[A case of obstructive jaundice due to the movement of pancreatic calculi].

A 44-year-old man with a history of chronic alcoholic pancreatitis and Crohn's disease presented with abdominal pain. Computed tomography revealed pancreatic calculi in the head of the pancreas and a dilated pancreatic duct. The patient was diagnosed with an acute exacerbation of chronic pancreatitis due to the impact of pancreatic calculi on the main pancreatic duct. During the clinical course, the movement of pancreatic calculi to the major papilla was confirmed, leading to obstructive jaundice. Endoscopic treatment with sphincterotomy of the pancreatic duct was successful. Herein, we report the case of an unusual clinical course involving obstructive jaundice caused by the movement of pancreatic calculi.

Utility and safety of a new uneven double-lumen sphincterotome in cases of difficult biliary cannulation.

BACKGROUND: We investigated the utility and safety of a new uneven double-lumen sphincterotome in biliary cannulation in comparison with the conventional pancreatic guidewire (PGW) method. METHODS: We retrospectively evaluated 119 patients who required PGW placement because of difficult biliary cannulation. Endoscopic retrograde cholangiopancreatography (ERCP) was performed using a conventional ERCP catheter or a new uneven double-lumen sphincterotome. The success rate of bile duct cannulation, the operation time of bile duct cannulation, and the incidence of post-ERCP pancreatitis (PEP) were evaluated. RESULTS: Forty-four patients were treated with a new double-lumen sphincterotome (the new sphincterotome group) and 75 patients underwent conventional PGW placement (the conventional group). The success rate of bile duct cannulation was 39/44 (88.6%) in the new sphincterotome group and 63/75 (84.0%) in the conventional group (not significant). The total biliary cannulation time (from the reach to the papilla to the finish of biliary cannulation) was 16.0 (6.5-78) min in the new sphincterotome group and 26.0 (5-80) min in the conventional group (P < 0.01). The time from PGW placement to bile duct cannulation was 3.5 (0.3-57) min in the magictome group and 12.0 (1-65) min in the conventional group (P < 0.01). Hyperamylasemia was observed in 13/44 (29.5%) and 17/75 (22.7%), respectively (not significant). Five of 44 (11.3%) of the new sphincterotome group and 14/75 (18.7%) of the conventional group were diagnosed with PEP (not significant). CONCLUSION: A new double-lumen sphincterotome allows selective bile duct cannulation to be performed in a shorter time than the conventional PGW method.

Dexmedetomidine is safe and reduces the additional dose of midazolam for sedation during endoscopic retrograde cholangiopancreatography in very elderly patients.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) often requires deep sedation. Dexmedetomidine, a highly selective α2-adrenoceptor agonist with sedative activity and minimal effects on respiration, has recently been widely used among patients in the intensive care unit. However, its use in endoscopic procedures in very elderly patients is unclear. In this study, we retrospectively investigated the safety and efficacy of dexmedetomidine sedation during ERCP. METHODS: The study included 62 very elderly patients (aged over 80 years) who underwent ERCP from January 2014, with sedation involving dexmedetomidine (i.v. infusion at 3.0 µg/kg/h over 10 min followed by continuous infusion at 0.4 µg/kg/h) along with midazolam. For comparison, the study included 78 patients who underwent ERCP before January 2014, with midazolam alone. We considered additional administration of midazolam as needed to maintain a sedation level of 3-4, according to the Ramsay sedation scale. The outcome measures were amount of midazolam, adverse events associated with sedation, and hemodynamics. RESULTS: The incidence of decreased SpO2 and median dose of additional midazolam were significantly lower in the dexmedetomidine group than in the conventional group. The minimum systolic blood pressure and minimum heart rate during and after examination was significantly lower in the dexmedetomidine group than in the conventional group. However, serious acute heart failure or arrhythmia was not noted. CONCLUSIONS: Dexmedetomidine can decrease the incidence of respiratory complications and the total dose of other sedative agents. It can be used as an alternative to conventional methods with midazolam for adequate sedation during ERCP in very elderly patients.

Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn's Disease.

BACKGROUND: The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. SUMMARY: Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera Bacteroides, Eubacterium, Faecalibacterium and Ruminococcus significantly decreased in CD patients as compared to healthy controls. In contrast, the genera Actinomyces and Bifidobacterium significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as Blautia faecis, Roseburia inulinivorans, Ruminococcus torques, Clostridium lavalense, Bacteroides uniformis and Faecalibacterium prausnitzii were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of Roseburia inulinivorans and Ruminococcus torques was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). KEY MESSAGE: The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species.

Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn's disease.

BACKGROUND AND AIMS: Dysbiosis is thought to be relevant to the etiology and pathogenesis of Crohn's disease (CD). In this study, we investigated the abundance of Faecalibacterium prausnitzii, as well as Bilophila wadsworthia, in the gut microbiota of Japanese CD patients. METHODS: Forty-seven CD patients and 20 healthy controls were enrolled. Abundance of F. prausnitzii in fecal samples was quantified by real-time polymerase chain reaction. The gut microbiota profile was evaluated by terminal restriction fragment length polymorphisms. RESULTS: The abundance of F. prausnitzii significantly decreased in CD patients compared with healthy subjects. B. wadsworthia was scarcely detected in the same samples. Among CD patients, the Crohn's Disease Activity Index, C-reactive protein levels, and erythrocyte sedimentation rate were significantly lower, and serum albumin levels were significantly higher in the high F. prausnitzii group compared with the low group. Terminal restriction fragment length polymorphisms analysis showed that fecal bacterial communities of CD patients differed from those of healthy individuals. The changes in simulated bacterial composition indicated that class Clostridia, including genus Faecalibacterium, was significantly less abundant in CD patients as compared with healthy individuals. The bacterial diversity measured by the Shannon Diversity Index was significantly reduced in CD patients compared with healthy individuals. CONCLUSION: The decreased abundance of class Clostridia, including F. prausnitzii, may translate into a reduction of commensal bacteria-mediated, anti-inflammatory activities in the mucosa, which are relevant to the pathophysiology of CD. In contrast, the role of B. wadsworthia was suspected to be minimal.

Neutralization of complement component C5 ameliorates the development of dextran sulfate sodium (DSS)-colitis in mice.

The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease, we evaluated the effects of anti-C5 antibodies on the development of dextran sulfate sodium-induced colitis in mice. Dextran sulfate sodium-colitis was induced in BALB/c mice with intraperitoneal administrations of anti-C5 antibodies (1 mg/body [DOSAGE ERROR CORRECTED]) every 48 h. Tissue samples were evaluated by standard histological procedures. The mucosal mRNA expression of the inflammatory cytokines was analyzed by real-time PCR. Body weight loss in the mice was completely blocked by the administration of anti-C5 antibody. The disease activity index was significantly lower in the anti-C5 antibody-treated mice than the dextran sulfate sodium mice. The colonic weight/length ratio, histological colitis score and mucosal myeloperoxidase activity were significantly lower in the anti-C5 antibody-treated mice than the dextran sodium sulfate mice. The administration of the anti-C5 antibody significantly reduced the mucosal expression of mRNAs for tumor necrosis factor-α, interleukin-1ß and interleukin-6. In conclusion, the complement system plays a role in the development of dextran sodium sulfate-induced experimental colitis.

Bile duct penetrating duodenal wall sign: a novel computed tomography finding of common bile duct stone impaction into duodenal major papilla.

PURPOSE: Impacted common bile duct stones cause severe acute cholangitis. However, the early and accurate diagnosis, especially iso-attenuating stone impaction, is still challenging. Therefore, we proposed and validated the bile duct penetrating duodenal wall sign (BPDS), which shows the common bile duct penetrating the duodenal wall on coronal reformatted computed tomography (CT), as a novel sign of stone impaction. METHODS: Patients who underwent urgent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis due to common bile duct stones were retrospectively enrolled. Stone impaction was defined by endoscopic findings as a reference standard. Two abdominal radiologists blinded to clinical information interpreted CT images to record the presence of the BPDS. The diagnostic accuracy of the BPDS to diagnose stone impaction was analyzed. Clinical data related to the severity of acute cholangitis were compared between patients with and without the BPDS. RESULTS: A total of 40 patients (mean age 70.6 years; 18 female) were enrolled. The BPDS was observed in 15 patients. Stone impaction occurred in 13/40 (32.5%) cases. Overall accuracy, sensitivity, and specificity were 34/40 (85.0%), 11/13 (84.6%), and 23/27 (85.2%), respectively; 14/16 (87.5%), 5/6 (83.3%), and 9/10 (90.0%) for iso-attenuating stones; and 20/24 (83.3%), 6/7 (85.7%), and 14/17 (82.4%) for high-attenuating stones. Interobserver agreement of the BPDS was substantial (κ = 0.68). In addition, the BPDS was significantly correlated with the number of factors in the systemic inflammatory response syndrome (P = 0.03) and total bilirubin (P = 0.04). CONCLUSION: The BPDS was a unique CT imaging finding to identify common bile duct stone impaction regardless of stone attenuation with high accuracy.

Terminal restriction fragment length polymorphism analysis of the gut microbiota profiles of pediatric patients with inflammatory bowel disease.

BACKGROUND/AIM: We analyzed the fecal microbiota profiles of pediatric patients with inflammatory bowel disease. METHOD: Terminal restriction fragment length polymorphism analysis was performed in 10 fecal samples from Crohn's disease (CD), 14 samples from ulcerative colitis (UC) and 27 samples from healthy individuals. The bacterial diversity was evaluated by the Shannon diversity index. RESULT: In CD patients, a setting of similarity generated three major clusters. The majority of CD patients were classified into CD clusters I and II (9 out of 10), but the majority of healthy individuals (21 of 27) were classified into CD cluster III. In UC patients, a setting of similarity also generated three major UC clusters, but each cluster was not characteristic for UC patients or healthy individuals. The changes in simulated bacterial composition indicated that the class Clostridia, including the genus Faecalibacterium, was significantly decreased in CD patients as compared to UC patients and/or healthy individuals. The genus Bacteroides was also decreased as compared to healthy individuals. The bacterial diversity measured by the Shannon diversity index was significantly reduced in CD patients as compared to healthy individuals. CONCLUSION: The gut microbiota profile of pediatric CD patients was different from that of healthy children.

Terminal-restriction fragment length polymorphism (T-RFLP) analysis for changes in the gut microbiota profiles of indomethacin- and rebamipide-treated mice.

BACKGROUND/AIMS: We investigated the effects of indomethacin and rebamipide on the gut microbiota profiles using terminal restriction fragment polymorphism (T-RFLP) analysis. MATERIALS AND METHODS: Female C57BL/6J mice were given indomethacin (10 mg/kg, s.c.) once a day and 2.5 mg rebamipide orally 3 times a day. After 7 days, they were sacrificed, and luminal contents were obtained from the ileum and cecum. The gut microbiota communities were analyzed by T-RFLP analysis with BslI digestion. RESULTS: T-RFLP analyses showed that rebamipide and indomethacin had no significant effects on the gut microbiota profiles in the ileum and cecum. In contrast, the combination of rebamipide + indomethacin induced a significant change in the gut microbiota. The changes in the microbiota composition induced by the combination of rebamipide + indomethacin were characterized by the increase in the orders Bifidobacteriales and Lactobacillales, the genera Bacteroides and Prevotella and the family Clostridiaceae. The diversity of the gut microbiota community generated by the combination of rebamipide + indomethacin was significantly higher than those induced by either rebamipide or indomethacin alone. CONCLUSION: The combination of rebamipide + indomethacin induces remarkable changes in the gut microbiota composition and diversity. The clinical activity of rebamipide on nonsteroidal anti-inflammatory drug-induced intestinal injury may be exerted through a modulation of the gut microbiota.

Bleeding anorectal varices treated by a direct puncture approach through the greater sciatic foramen: The utility of a steerable microcatheter for reverse catheterization.

Bleeding is less common from anorectal varices than from esophageal varices, but it is potentially life-threatening. Here, we present a case of a woman in her 70s with critical hemorrhage from anorectal varices. The endoscopic approach could not be performed due to the huge variceal formation and the transhepatic approach was also unsuitable due to the presence of portal vein thrombosis and ascites. A direct puncture to the right superior rectal vein was performed through the greater sciatic foramen under computed tomography fluoroscopic guidance. Using a steerable microcatheter, superior rectal veins were bilaterally embolized with a mixture of n-butyl cyanoacrylate and ethiodized oil, and microcoils. Endoscopy and contrast-enhanced computed tomography performed after the procedure confirmed a marked shrinkage of anorectal varices. When endoscopic or any other approaches are difficult, this technique can be a useful alternative therapeutic option.

Larger Volume and Higher Fat Content of the Pancreatic Head Are Predictive Factors for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVES: Acute pancreatitis is the most critical complication of endoscopic retrograde cholangiopancreatography (ERCP). In this study, we investigated the association between the volume/fat content of the pancreatic head and the incidence of post-ERCP pancreatitis (PEP). METHODS: We retrospectively enrolled 157 patients who underwent ERCP. The volume and fat content of the pancreas were calculated by multislice computed tomographic imaging by using a volume analyzer. Multivariate analysis was performed to identify risk factors for PEP. RESULTS: The mean volumes of the whole pancreas and pancreatic head were significantly larger, and the fat content of the pancreatic head was significantly higher in the PEP group (P < 0.01). There were no significant differences in the mean volume and fat content of the pancreatic body and tail in the PEP group. Multivariate analysis revealed that the pancreatic guidewire placement (odds ratio [OR], 12.4; P < 0.01), pancreatic head volume (OR, 5.3; P < 0.01), and the pancreatic head fat content (OR, 4.8; P < 0.01) were independent risk factors for PEP. CONCLUSIONS: The pancreatic head volume and fat content were independent predicting factors of PEP. Quantitative assessment of the pancreas may contribute to the prediction of PEP onset.

Exploratory analysis of target concentration of lenvatinib in the treatment of hepatocellular carcinoma.

PURPOSE: We aimed to evaluate exposure-toxicity/efficacy relationship of lenvatinib by determining its target trough concentration for patients with hepatocellular carcinoma (HCC). METHODS: In this retrospective, observational study, 28 HCC patients who had been treated with lenvatinib were enrolled between August 2018 and April 2020. We evaluated the association between the trough lenvatinib concentration and occurrence of grade ≥ 3 toxicities. Additionally, we estimated the association of the trough lenvatinib concentration with responder status (disease control; complete response, partial response, or stable disease), and progression-free survival (PFS). RESULTS: The mean trough lenvatinib concentration was significantly higher in the group with grade ≥ 3 toxicity (n = 15) than in the group with grade ≤ 2 toxicity (n = 13). Based on the receiver operating characteristic curve, the threshold values of the trough lenvatinib concentrations for predicting grade ≥ 3 toxicities and responder status were 71.4 ng/mL [area under the curve (AUC) 0.86, 95% confidence interval (CI) 0.71-1.00; p < 0.05] and 36.8 ng/mL (AUC 0.95, 95% CI 0.85-1.00; p < 0.05), respectively. Lenvatinib concentrations of 36.8-71.4 ng/mL resulted in longer PFS than concentrations < 36.8 ng/mL and ≥ 71.4 ng /mL [median 13.3 months (36.8-71.4 ng/mL) vs. 3.5 months (< 36.8 ng/mL) and 7.8 months (≥ 71.4 ng /mL), respectively]. CONCLUSIONS: Considering these results, we propose that the target trough concentration of lenvatinib could be 36.8-71.4 ng/mL for maintaining disease control status and reducing grade ≥ 3 toxicity in the treatment of HCC.

Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study.

PURPOSE: Severe adverse events frequently occur in patients treated with sorafenib, whereas some patients have suboptimal response to sorafenib. We aimed to evaluate the association of sorafenib-induced toxicities and clinical outcomes with the pharmacokinetics of sorafenib in patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective, observational study in which 26 HCC patients who had been treated with sorafenib were enrolled between September 2010 and March 2015. The association between trough sorafenib concentration and occurrence of grade ≥ 3 toxicities was evaluated. In addition, we estimated the association of trough sorafenib concentration with overall survival (OS). RESULTS: The median sorafenib concentration was 2.91 µg/mL (range 0.74-8.8 µg/mL). Based on the receiver operating characteristic curve, the threshold value of the trough sorafenib concentration for predicting grade ≥ 3 toxicities and responder (complete response or partial response at best response, or stable disease for ≥ 3 months) was 3.45 µg/mL [area under the curve (AUC) 0.74, 95% confidence interval (CI) 0.54-0.93; p <0.05] and 1.40 µg/mL (AUC 0.97, 95% CI 0.97-1.00; p <0.05), respectively. OS of patients with sorafenib 1.40-3.45 µg/mL had a tendency to be longer than those of patients administered < 1.40 µg/mL and ≥ 3.45 µg/mL [median 17.8 months (1.40-3.45 µg/mL) vs. 5.3 months (< 1.40 µg/mL) and 9.5 months (≥ 3.45 µg/mL)]. CONCLUSIONS: From results of this study, we proposed that the target range of sorafenib may be a trough concentration of 1.40-3.45 µg/mL in patients with HCC.

Two cases of benign hepatic nodules caused by sinusoidal dilatation with different hemodynamics.

We describe two cases of benign nodules caused by sinusoidal dilatation with different hemodynamic statuses. Case 1 was a 50-year-old woman with a 1-cm nodule that showed a low density in the arterial phase of computed tomography. Pathologically, there were no atypical cells with sinusoidal dilatation, and immunostaining was negative for CD34. We speculated that sinusoidal dilatation was caused by congestion due to loss of frequency of the central vein. In contrast, case 2 was a 50-year-old woman with a 1.5-cm nodule that was highly stained in the arterial phase of computed tomography. Although she had a sinusoidal dilatation similar to that in case 1, immunostaining was positive for CD34. Sinusoidal dilatation was thought to be caused by hyperperfusion of arterial blood. Moreover, CD34 may be potentially useful for the differentiation of the hemodynamic status.

Interval between hepatocellular carcinoma treatment and interferon-free direct-acting antiviral agents against hepatitis C is necessary to suppress tumor recurrence.

Interferon (IFN) has been identified to suppress carcinogenesis when used for treating hepatitis C virus (HCV) infections. Treatment with IFN-free direct-acting antiviral agents (DAAs) is an acceptable alternative, even in elderly patients or patients who have been treated for hepatocellular carcinoma (HCC), because it has a lower incidence of side effects and higher sustained virological response (SVR) rate compared with IFN treatment. However, the suppression of carcinogenesis by DAAs is unclear. In the present study, 19 patients who underwent DAA treatment following treatment for HCC between January 2015 and March 2017 were retrospectively investigated. The clinical data were compared between 9 patients with HCC recurrence following DAA treatment (recurrence group) and 10 patients without HCC recurrence (no-recurrence group). The 1-year cumulative recurrence rate of HCC following SVR was as high as 50.2%. Age and sex did not significantly differ between the two groups, and the average number of HCC treatments prior to DAA treatment was also not significantly different between the recurrence and no-recurrence groups (3.2 and 2.2, respectively). The median interval between the final HCC treatment and the commencement of DAA treatment was 88 days in the recurrence group, which was significantly less compared with 790 days in the no-recurrence group (P=0.018). An interval of 120 days or more from final HCC treatment to the commencement of DAA treatment was a significant independent factor of no HCC recurrence following DAA treatment (P=0.028). A high HCC recurrence rate was identified following DAA treatment in patients with a history of HCC treatment. Therefore, there should be at least a 4-month interval from the final HCC treatment to the commencement of DAA treatment to ensure no HCC recurrence.

Efficacy and safety of cold forceps polypectomy utilizing the jumbo cup: a prospective study.

BACKGROUND/AIMS: There are few prospective studies on cold forceps polypectomy (CFP) using jumbo cup forceps. Therefore, we examined patients with diminutive polyps (5 mm or smaller) treated with CFP using jumbo cup forceps to achieve an adenoma-free colon and also assessed the safety of the procedure and the recurrence rate of missed or residual polyp after CFP by performing follow-up colonoscopy 1 year later. METHODS: We included patients with up to 5 adenomas removed at initial colonoscopy and analyzed data from a total of 361 patients with 573 adenomas. One-year follow-up colonoscopy was performed in 165 patients, at which 251 lesions were confirmed. RESULTS: The one-bite resection rate with CFP was highest for lesions 3 mm or smaller and decreased significantly with increasing lesion size. Post-procedural hemorrhage was observed in 1 of 573 lesions (0.17%). No perforation was noted. The definite recurrence rate was 0.8% (2/251 lesions). The probable recurrence rate, which was defined as recurrence in the same colorectal segment, was 17%. Adenoma-free colon was achieved in 55% of patients at initial resection. Multivariate analysis revealed that achievement of an adenoma-free colon was significantly associated with number of adenomas and years of endoscopic experience. CONCLUSIONS: CFP using jumbo biopsy forceps was safe and showed a high one-bite resection rate for diminutive lesions of 3 mm or smaller. The low definite recurrence rate confirms the reliability of CFP using jumbo biopsy forceps. Number of adenomas and years of endoscopic experience were key factors in achieving an adenoma-free colon.

Anaplastic pancreatic cancer diagnosed with endoscopic ultrasound guided fine needle aspiration showing hypervascular tumor: A case report.

RATIONALE: Pancreatic ductal carcinoma is a hypovascular tumor, and characteristic findings are observed on imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), in most cases. PATIENT CONCERNS: Here we report a case of anaplastic carcinoma of the pancreas (ACP) with characteristics of hypervascular tumor diagnosed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). A 70-year-old woman was admitted to hospital because of exacerbation of diabetes. Contrast-enhanced CT revealed a hypervascular tumor at the head of the pancreas. DIAGNOSIS: EUS-FNA was performed. Osteoclast-like giant cells and tumor cells with polymorphic nuclei were found on pathological examination and she was diagnosed with ACP. INTERVENTIONS: Although it was a surgical indication at the time of diagnosis, the tumor rapidly worsened. Oral administration of TS-1 (tegafur/gimeracil/oteracil) was initiated. Chemotherapy was discontinued after the end of 2 courses because the tumor had increased prominently on CT. OUTCOMES: She died approximately a year since the onset of the illness. LESSONS: ACP occasionally exhibits the characteristics of a hypervascular tumor and may require differentiation from other pancreatic tumors, such as neuroendocrine tumor. Therefore, pathological diagnosis by EUS-FNA at an early stage is important to determine treatment strategies.