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.

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.

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 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.

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 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.

[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 primary biliary cirrhosis with systemic lymph node enlargement].

A 40's woman was hospitalized with cervical lymph node enlargement. Laboratory examinations showed elevated serum bile duct enzymes and the presence of anti-mitochondrial antibody. Abdominal ultrasonography and computed tomography showed enlargement of not only perihepatic lymph nodes, but also axillary and cervical lymph nodes. FDG-PET showed intense uptake concordant with these lymph nodes. We performed endoscopic ultrasonographic fine-needle aspiration biopsy of a perihepatic lymph node, but detected no malignant cells. We then performed liver biopsy, and obtained a histological diagnosed primary biliary cirrhosis. Systemic lymph nodes decreased together with serum bile duct enzyme levels during treatment with ursodeoxycholic acid.

[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.

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn's disease: relevance to local angiotensin II system.

BACKGROUND: Intestinal stricture lesions in Crohn's disease are characterized as submucosal fibromuscular accumulation. There has been a controversy about whether the fibrogenic cells in stricture lesions in Crohn's disease originate from a smooth muscle cell or a fibroblast lineage. In the present study, we aimed to elucidate: (1) the origin of the fibrogenic cells in stricture lesions; and (2) the roles of the local angiotensin II system, including mast cell chymase, in stricture formation. METHODS: Methanol-Carnoy's-fixed colonic tissues, obtained from the stricture sites of 18 patients with Crohn's disease, were analyzed by immunostaining for vimentin, smooth muscle actin (1A4 and CGA7), angiotensin II type-1 receptor, angiotensin II-converting enzyme, and mast cell tryptase and chymase. As controls, unaffected (normal) portions of 11 colonic tumor specimens were also investigated. RESULTS: Submucosal fibromuscular accumulation was seen in every stricture lesion. The majority of mesenchymal cells accumulated in the stricture lesions were moderately differentiated intestinal smooth muscle cells [vimentin(+), 1A4(+), and CGA7(+)]. Moreover, occasional intestinal smooth muscle cells in the muscular layers, adjacent to the site of the submucosal fibromuscular response, showed distinct positivity for vimentin, indicating phenotypic modulation toward an immature, or dedifferentiated state. These smooth muscle cells accumulated in the stricture lesions were positive for angiotensin II type-1 receptor. Abundant chymase-positive mast cells were distributed in these lesions. CONCLUSIONS: These results suggest that the proliferation and migration of moderately differentiated intestinal smooth muscle cells from the muscular layers are the major pathological mechanisms in stricture formation in Crohn's disease, and the angiotensin II system is involved in this process.

Two cases of hepatocellular adenomatosis treated with transcatheter arterial embolization.

Hepatocellular adenoma is a rare benign tumor of the liver. However, some complications, such as hemorrhage, rupture, and malignant transformation, have been reported previously. Surgical resection is considered to be the best choice of treatment, when adenomas are increasing in size, while resection is difficult to perform when multiple adenomas develop throughout the liver. Here, we report two cases of multiple hepatocellular adenomatosis. One patient had a history of aplastic anemia and the other had glycogen storage disease. We treated them with transcatheter arterial embolization (TAE) to prevent hemorrhage and rupture. After TAE, most parts of the adenomas showed necrotic change. These cases suggest that TAE is an effective treatment of hepatocellular adenomatosis.

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 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.

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.

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: impact on disease progression.

Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of non-alcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidase-positive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase-derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease.