Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis.

Tocilizumab is a monoclonal antibody against human interleukin-6 receptor which blocks the binding of interleukin-6 to its receptor. Tocilizumab is effective for the treatment of inflammatory disorders including rheumatoid arthritis. We report a case of multiple ulcers in the small and large intestines, which occurred during tocilizumab therapy. A 57-year-old woman started to use tocilizumab for rheumatoid arthritis. Three months later, she complained of hematochezia. Double-balloon endoscopy revealed multiple small aphthoid ulcers in the small and large intestines. One month after the woman had recovered, she was given tocilizumab again. The woman had hematochezia and abdominal pain again 2 weeks later. Colonoscopy revealed multiple round, discrete punched-out ulcers in the terminal ileum, and vast deep ulcers from the cecum to the descending colon. Bioptic histopathology and cultivation showed non-specific findings. Six weeks after discontinuation of tocilizumab, ulcers in the small and large intestine dramatically improved, leaving ulcer scars. This disease course and the results of examination made us strongly suspect that tocilizumab induced multiple ulcers in the small and large intestines. Interleukin-6 is a pleiotropic cytokine and involved in intestinal mucosal wound healing as well as in inflammatory processes. It is possible that tocilizumab inhibited tissue repair of the intestine and caused intestinal ulcers.

Differential diagnosis of cystic tumors of the pancreas by endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Generally, cystic tumors are divided into two categories: neoplastic cystic tumors and non-neoplastic cystic (NNC) tumors. Neoplastic cystic tumors include mucinous cystic neoplasm (MCN), intraductal papillary-mucinous neoplasm (IPMN), and serous cystic neoplasm (SCN). MCNs and IPMNs have the potential to progress to a malignant state, whereas SCNs are known for their almost benign behavior. Thus, in order to make management decisions, it is important to distinguish between potentially malignant (MCN and IPMN), and benign (SCN and NNC) tumors. The aim of this study was to retrospectively investigate the value of endoscopic ultrasonography (EUS) for the differential diagnosis of cystic tumors of the pancreas. PATIENTS AND METHODS: A total of 76 patients with cystic tumors of the pancreas were preoperatively examined by EUS. Eight cases were MCNs, 45 were IPMNs, 13 were SCNs, and 10 were NNC tumors. The EUS findings relevant to distinguishing between potentially malignant and benign were analyzed statistically. RESULTS: All patients with MCNs were female and all these tumors were located in the pancreatic body/tail. IPMN, however, occurred predominantly in men, and in the pancreatic head. Eight of 11 monolocular cystic tumors were NNC in nature. Eleven of 13 SCNs included microcystic areas within the tumors. All MCNs were round in appearance, whereas 93 % of IPMNs were not round in appearance. Mural nodules were present in 25 % of MCN and 38 % of IPMN cases. In univariate analysis, age, tumor size, locularity, the number of cystic formation, cystic component, and appearance were significant variables. In multivariate analysis, locularity and cystic component were important for differential diagnosis of potentially malignant cystic tumors. CONCLUSIONS: The characteristics of cystic tumors of the pancreas revealed by EUS are useful for their differential diagnosis.

Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas: a case series.

In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary gastrointestinal follicular lymphomas are frequently distributed to multiple sites in the gastrointestinal tract. Therefore, investigation into the spread of follicular lymphomas in the small bowel is important in order to determine the most appropriate treatment strategy. The performance of double-balloon endoscopy (DBE) in the diagnosis of jejunoileal follicular lymphoma lesions has not been fully evaluated. We aimed to investigate the value of DBE in addition to computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the diagnosis of jejunoileal follicular lymphoma. DBE with biopsy was performed in seven patients with primary duodenal follicular lymphoma diagnosed by EGD, in order to investigate jejunoileal involvement. Jejunoileal follicular lymphoma lesions were detected by DBE in six out of the seven patients (three in the jejunum and three in the jejunum and ileum), whereas CT and (18)F-FDG-PET failed to detect the existence of these lesions. Endoscopic findings of the jejunoileal lesions revealed multiple white nodules and white villi, which were similar to those of duodenal lesions. DBE was more useful for the diagnosis of jejunoileal involvement in primary intestinal follicular lymphoma than CT and (18)F-FDG-PET. The use of DBE will become important for determining the most appropriate treatment for gastrointestinal follicular lymphoma.

An increase in the serum amylase level in patients after peroral double-balloon enteroscopy: an association with the development of pancreatitis.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a novel technique that allows the enteroscope to be inserted deep into the small intestine. The procedure has been thought to be safe, but cases of acute pancreatitis after peroral DBE have recently been observed. The aim of this study was to confirm the occurrence of hyperamylasemia after peroral DBE. PATIENTS AND METHODS: Peroral DBE was carried out in 13 patients from July 2005 to February 2006. Blood samples were taken before and 3 h after the procedure, and serum pancreatic amylase levels were measured. The patients were also evaluated for pancreatic-type abdominal pain after the procedure. Hyperamylasemia after peroral DBE was defined as an elevation of the serum pancreatic amylase level to more than the upper normal limit and twice the level before the procedure. Pancreatitis was diagnosed on the basis of both pancreatic-type abdominal pain and hyperamylasemia. RESULTS: Hyperamylasemia after peroral DBE occurred in six patients (46.2 %). One of the six patients with hyperamylasemia had pancreatic-type abdominal pain after the procedure and developed acute pancreatitis. The average procedure time was 105 min (range 65 - 155 min) in the patients with hyperamylasemia, and did not significantly differ from that in the group without hyperamylasemia (99 min). CONCLUSIONS: Hyperamylasemia after peroral DBE occurs frequently and may be associated with development of pancreatitis.

Presence of C-type natriuretic peptide (CNP) in guinea pig caecum: role and mechanisms of CNP in circular smooth muscle relaxation.

The distribution and role of C-type natriuretic peptide (CNP) in the gastrointestinal tract are still unclear. This study was designed to investigate the distribution of CNP in guinea pig caecum and the inhibitory mechanisms of CNP in caecal circular smooth muscle cells. CNP immunoreactivity was recognized in smooth muscle cells, myenteric and submucosal neurons of the caecum by immunohistochemistry. CNP mRNA expression was demonstrated in both freshly dispersed and cultured smooth muscle cells by reverse-transcription polymerase chain reaction. CNP inhibited 1 nmol L(-1) cholecystokinin octapeptide (CCK-8)-induced smooth muscle cell contraction in a dose-dependent manner, with an IC(50) value of 0.24 nmol L(-1), and significantly stimulated the production of intracellular cyclic guanosine monophosphate. Furthermore, inhibitors of both soluble and particulate guanylate cyclase (GC) partially but significantly inhibited CNP-induced relaxation. This is the first report demonstrating that CNP localizes in gastrointestinal smooth muscle cells and the enteric nervous system. These results suggest that CNP acts locally through neural and autocrine pathways to modulate colonic motility via both particulate and soluble GC systems. These two pathways appear to be through natriuretic peptide receptor (NPR)-B, which has particulate GC domain, and NPR-C, which activates soluble GC, judging from previous findings that NPR-A is not expressed in these cells.

[A case of advanced hepatocellular carcinoma with lung and bone metastases effectively treated by orally administered UFT].

A 52-year-old male underwent hepatic subsegmentectomy for hepatocellular carcinoma (HCC). Five months later, a recurrent tumor was found in the liver and transcatheter arterial embolization (TAE) was performed. However, recurrent tumors were growing rapidly with multiple lung and bone metastases. The titer of serum AFP was elevated to 896,095 ng/ml and the titer of serum PIVKA-II was elevated to 1294.5 AU/ml. The patient was treated by oral administration of UFT (600 mg/day). Two weeks later, his general condition was improved, and several months later, the liver tumor, multiple lung metastases and multiple bone metastases had almost disappeared. The titers of serum AFP and PIVKA-II were reduced to the normal range. He has maintained a good state of health for about four years now. This case suggests the clinical usefulness of UFT for advanced HCC.