Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning.

BACKGROUND: Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers. METHODS: We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort. RESULTS: The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%). CONCLUSIONS: We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer.

Emergency surgery for hemobilia due to hepatic artery pseudoaneurysm rupture complicated by Mirizzi syndrome type II: a case report.

BACKGROUND: Hemobilia refers to bleeding into the biliary tract. Hepatic artery pseudoaneurysm (HAP) rupture is an uncommon cause of hemobilia, and cases of HAP associated with Mirizzi syndrome are extremely rare. Although transarterial embolization is recommended as the first-line treatment for hemobilia, surgery is sometimes required. CASE PRESENTATION: A 76-year-old woman was referred to our hospital with epigastric pain. She was febrile and had conjunctival icterus and epigastric tenderness. Laboratory tests revealed abnormal white blood cell count and liver function. An abdominal computed tomography (CT) revealed multiple calculi in the gallbladder, an incarcerated calculus in the cystic duct, and a slightly dilated common hepatic duct. Based on examination findings, she was diagnosed with Mirizzi syndrome type I, complicated by cholangitis. Intravenous antibiotics were administered, and we performed endoscopic retrograde cholangiopancreatography (ERCP) to place a drainage tube. The fever persisted; therefore, contrast-enhanced CT (CECT) was performed. This revealed portal vein thrombosis and hepatic abscesses; therefore, heparin infusion was administered. The following day, she complained of melena, and laboratory tests showed that she was anemic. ERCP was performed to change the drainage tube in the bile duct; however, bleeding from the papilla of Vater was observed. CECT demonstrated a right HAP with high-density fluid in the gallbladder and gallbladder perforation. Finally, she was diagnosed with hemobilia caused by HAP rupture, and emergency surgery was performed to secure hemostasis and control the infection. During laparotomy, we found that a right HAP had ruptured into the gallbladder. The gallbladder made a cholecystobiliary fistula, which indicated Mirizzi syndrome type II. Although we tried to repair the right hepatic artery, we later ligated it due to arterial wall vulnerability. Then, we performed subtotal cholecystectomy and inserted a T-tube into the common bile duct. There were no postoperative complications except for minor leakage from the T-tube insertion site. The patient was discharged after a total hospital stay of 7 weeks. CONCLUSIONS: We experienced an extremely rare case of emergency definitive surgery for hemobilia due to HAP rupture complicated by Mirizzi syndrome type II. Surgery might be indicated when controlling underlying infections was required.

Imported Hepatitis E Virus Genotype 1: A Rare Case of Acute Hepatitis Managed with Steroid Pulse Therapy.

A 26-year-old Indian man who had arrived in Japan 24 days prior presented to our hospital with abdominal pain and a fever. A blood test revealed marked hepatic dysfunction, and imaging tests confirmed a diagnosis of acute hepatitis. The patient's liver function and coagulability deteriorated, and his general condition was poor. Given the possibility of fulminant hepatic failure, we initiated steroid pulse therapy. Following the initiation of steroid therapy, the patient's liver function and subjective symptoms rapidly improved. Testing revealed positive findings for IgA-hepatitis E virus, and a genetic analysis of hepatitis E identified genotype 1, which is not endemic to Japan, leading to a definitive diagnosis of imported hepatitis E infection from India. The successful response to steroid therapy highlights the potential benefit of this approach in managing severe cases of acute hepatitis E, a rare occurrence in Japan. This case underscores the importance of considering hepatitis E infection in individuals with a recent travel history to regions with high prevalence and the potential benefits of steroid therapy in managing severe cases of acute hepatitis E.

Duodenal ulcer bleeding from a branch of the middle colic artery: A case report.

RATIONALE: Duodenal ulcer bleeding is a potentially life-threatening condition commonly caused by the erosion of the duodenal arteries. PATIENT CONCERNS: A 55-year-old male was referred to our hospital with abdominal pain for the past 3 days. Contrast-enhanced computed tomography of the abdomen revealed wall thickening in the descending part of the duodenum and a cystic lesion (27 × 19 mm) contiguous with the duodenum, with an accumulation of fluid. An esophagogastroduodenoscopy showed the significantly stenotic duodenum, which prevented passage of the endoscope and evaluation of the main lesion. Based on these findings, duodenal ulcer perforation and concomitant abscess formation were suspected. Two days after admission, he had massive hematochezia with bloody drainage from the nasogastric tube. DIAGNOSES: Emergency angiography revealed duodenal ulcer bleeding from the gastroduodenal artery and the branch artery of the inferior pancreaticoduodenal artery and middle colic artery (MCA). INTERVENTIONS: The patient was treated with transcatheter arterial embolization (TAE) of the gastroduodenal artery, the branch vessel of the inferior pancreaticoduodenal artery, and the main trunk of the MCA. OUTCOMES: Hemostasis was achieved with TAE. The patient recovered uneventfully and undergone a gastro-jejunal bypass surgery for the duodenal stenosis 2 weeks after TAE. He was discharged without any abnormal complaints on postoperative day 12. LESSONS: We have experienced a rare case of duodenal ulcer bleeding from a branch of the MCA. In patients with refractory upper gastrointestinal bleeding, careful evaluation of bleeding sites is recommended considering unexpected culprit vessels.

Primary Peritonitis due to Group A Streptococcus Successfully Treated with Intraperitoneal Drainage.

A 42-year-old woman was admitted to our hospital because of lower abdominal pain and diarrhea. Although the initial symptoms and imaging findings were similar to those of acute enteritis, blood and ascites cultures led to the diagnosis of primary peritonitis caused by group A Streptococcus. In many cases, the disease rapidly deteriorates, and laparotomy is performed for the early diagnosis and to reduce the number of bacteria in the abdominal cavity. In the present case, intraperitoneal drainage was effective for avoiding surgery. We suggest that intraperitoneal drainage is effective for the treatment of this disease.

[CT enterography with polyethylene glycol electrolyte solution for diagnosis of Crohn's disease].

This study aimed to assess the diagnostic usefulness of CT enterography (CTE) in Crohn's disease in Japanese patients. A total of 32 cases with bowel symptoms underwent CT enterography with polyethylene glycol electrolyte solution as oral contrast medium, among which 18 were clinically diagnosed as Crohn's disease and 14 were not: ulcerative colitis 1, Beçhet disease 1, simple ulcer 1, inflammatory bowel disease without definite diagnosis 5 and bowel symptoms of unknown origin 6. The incidence of bowel wall thickening, mural hyperenhancement, "the comb sign", mesenteric lymph nodes swelling, and stenosis were significantly higher in Crohn's disease than in other disease. Moreover, uneven bowel wall thickening and unilateral mural hyperenhancement on CTE were characteristic features of Crohn's disease, which our original quantitative evaluation with imaging analysis could support. Consequently, CTE is useful in Japanese patients with Crohn's disease.

Loss of RUNX3 expression by histone deacetylation is associated with biliary tract carcinogenesis.

RUNX3 is a candidate tumor suppressor gene localized in 1p36, a region frequently inactivated through hypermethylation, histone modulation, and other processes in various human tumors. In this study, to elucidate a causal link between RUNX3 expression and biliary tract cancer, we investigated 17 human biliary cancer specimens. In addition, to examine roles of RUNX3 in biliary tract cancer, we restored silenced RUNX3 in the human biliary cancer cell line Mz-ChA-2 using a histone deacetylase inhibitor. Thirteen of 17 human cancer specimens exhibited suppressed RUNX3 expression compared with normal biliary ducts. Moreover, the decreased RUNX3 expression was related to a lower accumulation of acetylated histone H3 associated with RUNX3. In in vitro experiments, vorinostat, a member of a new class of highly potent histone deacetylase inhibitors, restored RUNX3 expression in Mz-ChA-2 cells. Furthermore, vorinostat-induced RUNX3 significantly enhanced p21 expression and growth inhibition of Mz-ChA-2 cells through restoration of TGF-ß signaling. These data suggest the significance of histone deacetylation-associated suppression of RUNX3 expression in biliary tract carcinogenesis. Furthermore, vorinostat might hold promise for treating biliary tract cancer through enhancement of TGF-ß signaling by restoration of RUNX3.

Inflammatory Pseudo-tumor of the Liver Accompanied by Eosinophilia.

A 28-year-old woman was referred to our hospital for liver dysfunction and neck pain. Blood tests revealed elevated liver enzymes and eosinophilia. Ultrasonography, computed tomography, and magnetic resonance imaging showed a mass lesion near the hepatic hilus. The tumor was considered to be an inflammatory pseudo-tumor or malignancy. A liver-mass biopsy was performed and led to a diagnosis of inflammatory pseudo-tumor. In the present case, a markedly elevated eosinophil count was a characteristic clinical feature, and the patient underwent steroid therapy. Treatment resulted in a reduced eosinophil count, improved neck symptoms, and disappearance of the inflammatory pseudo-tumor.

Late-onset type-2 autoimmune pancreatitis with two mass lesions diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

A 65-year-old man with ulcerative colitis presented with aggravated diabetes. Computed tomography showed two masses in the body and tail of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed, with histopathological findings suggesting autoimmune pancreatitis (AIP). Type-2 AIP was suspected, and administration of prednisolone was initiated. The pancreatic masses had disappeared after the treatment. In this case, EUS-FNA was effective for the diagnosis of type-2 AIP. The two-lesion mass formation observed here is a rare presentation of the disease. In patients with a history of ulcerative colitis, the possibility of late-onset type-2 AIP should be kept in mind.

Lesser Omental Panniculitis.

A 44-year-old woman presented to our hospital with abdominal pain. Abdominal ultrasonography and computed tomography showed a mass-like change in the lesser omentum between the liver and stomach. Esophagogastroduodenoscopy revealed a submucosal tumor-like change, and endoscopic ultrasonography (EUS) revealed that the mass was located outside of the stomach wall. We performed EUS fine-needle aspiration and diagnosed panniculitis of the lesser omentum. Based on these findings, we suggest that mass-like lesions in the lesser omentum and submucosal tumor-like changes in the anterior wall on the lesser curvature side of the stomach be evaluated for the possibility of panniculitis of the lesser omentum.

Development of Disseminated Tuberculosis with Intestinal Involvement due to Adalimumab Administration Despite Latent Tuberculosis Treatment.

Treatment of latent tuberculosis infection (LTBI) reduces the probability of reactivation of tuberculosis associated with anti-tumor necrosis factor (TNF) α inhibitors, but no chemoprophylaxis is completely protective. We herein report a woman with rheumatoid arthritis who developed disseminated tuberculosis with intestinal involvement during adalimumab administration despite LTBI treatment. Tuberculosis reactivation was not detected in sputum or urine but was detected from the terminal ileal mucosa. Detection of intestinal tuberculosis is rare in patients being treated with anti-TNFα therapy after LTBI treatment. As anti-TNFα inhibitors have become more common, the rate of reactivation of tuberculosis, including intestinal tuberculosis, has increased in patients being treated for LTBI.

Cholecystoduodenal fistula caused by aggressive mucinous gallbladder carcinoma with a porcelain gallbladder.

Cholecystoduodenal fistula secondary to gallbladder carcinoma (GBC) is extremely rare and develops when the tumor penetrates into the adjacent duodenum. A porcelain gallbladder is also a very rare entity that involves the calcification of the gallbladder wall and can be associated with the development of GBC. Herein, we report an unusual case of a patient with cholecystoduodenal fistula, which has been caused by aggressive mucinous gallbladder carcinoma with a porcelain gallbladder. A 68-year-old man was referred to our department due to significant accumulation near the neck of the gallbladder detected by FDG positron emission tomography/computed tomography (PET/CT), which was performed as a check-up of postpneumonectomy for lung cancer. Abdominal contrast CT and magnetic resonance imaging revealed porcelain-like circumferential calcification of the gallbladder wall and a mass in the region detected by FDG PET/CT. Furthermore, upper endoscopy revealed a submucosal tumor with apical ulceration in the posterior wall of the duodenal bulb. Histopathological examination of its biopsy specimen rendered a diagnosis of adenocarcinoma. The patient was preoperatively diagnosed with either gallbladder cancer or duodenal cancer, and subtotal stomach-preserving pancreatoduodenectomy and radical cholecystectomy with gallbladder bed resection were performed. The resected gallbladder revealed a porcelain gallbladder, which formed the cholecystoduodenal fistula. These specimens were histopathologically diagnosed as mucinous adenocarcinoma of the gallbladder with an abundant mucin production.

Biliary complications in donors for living donor liver transplantation.

OBJECTIVES: With the increasing number of living donor liver transplantations, biliary complications in donors have emerged as a major postoperative problem. The aim of the present study was to characterize the features of the biliary complications that occur in donors. METHODS: The study subjects comprised 731 consecutive patients who donated liver grafts (434 right-lobe and 297 left-lobe grafts) for transplantation at Kyoto University Hospital from July 1999 to December 2006. Donors whose biliary complications could not be cured by conservative therapy were referred for endoscopic treatment. RESULTS: Postoperative biliary complications occurred in 55 (7.5%) donors. Initially, 48 of these 55 donors had biliary leakage and 7 had biliary stricture. Subsequently, 5 of 48 donors with leakage developed biliary stricture. The respective incidences of biliary leakage and overall biliary complications were significantly higher among donors of right-lobe grafts (9.9% and 11.1%) than among donors of left-lobe grafts (1.7% and 2.4%). Among 55 donors with biliary complications, 24 were cured by conservative therapy, and 1 was converted to surgical repair due to ileus. Endoscopic treatment was successful in 24 of 30 (80%) donors treated by endoscopic retrograde cholangiography, while the remaining 6 (20%) patients underwent surgery due to difficulties with cannulation (N = 2), excessive biliary leakage (N = 2), or complete biliary obstruction (N = 2). CONCLUSIONS: Donors of right-lobe grafts have a significantly higher incidence of biliary complications than donors of left-lobe grafts. When conservative therapy fails, endoscopic treatment is effective for these complications, and should be attempted as the first-line therapy before surgical repair.

"Proton-pump inhibitor-first" strategy versus "step-up" strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition, and acid-suppressing agents are the mainstays of treatment. For the acute medical management of GERD, two different strategies can be proposed: either the most effective therapy, i.e., proton-pump inhibitors (PPIs), can be given first, or histamine H2-receptor antagonists (H2RAs) can be attempted first (the "step-up" approach). METHODS: A clinical decision analysis comparing the PPI-first strategy and the H2RA-first "step-up" strategy for the acute treatment of reflux esophagitis in Japan was performed, using a Markov chain approach. RESULTS: The PPI-first strategy was consistently superior to the step-up strategy with regard to clinical outcomes for the patient and with regard to cost-effectiveness (direct cost per patient to achieve clinical success). This superiority was robust within the plausible range of probabilities according to the sensitivity analyses. CONCLUSIONS: The PPI-first strategy is superior to the H2RA-first "step-up" strategy with regard to both efficacy and cost-effectiveness and therefore, the PPI-first strategy is the preferred therapeutic approach for the acute medical treatment of reflux esophagitis.

[Evaluation of the efficacy and the cost-effectiveness of maintenance treatment of gastroesophageal reflux disease: proton pump inhibitor versus histamine-2-receptor antagonist].

GERD is a common condition and acid-suppressing agents are the mainstay of treatment. A cost-effectiveness analysis comparing a PPI, lansoprazole (LPZ) and a H2RA, famotidine (FAM) for the maintenance treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The time period studied was 6 months and payer perspective was chosen. Transition probabilities were estimated from meta-analyses. Expected days without esophagitis (healthy days) were 166 for LPZ 30 mg/day, 161 for LPZ 15 mg/day and 143 for FAM 40 mg/day. Direct costs were 55,624 yen for LPZ 30 mg/day, 42,078 yen for LPZ 15 mg/day and 67,969 yen for FAM 40 mg/day. Cost-effectiveness ratio (direct costs/healthy days) was 335 yen for LPZ 30 mg/day, 262 yen for LPZ 15 mg/day and 477 yen for FAM 40 mg/day. Lansoprazole was superior to famotidine with regard to both efficacy and cost-effectiveness and therefore is the preferred therapeutic agent for the maintenance treatment of GERD.

Endoscopic treatment of biliary complications after right-lobe living-donor liver transplantation with duct-to-duct biliary anastomosis.

BACKGROUND/PURPOSE: The aims of this study were to characterize the features of the biliary complications that occur after right-lobe living-donor liver transplantation (RL-LDLT) with duct-to-duct biliary anastomosis, and to evaluate the efficacy of treating biliary complications endoscopically. METHODS: The records of 273 consecutive patients who underwent RL-LDLT with duct-to-duct biliary anastomosis from July 1999 through July 2005 at Kyoto University Hospital were reviewed to determine the overall incidence of postoperative biliary complications and the outcome of endoscopic repair of those complications. RESULTS: Biliary complications occurred in 93 (34.1%) of the patients. These complications were: 80 biliary strictures (75 anastomotic and 5 nonanastomotic) and 16 biliary leakages (5 patients with biliary leakage also had a biliary stricture); most (72%) of the anastomotic strictures were complex (i.e., fork-shaped or trident-shaped). The strictures and leakages were repaired by the endoscopic placement of multiple inside stents above the sphincter of Oddi, and by nasobiliary drainage, respectively. The procedure was successful in repairing 51 (68.0%) of the anastomotic strictures and 8 (50.0%) of the biliary leakages. CONCLUSIONS: Endoscopic stenting of the bile ducts is efficacious in treating biliary complications related to RL-LDLT with duct-to-duct biliary anastomosis and the stenting should be attempted before surgical revision of strictures and leakages.