Thread-Traction with a Sheath of Polypectomy Snare Facilitates Endoscopic Submucosal Dissection of Early Gastric Cancers.

Although the thread-traction (TT) method has been found useful during endoscopic submucosal dissection (ESD) for early gastric cancers, the movement of the thread interferes with the movement of the endoscope, and the lesion can only be pulled to the mouth side. We have developed the novel TT method using a sheath of polypectomy snare (TTSPS). The TTSPS method enables free and independent movement of the thread and the endoscope and allows pulling the lesion towards the anal as well as oral side. The median dissection times, numbers of instances of arterial bleeding, and numbers of local injections into the submucosal layer were significantly lower for ESD with TTSPS than for conventional ESD. Countertraction ESD using the TTSPS method is straightforward, safe, easy, noninvasive, and cost effective, and it uses instruments readily available in most hospitals to enhance visualization of cutting lines. Therefore, the TTSPS method can be universally applied in conventional ESD.

G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells.

BACKGROUND: Short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fiber by intestinal microbiota, may positively influence immune responses and protect against gut inflammation. SCFAs bind to G protein-coupled receptor 43 (GPR43). Here, we show that SCFA-GPR43 interactions profoundly affect the gut inflammatory response. METHODS: Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (-/-) and wild-type mice. RESULTS: Dextran sulfate sodium-treated GPR43 mice exhibited weight loss, increased disease activity index (a combined measure of weight loss, rectal bleeding, and stool consistency), decreased hematocrit, and colon shortening, resulting in significantly worse colonic inflammation than in wild-type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the colonic mucosa of GPR43 mice were significantly higher than in wild-type mice. Treatment of wild-type mice with 150 mM acetate in their drinking water markedly improved these disease indices, with an increase in colon length and decrease in the disease activity index; however, it had no effect on GPR43 mice. Mononuclear cell production of tumor necrosis factor alpha after lipopolysaccharide stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43 antibody. CONCLUSIONS: SCFA-GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.

Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury.

Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.

Endoscopic submucosal dissection with sheath-assisted counter traction using a novel sheath for early gastric cancers.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. METHODOLOGY: Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. RESULTS: The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. CONCLUSIONS: Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.

Long-term survival and improved quality of life after chemoradiotherapy to treat esophageal small cell carcinoma: a report of two cases.

In case 1, endoscopy revealed a submucosal tumor with central ulceration in the esophagus of a 54- year-old man. A biopsy specimen revealed small cell carcinoma without metastasis and the stage of the cancer was stage I (T2N0M0). Two cycles of concurrent cisplatin, etoposide and radiotherapy resulted in an incomplete response/stable disease. The tumor recurred and had metastasized to the brain, lung, liver, lymph nodes of the mediastinum, abdomen and bones after six cycles. Two cycles of irinotecan and cisplatin then elicited a complete response in the primary esophageal lesion. However, progressive disease was identified in the metastatic bone tumors. Despite two further cycles of therapy, he died 447 days after the initial course. In case 2, a biopsy specimen of a tumor with central ulceration in the esophagus of a 77-year old man with swallowing difficulty indicated small cell carcinoma. The stage of the cancer was diagnosed as stage II (T3N0M0). Two cycles of irinotecan, cisplatin and concurrent radiotherapy elicited a complete response. However, the tumor metastasized to the brain and the liver 644 days after starting treatment. Two cycles of carboplastin plus irinotecan elicited a partial response in the metastatic tumors, but he died 988 days after starting chemotherapy.

Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/ß reduction.

TANK-binding kinase 1 (TBK1) regulates the interferon regulatory factor (IRF) 3 and IRF7 activation pathways by double strand RNA (dsRNA) via Toll-like receptor (TLR) 3 and by lipopolysaccharide (LPS) via TLR4. Rebamipide is useful for treating inflammatory bowel disease (IBD). Although IBD is associated with nuclear factor-κB (NF-κB), any association with the TBK1-IRF pathway remains unknown. How rebamipide affects the TBK1-IRF pathway is also unclear. We analyzed the relationship between IBD (particularly ulcerative colitis; UC) and the TLR-TBK1-IRF3/7 pathway using human colon tissue, a murine model of colitis and human colonic epithelial cells. Inflamed colonic mucosa over-expressed TKB1, NAP1, IRF3, and IRF7 mRNA compared with normal mucosa. TBK1 was mainly expressed in inflammatory epithelial cells of UC patients. The expression of TBK1, IRF3, IRF7, IFN-α and IFN-ß mRNA was suppressed in mice given oral dextran sulfate-sodium (DSS) and daily rectal rebamipide compared with mice given only DSS. Rebamipide reduced the expression of TBK1, IRF3 and IRF7 mRNA induced by LPS/dsRNA, but not of NF-κB mRNA in colonic epithelial cells. Rebamipide might suppress the TLR-TBK1 pathway, resulting in IRF3/7-induction of IFN-α/ß and inflammatory factors. TBK1 is important in the induction of inflammation in patients with UC. If rebamipide represses the TLR-TBK1 pathway, then rectal administration should suppress inflammation of the colonic mucosa in patients with UC.

Small, Depressed-Type Early Colon Cancer Invading Shallow Submucosal Layer With Extensive Lymph Node Metastasis: A Case Report.

Early colorectal cancers are defined as invasive tumors that are limited to the mucosal layer or submucosal layer (SM), regardless of the presence or absence of lymph node (LN) metastasis. The reported incidence of LN metastasis of SM1 colon cancers is 0 - 5.9%, but the incidence in SM2 and SM3 colon cancers could be as high as 11.3 - 25.0%, and risk factors for LN metastasis include depth of SM invasion, growth patterns (polypoid or non-polypoid), histological sub-classification (moderate or poor differentiation) and regional lymphatic and vascular invasion. Among colorectal cancers with non-polypoid growth, the malignant potential is higher for depressed, than polypoid types, even for small tumors. Herein, we describe a patient with small, depressed-type early colon cancer with extensive LN metastasis and superficial SM invasion (pSM 450 µm). Six courses of chemotherapy with mFOLFOX6 and bevacizumab reduced the size of the LN metastases, thus eliciting a partial response (PR) according to the response evaluation criteria in solid tumors (RECIST).

Intussusception in a child caused by capillary hemangioma of the colon.

Intussusception is one of the most common abdominal emergencies in children, but identifying the cause is very difficult. Hemangioma is a common tumor of the head and neck area in children, but it rarely arises in the gastrointestinal tract. This report describes a rare occurrence of intussusception caused by capillary hemangioma of the colon that was identified by ultrasonography (US), computed tomography (CT), and colonoscopy. A male child aged 2 years and 10 months developed painful abdominal cramps and hematochezia. Abdominal US and CT revealed both target and pseudo-kidney signs in the colon, indicating colonic intussusception. An initial diagnostic and therapeutic laparotomy did not reveal any abnormalities. Seven days later, severe abdominal pain recurred. A barium enema revealed the shadow of a 25-mm mass at the hepatic flexure of the colon. Colonoscopic findings revealed a submucosal tumor in the descending colon that was moved to the cecum by compressed air introduced through the colonoscope. We considered that the mass in the cecum had caused the intussusception. The tumor was removed at a second laparotomy, and microscopic pathological examination revealed that it was a capillary hemangioma.