Lymphoplasmacytic lymphoma with IgG-κ paraproteinemia presenting as a hepatic bulky mass.

Lymphoplasmacytic lymphoma (LPL) usually involves bone marrow (BM) and sometimes lymph nodes and spleen. LPL presenting as a hepatic mass lesion is extremely rare, with only one case reported in the English literature. A 70-year-old Japanese female presented to us with a right hypochondriac mass with tenderness. Computed tomography (CT) revealed a 14 cm-sized bulky hepatic mass. Laboratory findings showed a normal white blood cell count of 4.1×109/L with 4% plasmacytoid lymphocytes; normocytic anemia, Hb 9.4 g/dL; high soluble IL-2 receptor level, 2,290 U/mL; and elevated IgG, 10,306 mg/dL. Furthermore, IgG-κ monoclonal protein was detected. 18F-fluorodeoxyglucose-positron emission tomography/CT revealed abnormal uptake in the liver mass; left supraclavicular, parasternal, abdominal, and left inguinal lymph nodes; and bilateral lung bases. Magnetic resonance imaging showed no bone lesions. BM aspiration and liver biopsy showed predominant infiltration of small lymphocytes admixed with plasmacytoid lymphocytes and plasma cells. In the liver specimen, lymphoepithelial lesions were not observed. The small lymphocytes were positive for CD20, CD79a, and bcl-2, and negative for CD5, CD10, cyclin D1, and IRTA1; plasma cells in BM were positive for CD19, CD45, IgG, and κ-chain, and negative for CD20, and CD56. MYD88 L265P mutation, reported in approximately 40% of non-IgM LPL cases, was not detected in the liver specimen and BM cells. The frequency is lower than that of typical IgM LPL. These findings led us to a diagnosis of LPL with IgG-κ paraproteinemia. The patient underwent four courses of R-CHOP and two courses of Bendamustine-R. Partial remission was achieved.

Geranylgeranylacetone attenuates fibrogenic activity and induces apoptosis in cultured human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride-treated mice.

BACKGROUND: Geranylgeranylacetone (GGA), an anti-ulcer drug widely used in Japan, has attracted interest because of its various therapeutic effects. Therefore, we investigated the effects of GGA on human hepatic stellate cells (HSCs) in vitro and in a mouse model of liver fibrosis. METHODS: LX2, an immortalized human HSC line, was cultured and treated with GGA at concentrations up to 0.5 mM. After GGA treatment, changes in cellular morphology, apoptosis, and fibrosis-related gene expression were assessed. Male C57BL/6 J mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis was treated with GGA. Liver fibrosis was evaluated using Sirius red staining and immunohistochemistry for α-smooth muscle actin (SMA). RESULTS: GGA decreased the density of LX2 and primary human hepatic stellate cells but not that of HepG2 cells (a human hepatoma cell line), which was employed as control. In addition, GGA decreased the expression of fibrogenic genes and increased that of C/EBP homologous protein (CHOP). It also induced endoplasmic reticulum (ER) stress and increased apoptosis. CHOP knockdown, however, failed to suppress the GGA-induced decrease in LX2 cell density, suggesting the involvement of additional molecules in ER stress-associated apoptosis. Expression of death receptor 5, mitogen-activated protein kinase, heat shock protein 70, and Akt, all of which affect the activity of stellate cells, was unchanged in relation to LX2 cell fibrogenic activity. In the mouse model of liver fibrosis, GGA decreased the extent of Sirius red staining and SMA expression. CONCLUSIONS: GGA attenuated fibrogenic activity and induced apoptosis in cultured human HSCs, and suppressed liver fibrosis in mice, suggesting its potential as an agent for treating liver fibrosis.

Risk factors for osteoporosis in patients with end-stage liver disease.

Patients with end-stage liver disease (ESLD) were evaluated and their clinical features were compared with the aim of identifying risk factors for osteoporosis. Seventy-nine patients with ESLD were enrolled in the current study. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry and compared with clinical features in patients with ESLD. BMD was identified to be significantly correlated with body mass index (r=0.430; P=0.001) and inversely correlated with total bile acid (r=-0.228; P=0.049) and urine N-telopeptide type I collagen/creatinine ratio (r=-0.280; P=0.024). Patients with osteoporosis were significantly older (osteoporosis vs. no osteoporosis, 63.0 vs. 56.0 years; P<0.05) and had higher values for total bile acid (osteoporosis vs. no osteoporosis, 306.0 vs. 129.1 µmol/l; P<0.05) and corrected calcium [osteoporosis vs. no osteoporosis, 9.85 (8.7-10.7) vs. 9.70 (8.8-10.6) mg/dl; P<0.05]. In multivariate analysis, age (ß=-0.015±0.06; P=0.009) and total bile acid (ß=-0.001±0.0001; P=0.041) were identified as independent factors for osteoporosis. Finally, the risk score for osteoporosis was defined as follows: Risk score=1.78-0.001 × total bile acid-(0.16 × age). The area under the receiver operating characteristic (ROC) curve risk score for osteoporosis is 0.778. Thus, the risk scores calculated in the present study may be used to predict osteoporosis in patients with ESLD.

In vivo fluorescence navigation of gastric and upper gastrointestinal tumors by 5-aminolevulinic acid mediated photodynamic diagnosis with a laser-equipped video image endoscope.

OBJECTIVE: Photodynamic diagnosis (PDD) is an imaging technology that is based on the fundamental biological features of cancer cells. Five-aminolevulinic acid (ALA), a precursor of photosensitizing protoporphyrin IX (PpIX) has been applied. In fact, ALA-mediated PDD provides good visualization for certain tumors. However, there have been few studies on clinical application of PDD for gastrointestinal (GI) cancers. This study was aimed to investigate the feasibility of ALA-mediated PDD for navigation of upper GI tumors. MATERIALS AND METHODS: Using a newly developed endoscope equipped with a blue laser light excitation, ALA-mediated PDD was conducted in 27 lesions from 23 patients with upper GI tumors including 2 Barrett's intramucosal cancers. ALA solution was given orally 3h before PDD. All the adenocarcinomas came under clinical stage I, and the tumors were resected endoscopic submucosal dissection and/or laparoscopic surgery. Red fluorescence signal and intensity was assessed as for clinicopathological features of the cases. RESULTS: The laser-based endoscopy could detect upper GI tumors as red fluorescent navigation (PDD-positive) in 23 of the 27 lesions. All but one intestinal typed tumors in histopathology were significantly PDD-positive, whereas each signet ring cell carcinoma was PDD-negative. There was a significant difference in tumor size between the PDD-positive and -negative tumors. The elevated lesions emitted significantly more intense fluorescence. CONCLUSIONS: Fluorescence navigation by ALA-mediated PDD provided sufficient detection of upper GI tumors in particular for the intestinal typed tumors. Thus, ALA-PDD using the blue laser-equipped endoscope offers a promising diagnostic tool.

Incidence of and risk factors for bile duct stones after living donor liver transplantation: An analysis of 100 patients.

AIM: Although bile duct stone (BDS) is one of the biliary complications of liver transplantation, analytical studies, particularly on living donor liver transplantation (LDLT) cases, are rare. This study aimed to clarify the incidence of and risk factors for BDS following LDLT. METHODS: We retrospectively reviewed the medical records of 100 patients who underwent LDLT at our institute from August 2000 to May 2012, and analyzed their clinical characteristics and risk factors for BDS. RESULTS: Of these, 10 patients (10.0%) developed BDS during the observation period. The median follow-up period to BDS diagnosis was 45.5 months (range, 5-84) after LDLT. Univariate analysis revealed male sex, right lobe graft and bile duct strictures as factors that significantly correlated with BDS formation. Multivariate analysis revealed bile duct strictures (odds ratio, 7.17; P = 0.011) and right lobe graft (odds ratio, 10.20; P = 0.040) to be independent risk factors for BDS formation. One patient with BDS and biliary strictures succumbed to sepsis from cholangitis. CONCLUSION: In the present study, right lobe graft and bile duct strictures are independent risk factors for BDS formation after LDLT. More careful observation and monitoring are required in the patients with high-risk factors.

How to access photodynamic therapy for bile duct carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is a promising treatment option for local control of remnant cancer after surgical resection or biliary stenosis by the unresectable tumor in patients with bile duct carcinomas (BDC). To achieve effective tumor necrosis, an appropriate approach to laser irradiation is necessary. METHODS: The efficacy of endoscopy-guided PDT using porfimer (n=12) or talaporfin sodium (n=13) was investigated by evaluating the transhepatic biliary routes and endoscopic retrograde biliary (ERB) routes in 25 patients with BDC. RESULTS: Diseases included perihilar intrahepatic cholangiocarcinoma (ICC) in four patients, extrahepatic BDCs in 19 and ampular carcinoma (AC) in two patients. Adjuvant PDT after surgical resection was performed in 18 patients, and PDT for tumor biliary stenosis was performed in seven. In patients undergoing surgical resections, the mean period between the operation and PDT was 87±42 days. In patients who underwent prior surgical resections, the transhepatic route was used in five (28%), the jejunal loop was used in 11 (61%), the T-tube route was used in one, and the endoscopic retrograde cholangiography (ERC) route via papilla Vater was used in one. In unresectable BDC, the ERC route was used in four patients (57%), and the transhepatic biliary route was used in three (43%). Endoscopic-guided PDT could not be performed in one patient because of a technical failure. Except for the complication of photosensitivity, endoscopy-related complications were not observed in any patients. Patients undergoing PDT with porfimer sodium had a significantly longer admission period compared to patients undergoing PDT with talaporfin sodium (36 vs. 5 days, respectively) (P<0.01). CONCLUSIONS: PDT was safely and definitively performed using the endoscopy-guided approach via the transhepatic or ERC route. By considering the disadvantages of both routes, PDT must be adequately achieved for local control of BDC.

Successful management of cap polyposis with eradication of Helicobacter pylori relapsing 15 years after remission on steroid therapy.

A 37-year-old woman was evaluated at our hospital for a treatment-resistant proctosigmoiditis. Fifteen years previously, ulcerative colitis was suspected and she was cured by steroid therapy. Colonoscopy revealed multiple sessile polyps covered with white exudate from the rectum to the sigmoid colon. Histopathological examination revealed a mucosal surface cover of granulation tissue. Based on these findings, cap polyposis was diagnosed. She underwent Helicobacter pylori eradication therapy, and at 1 month after therapy, her symptoms had improved. We present a case of cap polyposis relapsing 15 years after remission with steroid therapy, and that was improved by H. pylori eradication therapy.

Apolipoprotein B and insulin resistance are good markers of carotid atherosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: It is widely known that low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerosis. However, recent studies reported that serum levels of apolipoprotein B (Apo B) and Apo B to apolipoprotein A-1 (Apo A-1) ratio were better predictors of atherosclerotic vascular disease compared with LDL-C. In this study, we investigated that Apo B concentrations and insulin resistance (HOMA-R) can be good markers of carotid atherosclerosis in patients with type 2 diabetes. METHODS: Sixty-six type 2 diabetic patients with carotid atherosclerosis and 66 age- and sex-matched patients without carotid atherosclerosis were compared. The usefulness in risk assessment of LDL-C, Apo B, and HOMA-R for carotid atherosclerosis were estimated by receiver-operating characteristics (ROC) curve analysis. The percentage of carotid atherosclerosis in combination with two of these markers was calculated. RESULTS: Type 2 diabetic patients with carotid atherosclerosis had significantly higher body mass index, higher blood pressure, higher LDL-C, and Apo B, and higher HOMA-R. The ranking of the area under the ROC curve was Apo B, HOMA-R, and LDL-C (0.70, 0.69, and 0.66, respectively). The percentage of patients with carotid atherosclerosis and high LDL-C was 60.7%, high LDL-C+high HOMA-R was 77.4%, and high Apo B+high HOMA-R was 90.9%, respectively. The usefulness of these combinations was significantly better than that of LDL-C alone (p<0.05 and p<0.01, respectively). CONCLUSIONS: In conclusion, the combination of Apo B and HOMA-R is a superior marker of carotid atherosclerosis compared with LDL-C alone in patients with type 2 diabetes.