Risk factor analysis for early rebleeding after endoscopic treatment for colonic diverticular bleeding with stigmata of recent hemorrhage.

BACKGROUND AND AIM: Colonic diverticular bleeding is a common cause of acute lower gastrointestinal bleeding. Endoscopic hemostasis is generally selected as the first-line treatment; however, a considerable number of patients experience early rebleeding after endoscopic treatment. We investigated the risk factors for early rebleeding after endoscopic treatment. METHODS: We retrospectively evaluated the data of 142 consecutive patients who underwent endoscopic treatment (endoscopic clipping or endoscopic band ligation) for colonic diverticular bleeding with stigmata of recent hemorrhage between April 2012 and April 2020. Multivariate logistic regression analysis was conducted to evaluate the statistical relationship between patient characteristics and the incidence of early rebleeding occurring within 30 days after endoscopic treatment. RESULTS: Of 142 patients, early rebleeding was detected in 34 (23.9%) patients. According to univariate analysis, platelet count of <10 × 104/µL, bleeding from the left-sided colon, and endoscopic clipping usage were associated with early rebleeding (P < 0.05). The subsequent multivariate logistic regression analysis identified bleeding from the left-sided colon (odds ratio [OR], 4.16; 95% confidence interval [CI], 1.73-10.0; P = 0.001) and endoscopic clipping usage (OR, 2.92; 95% CI, 1.21-7.00; P = 0.017) as the independent risk factors for early rebleeding. CONCLUSIONS: Bleeding from the left-sided colon and endoscopic clipping usage were the risk factors for early rebleeding after endoscopic treatment. Using endoscopic band ligation was associated with a decreased risk for early rebleeding compared with the use of endoscopic clipping, indicating that endoscopic band ligation was a preferable endoscopic modality to prevent early recurrent bleeding.

Evaluation of pharmaceutical intervention in direct-acting antiviral agents for hepatitis C virus infected patients in an ambulatory setting: a retrospective analysis.

BACKGROUND: Direct-acting antivirals (DAAs) are known to improve tolerability and have higher efficacy and shorter treatment durations compared with conventional interferon (IFN)-based treatments for hepatitis C virus (HCV) infection. Management of drug interactions and maintenance of patient adherence are important to achieve adequate therapeutic effects, sustained virological response (SVR). In order to maximize the benefits of oral DAA therapy, we established an ambulatory care pharmacy practice, a model of integrated collaboration between physicians and pharmacists, for patients receiving IFN-free DAA therapy. In this study, we evaluated pharmaceutical intervention for patients visiting the ambulatory care pharmacy practice. METHODS: HCV-infected outpatients who visited our ambulatory care pharmacy practice between September 2014 and May 2017 were eligible for inclusion in the study. When IFN-free DAAs were first prescribed, the physicians recommended all patients to visit the ambulatory care pharmacy practice after their clinical examination. Subsequently, at the second visit or later, the patients visited the pharmacy service before the physician's examination. The primary endpoint was SVR, defined as HCV RNA below the lower limit of quantification after the completion of treatment. We also evaluated the adherence rate to DAAs, suggestions to the physicians by the pharmacists, and questions from the patients. All data were obtained retrospectively using an electronic medical record system. RESULTS: Among the 401 study subjects, 386 patients completed the IFN-free DAA therapy. A total of 365 patients have reached 12 or 24 weeks after completing the treatment. The overall SVR rate was 98.1% (358/365). The proportion of patients with adherence ≥90% was 99.3% (398/401). Two-hundred and sixty-seven (84%) among 318 suggestions of prescription made by the pharmacists mainly to manage the adverse events were accepted by the physicians. The pharmacists received and answered 1072 questions on DAA therapy from the patients. CONCLUSIONS: This study indicates that the pharmaceutical intervention may contribute to enhanced adherence to DAAs and higher SVR rates in comparison with previous reports. This study also demonstrates that collaboration between physicians and pharmacists in an ambulatory setting provides favorable outcomes for patients receiving IFN-free DAAs.

CD68-Positive Cells in Hepatic Angiomyolipoma.

Four resected specimens of hepatic angiomyolipoma in which uptake of Sonazoid was observed in the postvascular phase of Sonazoid-enhanced ultrasonography were analyzed. Macrophage localization in the tumor was revealed pathologically by immunohistochemical staining for CD68. CD68-positive cells were observed in the tumor in all cases. The density of CD68-positive cells was 100/mm2, and the ratio of CD68-positive cell density in the tumor to that in the surrounding parenchyma was 32-171%. These results suggested that the uptake of the contrast agent Sonazoid was related to the density of CD68-positive cells.

[A case of jejunal ectopic pancreatic cancer: the diagnostic usefulness of MRI].

A 70-year-old man was referred to our hospital because of elevated CA19-9. Magnetic resonance imaging revealed a jejunal tumor having duct and retention cyst-like structures, which suggested ectopic pancreatic cancer. We resected that part of the jejunum and the lymph nodes around the tumor. Pathological examination revealed an adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Adjuvant chemotherapy with gemcitabine was performed for half a year. After 8 months, CA19-9 remained elevated, and liver metastasis occurred. We began treatment with tegafur/gimeracil/oteracil potassium (S-1) and particle beam therapy. After 7 months, CA19-9 was normal, and the patient has remained in partial remission with S-1 treatment. Ectopic pancreas tissues typically occur in the stomach and duodenum and rarely become cancerous. Here, we report the features of a rare and illustrative case of jejunal ectopic pancreatic cancer.

Outcomes and Prognostic Factors in Patients with Spontaneously Ruptured Hepatocellular Carcinoma.

BACKGROUND/AIMS: Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Although hemostasis can be achieved by transarterial embolization (TAE), the prognosis remains poor. The aims of this study were to evaluate the effectiveness of emergent TAE for ruptured HCC and to clarify the prognostic factors. METHODOLOGY: Thirty-six patients with spontaneously ruptured HCC were retrospectively analyzed. Prognostic factors of short-term (57 days) and long-term (>7 days) survival after HCC rupture were investigated by univariate and multivariate analyses. RESULTS: Emergent TAE was performed in 22 patients and conservative treatment was applied in 14. The hemostasis rate of TAE was 86.4%, and median survival time in patients with TAE was significantly longer than that in patients with conservative treatment (142 days vs. 5 days, p = 0.0006). In multivariate analysis, high serum creatinine (p = 0.036) was a significant independent predictor of poor 7-day survival, and low serum albumin (p = 0.050) and absence of emergent TAE (p = 0.061) tended to be associated with poor 7-day survival. HCC treatment within the past 12 months (p = 0.048) and, high serum total bilirubin (p = 0.016) were predictors of poor long-term survival. Conclusions: We identified some survival predictors after HCC rupture. Emergent TAE appears to be effective for improving short-term oroLnosis after HCC ruoture.

Case of primary hepatic gastrinoma: Diagnostic usefulness of the selective arterial calcium injection test.

Gastrinomas mainly occur in the duodenum and pancreas. Primary hepatic gastrinoma is rare and difficult to diagnose because the liver is a frequent site of metastatic gastrinomas. Clinical factors were assessed in a 28-year-old man with diarrhea and heartburn who was hospitalized for recurrent duodenal ulcers. Abdominal ultrasound, endoscopic ultrasound and computed tomography (CT) could not detect a tumor in the duodenum or pancreas. His gastrin level was 846 pg/mL and magnetic resonance imaging showed a mass 12 mm in diameter in the right robe of the liver. A selective intra-arterial calcium injection (SACI) test and 68-gallium edotreotide positron emission tomography CT (Ga-DOTATOC PET-CT) were therefore performed. Calcium gluconate injection into the proper hepatic artery resulted in a marked increase in serum gastrin concentration in the right hepatic vein, with Ga-DOTATOC PET-CT showing uptake only by the liver mass. Following a diagnosis of primary hepatic gastrinoma, the tumor was resected. A histopathological examination indicated gastrinoma. Six months postoperatively, he has no symptoms, is not taking proton-pump inhibitors and his gastrin level remains within the normal range. The SACI test and the clinical course of this patient strongly suggest that the tumor was a primary hepatic gastrinoma. The SACI test is helpful in the diagnosis of primary hepatic gastrinoma.

Fulminant hepatitis following crizotinib administration for ALK-positive non-small-cell lung carcinoma.

We herein report a case of fatal fulminant hepatitis secondary to crizotinib administration. The patient was 54-year-old female with a history of Hepatitis C infection (not current), dermatomyositis and steroid-induced diabetes mellitus. She was diagnosed with advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement. We began 400 mg of crizotinib as first-line therapy. No adverse effects were seen until Day 16. On Day 29, she was admitted to hospital with elevated liver enzymes (aspartate aminotransferase 3236 IU/l, alanine aminotransferase 5201 IU/l) and coagulopathy (prothrombin time <10%), and was diagnosed with crizotinib-induced fulminant hepatitis. We started intensive care, using plasma exchange, continuous hemodiafiltration and high-dose steroid therapy. Unfortunately, she did not respond to therapies, and died on Day 36. The mechanism and risk factors of crizotinib-induced hepatotoxicity are uncertain. Physicians should be aware of possible adverse effects of crizotinib. A systemic survey is imperative to identify possible risk factors of crizotinib-related hepatotoxicity.

[Analysis of factors affecting the duration of treatment with sorafenib in patients with hepatocellular carcinoma].

The current status of treatment with sorafenib, and factors affecting the duration of treatment in patients started on sorafenib for hepatocellular carcinoma from July 2009 until April 2011 in the Department of Gastroenterology at Kobe City Medical Center General Hospital, were examined. Of 21 patients, 12 were able to continue the administration of sorafenib for more than one month, but 9 had to be discontinued within one month due to disease progression, worsening of general condition, and severe adverse reactions. In the group that was discontinued early, the rate of discontinuation due to side effects such as general fatigue, diarrhea, and hepatic encephalopathy was higher than in the long-term treatment group. On the other hand, hand-foot syndrome developed only in one case in both groups. The median value of PIVKA- II at the start of treatment in the long-term and early discontinued treatment groups were 672.5 and 14, 203 mAU/mL, respectively, and the values in the long-term group were significantly lower than those in the early-discontinued group (p < 0.05). From these results, the values of PIVKA-II at the start of sorafenib were considered to be factors affecting the continuation of sorafenib treatment. In addition, the dosing period was considered to be extended to focus on measures to take against the side effects of sorafenib within the early phase. Therefore, it was considered that these factors improved the effect of treatment with sorafenib in patients with hepatocellular carcinoma.

[Signet ring cell carcinoma of the bile duct: a case report].

A 72-year-old man was admitted with obstructive jaundice. Computed tomography revealed a 4cm tumor with multiple cystic components obstructing the common bile duct. Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography and intraductal ultrasonography demonstrated the tumor, which derived from the lower bile duct, grew into the bile duct lumen. Peroral cholangioscopy revealed distended tumor vessels on the surface of the tumor. Signet ring cell carcinoma of the bile duct was diagnosed by biopsy. The patient died 3 months after the first hospital admission despite chemotherapy.

Virulent strain of hepatitis E virus genotype 3, Japan.

Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection in Japan, induced severe hepatitis in 8 patients. To better understand genetic features of HEV associated with increased virulence, we determined the complete or near-complete nucleotide sequences of HEV from these 8 patients and from 5 swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that the isolates from the 8 patients and the 5 swine grouped separately from the other genotype 3 isolates to create a unique cluster, designated JIO. The human JIO-related viruses encoded 18 amino acids different from those of the other HEV genotype 3 strains. One substitution common to almost all human HEV strains in the JIO cluster was located in the helicase domain (V239A) and may be associated with increased virulence. A zoonotic origin of JIO-related viruses is suspected because the isolates from the 5 swine also possessed the signature V239A substitution in helicase.

Impaired IFN-alpha production and the risk of cancer development.

Type I interferons (IFNs) play a pivotal role not only in antiviral immunity but also in the surveillance of cancer development. In order to quantify the critical function of type I IFNs in the suppression of human cancer development, IFN-alpha production in response to Sendai virus stimulation has been compared between healthy control subjects and hepatitis C virus (HCV)-infected patients, the latter being an ideal population for longterm monitoring of cancer development. Data for IFN-alpha production were obtained retrospectively over a 17-year period by examining medical records in a study population of 2315 individuals, of which 112 healthy controls and 20 HCV-infected patients were selected. Sixty percent of the HCV-infected patients had impaired or declining IFN-alpha production, in comparison to 17% in the healthy control group. Mean IFN-alpha levels were lower in patients who developed hepatocellular carcinoma than in the HCV-infected patients who remained cancer free. Our findings suggest that impairment of IFN-alpha production may be linked to an increased cancer risk and that dysfunction of the IFN system is associated with some types of cancer. Therefore, periodic assessment and quantification of IFN-alpha production can be a potential test for the early detection of cancer in humans.

Clinical utility of 2',5'-oligoadenylate synthetase activity measurement: using whole blood as a highly sensitive method to detect the effects of IFN.

Research progress on the pleiotropic effects of interferons (IFN) has thus far required detecting responses by weak IFN signals. The activity of 2',5'-oligoadenylate synthetase (2-5OAS) is a valuable indicator in the prognosis and IFN treatment of patients with viral diseases such as hepatitis B and C. Although serum samples generally are used to measure enzyme activity, their values depend on the exact conditions under which blood is stored and the degree of haemolysis that occurs during blood drawing or serum separation. This study presents an improved method of evaluating 2-5OAS activity by using whole blood samples containing heparin, which are frozen and then thawed, instead of serum samples. This method is more reliable, convenient, and 50-100 times more sensitive than the conventional methods of measuring serum 2-5OAS activity. The reliability and sensitivity of this improved method enables detection of the effects of low doses of oral IFN administration or changes in the IFN and cytokine system by infection or autoimmune diseases.

Impairment of IFN-alpha production capacity in patients with hepatitis C virus and the risk of the development of hepatocellular carcinoma.

AIM: To determine the utility of interferon (IFN)-alpha production capacity in patients with hepatitis C virus (HCV) infection for the measurement of immuno-surveillance potential and for the early detection of hepatocellular carcinoma (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-alpha production capacity of patients with HCV infection. METHODS: HVJ stimulated IFN-alpha production was determined in a large number of patients with HCV infection and the development of HCC was monitored for 3 years in patients with liver cirrhosis (LC). RESULTS: IFN-alpha production capacity decreases gradually with the progression of liver disease from chronic hepatitis (CH) to HCC. A significant correlation between the duration of HCV infection and impaired IFN-alpha production capacity was observed. IFN-alpha production in patients who developed HCC within 3 years was significantly lower than that of patients who remained in LC without developing HCC. CONCLUSION: Measurement of IFN-alpha production in LC patients may be useful for the early detection of HCC.

Liver targeting of human interferon-beta with pullulan based on metal coordination.

Although interferon (IFN)-beta is widely used for the elimination of hepatitis C virus in patients with chronic liver disease, its clinical efficacy is unsatisfactory. Targeting IFN-beta to the liver might enhance its efficacy without increasing its side effects. The objective of the present study was to target IFN-beta to the liver to enhance its biological activity and reduce its side effects. A chelating residue, diethylenetriaminepentaacetic acid (DTPA), was introduced to pullulan, a water-soluble polysaccharide with a high affinity to the liver (DTPA-pullulan) and natural human IFN-beta was coordinately conjugated with the DTPA-pullulan by mixing in an aqueous solution containing zinc ions (Zn(2+)). Intravenous injection of the IFN-beta-DTPA-pullulan conjugate with Zn(2+) coordination into mice enhanced induction of an antiviral enzyme, 2',5'-oligoadenylate synthetase (2-5AS), specifically in the liver to a significantly greater extent than free natural IFN-beta. The enhanced 2-5AS level in the liver depended on the molar mixing ratio of IFN-beta, DTPA residue of the DTPA-pullulan, and Zn(2+). Moreover, the duration of the liver 2-5AS induction by the IFN-beta-DTPA-pullulan conjugate was longer than that by free natural IFN-beta. Thus, human IFN-beta-DTPA-pullulan conjugate appears to be applicable for clinical use, which is promising for treatment of patients with chronic hepatitis C.