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l-Carnitine supplementation is effective in improving muscle cramps, hyperammonemia, and hepatic encephalopathy in patients with cirrhosis. However, limited evidence is available on the effect of l-carnitine supplementation on the survival of patients with cirrhosis.In this retrospective study, 674 patients with cirrhosis admitted to Gifu University Hospital or Chuno Kosei Hospital between October 2011 and December 2018 were enrolled. l-carnitine supplementation was defined as the use of l-carnitine for30 consecutive days during the follow-up period. Propensity score matching was applied to create comparable groups between l-carnitine-treated and untreated patients. Mortality was evaluated using the Cox proportional hazards model.Among the patients, 93 were excluded. Of the remaining 581 patients, 71 (12%) received l-carnitine supplementation. Propensity matching identified 189 patients (63 l-carnitine-treated and 126 untreated patients) with comparable baseline characteristics in both groups. Of the matched patients, 33 (52%) l-carnitine-treated and 74 (59%) untreated patients died during the median follow-up period of 36.3 months. Overall survival was significantly higher in l-carnitine-treated patients than in untreated patients (hazard ratio [HR], 0.66; 95% CI, 0.43-0.99). A subgroup analysis showed that the survival benefit of l-carnitine supplementation was prominent in patients with Child-Pugh Class B or C (HR, 0.39; 95% CI, 0.23-0.68), serum albumin levels ≤3.5 g/dl (HR, 0.59; 95% CI, 0.37-0.95), and ammonia levels ≥90 mcg/dl (HR, 0.50; 95% CI, 0.26-0.97), and in those without sarcopenia (HR, 0.56; 95% CI, 0.35-0.90).l-Carnitine supplementation may improve survival in patients with cirrhosis.

Liposarcoma is one of the most common types of soft tissue sarcomas and can develop at any site, although omental liposarcoma is extremely rare. Omental liposarcoma has a poor prognosis because the diagnosis is difficult, until it presents as a large tumor causing severe noticeable clinical symptoms. A 51-year-old male with lower abdominal pain was referred to our clinic. Abdominal ultrasonography revealed an ill-defined, solid, heterogeneous, and hypoechoic tumor deep in the lower abdomen. Generally, liposarcomas are hyperechoic, though 20% of liposarcomas present as hypoechoic tumors. This variation might occur depending on the pathological classification. We should consider the possibility of a dedifferentiated component if ultrasonography reveals typical features of soft tissue sarcoma with hypoechoic lesion.

Muscle cramps are frequently overlooked and worsen the quality of life in patients with chronic liver disease (CLD). Therefore, a valuable biomarker for predicting muscle cramps is required in the clinical setting. This study aimed to investigate whether the serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels, a reliable liver fibrosis marker, could predict muscle cramps in patients with CLD. This retrospective study included 80 patients with CLD. Muscle cramps were assessed using a questionnaire regarding their presence, frequency, pain severity, and duration. The associated predictors were analyzed using logistic regression analysis. The diagnostic accuracy and optimal cutoff values were evaluated using receiver operating characteristic curves. Of the 80 patients, 55% had muscle cramps and showed significantly higher serum M2BPGi levels than those without them (4.54 cutoff index [COI] vs 2.20; P = .001). Multivariate analysis revealed that M2BPGi (odds ratio [ORs], 1.19; 95% confidence interval, 1.003-1.42; P = .046) was independently associated with the presence of muscle cramps. The optimal COI value for predicting muscle cramps was 3.95, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.4%, 80.6%, 79.4%, 63.0%, and 70.0%, respectively. Patients with a COI value ≥3.95 had a 2-fold higher incidence of muscle cramps than patients with a COI value 3.95 (79% vs 37%; P .001). M2BPGi levels were also associated with the duration of muscle cramps. Serum M2BPGi appears useful as a biomarker for predicting muscle cramps in patients with CLD.

AIM Minimal hepatic encephalopathy (MHE) is associated with poor outcomes and the development of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis (LC). Zinc plays a key role in the detoxification of ammonia, a risk factor of hepatic encephalopathy. This study aimed to investigate whether zinc deficiency predicts OHE occurrence and mortality in LC patients with MHE. METHOD This retrospective study included 100 LC patients with MHE. MHE was diagnosed using a computer-aided neuropsychiatric test. Predictors associated with the development of OHE were analyzed using the Fine-Gray competing risk regression model. Cox proportional hazards regression analysis was carried out to evaluate the risk factors of mortality. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS Of the 100 LC patients with MHE, 41% had zinc deficiency (

Spur cell anemia is an acquired hemolytic anemia associated with liver cirrhosis and is characterized by the presence of increased large red blood cells, which are covered with spike-like projections that vary in width, length, and distribution. A 26-year-old man was referred to our hospital presenting with jaundice, lower limb edema, and dyspnea. The patient was subsequently diagnosed with spur cell anemia related to alcoholic liver cirrhosis. Spur cell anemia is an independent predictor of mortality in liver cirrhosis and has been associated with extremely poor prognosis. The most effective treatment for spur cell anemia is liver transplantation. As seen in the literature, the treatment of spur cell anemia without liver transplantation is quite challenging. This report highlights the importance of management and treatment strategies, including control of fluid retention, blood transfusion, plasma diafiltration, and administration of diuretics. Our treatment strategies might be useful in patients who are not candidate of liver transplantation or patients waiting for liver transplantation.

Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2 months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P = .82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP.

Bowel endometriosis is a condition caused by endometrial glands and stroma infiltrating the bowel wall and reaching the subserous fat tissue or the adjacent subserous plexus. A 42-year-old woman with changes in stool habits, nausea, and stomach aches experienced complete obstruction in the rectum. Endoscopic ultrasound demonstrated a low echoic lesion outside the rectal mucosa and endoscopic ultrasound-guided fine needle aspiration confirmed the diagnosis of bowel endometriosis. The clinical characteristics of bowel endometriosis are unspecific and this condition is sometimes misdiagnosed as a malignant tumor, irritable bowel syndrome, or any other colorectal disorder. Our aim is to show that endoscopic ultrasound-guided fine needle aspiration might be helpful for bowel endometriosis diagnosis and exclusion of other malignant disease.

l-carnitine, a compound responsible for transportation of acyl groups across cell membranes and modulating intracellular acyl-coenzyme A levels, is reported to reduce muscle cramps in patients with liver cirrhosis and diabetes and those on dialysis. A 79-y-old man with right-sided paralysis was admitted to our hospital and diagnosed with cerebral infarction. Nocturnal leg cramps appeared in the affected side and caused sleep disturbance. Supplementation with l-carnitine reduced the number of nocturnal leg cramps and alleviated sleep disturbance. It also plays an important role in nerve protection and treatment for carnitine deficiency. Patients with stroke-induced paralysis experience muscle wasting, which might reduce pooled carnitine in the affected side. This case suggests that stroke may cause localized carnitine deficiency, and l-carnitine supplementation might be effective for muscle cramps induced by stroke. To the best of our knowledge, this is the first case of l-carnitine supplementation for muscle cramps triggered by cerebral infarction.

We previously reported that serum concentrations of soluble Fas (sFas) predict the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) after treatment with CHOP but without rituximab (R). Here, we investigated whether the role of sFas as a prognostic factor remains valid in the R-CHOP era.We treated 132 patients with DLBCL between October 1995 and September 2002 (group A: without rituximab), and 75 between December 2002 and March 2007 (group B: with rituximab). The patients received eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin)-COP before September 2002, and R-CHOP or R-THP-COP after October 2002. The distribution of patients according to the International Prognostic Index did not significantly differ between the groups.The 5-year overall survival (OS) rates for patients with sFas levels ofor = 3.0 and3.0 ng/ml in group A were 19.8 and 61.9% (P0.0001), whereas the 3-year OS rates in group B were 54.7 and 92.2% (P0.01), respectively. Multivariate analysis using the proportional hazards model revealed that sFas most significantly correlated with overall survival (P0.05).Serum sFas is thus a useful tool for selecting the appropriate therapeutic strategy for DLBCL.

To evaluate the predictive value of early virologic response (EVR) of achieving a sustained virologic response (SVR), an open, prospective trial including 42 patients with chronic hepatitis C genotype 1b was performed with directly observed 24-week treatment with interferon α-2b plus ribavirin. We assessed the predictive values of EVR at days 3, 7, 14, and weeks 4, 8, and 12 of the SVR. The SVR in an intention-to-treat analysis was 19.0%. Patients who reached SVR presented a significantly faster reduction in plasma viral load. Stepwise multiple logistic regression analysis of the factors (gender, age, IFN dosage, ribavirin dosage, HCV RNA, ISDR, and loss of HCV RNA at week 4) revealed that loss of HCV RNA at week 4 was the only independent variable of treatment outcome (P = 0.0039). A viral load at treatment day 3 above 100 kIU/ml, at day 7 above 50 kIU/ml, and at day 14 above 10 kIU/ml was 100% predictive for virologic non-response in all except 1 patient. The cutoff levels for HCV RNA at days 3 and 14 of treatment were associated with an algorithm of the failure to detect HCV RNA after 12 weeks of treatment. In conclusions, a very early virologic response assessment could be useful for prediction of later outcome of combination therapy in chronic hepatitis C genotype 1b.

We report a case of lacrimal gland pseudotumor as the presenting sign of ulcerative colitis. A 25-year-old woman presented with a right upper eyelid swelling and pain. Intravenous administration of prednisolone was initiated on suspicion of lacrimal gland inflammation (pseudotumor). Although the treatment markedly reduced her ocular symptoms, she developed lower abdominal cramping and diarrhea with the 5 mg/day of oral prednisolone. Sigmoid colonoscopy and colon biopsy led to make a diagnosis of ulcerative colitis. Ulcerative colitis improved significantly with increased dose of steroid and additive mesalazine therapy. Ulcerative colitis should be included in the differential diagnosis of lacrimal gland pseudotumor.

去2年間に当院を受診した農薬中毒の4例について報告した。症例はパラコート2例, スミチオン2例で, それぞれ生存1例, 死亡1例で死因はともに呼吸不全であった。パラコートの生存例は死亡例より多くの量を服毒していたが, 嘔吐が強いため, 実際の吸収量は少なく, また超急性期に胃洗浄, 人工透析, 血液吸着が行われたため救命し得たと考えられた。またスミチオンの死亡例は来院時, 原因物質が不明であり, 人工透析および血液吸着導入までの時間を要し, 呼吸不全を招来したことが死亡原因と考えられた。したがって, 原因物質の如何にかかわらず, 農薬中毒に対しては, 早期より人工透析および血液吸着を含めた集中治療を実施することが予後の改善につながると考えられた。

A 68-year-old man complaining of back pain was given the diagnosis of mucinous adenocarcinoma of the sigmoid colon with disseminated carcinomatosis of bone marrow and disseminated intravascular coagulation(DIC). We started chemotherapy using FOLFOX4. After we confirmed that DIC had improved following 2 courses of FOLFOX4, bevacizumab was added to FOLFOX4. Laboratory studies revealed a serum CEA level of 11, 432 ng/mL, which improved to 245 ng/mL after a total of 9 courses of chemotherapy. Chemotherapy is continuing as scheduled at 6 months from the onset of this disease.

Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c-myc, were simultaneously suppressed in papillomas in carotenoid-treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid-inducible gene, retinoic acid receptor-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-carotene might exert the tumor-suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.

We previously described the effectiveness of the THP-COP regimen comprising cyclophosphamide, pirarubicin (tetrahydropyranyl adriamycin; THP), vincristine and prednisolone in patients with diffuse large B-cell lymphoma (DLBCL). The anthracycline drug THP was apparently less cardiotoxic than doxorubicin. However, that study was completed before rituximab was introduced into clinical practice. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) against DLBCL.Six to 8 courses of the regimen were administered every 2 weeks in 48 patients who were younger than 70 years.The complete remission rate was 92%, the 3-year overall survival rate was 83% and 3-year progression free survival rate was 74%. No deaths were associated with the treatment regimen.We conclude that R-THP-COP regimen is very effective against DLBCL. The results of our study urge randomized trials of R-CHOP and R-THP-COP among patients with CD20+ DLBCL.

A 52-year-old man was admitted to our hospital in October 2001 with abdominal pain. Abdominal X-ray indicated a diagnosis of ileus. Histopathological and immunological examination resulted in a diagnosis of immunoproliferative small intestinal disease (IPSID). He was treated with THP-COP therapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone), which resulted in complete remission. Outpatient follow-up revealed hypoalbuminemia in May 2003 and upper gastrointestinal endoscopy showed duodenal mucosal nodularity. He was diagnosed with relapsed IPSID and salvage chemotherapy was started. Follow-up endoscopy confirmed that the therapy was effective, but uncovered another duodenal mucosal nodularity. Immunohistochemical staining revealed T-cell lymphoma. Chemotherapy was discontinued and the patient died in December 2004.