[Show abstract][Hide abstract] ABSTRACT: Behҫet's disease (BD) is a chronic disorder involving multiple organ systems including the small and large intestines. A 46-year-old female diagnosed with intestinal BD presented with ileocecal perforation and diffuse peritonitis and subsequently underwent ileocolic resection with ileostomy. After surgery, she suffered from refractory para-ileostomal ulceration associated with BD. Most importantly, however, treatment with infliximab was significantly effective in healing the ulceration. This is the first report of para-ileostomal ulceration associated with BD successfully treated with infliximab, suggesting the possible use of infliximab as a therapeutic option for para-stomal ulcers related to BD.
Clinical Journal of Gastroenterology 06/2015; 8(4). DOI:10.1007/s12328-015-0576-9
[Show abstract][Hide abstract] ABSTRACT: We describe the case of a 74-year-old female with a mesenteric lymph node abscess caused by a Yersinia enterocolitica infection. She had been administered an immunosuppressive drug and was admitted to the hospital due to a high fever, right lower abdominal pain and advanced leukocytosis. We initially diagnosed her with lymphadenitis based on the symptoms and the imaging studies. However, conservative treatment with antibiotics did not yield any improvement, and abscess formation was suspected. Surgical treatment was performed, and the culture from the drainage fluid grew Y. enterocolitica. The histological findings suggested that an ulcerative lesion of the terminal ileum was the entry port of Y. enterocolitica. The pathogen infected the mesenteric lymph nodes and spread along the ileocecal lymphatic vessels, resulting in the formation of an abscess. We also provide a review of the previously published literature on lymph node abscesses due to Y. enterocolitica infections.
Clinical Journal of Gastroenterology 02/2014; 7(1). DOI:10.1007/s12328-013-0452-4
[Show abstract][Hide abstract] ABSTRACT: We herein describe the case of a 51-year-old man with a duodenocolic fistula (DCF) caused by a stomal ulcer. The patient complained of watery diarrhea, dysgeusia and malnutrition. His medical history included distal gastrectomy with Billroth I reconstruction for duodenal ulcer perforation. A combination study using endoscopy and contrast imaging confirmed the presence of DCF. Laparotomic fistulectomy was performed, which resulted in the patient's recovery from diarrhea and malnutrition. The histological findings suggested that the fistula had originated from a stomal ulcer. In patients with chronic watery diarrhea of obscure origin following gastrectomy, DCF is a possible cause of the diarrhea.
Internal Medicine 07/2013; 52(14):1579-83. DOI:10.2169/internalmedicine.52.0496 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate treatment outcomes of chemoradiotherapy for patients with stage IVA esophageal cancer and to estimate prognostic factors.
Materials and methods:
Patients with stage IVA esophageal cancer treated with chemoradiotherapy between April 2003 and March 2009 were evaluated. Patients received concurrent chemoradiotherapy comprising cisplatin plus 5-fluorouracil and 61.2 Gy of radiotherapy. Therapeutic response, overall survival time, and toxicity were examined and statistical evaluation was performed.
Ninety patients were treated using chemoradiotherapy. Among these, 71 patients (78.9 %) received the complete course of chemoradiotherapy. Seventeen patients (18.9 %) showed complete response, 64 patients (71.1 %) had partial response, 7 patients (7.8 %) experienced no change, and 2 patients (2.2 %) exhibited progressive disease. Mean duration of follow-up was 16.1 months (range 2-88 months). Median overall survival was 12.8 months. Two- and 3-year overall survival rates were 35.1 and 18.6 %, respectively. Severe hematological toxicities included Grade 3 leukopenia in 33 patients (36.7 %). Treatment-related death was estimated to have occurred in 7 patients. Performance status and body weight loss were identified as significant prognostic factors.
Our treatment outcomes appeared similar to those of previous studies that used chemoradiotherapy for advanced esophageal cancer. This treatment is useful for stage IVA esophageal cancer.
Japanese journal of radiology 02/2013; 31(4). DOI:10.1007/s11604-013-0180-1 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
Transforming growth factor-β1 (TGF-β1) is one of the growth factors expressed in the gut, and has been shown to play an important role in intestinal mucosal healing. We investigated the effects of TGF-β1 on the cellular functions of intestinal epithelial cells, and also evaluated its signaling pathways in these cells.
We used the rat IEC-6 intestinal epithelial cell line for these studies. The expression of TGF-β1/Smad signaling molecules was examined. We evaluated the effect of TGF-β1 on the proliferation and differentiation by the BrdU incorporation assay and real-time PCR. We manipulated the expression levels of Smad2 and Smad3 using an adenovirus system and small interfering RNA to examine the signaling pathways. The expression of Smad2 and Smad3 along the crypt-villus axis was also examined in the murine intestine.
IEC-6 cells produced TGF-β1 and expressed functional TGF-β/Smad signaling molecules. The addition of TGF-β1 in the culture medium suppressed the proliferation and increased the expression of a differentiation marker of enterocytes, in a dose-dependent manner. The adenovirus-mediated and small interfering RNA-mediated studies clearly showed that the growth inhibitory effect and the promotion of differentiation were exerted through a Smad3-dependent and a Smad2-dependent pathway, respectively. IEC-6 cells exhibited upregulated expression of an inhibitory Smad (Smad7) as a form of negative feedback via a non-Smad pathway. Smad2 was predominantly expressed in villi, and Smad3 in crypts.
TGF-β1 regulates the cellular functions of intestinal epithelial cells through both Smad-dependent and non-Smad pathways.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
This study investigated the actual rate or extent of lymph node metastasis or the survival outcomes among patients that underwent esophagectomy with lymph node dissection after ESD for clinical mucosal, but pathological submucosal, esophageal cancer.
Seventeen patients that received esophagectomy with two- or three-field lymph node dissection as additional treatment after ESD for clinical mucosal, but pathological submucosal, esophageal cancer between 2006 and 2010 were analyzed. The rate and extent of lymph node metastasis and the patient outcomes were determined.
The tumor depths were diagnosed as SM1 in 8 (47 %) patients and SM2 in 9 (53 %), based on the analyses of resected specimens. Lymphatic invasion was evident in 13 (76 %) patients, while venous invasion was detected in 5 (29 %). Five (29 %) patients had pathologically detected lymph node involvement. Seven (0.8 %) of the 890 dissected nodes showed cancer involvement. Three patients had one involved node in the mediastinum or abdomen, and 2 patients had 2 involved nodes in the abdomen. The patients were followed up for 11-71 months (median 23 months), and all were alive without recurrence at the final follow-up.
Twenty-nine percent of the patients diagnosed with clinically mucosal, but pathologically submucosal, thoracic squamous cell esophageal cancer after ESD had 1-2 cancer-involved lymph nodes in the lower mediastinum and abdomen. Esophagectomy with lymph node dissection is therefore considered to be a necessary and effective additional treatment for these patients.
Surgery Today 08/2012; 43(6). DOI:10.1007/s00595-012-0295-5 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Imatinib mesylate is a tyrosine kinase inhibitor of c-KIT and PDGFRA. Imatinib mesylate is an effective drug that can be used as a first-choice agent for treatment of GISTs. Prior to treatment, molecular diagnosis of c-KIT or PDGFRA is necessary; however, in some types of GISTs, it is impossible to obtain a sufficient amount of specimen for diagnosis. An inoperable or marginally resectable GIST in a 79-year-old female was difficult to be diagnosed at a molecular pathological level, and hence, exploratory treatment was initiated using imatinib combined with 18FDG-PET evaluation at 1-month intervals. PET imaging indicated a positive response, and so we continued imatinib treatment in an NAC setting for 4 months. As a result, curative resection of the entire tumor was successfully performed with organ preservation and minimally invasive surgery.
18FDG-PET evaluation at 1-month intervals is beneficial for GISTs that are difficult to be diagnosed histopathologically.
Case Reports in Oncological Medicine 10/2011; 2011:638794. DOI:10.1155/2011/638794
[Show abstract][Hide abstract] ABSTRACT: Many investigations have demonstrated that cell injuries caused by generation of reactive oxygen species (ROS) is a common mechanism of various hepatic disorders. Recently, we have demonstrated that epimorphin, originally cloned as a mesenchymal protein, protects cultured intestinal epithelial cells from ROS. We therefore examine whether epimorphin protects primary cultured hepatocytes from ROS-induced cell injury.
We explored the cell viability and the intracellular ROS levels of purified murine hepatocytes after exposure to 0.5 mM H(2)O(2) with or without pretreatment of epimorphin. Then, we observed mitochondrial permeability transition (MPT) and depolarization using confocal microscopy to make clear the mechanism that epimorphin inhibited cell injuries after exposure to H(2)O(2). In addition, to clarify the signaling pathways related to cell survival, we carried out Western blotting analysis with phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) polyclonal antibody to evaluate the inhibition of JNK by epimorphin. Finally, we evaluated the cell viability in hepatocytes administered JNK inhibitor.
Epimorphin protected primary cultured hepatocytes from H(2)O(2)-induced cell injuries independent of intracellular ROS levels. Epimorphin also inhibited onset of MPT, depolarization of the mitochondrial membrane potential, and eventually cell killing. The cell protective function of epimorphin after exposure to H(2)O(2) was not dependent on Akt signaling but on JNK signaling.
Epimorphin can protect hepatocytes from MPT-dependent cell injury induced by ROS. Since hepatic disorders could be caused by MPT-dependent cell injuries with excessive ROS, epimorphin might open a new therapeutic avenue for hepatic disorders.
Journal of Gastroenterology and Hepatology 01/2011; 26(1):201-6. DOI:10.1111/j.1440-1746.2010.06327.x · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin induce gastric mucosal lesions in part by the activation of inflammatory cells and the production of proinflammatory cytokines. The activation of adenosine A(2A) receptors inhibits inflammation by increasing cyclic AMP in leukocytes and reducing both the production of various proinflammatory cytokines and neutrophil chemotaxis. The aim of present study was to determine whether administration of an orally active adenosine A(2A) receptor agonist (4-[3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-piperidine-1-carboxylic acid methyl ester; ATL-313) ameliorated indomethacin-induced gastric mucosal lesions in rats.
Gastric lesions were produced by oral gavage of indomethacin (30 mg/kg). ATL-313 (1-10 microg/kg) was given orally just before the indomethacin administration.
The ulcer index induced by indomethacin was significantly (>50%) reduced by pretreatment with ATL-313 and this effect was blocked completely by the addition of equimolar ZM241385, a selective A(2A) receptor antagonist. The gastric content of myeloperoxidase (MPO) and proinflammatory cytokines was significantly reduced by 10 microg/kg ATL-313, but gastric mucosal prostaglandin 2 (PGE2) was not affected.
We conclude that ATL-313 does not inhibit the mucosal damaging effect of indomethacin, but it does block secondary injury due to stomach inflammation. A(2A) agonists may represent a class of new therapeutic drugs for NSAID-induced gastric ulcers.
Journal of Gastroenterology 05/2009; 44(5):419-25. DOI:10.1007/s00535-009-0028-8 · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of gastric hamartomatous inverted polyps that are a rare histological type of gastric polyp and difficult to diagnose. Gastric submucosal tumor was detected by upper gastrointestinal X-ray series in 37-year-old man. Endoscopy revealed a submucosal tumor (SMT) , which eroded with a depression on its surface in the fornix. Endoscopic ultrasonography showed a heterogeneous tumor in the third layer. Endoscopic submucosal dissection (ESD) was performed to resect the tumor completely. The pathological diagnosis was a gastric hamartomatous inverted polyp. The patient was later discharged without any complications. Hamartomatous inverted polyps without a stalk are classified as the SMT type because the tumor is inverted down growth into the submucosal layer, otherwise polyps with a stalk are classified as the polyp type. All of the polyps were resected endoscopically, however, surgical resection was performed for those of the SMT type, because it is difficult to remove this type completely by en-block resection using conventional EMR technique. ESD method may be indicated for SMT-type hamartomatous inverted polyps.
Internal Medicine 02/2008; 47(4):259-62. DOI:10.2169/internalmedicine.47.0360 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The major heat shock protein, HSP70, is known to be involved in cytoprotection against environmental stresses mediated by their function as a "molecular chaperone." However, the influence of HSP70 on gastric mucosal healing under physical stimulation or stress is not completely understood. Rat gastric mucosal cells (RGM-1) were stably transfected with pBK-CMV containing the human HSP70 gene (7018-RGM-1) or pBK-CMV alone (pBK-CMV-12). Artificial wounds were created. Mechanical stretch was applied to 7018-RGM-1 cells or pBK-CMV-12 cells. The effect of mechanical stretch on HSP70 expression was assessed by Western blot analysis. Expression of HSP70 was decreased by mechanical stretch in pBK-CMV-12 cells. However, expression of HSP70 was not decreased by mechanical stretch in 7018-RGM-1 cells. Furthermore, the wound restoration of pBK-CMV-12 cells was suppressed under mechanical stretch condition. On the other hand, the wound restoration of 7018-RGM-1 cells was not affected by mechanical stretch. These results suggest that HSP70 plays an important role in gastric wound healing under physical stress.