[A case of biliary panperitonitis due to intrahepatic bile duct rupture with intrahepatic bile duct tumor].

An 87-year-old man visited his previous doctor because of jaundice, abdominal pain, and disturbance of consciousness. He was diagnosed with cholangitis and panperitonitis and was referred to our hospital. Emergency laparotomy revealed biliary peritonitis. However, the bile leak point was unclear. Two days after surgery, endoscopic retrograde cholangiopancreatography was performed and revealed hilar bile duct stenosis, slight dilation of the intrahepatic bile duct, and bile leakage from the peripheral left intrahepatic bile duct to the abdominal free space. Endoscopic nasobiliary drainage was performed, and bile leakage decreased. He was discharged from our hospital with improvement from jaundice and peritonitis. Intrahepatic bile duct rupture with neoplastic obstruction of the bile duct is extremely rare. To date, only two cases of intrahepatic bile duct rupture with intrahepatic cholangiocarcinoma have been published.

Enhanced glucose metabolism through activation of HIF-1α covers the energy demand in a rat embryonic heart primordium after heartbeat initiation.

The initiation of heartbeat is an essential step in cardiogenesis in the heart primordium, but it remains unclear how intracellular metabolism responds to increased energy demands after heartbeat initiation. In this study, embryos in Wistar rats at embryonic day 10, at which heartbeat begins in rats, were divided into two groups by the heart primordium before and after heartbeat initiation and their metabolic characteristics were assessed. Metabolome analysis revealed that increased levels of ATP, a main product of glucose catabolism, and reduced glutathione, a by-product of the pentose phosphate pathway, were the major determinants in the heart primordium after heartbeat initiation. Glycolytic capacity and ATP synthesis-linked mitochondrial respiration were significantly increased, but subunits in complexes of mitochondrial oxidative phosphorylation were not upregulated in the heart primordium after heartbeat initiation. Hypoxia-inducible factor (HIF)-1α was activated and a glucose transporter and rate-limiting enzymes of the glycolytic and pentose phosphate pathways, which are HIF-1α-downstream targets, were upregulated in the heart primordium after heartbeat initiation. These results suggest that the HIF-1α-mediated enhancement of glycolysis with activation of the pentose phosphate pathway, potentially leading to antioxidant defense and nucleotide biosynthesis, covers the increased energy demand in the beating and developing heart primordium.

Non-negligible rate of needle tract seeding after endoscopic ultrasound-guided fine-needle aspiration for patients undergoing distal pancreatectomy for pancreatic cancer.

BACKGROUND AND AIMS: Needle tract seeding after preoperative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic body and tail cancer has been reported. This study aimed to investigate the long-term outcomes, including the needle tract seeding ratio, of patients undergoing distal pancreatectomy for pancreatic body and tail cancer diagnosed preoperatively by EUS-FNA. METHODS: This retrospective, observational cohort study assessed patients from three university hospitals and 11 tertiary referral centers. All patients who underwent distal pancreatectomy for invasive cancer of the pancreatic body and tail between January 2006 and December 2015 were identified and reviewed. Needle tract seeding rate, recurrence-free survival (RFS), and overall survival (OS) were evaluated. RESULTS: Of the 301 total patients analyzed, 176 underwent preoperative EUS-FNA (EUS-FNA group) and 125 did not (non-EUS-FNA group). The median follow-up periods of the EUS-FNA group and non-EUS-FNA group were 32.8 and 30.1 months. Six patients (3.4%) in the EUS-FNA group were diagnosed as having needle tract seeding. The 5-year cumulative needle tract seeding rate estimated using Fine and Gray's method was 3.8% (95% CI 1.6-7.8%). The median RFS or OS was not significantly different between the EUS-FNA group and the non-EUS-FNA group (23.7 vs 16.9 months: P = 0.205; 48.0 vs 43.9 months: P = 0.392). CONCLUSION: Although preoperative EUS-FNA for pancreatic body and tail cancer has no negative effect on RFS or OS, needle tract seeding after EUS-FNA was observed to have a non-negligible rate. (UMIN000030719).

Prospective, multicenter, observational study of tissue acquisition through EUS-guided fine-needle biopsy using a 25G Franseen needle.

BACKGROUND: Recently, EUS-guided fine-needle biopsy (EUS-FNB) using a Franseen needle was developed for histological tissue acquisition. However, the yield of a 25G Franseen needle when acquiring histological core tissue has been unclear. PATIENTS AND METHODS: We performed a prospective, multicenter, and observational cohort study that included 100 solid lesions scheduled for EUS-FNB using a 25G Franseen needle at eight centers in Hokkaido, Japan. Only EUS-FNB specimens acquired at the first pass were evaluated without a rapid on-site evaluation. The tissue acquisition rate, acquisition rate of an adequate specimen for histological assessment, the quality of tissue sample, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and adverse events were evaluated. RESULTS: We analyzed a total of 100 solid lesions in 100 patients. The patients were 57 males and 43 females with a median age of 70 years. The technical success rate was 100%. The tissue acquisition rate was 95.0%. The acquisition rate of an adequate specimen for histological assessment was 82.0%. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 87.0%, 100%, 100%, 40.0%, and 88.0%, respectively. The adverse event rate was 1.0%, and it was reported in only one patient who had a moderate pancreatic fistula. CONCLUSIONS: EUS-FNB using the 25G Franseen needle was feasible, and adequate histological core tissue samples were acquired with this method.

[A case of mixed adenoneuroendocrine carcinoma of the distal bile duct].

We diagnosed distal cholangiocarcinoma in a 76-year-old woman who was then treated by subtotal stomach-preserving pancreaticoduodenectomy. Histopathological examination revealed a well-differentiated tubular adenocarcinoma on the side of the bile duct, and a neuroendocrine carcinoma in an area outside the bile duct where the tumor had infiltrated. Immunohistochemical staining identified homology between cytokeratins and MUC, indicating a similar origin. This report discusses problems associated with diagnosis and treatment by summarizing 22 patients who underwent curative resection and subsequently had a confirmed prognosis.

[A Case of Unknown Primary Carcinoma with Dermatomyositis].

A 50-year-old woman was diagnosed with dermatomyositis at the department of neurology in our hospital; she then received steroid pulse therapy. A positron emission computed tomography(PET-CT)revealed swollen lymph nodes near the aorta and in the left inguinal region. She presented at our institution for examination to determine the cause of her lymphadenopathy, but the primary site of the carcinoma was unknown. A histopathological examination of the lymph node specimen obtained using endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)revealed a moderately to poorly differentiated adenocarcinoma. The patient underwent lymphadenectomy. After the surgery, a new lymph node metastasis appeared in the lower abdomen. We initiated a combination treatment with chemotherapy and radiotherapy. The patient died because of disease progression 31 months after her first visit.

A Prospective Multicenter Study Evaluating Bleeding Risk after Endoscopic Ultrasound-Guided Fine Needle Aspiration in Patients Prescribed Antithrombotic Agents.

BACKGROUND/AIMS: Although the risk of bleeding after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is low, the safety of EUS-FNA in patients prescribed antithrombotic agents is unclear. Therefore, this study evaluated the incidence of bleeding after EUS-FNA in those patients. METHODS: Between September 2012 and September 2015, patients who were prescribed antithrombotic agents underwent EUS-FNA at 13 institutions in Japan were prospectively enrolled in the study. The antithrombotic agents were managed according to the guidelines of the Japanese Gastrointestinal Endoscopy Society. The rate of bleeding events, thromboembolic events and other complications within 2 weeks after EUS-FNA were analyzed. RESULTS: Of the 2,629 patients who underwent EUS-FNA during the study period, 85 (62 males; median age, 74 years) patients were included in this stduy. Two patients (2.4%; 95% confidence interval [CI], 0.6% to 8.3%) experienced bleeding events. One patient required surgical intervention for hemothorax 5 hours after EUS-FNA, and the other experienced melena 8 days after EUS-FNA and required red blood cell transfusions. No thromboembolic events occurred (0%; 95% CI, 0.0% to 4.4%). Three patients (3.5%; 95% CI, 1.2% to 10.0%) experienced peri-puncture abscess formation. CONCLUSIONS: The rate of bleeding after EUS-FNA in patients prescribed antithrombotic agents might be considerable.

Autopsy of invasive ductal pancreatic carcinoma that transformed into a tumor producing granulocyte colony-stimulating factor.

A 64-year-old woman was diagnosed with unresectable pancreatic cancer and underwent chemotherapy. However, the number of leukocytes significantly increased as the disease progressed. Serum G-CSF values also increased, and she eventually died on day 511 after diagnosis. Immediately after autopsy, immunohistochemical staining with an anti-G-CSF monoclonal antibody was positive in the poorly differentiated adenocarcinoma area of the primary pancreatic cancer and liver metastatic foci, but negative in the well-differentiated tubular adenocarcinoma part of the primary pancreatic cancer. During de-differentiation, invasive pancreatic ductal carcinoma appeared to have changed to a tumor that produced G-CSF.

Non-islet cell tumor hypoglycemia caused by a big insulin-like growth factor II- producing hepatocellular carcinoma:an autopsy case report.

A 73-year-old man with a hepatocellular carcinoma was admitted to our hospital. He suffered from recurrent severe hypoglycemia. An autopsy was performed after his death. Anti-insulin-like growth factor II (IGF-II) monoclonal antibody immunostaining of the hepatocellular carcinoma was positive. Western immunoblot analysis of the serum revealed highly elevated IGF-II. Therefore, we diagnosed this case as a non-islet cell tumor hypoglycemia caused by a big IGF-II-producing hepatocellular carcinoma.

Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma.

AIM: To identify the most effective endoscopic biliary drainage technique for patients with hilar cholangiocarcinoma. METHODS: In total, 118 patients with hilar cholangiocarcinoma underwent endoscopic management [endoscopic nasobiliary drainage (ENBD) or endoscopic biliary stenting] as a temporary drainage in our institution between 2009 and 2014. We retrospectively evaluated all complications from initial endoscopic drainage to surgery or palliative treatment. The risk factors for biliary reintervention, post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis, and percutaneous transhepatic biliary drainage (PTBD) were also analyzed using patient- and procedure-related characteristics. The risk factors for bilateral drainage were examined in a subgroup analysis of patients who underwent initial unilateral drainage. RESULTS: In total, 137 complications were observed in 92 (78%) patients. Biliary reintervention was required in 83 (70%) patients. ENBD was significantly associated with a low risk of biliary reintervention [odds ratio (OR) = 0.26, 95%CI: 0.08-0.76, P = 0.012]. Post-ERCP pancreatitis was observed in 19 (16%) patients. An absence of endoscopic sphincterotomy was significantly associated with post-ERCP pancreatitis (OR = 3.46, 95%CI: 1.19-10.87, P = 0.023). PTBD was required in 16 (14%) patients, and Bismuth type III or IV cholangiocarcinoma was a significant risk factor (OR = 7.88, 95%CI: 1.33-155.0, P = 0.010). Of 102 patients with initial unilateral drainage, 49 (48%) required bilateral drainage. Endoscopic sphincterotomy (OR = 3.24, 95%CI: 1.27-8.78, P = 0.004) and Bismuth II, III, or IV cholangiocarcinoma (OR = 34.69, 95%CI: 4.88-736.7, P < 0.001) were significant risk factors for bilateral drainage. CONCLUSION: The endoscopic management of hilar cholangiocarcinoma is challenging. ENBD should be selected as a temporary drainage method because of its low risk of complications.

Multi-organ disseminated mucosa-associated lymphoid tissue lymphoma.

A 61-year-old man was admitted to our hospital with extreme weight loss. Abdominal ultrasonography revealed an 8-cm tumor of the pancreatic head. Further investigation revealed orbital, pulmonary, pancreatic, colonic, and bone marrow lesions. A histopathological examination of the pancreatic tumor specimen obtained using endoscopic ultrasound-guided fine-needle aspiration revealed mucosa-associated lymphoid tissue (MALT) lymphoma. Monoclonal rearrangement of immunoglobulin heavy chain was found in the pulmonary, pancreatic, colonic, and bone marrow lesions. We diagnosed multi-organ disseminated MALT lymphoma, with the largest lesion located in the pancreatic head. Chemo-radiation therapy resulted in complete remission.

Single-step simultaneous side-by-side placement of a self-expandable metallic stent with a 6-Fr delivery system for unresectable malignant hilar biliary obstruction: a feasibility study.

BACKGROUND: Bilateral self-expandable metallic stent (SEMS) placement for the management of unresectable malignant hilar biliary obstruction (UMHBO) is technically challenging to perform using the existing metallic stents with thick delivery systems. The recently developed 6-Fr delivery systems could facilitate a single-step simultaneous side-by-side placement through the accessory channel of the duodenoscope. The aim of this study was to evaluate the feasibility of this procedure. METHODS: Between May and September 2013, 13 consecutive patients with UMHBO underwent a single-step simultaneous side-by-side placement of SEMS with the 6-Fr delivery system. The technical success rate, stent patency, and rate of complications were evaluated from the prospectively collected database. RESULTS: Technical success was achieved in 11 (84.6%, 95% confidence interval [CI]: 57.8-95.8) patients. The median procedure time was 25 min. Early and late complications were observed in 23% (one segmental cholangitis and two liver abscesses) and 15% (one segmental cholangitis and one cholecystitis) patients, respectively. Median dysfunction free patency was 263 days (95% CI: 37-263). Five patients (38%) experienced stent occlusion that was successfully managed by endoscopic stent placement. CONCLUSIONS: A single-step simultaneous side-by-side placement of SEMS with a 6-Fr delivery system was feasible for the management of UMHBO.

CTNNB1 mutational analysis of solid-pseudopapillary neoplasms of the pancreas using endoscopic ultrasound-guided fine-needle aspiration and next-generation deep sequencing.

BACKGROUND: Solid-pseudopapillary neoplasm (SPN), a rare neoplasm of the pancreas, frequently harbors mutations in exon 3 of the cadherin-associated protein beta 1 (CTNNB1) gene. Here, we analyzed SPN tissue for CTNNB1 mutations by deep sequencing using next-generation sequencing (NGS). METHODS: Tissue samples from 7 SPNs and 31 other pancreatic lesions (16 pancreatic ductal adenocarcinomas (PDAC), 11 pancreatic neuroendocrine tumors (PNET), 1 acinar cell carcinoma, 1 autoimmune pancreatitis lesion, and 2 focal pancreatitis lesions) were analyzed by NGS for mutations in exon 3 of CTNNB1. RESULTS: A single-base-pair missense mutations in exon 3 of CTNNB1 was observed in all 7 SPNs and in 1 of 11 PNET samples. However, mutations were not observed in the tissue samples of any of the 16 PDAC or other four pancreatic disease cases. The variant frequency of CTNNB1 ranged from 5.4 to 48.8 %. CONCLUSIONS: Mutational analysis of CTNNB1 by NGS is feasible and was achieved using SPN samples obtained by endoscopic ultrasound-guided fine needle aspiration.

High and low negative pressure suction techniques in EUS-guided fine-needle tissue acquisition by using 25-gauge needles: a multicenter, prospective, randomized, controlled trial.

BACKGROUND: EUS-guided FNA (EUS-FNA) has a high diagnostic accuracy for pancreatic diseases. However, although most reports have typically focused on cytology, histological tissue quality has rarely been investigated. The effectiveness of EUS-FNA combined with high negative pressure (HNP) suction was recently indicated for tissue acquisition, but has not thus far been tested in a prospective, randomized clinical trial. OBJECTIVE: To evaluate the adequacy of EUS-FNA with HNP for the histological diagnosis of pancreatic lesions by using 25-gauge needles. DESIGN: Prospective, single-blind, randomized, controlled crossover trial. SETTING: Seven tertiary referral centers. PATIENTS: Patients referred for EUS-FNA of pancreatic solid lesions. From July 2011 to April 2012, 90 patients underwent EUS-FNA of pancreatic solid masses by using normal negative pressure (NNP) and HNP with 2 respective passes. The order of the passes was randomized, and the sample adequacy, quality, and histology were evaluated by a single expert pathologist. INTERVENTION: EUS-FNA by using NNP and HNP. MAIN OUTCOME MEASUREMENTS: The adequacy of tissue acquisition and the accuracy of histological diagnoses made by using the EUS-FNA technique with HNP. RESULTS: We found that 72.2% (65/90) and 90% (81/90) of the specimens obtained using NNP and HNP, respectively, were adequate for histological diagnosis (P = .0003, McNemar test). For 73.3% (66/90) and 82.2% (74/90) of the specimens obtained by using NNP and HNP, respectively, an accurate diagnosis was achieved (P = .06, McNemar test). Pancreatitis developed in 1 patient after this procedure, which subsided with conservative therapy. LIMITATIONS: This was a single-blinded, crossover study. CONCLUSION: Biopsy procedures that combine the EUS-FNA with HNP techniques are superior to EUS-FNA with NNP procedures for tissue acquisition. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000005939.).

Influence of the safety and diagnostic accuracy of preoperative endoscopic ultrasound-guided fine-needle aspiration for resectable pancreatic cancer on clinical performance.

AIM: To evaluate the safety and diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a cohort of pancreatic cancer patients. METHODS: Of 213 patients with pancreatic cancer evaluated between April 2007 and August 2011, 82 were thought to have resectable pancreatic cancer on the basis of cross-sectional imaging findings. Of these, 54 underwent EUS-FNA before surgery (FNA+ group) and 28 underwent surgery without preoperative EUS-FNA (FNA- group). RESULTS: All 54 lesions were visible on EUS, and all 54 attempts at FNA were technically successful. The diagnostic accuracy according to cytology and histology findings was 98.1% (53/54) and 77.8% (42/54), respectively, and the total accuracy was 98.1% (53/54). One patient developed mild pancreatitis after EUS-FNA but was successfully treated by conservative therapy. No severe complications occurred after EUS-FNA. In the FNA+ and FNA- groups, the median relapse-free survival (RFS) was 742 and 265 d, respectively (P = 0.0099), and the median overall survival (OS) was 1042 and 557 d, respectively (P = 0.0071). RFS and OS were therefore not inferior in the FNA+ group. These data indicate that the use of EUS-FNA did not influence RFS or OS, nor did it increase the risk of peritoneal recurrence. CONCLUSION: In patients with resectable pancreatic cancer, preoperative EUS-FNA is a safe and accurate diagnostic method.

Difference from bile duct cancer and relationship between bile duct wall thickness and serum IgG/IgG4 levels in IgG4-related sclerosing cholangitis.

BACKGROUND/AIMS: IgG4-related sclerosing cholangitis (IgG4-SC) is a newly established entity. The purpose of this study was to investigate the differences in intraductal ultrasonography (IDUS) findings between IgG4-SC and bile duct (BD) cancer (BDC) as well as the relationship among BD wall thickness, serological and pathological findings in IgG4-SC. METHODOLOGY: Based on the diagnostic criteria of IgG4-SC, we reviewed patients in our hospital between April 2005 and June 2013, and analyzed the data obtained from 32 patients with IgG4-SC and 40 patients with BDC. RESULTS: Regarding IDUS findings, significantly more cases in BDC indicated rigid/papillary inner margin than in IgG4-SC, while biopsy was more efficient. There were no significant correlations between BD wall thickness and serum IgG/IgG4 levels or the number of IgG4-positive cells of the BD specimens. All the IgG4-SC patients without steroid treatment revealed discordant results in the shifts of IgG, IgG4 and BD wall thickness between the 1st and 2nd examinations, while all patients with steroid had completely concordant results of the shifts. CONCLUSIONS: IDUS findings alone are insufficient for differentiation between IgG4-SC and BDC. BD wall thickness, serum IgG and IgG4 proportionally shift and reflect the effect of steroid on IgG4-SC after steroid treatment, not before it.