[A case of difficult to diagnose duodenal gastrinoma].

A 42-year-old man, after remission of MALT lymphoma of the small intestine, was repeatedly hospitalized because of abdominal pain and severe dehydration caused by frequent vomiting and watery diarrhea. His symptoms would improve quickly every time when he was fasted and inserted a nasogastric tube. We were unable to find abnormalities on endoscopic examination and computed tomography. He was suspected to have gastrinoma because of active bleeding from a duodenal ulcer. High-level serum gastrin, endoscopic ultrasound, somatostatin receptor scintigraphy, and selective arterial calcium injection test were done. He was diagnosed with pancreatic gastrinoma in the pancreatic head by endoscopic ultrasound fine needle aspiration and subsequently underwent pancreatoduodenectomy. Histopathologic findings showed a 3-mm neuroendocrine tumor located in the duodenal submucosal layer. The presence of metastasis was confirmed in one of the peripancreatic lymph nodes. The pancreatic gastrinoma in the pancreatic head that we initially diagnosed was a lymph node metastasis behind the pancreas. Because additional resection was performed on the duodenum, we were able obtain a diagnosis of duodenal gastrinoma.

[A case of pancreatic neuroendocrine tumor with ring-like enhancement].

An 82-year-old female underwent contrast computed tomography (CT) that revealed multiple ring-like enhanced masses in the pancreatic tail. Additionally, the inside of the masses showed enhancement on contrast endoscopic ultrasound (EUS). She was diagnosed with a pancreatic neuroendocrine tumor on histopathological examination after EUS-guided fine-needle aspiration, and distal pancreatectomy and splenectomy were performed. In the resected specimen, toward the tumor center, tumor cells with lipid droplets and fibrosis were remarkably observed. These rare histopathological features well reflected the image findings of contrast CT and contrast EUS.

[A case of paralytic ileus associated with varicella zoster virus infection].

A 79-year-old woman with a history of pyothorax was admitted with a 4-day history of abdominal distension. Physical examination revealed marked abdominal distention, absent bowel sounds, and a vesicular rash over the left Th8-10 dermatome. Abdominal radiography showed gaseous distension of the colon and ileum. Colonoscopy excluded any obstructive process of the colon. Laboratory findings yielded positive results for serum IgM and IgG against the varicella zoster virus (VZV) . Paralytic ileus associated with the VZV was therefore diagnosed. The ileus improved after conservative treatment with intravenous acyclovir. Although shingles is frequently encountered, it is a rare cause of paralytic ileus. In the future, the VZV should be considered as one of the causes of paralytic ileus, and complete resolution can be achieved with conservative management.

A case of pyloric gland adenoma with high-grade dysplasia in the duodenum arising from heterotopic gastric mucosa observed over 5 years.

Pyloric gland adenoma (PGA) in the duodenum is a rare gastric phenotype duodenal neoplasm. Although heterotopic gastric mucosa in the duodenum has been recognized as a benign lesion, it is a potential precursor of PGA and gastric phenotype adenocarcinoma. Herein, we present a case follow-up of endoscopic and histological changes in the PGA in the duodenum from low-grade to high-grade dysplasia. PGA was considered to arise from the heterotopic gastric mucosa, because the heterotopic gastric mucosa was observed in the initial examination. It is difficult to distinguish heterotopic gastric mucosa from PGAs, both endoscopically and histologically. This increase in size may be useful for their differentiation. Therefore, endoscopists should not underestimate the growth of the heterotopic gastric mucosa compared to that in the previous examination.

[A case of autoimmune pancreatitis with multifocal mass lesions].

We present a case of a 73-year-old man with multifocal autoimmune pancreatitis (AIP) in the pancreatic head and tail, and who had undergone sigmoidectomy and rectectomy 28 months before presenting to our department. Upon presentation, his serum IgG4 level was elevated at 267mg/dl, but tumor marker levels were within normal ranges. CT and MRI showed two localized pancreatic masses with delayed enhancement, but endoscopic retrograde pancreatography revealed neither stenosis nor dilatation of the main pancreatic duct. FDG-PET examination showed intense uptake in regions concordant with both tumors. The possibility of atypical AIP was a concern, but malignant tumor could not be clinically or radiologically excluded. Endoscopic ultrasonographic fine-needle aspiration biopsy was performed, but no malignant cells were detected. The patient underwent subsequent distal pancreatectomy. Histological evaluation of the tumors showed the presence of many IgG4-positive plasma cells without any evidence of malignancy.

Asystole-induced Bradycardia by Dexmedetomidine during Endoscopic Submucosal Dissection.

Although dexmedetomidine (DEX) is a widely used analgesic and sedative agent for endoscopic procedures, cardiovascular complications, such as bradycardia and hypotension, are frequently experienced. We herein report the first case of asystole-induced bradycardia due to DEX during endoscopic submucosal dissection (ESD). An 81-year-old man without cardiovascular diseases was referred for gastric carcinoma. ESD was started after administering a loading dose of DEX followed by a continuous maintenance infusion of DEX. The patient's heart rate gradually decreased, and then cardiac arrest occurred. DEX has a risk of cardiac arrest, so bradycardia should not be underestimated during sedation with DEX.

Perforation of a Gastric Tear during Esophageal Endoscopic Submucosal Dissection under General Anesthesia.

Mallory-Weiss tears (MWT) are occasionally encountered during endoscopic procedures. Esophageal endoscopic submucosal dissection (ESD) is widely performed under general anesthesia to avoid unexpected body movements. We present the case of a 68-year-old woman with squamous cell carcinoma. Although ESD was performed under general anesthesia, a gastric perforation at the MWT caused by gastric inflation was observed after the procedure. The perforation was closed endoscopically, and she was discharged without any sequelae. Although general anesthesia is useful for esophageal ESD, it should be noted that it can cause MWT, and in rare cases, gastric perforation, due to gastric inflation during the procedure.

A case of esophageal squamous cell carcinoma with neuroendocrine, basaloid, and ciliated glandular differentiation.

Esophageal carcinomas have multidirectional differentiation abilities and different histological components have been reported. Herein, we report a case of esophageal carcinoma with four different differentiations. A 64-year-old man was referred to our hospital for treatment of an esophageal tumor detected during an esophagogastroduodenoscopy, which revealed an elevated lesion accompanied by a slightly depressed lesion in the middle of the esophagus. Examination of the biopsy specimen obtained from the elevated lesion revealed an adenocarcinoma, while that from the depressed lesion revealed a squamous cell carcinoma. Fluorodeoxyglucose-position emission tomography and enhanced computed tomography showed an esophageal carcinoma in the middle of the esophagus with no signs of metastasis. The preoperative diagnosis was adenosquamous cell carcinoma classified as T2N0M0 according to the TNM classification (seventh edition). Thoracoscopic esophagectomy was performed. Examination of the resected specimen revealed esophageal squamous cell carcinoma with neuroendocrine, basaloid, and ciliated glandular differentiation. Although they may be totipotent, an esophageal carcinoma consisting of four components is extremely rare. Moreover, ciliated glandular differentiation is rarely observed in the esophagus, except in individuals with bronchial esophageal duplication cysts and adenocarcinoma arises from a Barrett's esophagus.

Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

BACKGROUND: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. METHODS: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. DISCUSSION: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. TRIAL REGISTRATION: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.

A rare case of plexiform neurofibroma of the liver in a patient without neurofibromatosis type 1.

Plexiform neurofibroma is mainly associated with neurofibromatosis type 1 and is seldom observed in the liver. Its occurrence in the liver without neurofibromatosis type 1 is even rarer. We report an extremely rare case of plexiform neurofibroma of the liver diagnosed by laparoscopic biopsy in a patient without neurofibromatosis type 1. The patient was a 35-year-old man who had neither clinical signs nor any family history of neurofibromatosis type 1. Abdominal ultrasonography, as part of a health screening, had detected a hepatic tumor. Subsequent contrast ultrasonography, computed tomography, and magnetic resonance imaging showed the tumor extending from the retroperitoneal space around the aorta to the hepatic hilum and distal portal branches in the right hepatic lobe, gallbladder, and left hepatic lobe. 18F-fluorodeoxyglucose positron emission tomography showed no abnormal accumulation. Histopathological examination of the tumor obtained laparoscopically led to a diagnosis of plexiform neurofibroma. Because the patient was asymptomatic with no features of malignancy, he was only monitored and managed. At follow-up 10 years later, computed tomography showed a decrease in tumor size. It is important to recognize that, while rare, plexiform neurofibroma can occur without neurofibromatosis type 1. We recommend follow-up instead of unreasonable surgery in such cases.

Usefulness of double-balloon endoscopy in the diagnosis of malignant small-bowel tumors.

BACKGROUND & AIMS: Double-balloon endoscopy (DBE) enables endoscopic and histopathologic diagnosis of malignant small-bowel tumors (MSBT). This study examined the clinical features of patients with MSBT and evaluated the usefulness of DBE in the diagnosis of MSBT. METHODS: We retrospectively examined consecutive DBE studies of 358 patients who underwent DBE in our hospital between December 2003 and October 2007 because of suspected or established small-bowel disease. RESULTS: Fourteen patients with MSBT were diagnosed by DBE. The most common type was primary adenocarcinoma (8 patients), followed by metastatic carcinoma (3 patients) and malignant lymphoma (3 patients). Half of these patients presented with obscure gastrointestinal bleeding (OGIB). Histopathologic diagnosis was obtained in 11 of 14 patients. CONCLUSIONS: Of 180 patients with OGIB, MSBT accounted for only 3.9%, however, 50% of patients with MSBT presented with OGIB. OGIB is an important clinical feature of small-bowel malignancy, which can be diagnosed by DBE.

Signet-ring cell carcinoma of the jejunum diagnosed by double balloon enteroscopy.

The small bowel rarely develops neoplasms, accounting for only 1-2% of all gastrointestinal neoplasms. Most cases of jejunal and ileal adenocarcinoma are of well or moderately differentiated type, and other types are rare. This study reports a rare case of signet-ring cell carcinoma of the jejunum diagnosed by double balloon enteroscopy. The patient was a 79-year-old woman who complained of passing tarry stool. Esophagogastroduodenoscopy and total colonoscopy yielded no evidence of gastrointestinal bleeding. Small intestinal barium study demonstrated stenosis with pocket formation in the middle portion of the jejunum. Double balloon enteroscopy was performed to identify the cause of stenosis. Double balloon enteroscopy showed stenosis of the middle portion of the jejunum with pocket formation. The surface of the stenotic portion was covered with shallow ulcerations, but was not markedly irregular. Histologically, the lesion was found to be a signet-ring cell carcinoma of the jejunum. Formation of a lesion of this type may be associated with a rare type of histological morphology such as signet-ring cell carcinoma. The endoscopic findings are important in diagnosing such lesions, and are useful in distinguishing them from other diseases.

Enhanced expressions of endothelin-converting enzyme and endothelin receptors in human colonic tissues of Crohn's disease.

Endothelin-1, a powerful vasoconstrictor, forms the endothelin system together with endothelin-converting enzyme and endothelin type A and type B receptors. These endothelin system components are considered to participate in inflammatory and wound healing responses. Previous reports have suggested a role for the endothelin-1 in the pathology of Crohn's disease. In the present study, we immunohistochemically investigated the expressions of the endothelin system components in affected human intestinal tissues of Crohn's disease. Eighteen surgical specimens of colonic tissue obtained from patients with Crohn's disease and 12 normal colonic tissues as controls were examined. Frozen tissue sections cut from the samples were subjected to the immunohistochemical single and double staining. The endothelin system components were expressed mainly in the muscular layers and blood vessels. In diseased colonic tissues, inflammatory infiltration and fibrotic tissue reactions with marked smooth muscle cell proliferation were frequently seen, and were closely associated with increased expressions of the endothelin system components. These results strongly suggest that endothelin-converting enzyme and endothelin type A and type B receptors collectively play a role in the inflammatory and fibrogenic processes of Crohn's disease. Especially, submucosal smooth muscle proliferation, a histological hallmark of strictures, may be attributable to the upregulated endothelin system.

Enhanced expression of angiotensin II type 1 receptor in usual interstitial pneumonia.

BACKGROUND: Angiotensin II, a potent vasoconstrictor, has been considered to be involved in various fibrotic disorders including idiopathic interstitial pneumonias. To clarify whether this agent contributes to the development and progression of usual interstitial pneumonia, a major entity of idiopathic interstitial pneumonias, we immunohistochemically examined expression of its specific receptor, angiotensin II type 1 receptor, in human normal and diseased lung tissues. METHODS: Video-assisted thoracoscopic lung biopsy specimens obtained from patients with usual interstitial pneumonia (n=8) were sectioned and stained using single or double immunostaining techniques with specific antibodies against angiotensin II type 1 receptor and smooth muscle actin. Lung tissues of desquamative interstitial pneumonia (n=2) and normal lung tissues (n=6) were also examined for comparative analyses. RESULTS: Expression of angiotensin II type 1 receptor was limited in vascular and bronchial smooth muscle cells in normal lungs. In contrast, the receptor-positive mesenchymal cells, most of which were also positive for smooth muscle actin and arranged like a bundle, were markedly increased in association with dense collagen deposition in thickened alveolar walls of usual interstitial pneumonia. In desquamative interstitial pneumonia, the fibroproliferative change, including angiotensin II type 1 receptor-positive mesenchymal cell proliferation, was milder than that in usual interstitial pneumonia. CONCLUSIONS: These findings suggest that angiotensin II and its type 1 receptor play a profibrogenic role in idiopathic interstitial pneumonias, particularly in usual interstitial pneumonia. Furthermore, angiotensin II type 1 receptor-positive smooth muscle cells increased in diseased lung tissues may be contractile and may contribute to reduction of airspaces in usual interstitial pneumonia.

Close association between activated platelets and neutrophils in the active phase of ulcerative colitis in humans.

BACKGROUND: Neutrophils are considered to play a causative role in inflammatory mucosal injury in ulcerative colitis (UC), and an association between platelets and neutrophils may contribute to the progression of the inflammatory processes. To test this hypothesis, we performed immunohistochemical and flow cytometric analyses on tissue and blood samples from patients with UC. MATERIALS AND METHODS: Colonic mucosal tissues of patients with active (n = 27) or inactive (n = 16) UC and normal controls (n = 11) were subjected to immunohistochemical staining for markers of activated platelets (glycoprotein IIb/IIIa and P-selectin) and neutrophils (neutrophil elastase, myeloperoxidase, and CD66b). The amounts of stained cells were evaluated by computer-aided morphometry. Peripheral blood samples from patients (n = 8) and healthy volunteers (n = 8) were subjected to comparative flow cytometric analysis of activated platelets. RESULTS: P-selectin-positive activated platelets were frequently aggregated in the inflamed mucosa, especially in ulcerative lesions, and were close to regions of dense neutrophil infiltration. An increase in the number of activated platelets in the colonic lesions was associated with an increase in infiltrating neutrophils and was related to the severity of the disease. The flow cytometric analysis indicated that circulating platelets of patients with UC were highly activated. CONCLUSIONS: The present study demonstrated that a close association between activated platelets and neutrophils is a prominent pathological change in both the affected colonic mucosa and peripheral blood of patients with active-phase UC. This suggests that platelet-neutrophil association may play an important role in the progression of inflammatory processes in UC.

Expression of cyclooxygenase-2 in Hodgkin's lymphoma: its role in cell proliferation and angiogenesis.

Although many studies have revealed the association between cyclooxygenase-2 (COX-2) and carcinogenesis, the association between COX-2 and Hodgkin's lymphoma (HL) remains unknown. We examined the immunohistochemical expression of COX-2, p53, bcl-2, and Ki-67 in 33 patients with HL, and counted microvessels stained with CD34. Hodgkin and Reed - Sternberg (HRS) cells with COX-2 expression were scored as 0 = no staining; 1 = <25% of cells staining; 2 = 25-49%; 3 = 50-75%; and 4 = > or =75%. COX-2 expression was observed in 15 cases of classical HL. Nevertheless, neither accumulation of p53 nor bcl-2 expression was associated with COX-2 expression. The percentage of Ki-67 positive-HRS cells and microvessel density in COX-2 score groups 2-4 were significantly higher than those in score group 0, respectively. We show that COX-2 expression is associated with cell proliferation and angiogenesis in HL. These findings suggest that COX-2 may be a target for therapy in HL.

Endothelin-converting enzyme expression in the neointima after percutaneous coronary intervention.

Smooth muscle cells (SMCs) are the major cellular component of neointimal tissues after percutaneous coronary intervension (PCI). Endothelin-1 (ET-1) is a powerful vasoconstrictor and has a mitogenic effect on SMCs. Endothelin-converting enzyme (ECE) is a key enzyme in the process of ET-1 generation. However, the expression of ECE in association with post-PCI repair processes has not been reported. Thirteen coronary sites after PCI obtained at autopsy and 6 atherectomy specimens obtained from restenotic sites were investigated. Frozen sections were stained with antibodies against ECE, SMCs, macrophages, and endothelial cells. The immunoreactivity of ECE was quantified using computer-aided planimetry. At the early stage after PCI, most neointimal SMCs expressed ECE. The ECE-positive cell area was significantly (p<0.005) larger in the sites within 3 months after PCI than in the sites from 6 months onward. In atherectomy specimens, neointimal SMCs showed distinct ECE positivity. These findings suggest that ECE is upregulated in the neointima at early stages after PCI injury. ECE may be one of the mediators in the repair processes after PCI in humans.

Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension.

Angiotensin II (ANG-II) and its receptor (AT1) have been potential targets of therapy for liver cirrhosis. However, AT1 expression in human cirrhotic livers has not been clarified. We studied AT1 and ANG-II generating enzymes in human autopsy (20 cirrhotics and 20 normal controls) and biopsy (10 cirrhotics) livers. AT1 immunoreactivity in tissue sections was quantified by computer-aided morphometry. AT1 protein and mRNA levels were assessed by Western blotting and real-time polymerase chain reaction. Concerning ANG-II generating system, angiotensin-converting enzyme (ACE) and mast cell chymase were examined. AT1 expression was seen not only in vascular smooth muscle cells, but also in activated stellate cells/myofibroblasts and liver parenchymal cells. AT1-positive vessels and myofibroblasts were significantly increased in fibrous septa of cirrhosis, although overall hepatic AT1 expression was reduced in the cirrhotic livers compared with the controls. Augmentation of AT1-positive vessels was related to severity of portal hypertension. Expressions of ACE and chymase were enhanced in the cirrhotic livers. These results suggest that hepatic AT1 expression is shifted to and concentrated in vessels and myofibroblasts in cirrhotic settings, and increased ANG-II generation by ACE and chymase contributes to portal hypertension and liver fibrosis via binding to AT1 expressed on vessels and myofibroblasts.