Extensive Hepatic Infarction due to Polycythemia Vera.

Polycythemia vera (PV) is one of the three BCR-ABL1-negative myeloproliferative neoplasms characterized by activating mutations in JAK2, which clinically presents as erythrocytosis and has an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia. Splanchnic vein thrombosis is a rare manifestation of venous thromboembolism involving one or more abdominal vessels and is strongly associated with PV. We herein report a case in which hepatic infarction due to PV was saved by conservative treatment.

Usefulness of contrast-enhanced ultrasonography for biliary tract disease.

Conventional ultrasonography (US) for biliary tract disease shows high time and spatial resolution. In addition, it is simple and minimally invasive, and is selected as a first-choice examination procedure for biliary tract disease. Currently, contrast-enhanced US (CEUS), which facilitates the more accurate assessment of lesion blood flow in comparison with color and power Doppler US, is performed using a second-generation ultrasonic contrast agent. Such agents are stable and provide a timeline for CEUS diagnosis. Gallbladder lesions are classified into three types: gallbladder biliary lesion (GBL), gallbladder polypoid lesion (GPL), and gallbladder wall thickening (GWT). Bile duct lesions can also be classified into three types: bile duct biliary lesion (BBL), bile duct polypoid lesion (BDPL), and bile duct wall thickening (BDWT). CEUS facilitates the differentiation of GBL/BBL from tumorous lesions based on the presence or absence of blood vessels. In the case of GPL, it is important to identify a vascular stalk attached to the lesion. In the case of GWT, the presence or absence of a non-contrast-enhanced area, the Rokitansky-Aschoff sinus, and continuity of a contrast-enhanced gallbladder wall layer are important for differentiation from gallbladder cancer. In the case of BDWT, it is useful to evaluate the contour of the contrast-enhanced medial layer of the bile duct wall for differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis. CEUS for ampullary carcinoma accurately reflects histopathological findings of the lesion. Evaluating blood flow in the lesion, continuity of the gallbladder wall, and contour of the bile duct wall via CEUS provides useful information for the diagnosis of biliary tract disease.

[Mitral Valve Infective Endocarditis Complicated with Meningitis in a Patient with Atopic Dermatitis;Report of a Case].

Meningitis has not been described to the same extent as other neurological complications of infective endocarditis(IE). The appropriate selection and dosing of antibiotics for patients with IE and meningitis do not exist. Herein, we described an instructive surgical case of mitral valve endocarditis and meningitis caused in a patient with atopic dermatitis, that was successfully treated using a multi-disciplinary approach.

[Gastric tuberculosis in an elderly patient:a case report].

A woman in her 70s presented to our hospital with epigastric pain, back pain, and weight loss. Esophagogastroduodenoscopy was performed, and numerous protuberances, which were suspected to be submucosal tumors, were found at the gastric corpus. The patient was diagnosed with gastric tuberculosis based on the biopsy results of these protuberances. Histopathological analysis demonstrated non-caseating epithelioid granuloma. A positive culture for Mycobacterium tuberculosis was also obtained on gastric juice analysis and confirmed using polymerase chain reaction assay. In the rapidly aging population in Japan, our findings emphasize on the importance of differentiating gastrointestinal tuberculosis, including gastric tuberculosis, from other diseases. This case may provide information about the development of gastric tuberculosis.

Daclatasvir and asunaprevir treatment in patients infected by genotype 1b of hepatitis C virus with no or subtle resistant associated substitutions (RAS) in NS5A-Y93.

In this study, we investigated the real-world data of the first approved interferon-free regimen in Japan, daclatasvir and asunaprevir (DCV+ASV), in chronic hepatitis C patients infected HCV genotype 1b with no or subtle amount of baseline resistant associated substitutions (RAS). Among 924 patients registered in our multicenter study, 750 patients who were proven not to be infected with NS5A-Y93H RAS by direct sequencing and to have no or subtle amount (less than 20%) of NS5A-Y93H RAS by probe assays (Cycleave or PCR invader assay) were included in this study. We investigated the anti-viral effect and factors associated with SVR12. In statistical analysis, P < 0.05 was considered as significant. The SVR12 rate in this population was 92.1% (562/618). Factors associated with SVR12 were male (odds ratio: 2.128; 95%CI: 1.134-4.000, P = 0.019); lower serum γGTP (odds ratio: 1.007; 95%CI: 1.002-1.012, P = 0.006); lower HCV-RNA (odds ratio: 1.848; 95%CI: 1.087-3.145, P = 0.023), and RVR (odds ratio: 6.250; 95%CI: 2.445-15.873, P < 0.001). No patients with γGTP ≧ 80 IU/L without RVR showed SVR12 (0/4, 0%) and one patients with γGTP ≧ 20-< 80 IU/L and HCV-RNA ≧ 6.5 logIU/mL without RVR (5/10, 50%) and two female patients with RVR but γGTP ≧ 80 IU/L and HCV-RNA ≧ 6.5 logIU/mL (7/13, 53.8%) showed a low SVR12 rate. In the present study, we showed a good viral response with DCV-ASV treatment and identified four predictive factors associated with SVR12. These four markers could be a good predictive markers for the viral effect of this treatment regimen in patients with no or subtle amount of RAS in NS5A-Y93.

A case of a patient with granulocyte-colony stimulating factor-producing pancreatic cancer who responded to nab-paclitaxel plus gemcitabine.

A 67-year-old male patient presented with an irregular mass involving the pancreatic body and tail with multiple liver/lymph node metastases. A biopsy indicated the presence of a poorly differentiated adenocarcinoma. Fever and increased white blood cell count, C-reactive protein levels, and granulocyte-colony stimulating factor (G-CSF) levels led to the diagnose of G-CSF-producing pancreatic cancer. The patient did not respond to FOLFIRINOX therapy (leucovorin, fluorouracil, irinotecan, and oxaliplatin), but nab-paclitaxel plus gemcitabine treatment was effective, resulting in tumor shrinkage and reduced G-CSF levels. After the fifth course of this therapy, exacerbation was noted, and the patient died of primary cancer 6 months after initiating the therapy. Here we report the case of this patient with G-CSF-producing pancreatic cancer who responded to chemotherapy.

Analysis of the risk factors for severity in post endoscopic retrograde cholangiopancreatography pancreatitis: The indication of prophylactic treatments.

AIM: To determine the risk factors of severe post endoscopic retrograde cholangiopancreatography pancreatitis (sPEP) and clarify the indication of prophylactic treatments. METHODS: At our hospital, endoscopic retrograde cholangiopancreatography (ERCP) was performed on 1507 patients from May 2012 to December 2015. Of these patients, we enrolled all 121 patients that were diagnosed with post endoscopic retrograde PEP. Fourteen of 121 patients diagnosed as sPEP were analyzed. RESULTS: Forty-one patients had contrast media remaining in the pancreatic duct after completion of ERCP. Seventy-one patients had abdominal pain within three hours after ERCP. These were significant differences for sPEP (P < 0.05). The median of Body mass index, the median time for ERCP, the median serum amylase level of the next day, past histories including drinking and smoking, past history of pancreatitis, sphincter of Oddi dysfunction, whether emergency or not, expertise of ERCP procedure, diverticulum nearby Vater papilla, whether there was sphincterotomy or papillary balloon dilation, pancreatic duct cannulation, use of intra-ductal ultrasonography enforcement, and transpapillary biopsies had no significant differences with sPEP. CONCLUSION: Contrast media remaining in the pancreatic duct and the appearance of abdominal pain within three hours after ERCP were risk factors of sPEP.

Daclatasvir and asunaprevir treatment in patients with severe liver fibrosis by hepatitis C virus genotype 1b infection: Real-world data.

BACKGROUND AND AIM: In this study, we investigated the real-world data of the first approved interferon-free regimen in Japan: daclatasvir and asunaprevir in chronic hepatitis C patients with severe fibrosis. METHODS: Among 924 patients registered in our multicenter study, 535 patients were defined as having severe fibrosis with Fib-4 index â‰§ 3.25 and were included in this study. We investigated antiviral effect and factors associated with sustained viral response 12 (SVR12), and the additional effects on serum α-fetoprotein and albumin levels by eradicating virus in patients who attained SVR were investigated. In statistical analysis, P < 0.05 was considered as significant levels. RESULTS: Antiviral effect was lower in patients with severe fibrosis at 8 and 12 weeks after start of the treatment (96.3%, 97.1% with severe fibrosis vs 99.5%, 99.2% without severe fibrosis, P = 0.002 and P = 0.036, respectively), and more early relapse (SVR4; 90.4% with severe fibrosis vs 95.4% without fibrosis, P = 0.008) was seen in patients with severe fibrosis; however, there were no differences in SVR12 and SVR24. In the safety profiles, discontinuation rate due to liver injury (2.8% with severe fibrosis vs 3.3% without severe fibrosis) or other causes of discontinuation was not different between two groups. Serum α-fetoprotein significantly decreased, and serum albumin levels significantly increased as early as 4 weeks after the start of treatment. CONCLUSION: Although the antiviral effect was slightly lower in patients with severe fibrosis compared with those without, treatment with daclatasvir and asunaprevir is basically an effective and well-tolerable treatment in these populations.

Nab-paclitaxel+gemcitabine therapy for adenosquamous carcinoma of the pancreas: an autopsy case.

A male patient aged over 60 years presented with abdominal pain. A solid lesion measuring 7cm was detected in the pancreatic body and tail, along with periaortic lymphadenopathy. Endoscopic ultrasound-guided fine-needle aspiration suggested squamous cell carcinoma. Nab-paclitaxel+gemcitabine therapy was effective;however, tumor progression was noted after the completion of the fourth course, and the patient died from the primary cancer 7 months after the initial consultation. Autopsy led to a definitive diagnosis of adenosquamous carcinoma of the pancreas. Non-resected adenosquamous carcinoma of the pancreas treated by chemotherapy is rare. Here, we report such an example in the present case study.

Effect of peginterferon alfa-2b and ribavirin on hepatocellular carcinoma prevention in older patients with chronic hepatitis C.

BACKGROUND AND AIMS: The population of patients chronically infected with hepatitis C virus (HCV) is aging, and the number of older patients with HCV-related hepatocellular carcinoma (HCC) is increasing. The purpose of this study was to elucidate the effects of peginterferon and ribavirin combination therapy on prevention of HCC in older patients with chronic hepatitis C (CH-C). METHODS: We compared the sustained virological response (SVR) and treatment discontinuation rates between older (≥ 65 years) and younger patients (< 65 years) among 1280 CH-C patients treated with peginterferon alfa-2b and ribavirin. Cumulative incidence of HCC was determined by Kaplan-Meier analysis, and factors associated with liver carcinogenesis were analyzed by Cox proportional hazards regression. RESULTS: Older patients had a significantly lower SVR rate and a significantly higher discontinuation rate of treatment than younger patients. Fifty patients developed HCC during median follow-up period of 47 months. Cox proportional hazards regression analysis indicated that the following were independent risk factors associated with the development of HCC: older age, male, advanced fibrosis, non-SVR in all patients: higher gamma-glutamyltranspeptidase, and non-SVR in older patients. Older patients who achieved SVR had a significantly reduced rate of HCC compared with those who did not achieve SVR, especially those who had gamma-glutamyltranspeptidase over 44 IU/L. CONCLUSIONS: The SVR rate was lower and the combination therapy discontinuation rate was higher in older CH-C patients than in younger patients. However, older patients who achieved SVR had a markedly lower rate of HCC development compared with older patients who did not achieve SVR.

Pegylated interferon monotherapy in patients with chronic hepatitis C with low viremia and its relationship to mutations in the NS5A region and the single nucleotide polymorphism of interleukin-28B.

AIM: Previous studies have suggested that patients with chronic hepatitis C with a low pretreatment hepatitis C virus (HCV) level have a high sustained virological response (SVR) rate, and that there would be a subpopulation of patients in which HCV can be eradicated with pegylated interferon (PEG IFN) alone without a decrease in SVR. However, the efficacy of PEG IFN monotherapy in patients with low HCV RNA levels is unclear. Several studies have reported that interferon sensitivity-determining region (ISDR) and the single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) contribute to IFN response, but these relationships are controversial. The aim of this study was to determine whether the SNP of IL-28B (rs8099917) and amino acid substitutions in the ISDR among patients with low HCV levels affect the response to PEG IFN monotherapy. METHODS: One hundred and four patients with low-level HCV infection were studied. Low HCV level was defined as 100 KIU/mL or less. RESULTS: SVR was achieved in 94 patients (92.2%). HCV levels (≤50 KIU/mL) and ISDR (≥2 mutations) were associated with SVR on univariate analysis. The rates of SVR in the patients with IL-28B genotypes TT, TG and GG were 94.5%, 77.8% and 100%, respectively. The G allele tended to be associated with poor response to IFN therapy (P = 0.0623). On multivariate analysis, the ISDR was the factor predictive of SVR (P = 0.004). CONCLUSION: The ISDR is significantly associated with a good response to PEG IFN monotherapy in patients with low HCV levels.

Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single-nucleotide polymorphism of interleukin-28B with the response to combination therapy with pegylated-interferon-alpha 2b and ribavirin.

Hepatitis C virus (HCV) genotype 1a is rare in Japanese patients and the clinical characteristics of this genotype remain unclear. The interferon (IFN) sensitivity-determining region (ISDR) and single-nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) among patients with HCV genotype 1b are associated with IFN response, but associations among patients with genotype 1a are largely unknown. This study investigated the clinical characteristics of genotype 1a and examined whether genomic heterogeneity of the ISDR and SNPs of IL28B among patients with HCV genotype 1a affects response to combination therapy with pegylated-IFN-α2b and ribavirin. Subjects comprised 977 patients infected with HCV genotype 1, including 574 men and 412 women (mean age, 55.2 ± 10.6 years). HCV was genotyped by direct sequencing of the 5'-untranslated region and/or core regions and confirmed by direct sequencing of the NS5A region. HCV genotypes 1a (n = 32) and 1b (n = 945) were detected. Twenty-three (71.9%) of the 32 patients with genotype 1a were patients with hemophilia who had received imported clotting factors. Prevalence of genotype 1a after excluding patients with hemophilia was thus 0.9%. Of the 23 patients with genotype 1a who completed IFN therapy, 11 (47.8%) were defined as achieving sustained virological response. Factors related to sustained virological response by univariate analysis were IL28B and ISDR. In conclusion, HCV genotype 1a is rare in Japan. The presence of IL28B genotype TT, and more than two mutations, in the ISDR are associated with a good response to IFN therapy in patients with HCV genotype 1a.

Contrast-enhanced US of ampullary carcinoma: correlations with pathological findings.

PURPOSE: To investigate the utility of contrast-enhanced transabdominal ultrasonography (CEUS) in the diagnosis of ampullary cancer (AC). METHODS: In 12 patients with AC, the presence of tumor enhancement, histological type, amount of connective tissue in cancer, and tumor growth pattern were evaluated. The correlation between the tumor growth pattern and enhancement shape, that between the enhancement pattern and surrounding tissue, and the presence of pancreatic infiltration were evaluated. The depth of cancer invasion was mucosa in five patients, within Oddi's sphincter in four, beyond the duodenum but not to the pancreas in two, and pancreatic invasion less than 5 mm in one. RESULTS: The tumor was enhanced in 11 patients but not in the patient with much connective tissue in the tumor. Enhancement was observed in all patients with the intraluminal papillary or mixed type, but not in those with the periductal invasive type. The enhancement shape was predominantly round or irregular in the intraluminal papillary type and predominantly serrated in the mixed type. The enhancement shape differed among the growth patterns. The normal pancreatic parenchyma around the tumor was enhanced in all patients, and pancreatic infiltration was regarded as absent when there was a continuous unenhanced area between the tumor and pancreatic parenchyma. CONCLUSION: CEUS correlates with pathological findings of ampullary cancer.

Efficacy of peginterferon-alpha-2b plus ribavirin in patients aged 65 years and older with chronic hepatitis C.

OBJECTIVES: The aim of this study was to evaluate the efficacy and indication of combination therapy with ribavirin plus peginterferon-alpha-2b in chronic hepatitis C virus (HCV) patients aged 65 years and older. METHODS: Five hundred and ninety-one consecutive HCV patients were treated with combination therapy. These patients were divided into elder patients (> or = 65 years) (n=115) and younger patients (< 65 years) (n=476). The clinical characteristics, sustained virological response (SVR) rates and discontinuation rates were compared between the two groups. RESULTS: Compared with younger patients, baseline haemoglobin levels and baseline platelet counts were significantly lower (P<0.0001, P=0.013 respectively) and fibrosis was more advanced in elderly patients (P=0.0310). Moreover, the SVR rate was significantly lower (37.4 vs. 51.5%; P=0.0067) while the combination therapy discontinuation rate was significantly higher (32.2 vs. 17.0%; P=0.0003) in elderly patients. A multivariate analysis revealed that HCV load and genotype were significantly associated with an SVR in elderly patients. An SVR was achieved in over 50% of elderly male patients with genotype 1 and HCV RNA concentrations under 2,000,000 IU/ml. In contrast, the SVR rate was under 30% in elderly male patients with genotype 1 and with HCV RNA concentrations over 2,000,000 IU/ml and in all elderly female patients with genotype 1. CONCLUSIONS: The SVR rate was lower in elderly patients than in younger patients. However, in elderly patients combination therapy was most beneficial for genotype 1 patients, male patients with HCV RNA concentrations < 2,000,000 IU/ml and patients with genotype 2.

Mutations in the interferon sensitivity-determining region of hepatitis C virus genotype 2a correlate with response to pegylated-interferon-alpha 2a monotherapy.

The interferon sensitivity-determining region (ISDR) is thought to be inhibited by the double-stranded RNA-dependent protein kinase (PKR). Several studies have reported a relationship between the ISDR and interferon (IFN) responsiveness. However, this relationship is controversial. The aim of this study was to investigate whether genomic heterogeneity of the ISDR among patients with hepatitis C virus (HCV) genotype 2a affects the response to pegylated-IFN-alpha 2a monotherapy. Eighty patients (47 men, 33 women; mean age: 54.2 +/- 12.9 years) infected with HCV genotype 2a were evaluated. HCV viral loads were determined by real-time PCR. The ISDR (amino acids 2193-2228) was examined by direct sequencing. Thirty-one patients received subcutaneous injections of pegylated-IFN-alpha 2a (180 microg) once weekly for 24 weeks, and 35 patients received injections for 48 weeks. Fourteen patients withdrew from treatment. Of the remaining 66 patients, 51 (77.3%) showed a sustained virologic response. Factors related to sustained virologic response on multivariate analysis were rapid virologic response (negative HCV at 4 weeks; odds ratio: 0.033; 95% confidence interval (95% CI) 0.003-0.363; P = 0.0052) and the number of mutations in the ISDR (odds ratio: 0.025; 95% CI 0.001-0.476; P = 0.0141). There were no significant differences in other factors, including sex, age, aspartate aminotransferase, alanine aminotransferase, platelet count, duration of treatment, and HCV viral load. Rapid virologic response and the ISDR sequence variations are significantly associated with response to pegylated-IFN-alpha 2a monotherapy in Japanese patients with HCV genotype 2a.

Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC.

BACKGROUND/AIMS: We evaluated the prognostic value of the pretreatment elevation of tumor markers for hepatocellular carcinoma (HCC) in patients who underwent curative treatment. METHODS: We studied 801 patients who had been diagnosed as initial HCC and fulfilled the following criteria: maximum tumor size, < or = 3 cm; number of tumors, < or = 3; remnant liver function, Child-Pugh class A or B; treated by hepatectomy or locoregional thermal ablation (LTA); and alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma carboxy prothrombin (DCP) were measured at diagnosis. We analyzed the effects of elevated tumor markers on patient survival in these 2 distinct groups with different types of treatment, i.e. hepatectomy and LTA. RESULTS: By multivariate analysis in 345 patients who underwent hepatectomy, no tumor marker significantly affected decreased survival rate. In the 456 patients who underwent LTA, the elevation of AFP-L3 (p=0.0171) and DCP (p=0.0004) significantly affected decreased survival rate; DCP elevation had the strongest effect on patient survival. CONCLUSIONS: The prognostic value of pretreatment tumor marker elevation was different in patients who underwent the curative treatment according to the type of treatment. Pretreatment elevation of AFP-L3 and DCP had prognostic values only in patients treated with LTA.

Clinicopathological variables associated with lymph node metastasis in submucosal invasive gastric cancer.

BACKGROUND: We aimed to elucidate clinicopathological variables associated with lymph node metastasis of submucosal invasive gastric cancer. METHODS: Specimens were surgically resected from 201 patients who had primary submucosal gastric cancer. We studied 39 consecutive patients with lymph node metastasis and 162 patients without lymph node metastasis. We compared the following clinicopathological characteristics of the patients in relation to lymph node metastasis: age, sex, tumor size, histology, extent of submucosal invasion, lymphatic and venous invasion, and ulceration of the tumor. Submucosal invasion was divided subjectively into sm1, sm2, and sm3 (representing invasion of the upper-, middle-, and lower-third of the submucosa, respectively). We also studied the relationship between lymph node metastasis of submucosal gastric cancer and immunohistochemistry for p53, Ki67, vascular endothelial growth factor (VEGF), alpha-fetoprotein, sLe(a), and dendritic cells (DCs). RESULTS: In terms of conventional pathological factors, lymph node metastasis in submucosal gastric cancer was related to tumor size (P = 0.002), depth of submucosal invasion (P = 0.001), lymphatic invasion (P < 0.0001), and venous invasion (P = 0.012). Lymph node metastasis in sm1 gastric cancer was significantly related to VEGF expression (P = 0.047). Also, lymph node metastasis in sm3 gastric cancer was significantly correlated with DC expression (P = 0.016). Multivariate analysis showed that tumor size, tumor invasion depth in the submucosal layer, and lymphatic invasion were independent predictors of nodal metastasis in submucosal gastric cancer. CONCLUSION: Conventional pathological factors, such as tumor size, depth of submucosal invasion, and lymphatic invasion, have a significant influence on lymph node metastasis. VEGF expression and DC expression may be helpful predictors of lymph node metastasis in patients with sm1 and sm3 gastric cancer, respectively.

Efficacy of ribavirin plus interferon-alpha in patients aged >or=60 years with chronic hepatitis C.

BACKGROUND: In Japan, patients with hepatitis C virus (HCV)-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of combination therapy in such patients. METHODS: Two hundred and twenty consecutive patients with chronic hepatitis C were treated with combination therapy. These patients were divided into two groups according to age: patients >or= 60 years (n = 66) and patients < 60 years (n = 154). Clinical characteristics, the sustained virologic response (SVR) rate obtained by intention-to-treat analysis, and the rate of reduction or discontinuation of ribavirin were compared between the two groups. RESULTS: The ribavirin discontinuation rate was significantly higher in the patients aged >or=60 years than in the patients aged <60 years. However, the SVR rates did not differ significantly between patients aged >or=60 years and those aged <60 years (31.8% vs 38.3% by intention-to-treat analysis). According to multivariate analysis, genotype and HCV viral load were significantly associated with SVR while patient age did not affect SVR. CONCLUSIONS: Treatment of chronic hepatitis C with combination therapy was comparably effective between patients aged >or=60 years and those aged <60 years, although the ribavirin discontinuation rate was higher among the older patients than the younger patients.