnormal. No patient refused the drug. CPDX-PR was considered to be very useful drug because of its excellent efficacy and safety in pediatrics in treating infectious diseases.

The sensitivity of leukemic progenitor cells (L-CFU) to cytosine arabinoside (Ara-C) and daunomycin (DM) in vitro was studied using PHA -LCM two step assay for L-CFU. Continuous exposure of leukemic and normal bone marrow cells to DM as well as Ara-C in vitro appeared to be more effective than pulse exposure because colony formation was suppressed by a dose dependent fashion. The relationship between in vitro sensitivity to DM and Ara-C and that of in vivo to chemotherapy was investigated in 17 untreated and 5 relapsed patients with acute nonlymphocytic leukemia. The sensitivity of L-CFU to the two chemotherapeutic agents varied from patient to patient. These studies indicated a clear-cut relationship between in vitro drug sensitivity and in vivo response to patients whose L-CFU were sensitive to both agents and entered complete remission, whereas patients whose L-CFU were insensitive to one or both drugs in vitro failed to enter remission. This assay system appears to be useful in predicting response of patients to chemotherapy and in selecting the most effective drugs for an individual patient use.

We performed PMU hepatic arterial chemotherapy (a combination therapy consisting of intra-hepatic arterial infusion of CDDP and MMC, oral administration of UFT) in 20 patients with gastric cancer and liver metastases. In this method, 1-6 courses of one infusion of CDDP at 70-100 mg/body and MMC of 10 mg/body into the proper hepatic artery were administered at intervals of 3-4 weeks. UFT of 300-400 mg/day was orally administered with the infusion. The primary response for hepatic metastatic lesions was observed in one case of CR, 14 cases of PR, 4 cases of NC, and one case of PD. The efficacy for CR and PR was high at 75%. The median disease-free interval was 56 weeks in responders. The 50% survival period was 11.1 months; one-year survival rate, 42.1%; two-year survival rate, 12.3%; the longest survival period was 108 weeks. Mild and transient side effects were recognized in 17 cases (85%): gastrointestinal symptoms, sense of general malaise, fever, leukocytopenia, and elevated BUN. Thus, the results indicated that this combination chemotherapy was effective for liver metastases of gastric cancer.

The usefulness of a new cephem antibiotic, cefteram pivoxil (CFTM-PI, T-2588), was evaluated in the field of pediatrics. 1. Thirty-one patients were enrolled in the study. They included 20 boys and 11 girls with ages 8 months to 8 years 7 months. 2. The patients were treated with CFTM-PI at a dose levels ranging 3.0-4.2 mg/kg in 3 divided portions. The administration was done orally for a duration between 3 and 13 days, with a total dose between 27.3 and 130.0 mg/kg. 3. The patients were diagnostically classified into the following categories: 11 with acute pharyngitis, 1 with acute nasopharyngitis, 6 with acute tonsillitis, 9 with acute bronchitis, 2 with scarlet fever, 1 with purulent parotitis and 1 with purulent cervical lymphadenitis. 4. Clinical responses to the treatment were excellent in 14, good in 13, fair in 1 and poor in 3 patients with an overall efficacy rate of 87.1%. 5. Bacteriological responses were as follows: of 29 bacterial strains presumed to be pathogens, 23 were eradicated, 2 unchanged and 4 unknown, with an eradication rate of 92.0%. 6. Neither adverse reactions nor abnormal changes in laboratory test values were observed with the medication in any patients during and after the end of the treatment. None of the patients refused the medication. CFTM-PI was found very effective and safe in treating pediatric infections: it is a useful drug in the field of pediatrics.