[Show abstract][Hide abstract] ABSTRACT: . Although the usefulness of capsule endoscopy (CE) and double-balloon endoscopy (DBE) for the evaluation of Crohn’s disease (CD) is established, their capabilities in the differential diagnosis of small bowel stenosis have not been sufficiently addressed. The present study therefore aimed to retrospectively determine the types of patients for whom CE and DBE would confer the most benefit.
Patients and Methods
. We retrospectively reviewed data from 185 patients with established CD. A change of treatment based on CE or DBE results or successful DBE balloon dilation was defined as clinically useful indication. We then analyzed the factors significantly related to useful and poor indications.
. CE results were assessed as useful indications in 28 (45%) of 62 patients. Multivariate analysis demonstrated that positive CRP and low IOIBD score are factors significantly related to a useful indication. DBE results were recognized as useful indications in 118 (77%) of 153 patients. Multivariate analysis indicated small bowel stenosis and abdominal pain as factors significantly associated with useful indications. All patients with a poor indication on CE had small bowel stenosis.
. CE was most useful for patients in clinical remission with positive CRP and without stenosis, whereas DBE was useful for patients with symptoms of stenosis.
Preview · Article · Feb 2016 · Gastroenterology Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
In the international consensus diagnostic criteria (ICDC), autoimmune pancreatitis (AIP) is classified into Types 1 and 2, and its definite histopathological diagnosis can only be made based on surgical or core biopsy specimens. Although EUS-guided fine-needle aspiration biopsy (EUS-FNB) is a safe technique for the collection of pancreatic tissue; however, no consensus viewpoint has been reached with regard to the role of EUS-FNB in the diagnosis of AIP. This study investigated the utility of pancreatic tissue collected by EUS-FNB using a standard 22G aspiration needle in the diagnosis of AIP.
Patients with suspected AIP were prospectively enrolled in Nagoya University Hospital and Nagoya University-affiliated institutions. Pancreatic tissue was collected from each by EUS-FNB with a standard 22G aspiration needle.
Fifty patients were registered, including 45 with a final diagnosis of AIP. Lymphoplasmacytic infiltration and abundant IgG4-positive plasmacyte infiltration (>10/HPF) were detected in 36 (72%) and 27 (54%) of patients, respectively. Obliterative phlebitis and storiform fibrosis were not detected in our study. Granulocytic epithelial lesions (GEL) were observed in 3 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EUS-FNB to definitively diagnose AIP were 7.9% (3/38), 100% (12/12), 100% (3/3), and 25.5% (12/47), respectively. Pathological evaluation of pancreatic tissue collected by EUS-FNB improved the diagnostic accuracy in 8 (16%) of the 50 patients.
In this study, EUS-FNB using a standard 22G aspiration needle is not an effective diagnostic method for most patients with AIP. The combination of level 2 histologic diagnosis of AIP with other findings specified that ICDC slightly improved the diagnostic accuracy, although it still remains insufficiently accurate for routine clinical use.
No preview · Article · Jan 2016 · Gastrointestinal endoscopy
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease.
Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines.
All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure.
All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD.
[Show abstract][Hide abstract] ABSTRACT: Abstract
Background and Aims: Eradicating chronic hepatitis C virus (HCV) infection improves liver fibrosis and reduces hepatocellular carcinoma (HCC) incidence in chronic HCV patients. We evaluated the relationship between fibrosis regression, as assessed by sequential biopsies, and clinical factors of patients with sustained virological response (SVR).
Methods: We retrospectively enrolled 130 patients (74 men; 60.1 ± 8.1 years) with chronic HCV treated with interferon and ribavirin therapy who achieved SVR. To evaluate the change in fibrosis stage over time, all patients underwent a pre-therapy initial biopsy and a second biopsy after achieving SVR.
Results: The mean time between biopsies was 5.5 ± 1.2 years. Fibrosis stage regressed in 55 patients (42.3%), remained stable in 69 (53.1%), and progressed in 6(4.6%). The mean fibrosis stage significantly decreased, from 2.01 ± 0.99 units to 1.61 ± 1.24 units (P < 0.001). Aspartate aminotransferase, γ-glutamyltransferase and α-fetoprotein (AFP) levels at 24 weeks after the end of treatment (EOT) were significantly lower and the platelet count at 24 weeks after the EOT was significantly higher in the patients with fibrosis regression than in those without. Logistic regression analysis confirmed that lower AFP levels (<5.4 ng/ml) at 24 weeks after the EOT (odds ratio [OR], 4.626; 95% confidence interval [CI], 1.557-13.153; P=0.006), and HCV genotype 2 (OR, 2.198; 95% CI, 1.010 - 4.786; P=0.047) were significant independent predictive factors for regressed fibrosis after SVR.
Conclusions: Lower post-treatment AFP levels and HCV genotype 2 significantly correlated with liver fibrosis regression after SVR.
[Show abstract][Hide abstract] ABSTRACT: Low skeletal muscle density (SMD) and low skeletal muscle index (SMI) are associated with poor overall survival (OS) in patients with various types of cancer. We retrospectively studied SMD and SMI using computed tomographic (CT) scans in patients with gastric cancer receiving chemotherapy to evaluate its prognostic significance. SMD and SMI were obtained from CT-based analysis using Slice-O-Matic® medical imaging software in patients who received S-1 plus cisplatin chemotherapy for metastatic gastric cancer. The CT images taken within 1 month before starting chemotherapy were used. The cut-off values for determining low SMD [<33 Hounsfield units (HU) in obese and <41 HU in non-obese patients] and low SMI (<41 cm2/m2 in females, <43 cm2/m2 in non-obese males and <53 cm2/m2 in obese males) were referenced from a large population based study. The CT images of 53 patients were reviewed. The median SMD was 36.8 HU (range, 19.5-59.3 HU), and the median SMI was 39.8 cm2/m2 (range, 23.7-60.0 cm2/m2). Patients with low SMD had significantly shorter OS compared with patients having normal SMD (8.9 vs. 12.8 months, P=0.03). However, OS did not differ significantly between patients with low and normal SMI (11.1 and 14.3 months, P=0.18). Multivariate analyses confirmed that low SMD was an independent predictor of poor outcomes (P<0.01). SMD is an important prognosticator of survival in patients with metastatic gastric cancer receiving chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Non-alcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis.
No preview · Article · Dec 2015 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma.
Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated.
After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively).
Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma.
[Show abstract][Hide abstract] ABSTRACT: A few decades ago, liver transplantation in patients with chronic hepatitis B virus (HBV) infection was considered a relative contraindication because of the high rate of graft infections and poor prognosis. Since then, remarkable progress was introduced by using nucleos(t)ide analogues and/or hepatitis B immunoglobulin (HBIg) and liver transplantation for HBV-related disease is now becoming one of the good indication. However, high cost burden is the main problem for this combination prophylaxis for a long time use, and this issue should be emerged to be resolved. In this review, we show the progress of post anti-HBV strategies showing the history from introduction of HBIg and nucleos(t)ide analogues to recent new strategies with hepatitis B vaccine or saving or stopping protocols of HBIg, and clarify and discuss how to do for further improvement of prevention strategies with better quality.
No preview · Article · Sep 2015 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The aim of this study was to investigate of the relationship between pancreas and small intestine evaluating the endoscopic and histopathologic findings of the proximal small intestine in pancreatic diseases.
Fifty patients (18 patients with chronic pancreatitis, 17 patients with pancreatic cancer, 15 control subjects) underwent enteroscopy using a prototype enteroscope. The villous height of the jejunum on bioptic specimens was measured, and the mean values of the villi were compared among the 3 groups. Exocrine function was calculated by the pancreatic function diagnostic test, and the correlation between the recovery rate of p-aminobenzoic acid and the villous height was assessed. Finally, the distribution of the K cells secreting glucose-dependent insulinotropic polypeptide and the L cells secreting glucagon-like peptide 1 in the duodenum and jejunum was investigated using immunohistochemistry for glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1.
The mean villous height in chronic pancreatitis (328 ± 67 μm) was significantly lower than that in pancreatic cancer (413 ± 57 μm) and control subjects (461 ± 97 μm) (P = 0.004 and P < 0.0001, respectively). A positive correlation was found between the recovery rate of p-aminobenzoic acid and the villous height (r = 0.52, P = 0.0001). The presence of K and L cells was verified in the duodenum and the jejunum.
Close relationship between pancreas and small intestine was demonstrated.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease (mSES-CD).
Seventy-six Crohn's disease (CD) patients who underwent transanal double balloon endoscopy (DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new mSES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE, in addition to the activity of four colorectal segments. To compare the usefulness of mSES-CD with SES-CD, we similarly divided the patients into two groups according to total mSES-CD score (low disease activity group, < 4; high disease activity group, ≥ 4). The clinical value of mSES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.
Median age of the 76 CD patients was 36 years (range, 16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm (range, 3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE, of which 62 (83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients (2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high mSES-CD scores showed significantly shorter surgery-free survival than those with low scores (P < 0.05). In contrast, surgery-free survival did not significantly differ between the low and high SES-CD groups (P > 0.05). Multivariate analysis by a Cox proportional hazards model identified mSES-CD as an independent factor for surgery-free survival.
mSES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.
[Show abstract][Hide abstract] ABSTRACT: The use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer is known to be effective. However, whether the use of a SEMS as a BTS for obstruction induced by effective chemotherapy (CTx) is useful is unknown. We present the case of a 54-year-old female patient with colorectal cancer who underwent SEMS placement as a BTS for colorectal obstruction induced by bevacizumab-based CTx. The patient was diagnosed as having transverse colon cancer with multiple liver metastases invading the inferior vena cava. Bevacizumab-based CTx was started; however, although it was effective, colonic obstruction occurred at the primary site after 31 months. A SEMS was placed as a BTS, and surgical resection of the primary lesion was performed after cessation of bevacizumab. However, the liver metastases remained unresectable. CTx was restarted after surgery, and 48-month survival was achieved. This case shows that SEMS placement as a BTS for colorectal obstruction induced by a good response to bevacizumab-based CTx was safe and beneficial. With the development of CTx and molecular-targeted agents, the frequency of colorectal obstruction associated with effective CTx is expected to increase. SEMS placement as a BTS might be one of the treatment options.
No preview · Article · Sep 2015 · Clinical Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Background and AimPatients with advanced pancreatic cancer have severe pain, anxiety, and depression, and these symptoms deteriorate quality of life (QOL). Previous study reported that early psychiatric intervention for advanced cancer patients may improve QOL. We evaluated the trajectory of health-related QOL (HRQOL) in patients with pancreatic cancer after an early psychiatric intervention.MethodsA prospective cohort study was performed in 108 pancreatic cancer patients who received consultation liaison psychiatry from November, 2011 to October, 2014 at Nagoya University Hospital. Longitudinal changes in HRQOL and the association between aspects of HRQOL and survival were evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 before treatment and every month after the start of treatment.ResultsPhysical functioning significantly decreased after 1, 3 and 6 months of treatment compared with baseline, but global health status(GHS), role functioning, emotional functioning, and social functioning showed a tendency to improve. Severe impairment of GHS, fatigue, and appetite loss were apparent at 3 months prior to death. In multivariate analysis, pain was a significant prognostic factor for survival (hazard ratio [HR], 1.109; 95% confidence interval [CI], 1.021-1.204; P =0.013), in addition to poor performance status (HR, 5.473; 95%CI, 2.338-12.816; P < .0001) and distant metastases at diagnosis (HR, 3.274; 95%CI, 1.872-5.725; P < .0001).Conclusions
Early psychiatric intervention in patients with pancreatic cancer may maintain HRQOL. More effective pain management and reduction of psychological distress are important for patients with pancreatic cancer.
No preview · Article · Sep 2015 · Journal of Gastroenterology and Hepatology
[Show abstract][Hide abstract] ABSTRACT: Immunoglobulin G4 (IgG4)-associated autoimmune hepatitis (AIH) is a new disease entity with elevated levels of serum IgG4 and marked IgG4-positive plasma cell infiltration of the liver, and its clinical course remains unknown. A patient with IgG4-associated AIH who later developed autoimmune pancreatitis (AIP) is reported. A 73-year-old man was admitted to our hospital due to elevated liver transaminase levels, hypergammaglobulinemia, and positive antinuclear antibody. A liver biopsy specimen showed severe interface hepatitis with marked lymphoplasmacytic infiltration without damage to the interlobular bile ducts, and a diagnosis of AIH was made. Abdominal computed tomography showed no abnormalities in the pancreas. Prednisolone therapy normalized the transaminase levels. Two years later, the patient developed AIP, which recurred after five years due to a reduction in the prednisolone dose. Three years later, he had a recurrence of AIH after discontinuation of prednisolone treatment. Evaluation of serum IgG4 levels and IgG4-bearing plasma cell infiltration of the liver at both the onset and recurrence of AIH showed that the serum IgG4 levels were 284 mg/dL and 208 mg/dL, respectively, and the IgG4-bearing plasma cell infiltration levels were 30-40 cells/high-power field (HPF) per portal area and 4-10 cells/HPF per portal area, respectively. From these results, this case was finally diagnosed as IgG4-associated AIH. The course of this patient demonstrates two important clinical lessons: (1) IgG4-associated AIH can later be complicated by AIP; and (2) discontinuation of prednisolone treatment can cause recurrence of IgG4-associated AIH.
No preview · Article · Sep 2015 · Hepatology Research
[Show abstract][Hide abstract] ABSTRACT: FOLFIRINOX is a standard chemotherapeutic regimen for patients with advanced pancreatic cancer who have a good performance status. In this study, we present the case of a 64yearold male who developed dysarthria following FOLFIRINOX treatment, and review all four cases of dysarthria encountered among the nine patients who received this treatment in our hospital. In all cases, dysarthria occurred during the infusion of irinotecan in the first course of treatment, persisted for several hours, and then resolved rapidly without any sequelae. Physical and neurological examinations at the onset of dysarthria revealed no other abnormalities. Imaging studies revealed no abnormal findings. Atropine was prophylactically administered in the second and subsequent courses of treatment and effectively prevented or alleviated dysarthria. This acute neurological symptom is surprising and uncommon in traditional cancer chemotherapy, and medical oncologists may initially suspect the onset of stroke or cerebrovascular disease. However, consistent with our experience, all reported cases resolved completely, with no need for dose reduction or treatment interruption.
[Show abstract][Hide abstract] ABSTRACT: Double-balloon endoscopy (DBE) has enabled precise diagnosis and endoscopic intervention deep within the small bowel. In this study, we determine the factor related to the risk of endoscopic and clinical recurrences in the diagnosis of postoperative lesions including anastomosis for the patients with Crohn's disease. Forty-eight patients (40 men and 8 women) had undergone small bowel resection previously and anastomotic sites were evaluated by Rutgeerts' endoscopic scoring. The factors related to endoscopic and clinical recurrences at anastomosed sites were investigated. The analyzed items included the disease type, anastomosis procedure, frequency of surgery, time to endoscopy after surgery, the presence or absence of treatment with 5-aminosalicylic acid (5-ASA), immunomodulators, steroids, maintenance administration of infliximab, and an elemental diet that required the ingestion of 900 kcal or more per day. Outcome of the anastomosed lesions was analyzed in the groups treated with and without postoperative anti-TNFα antibody including infliximab and adalimumab. DBE was performed 133 times, and 168 anastomosed lesions were observed for enrolled patients. Univariate analysis showed that time to DBE after surgery of 1.5-year or longer and the absence of 5-ASA administration were found to be significant factors leading to both endoscopic and clinical recurrences. The results of Kaplan-Meier estimate and the log rank test demonstrated that the clinical recurrence was avoided more often in the anti-TNFα antibody-treated group compared with the non-treated group. In conclusion, DBE was useful for accurate diagnosis of small-bowel lesions after surgery. Anti-TNFα antibody may help to decrease the postoperative recurrence rate of Crohn's disease.
No preview · Article · Aug 2015 · Nagoya journal of medical science
[Show abstract][Hide abstract] ABSTRACT: Liver fibrosis remains an important risk factor for hepatocarcinogenesis in patients with chronic hepatitis C even after the eradication of hepatitis C virus (HCV). However, it is difficult to estimate liver fibrosis based on liver biopsy after the eradication of HCV. We investigated the ability of laboratory indices to predict liver fibrosis in patients with sustained virologic response (SVR) to antiviral therapy. Three laboratory liver fibrosis indices (aspar-tate aminotransferase-platelet ratio index (APRI), FIB-4 index, and Forns index) were calculated based on data at the time of initial pretreatment liver biopsy and at second liver biopsy performed approximately 5 years after SVR in 115 patients who underwent serial liver biopsies. The indices at the time of initial biopsy were compared to histological degree of liver fibrosis in initial biopsy, and laboratory indices at the time of second liver biopsy were compared to the degree of fibrosis in second biopsy. In both comparisons, there were significant increases in all 3 indices with the increase of liver fibrosis grade as assessed in liver biopsy specimens. All 3 indices at the time of second biopsy were able to predict moderate to advanced (METAVIR score F2-4) and advanced (F3-4) fibrosis on liver biopsy, with the area under the receiver-operating characteristics curve >0.8 and the accuracy >70%. All 3 laboratory indices of fibrosis accurately reflected liver fibrosis in patients with SVR for 5 years despite the normalization of serum liver transaminase activity and the lack of liver inflammation.
[Show abstract][Hide abstract] ABSTRACT: Cancer remains one of the leading causes of human mortality worldwide. Radiation and chemotherapy are commonly used for cancer treatment; however, the combination of these therapies and surgery do not completely eradicate cancer cells. Near‑infrared radiation (NIR) is a low‑energy form of radiation that exerts multiple effects on mammalian cells. Previous studies have reported that NIR induces DNA double‑strand breaks and apoptosis of cancer cells. In the present study, a 915‑nm laser was used to examine the effects of NIR on pancreatic cancer cells. Irradiation of pancreatic cancer cells using a 915‑nm laser significantly induced caspase‑3 activation and apoptosis. In addition, the combination of gemcitabine treatment and a 915‑nm laser synergistically increased the number of apoptotic cells. The results of the present study indicate the use of infrared irradiation and chemotherapy may be a possible therapy for the treatment of cancer.