Efficacy of Magnifying Narrow Band Imaging with Acetic Acid Spray in Diagnosing Superficial Non-Ampullary Duodenal Epithelial Tumors.

BACKGROUND/AIMS: The aim of the present study was to evaluate the efficacy of magnifying narrow band imaging with acetic acid spray (MA-NBI) in differentiating category 4/5 lesions from category 3 lesions of superficial non-ampullary duodenal epithelial tumors (SNADETs) as per Vienna Classification and to compare the diagnostic performances of both MA-NBI and magnifying narrow band imaging (M-NBI). METHODS: We retrospectively identified 60 resected SNADETs (31 category 3 lesions and 29 category 4/5 lesions) in 60 patients who underwent M-NBI and MA-NBI preoperatively. We evaluated vascular and surface patterns using M-NBI and MA-NBI for characterizing category 3 and 4/5 lesions. The surface pattern was classified as tubular, villous, or mix structure using MA-NBI. In addition, lesions with disorganized and unclear structures with irregular margins that can be clearly recognized by MA-NBI were defined as irregular surface structures. RESULTS: For MA-NBI, category 4/5 lesions had a significantly higher mix structure rate and higher irregular surface structure rate than category 3 lesions (62 vs. 16%, p < 0.001, and 86 vs. 19%, p < 0.001, respectively). The diagnostic accuracy of MA-NBI using mix and irregular surface structures for identifying category 4/5 lesions was as follows: sensitivity, 62/86%; specificity, 84/77%; positive predictive value, 78/78%; negative predictive value, 70/86%; and accuracy, 73/82%. The diagnostic accuracy of MA-NBI using irregular surface structure was significantly higher than that of M-NBI (p < 0.05). CONCLUSION: MA-NBI may be useful in differentiating between category 3 and category 4/5 lesions of SNADETs.

A fat containing combined neuroendocrine carcinoma and hepatocellular carcinoma in the liver: A case report.

A 79-year-old man was admitted to our hospital because of increased hepatobiliary enzyme levels. Dynamic computed tomography and magnetic resonance imaging showed a liver tumor measuring 60mm containing fat foci at the cranial aspect of the tumor. We diagnosed the patient with hypovascular hepatocellular carcinoma (HCC) and fat deposition, and performed a caudate lobe resection. Pathology examination revealed two intermingled components: moderately differentiated HCC with fat deposition and neuroendocrine carcinoma (NEC). Primary combined NEC and HCC is extremely rare. To our knowledge, this is the first report of combined NEC and HCC including a fat component. HCC is the most common primary hepatic malignancy with fat. HCC might include fat, even if HCC coexists with another type of cancer. The imaging characteristics of and HCC with another type of cancer vary depending on the amount of each component. We should not simply diagnose such tumors as HCC, but think about the possibilities of HCC with another type of cancer, because there is a fat component.

[A case of concomitant pancreatic neuroendocrine neoplasm and intraductal papillary mucinous neoplasm in which preoperative diagnosis was difficult].

A 75-year-old male patient has been followed-up for mixed-type intraductal papillary mucinous neoplasm (IPMN) in the tail of the pancreas for about 20 years. Upon close examination, he was diagnosed of high-risk stigmata due to a nodule having a contrast effect of 5mm or more in the tumor. Based on this, a distal pancreatectomy was performed. Histopathological analysis revealed concomitant IPMN (low-grade) and pancreatic neuroendocrine neoplasm (PNEN) (G1). This prompted us to report a very rare case of coexisting PNEN and IPMN with an interesting pathological finding that might suggest its pathogenic mechanism.

[Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography].

OBJECTIVE: The aim of this study was to determine if the difference in serum amylase levels prior to, and two hours following, an endoscopic retrograde cholangiopancreatography (ERCP), or the ratio of the two-hour post-ERCP amylase level to the pre-ERCP amylase level was a better predictor of post-ERCP pancreatitis (PEP). METHODS: This was a retrospective, single-center study of consecutive patients, who underwent ERCP between April 2015 and August 2018. Serum amylase was measured before and two hours following ERCP. We compared the difference and the ratio of the two levels in predicting PEP using a receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 1029 patients underwent ERCP, with PEP occurring in 118 (11.5%). Multivariate analysis revealed that an elevated two-hour post-ERCP serum amylase level was a significant predictor of PEP. ROC analysis of the difference and the ratio of the two levels found good performance for both parameters, with an area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.823-0.900) and 0.847 (95% CI, 0.809-0.886), respectively. The difference between the values was a significantly more effective predictor of PEP, based on the AUC analysis (P = 0.011). CONCLUSION: The difference between pre and two-hour post-ERCP amylase levels is a better predictor of PEP than the ratio of the two.

[Successful biliary drainage by percutaneous transhepatic puncture common bile duct and rendezvous technique for a case of recurrent biliary pancreatitis with a Roux-en-Y reconstruction and without extension of the bile duct].

A 92-year-old woman was hospitalized with upper abdominal pain. She had a history of acute biliary pancreatitis and chronic heart failure and had undergone gastrectomy with Roux-en-Y reconstruction. She was admitted with recurrent pancreatitis and an exacerbation of heart failure. Biliary drainage could not successfully be achieved endoscopically or with percutaneous transhepatic biliary drainage and EUS-guided biliary drainage because of the Roux-en-Y reconstruction and non-dilation of bile duct. We successfully accomplished biliary drainage in one session with percutaneous transhepatic puncture of the common bile duct with ultrasound guidance and the rendezvous technique. We report this case because it is rare.

[Vitamin K deficiency caused by nutritional malabsorption accompanying afferent loop obstruction:a case report].

This case involves a 73-year-old man who visited a clinic because he was experiencing dyspnea on exertion and acid reflux. He was diagnosed with anemia and referred for a medical check-up and treatment by his primary care physician. Iron deficiency anemia and prolonged prothrombin time were confirmed with a blood test and an abdominal enhanced CT revealed marked expansion of the afferent loop after a gastrectomy. The medical check-up revealed abnormal blood coagulation due to afferent loop obstruction, which resulted in vitamin K deficiency. He was supplemented with vitamin K, and surgery was performed for the afferent loop obstruction. Postoperatively, his anemia, nutritional status, serum vitamin K levels, and prothrombin time improved steadily. In conclusion, nutrient malabsorption may occur in cases of afferent loop obstruction and abnormal blood coagulation due to vitamin K deficiency.

[A case of relapsed hemosuccus pancreaticus successfully treated with interventional radiology].

A 67-year-old male with chronic pancreatitis presented with upper abdominal pain and melena. Abdominal dynamic computed tomography revealed a splenic artery aneurysm in the main pancreatic duct. Esophagogastroduodenoscopy showed active bleeding from Vater's papilla. The patient was diagnosed with hemosuccus pancreaticus (HP) due to rupture of the aneurysm and treated with interventional radiology (IVR). The patient's poor lung function did not allow for a radical operation and a follow-up examination was recommended. The HP relapsed 7 months later and was successfully retreated with IVR. Although IVR is associated with a high recurrence rate, it is less invasive and therefore effective for treating relapsing HP in patients with a poor general condition.

Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C.

BACKGROUND: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown. AIM: This study is aimed at clarifying the factors affecting IFNL3 production and assessing the roles of IFNL3 in AHC. MATERIALS AND METHODS: A total of 21 AHC patients who visited the hospital within 10 days after symptom onset were assessed. As controls, 23 healthy volunteers (HVs) were examined. Serum IFNL3 levels were quantified using an in-house, IFNL3-specific chemiluminescence enzyme immunoassay (CLEIA) kit. Serum IFNL1, IFN-α, IFN-ß, and IFN-γ induced protein-10 (IP-10) levels were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: At baseline, serum IFNL3 levels were higher in AHC patients than in HVs (p < 0.0001). The higher levels in AHC patients did not differ between patients with the rs8099917 TT genotype and those with the non-TT (TG/GG) genotype (p = 0.546). Serial measurement of serum IFNL3 levels did not predict the outcome of conventional AHC. However, serum IFNL3 levels at baseline correlated positively with the HCV RNA levels (p = 0.005). Following HCV eradication, serum IFNL3 levels reduced to within the range obtained for HVs. Baseline serum IFNL1 levels did not differ significantly between AHC patients and HVs (p = 0.284). Serum levels of IFNL1 and IFNL3 at baseline also showed no correlative power (p = 0.288). Serum IFN-α and IFN-ß were detected together with remarkably high serum IFNL3 levels in only one patient who progressed to acute liver failure (ALF). CONCLUSION: These findings indicate that serum IFNL3 levels at baseline are higher in AHC patients regardless of the rs8099917 polymorphism, and primary HCV infection triggers the production of IFNL3. As a first line of defense in the innate immune system against invading HCV, increased IFNL3 levels play an important role, but serum IFNL3 levels are not the principal determinant of the clinical course of conventional AHC.

Hepatitis C Treatment with Sofosbuvir and Ledipasvir Accompanied by Immediate Improvement in Hemoglobin A1c.

BACKGROUND/AIMS: Direct-acting antiviral agents (DAAs) have increased the sustained viral response rate with minimal adverse effects and short treatment duration. In addition, recent data suggest the possibility that hepatitis C virus (HCV) clearance results in rapid improvement in metabolic pathways. The aim of the present study was to evaluate whether the DAA treatment without ribavirin lowers hemoglobin A1c (HbA1c) at 12 weeks after therapy completion. METHODS: We performed an observational study to assess the effect of sofosbuvir and ledipasvir (SOF/LED) treatment on glycemic control. We compared HbA1c levels before and after treatment with SOF/LED, considering that anemia is not a side effect of these drugs. RESULTS: In the 36 patients with HCV eradication, HbA1c levels decreased significantly after treatment (pre-treatment 5.85% vs. post-treatment 5.65%, p < 0.01). CONCLUSION: This pilot study shows the possibility that HCV eradication by SOF/LED was accompanied by an improvement of glucose metabolism in the population with or without diabetes, and suggests further investigation.

A case of resected hepatocellular carcinoma after drug-eluting bead transarterial chemoembolization.

We report a case of resected hepatocellular carcinomas (HCCs) after drug-eluting bead transarterial chemoembolization (DEB-TACE). A 67-year-old man with alcoholic liver disease was diagnosed with HCCs. Serological markers for hepatitis B and C viruses were negative. Among tumor markers, alpha-fetoprotein was 2.7ng/mL, and protein induced by vitamin K absence II was 868mAU/mL. Two HCCs were detected using dynamic computed tomography: one was 9cm in diameter in S8 and the other was 2cm in diameter in S4. We performed DEB-TACE using HepaSphere(®) and epirubicin. DEB-TACE was repeated three times in three months. Severe postembolization syndrome was not seen with any treatment. Four weeks after the last DEB-TACE, we performed surgical resection. Histopathological study revealed dense distribution of numerous bead particles in necrotic tumor tissue. Otherwise, in non-cancerous tissue, some beads were in portal areas, without necrotic change. Granulomas from foreign body reaction with giant cells were present around the beads. There were no necrotic changes in the smaller HCC, the intrahepatic metastatic nodules, or the microscopic invasion to the portal vein. In conclusion, DEB-TACE would be a useful treatment for huge HCCs; however, patients should be monitored for early recurrence from residual tumor tissue. This study will be helpful to perform DEB-TACE in the future.

[A patient with sepsis and a gas-forming liver abscess caused by Clostridium perfringens treated with continuous perfusion drainage].

A 64-year-old man presented with diarrhea, fever, and disturbance of consciousness; he was subsequently diagnosed with acute renal and hepatic disorder. Abdominal computed tomography identified a gas-forming liver abscess, and the patient underwent emergency drainage. However, his condition did not improve, and Clostridium perfringens was observed in his blood culture. Continuous perfusion drainage was performed by placing an additional drainage tube, which resulted in abscess shrinkage and improved the patient's general condition. Despite the low survival rate in patients with gas-forming liver abscesses caused by C. perfringens, therapy was successful in this patient.

Risk of cancer in patients with autoimmune pancreatitis.

OBJECTIVES: Although simultaneous occurrences of autoimmune pancreatitis (AIP) and cancer are occasionally observed, it remains largely unknown whether cancer and AIP occur independently or these disorders are interrelated. The aim of this study was to examine the relationship between AIP and cancer. METHODS: We conducted a multicenter, retrospective cohort study. One hundred and eight patients who met the Asian diagnostic criteria for AIP were included in the study. We calculated the proportion, standardized incidence ratio (SIR), relative risk, and time course of cancer development in patients with AIP. We also analyzed the clinicopathological characteristics of AIP patients with cancer in comparison with those without cancer. RESULTS: Of the 108 AIP patients, 18 cancers were found in 15 patients (13.9%) during the median follow-up period of 3.3 years. The SIR of cancer was 2.7 (95% confidence interval (CI) 1.4-3.9), which was stratified into the first year (6.1 (95% CI 2.3-9.9)) and subsequent years (1.5 (95% CI 0.3-2.8)) after AIP diagnosis. Relative risk of cancer among AIP patients at the time of AIP diagnosis was 4.9 (95% CI 1.7-14.9). In six of eight patients whose cancer lesions could be assessed before corticosteroid therapy for AIP, abundant IgG4-positive plasma cell infiltration was observed in the cancer stroma. These six patients experienced no AIP relapse after successful cancer treatment. CONCLUSIONS: Patients with AIP are at high risk of having various cancers. The highest risk for cancer in the first year after AIP diagnosis and absence of AIP relapse after successful treatment of the coexisting cancers suggest that AIP may develop as a paraneoplastic syndrome in some patients.

Effect of vitamin K2 on the recurrence of hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P=0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. CONCLUSION: Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study.

Sorafenib Rechallenge and Sorafenib after Lenvatinib Failure in a Patient with Hepatocellular Carcinoma.

A 70-year-old man was diagnosed with multiple lung metastases from hepatocellular carcinoma, and lenvatinib was initiated. Three months later, the response was progressive disease. Sorafenib therapy as a second-line drug was started. Three months later, the lung metastases had shrunk. After the sorafenib failure, the patient received regorafenib treatment for six months until failure. After the regorafenib failure, sorafenib rechallenge therapy as a fourth-line treatment was initiated. The sorafenib rechallenge, which continued for two months, induced a partial response. Sorafenib after lenvatinib failure and sorafenib rechallenge may be a good option, but further prospective studies are needed.

Gastric Cancer with Multiple Lymph Node Enlargement at the Time of the Sarcoidosis Diagnosis.

An 80-year-old woman was found to have a 40-mm depressed-type gastric cancer. Computed tomography showed multiple lymph node enlargement, including paraaortic lymph nodes. The extent of lymph node enlargement was significant compared with the depth of the primary lesion. We conducted distal gastrectomy, D2 lymph node dissection, and a paraaortic lymph node biopsy. Microscopically, the tumor was diagnosed as mucosal cancer. In the dissected lymph nodes, noncaseating granuloma was found without metastasis of adenocarcinoma. Immunohistochemical staining using Propionibacterium acnes-specific antibodies showed a large number of P. acnes-positive cells in the granulomas. Finally, the tumor was diagnosed as early-stage gastric cancer and sarcoidosis.

Gastric MiNEN Arising from the Heterotopic Gastric Glands.

An 80-year-old woman presented with a 30-mm protruding lesion-like submucosal tumor with a central depression located at the anterior wall of the upper gastric body. The depressed area had a well-demarcated margin, while the other area was covered by a non-neoplastic mucosa. A biopsy specimen revealed neuroendocrine carcinoma. Endoscopic ultrasonography revealed a heterogeneous mass with a clearly distinguished border in the submucosal layer. The mass had two distinct areas adjacent to each other. In addition, a hypoechoic zone was observed on the margin of the mass. Distal gastrectomy was performed. The final diagnosis was a mixed neuroendocrine-non-neuroendocrine neoplasm arising from the heterotopic gastric gland.

Contrast-enhanced ultrasonography evaluation of hepatocellular carcinoma with peritumoral fat-spared area: a case report.

Peritumoral fat-spared area (PTFSA), a focal spared area surrounding hepatic tumors, is a specific finding of liver tumors in fatty livers. PTFSA mimics a liver tumor, making it difficult to recognize the tumor boundary. We report a case of a 56-year-old man with fatty liver who was diagnosed with a liver tumor. Ultrasonography (US) revealed a nearly homogeneous hyperechoic liver tumor measuring 40 mm in the left lobe. A thick hypoechoic area was observed around the tumor that spread more widely than an ordinary halo. Histological examination revealed that the hypoechoic area comprised a thin fibrous capsule and normal liver parenchyma without fat, which is PTFSA. Contrast-enhanced US (CEUS) indicated corona enhancement only at the inner part of the PTFSA. The inner part showed the same pattern as that of an ordinary halo and was a part of hepatocellular carcinoma, whereas the outer part showed the same pattern as that of the other liver parenchyma. CEUS was an effective modality for distinguishing the difference. Thus, CEUS was useful in defining the tumor boundary. Before initiating treatment, tumors should be evaluated using various modalities to detect their accurate boundary. CEUS may be a useful modality for detecting the boundary and making a diagnosis.

Bezafibrate may attenuate biliary damage associated with chronic liver diseases accompanied by high serum biliary enzyme levels.

BACKGROUND: Bezafibrate is a commonly used medicine for hyperlipidemia, and recently several reports have suggested the efficacy of bezafibrate for the treatment of primary biliary cirrhosis (PBC). To assess its efficacy for other liver diseases, we administered bezafibrate to patients with various categories of hepatobiliary impairment. METHODS: Bezafibrate (400 mg/day) was orally administered to 67 patients with chronic liver disease [22 with PBC, six with primary sclerosing cholangitis (PSC), 20 with chronic liver disease associated with hepatitis C virus (HCV) infection (CLD-C), seven with auto immune hepatitis (AIH), ten with alcoholic liver injury, and two with drug-induced liver injury]. RESULTS: The levels of biliary enzymes, such as alkaline phosphatase and gamma-glutamyltranspeptidase, decreased promptly and dramatically. The abnormally high level of alanine aminotransferase also showed a gradual decrease over 6 months in five of the eight PBC patients, all three PSC patients, eight of the 17 CLD-C patients, and all seven alcoholic liver injury patients. The level of immunoglobulin M showed a gradual decrease in 17 of the 22 PBC patients. CONCLUSIONS: Bezafibrate significantly reduced the level of biliary enzymes in various chronic liver diseases and may be useful for the treatment of certain liver disease subsets.