Guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding.

Japan Gastroenterological Endoscopy Society (JGES) has compiled a set of guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding using evidence-based methods. The major cause of non-variceal upper gastrointestinal bleeding is peptic gastroduodenal ulcer bleeding. As a result, these guidelines mainly focus on peptic gastroduodenal ulcer bleeding, although bleeding from other causes is also overviewed. From the epidemiological aspect, in recent years in Japan, bleeding from drug-related ulcers has become predominant in comparison with bleeding from Helicobacter pylori (HP)-related ulcers, owing to an increase in the aging population and coverage of HP eradication therapy by national health insurance. As for treatment, endoscopic hemostasis, in which there are a variety of methods, is considered to be the first-line treatment for bleeding from almost all causes. It is very important to precisely evaluate the severity of the patient's condition and stabilize the patient's vital signs with intensive care for successful endoscopic hemostasis. Additionally, use of antisecretory agents is recommended to prevent rebleeding after endoscopic hemostasis, especially for gastroduodenal ulcer bleeding. Eighteen statements with evidence and recommendation levels have been made by the JGES committee of these guidelines according to evidence obtained from clinical research studies. However, some of the statements that are supported by a low level of evidence must be confirmed by further clinical research.

Diagnostic performance of ¹8F-fluorothymidine PET/CT for primary colorectal cancer and its lymph node metastasis: comparison with ¹8F-fluorodeoxyglucose PET/CT.

PURPOSE: To examine the diagnostic performance of (18)F-fluorothymidine (FLT) PET/CT in primary and metastatic lymph node colorectal cancer foci in comparison with (18)F-fluorodeoxyglucose (FDG) PET/CT. METHODS: The study population comprised 28 patients with 30 newly diagnosed colorectal cancers who underwent surgical resection of the primary lesion and regional lymph nodes after both FLT and FDG PET/CT. The associations between SUVmax levels and pathological factors were evaluated using the Mann-Whitney U or Kruskal-Wallis test. Differences in diagnostic indexes for detecting nodal metastasis between the two tracers were estimated using the McNemar exact or χ(2) test. RESULTS: All 30 primary cancers (43.0 ± 20.0 mm, range 14 - 85 mm) were visualized by both tracers, but none of the FLT SUVmax values exceeded the FDG SUVmax values in any of the primary cancers (6.6 ± 2.4 vs. 13.6 ± 5.8, p < 0.001). The sensitivity, specificity and accuracy for detecting nodal metastasis were 41% (15/37), 98.8% (493/499) and 94.8% (508/536) for FDG PET/CT, and 32% (12/37), 98.8% (493/499) and 94.2% (505/536) for FLT PET/CT, respectively. The sensitivity (p = 0.45), specificity (p = 0.68) and accuracy (p = 0.58) were not different between the tracers. Nodal uptake of FLT and FDG was discordant in 7 (19%) of 37 metastatic nodes. There were ten concordant true-positive nodes of which six showed higher FDG SUVmax and four showed higher FLT SUVmax, but the difference between FDG and FLT SUVmax was not significant (5.56 ± 3.55 and 3.62 ± 1.45, respectively; p = 0.22). CONCLUSION: FLT has the same potential as FDG in PET/CT for the diagnosis of primary and nodal foci of colorectal cancer despite significantly lower FLT uptake in primary foci.

[Two cases of circumferential rectal invasion from prostatic cancer].

We report two cases of prostatic cancer invading the rectum with circumferential rectal wall thickening. In both cases, reddish and uneven edematous mucosa was observed by colonoscopy and the boundary of the lesion was indistinct. No mass or ulcer formation was not observed. CT scan showed irregular prostatic swelling and circumferential rectal wall thickening adjacent to the prostate. The rectal biopsy specimen showed moderately to poorly differentiated adenocarcinoma, and it was positive on PSA immunostaining. Although rectal invasion of prostatic cancer is relatively rare, it is important to be aware that prostatic cancer can cause circumferential stenosis of the rectum.

[A retrospective endoscopic case of adenoid cystic carcinoma of the esophagus].

We report a case of a 64-year-old Japanese man with adenoid cystic carcinoma. An elevated lesion covered by intact epithelium in the thoracic esophagus was found in September, 2007 and been followed. After dysphagia appeared follow-up endoscopy was performed in January, 2010, and morphological change into a protruding tumor was recognized. Since adenoid cystic carcinoma was detected by endoscopic biopsy, the patient underwent esophageal resection. The resected specimen showed a cribriform pattern and a certain amount of mucous substance which was positive for Alcian blue, within a solid nest. The tumor cells were positive for S-100 protein and negative for αSMA, so the tumor was diagnosed as an adenoid cystic carcinoma.

Robot-assisted excision of rectal duplication cysts: A case report.

Rectal duplication cysts are extremely rare and account for only 4% of all gastrointestinal duplication cysts. They may become challenging for removal in the case of a large tumor in a narrow pelvis. Herein, we report a case of rectal duplication cysts excision via robotic-assisted laparoscopic surgery and its utility.

Clinical significance of primary lesion FDG uptake for choice between oesophagectomy and endoscopic submucosal dissection for resectable oesophageal squamous cell carcinomas.

OBJECTIVES: To correlate primary oesophageal squamous cell carcinoma (SCC) (18)F-fluoro-deoxyglucose (FDG) uptake with pathological factors and examine its significance regarding choice of therapy. METHODS: We retrospectively examined the factors affecting visible and non-visible FDG uptake in 37 primary lesions in 32 oesophageal SCC patients who underwent PET/CT before oesophagectomy or endoscopic submucosal dissection (ESD). We divided the lesions into pathological depth invasion ≥sm2 oesophagectomy (n = 18) and ≤sm1 ESD (n = 19) indicated groups and compared the diagnostic accuracy of FDG-PET with that of endoscopic ultrasound (EUS) performed for 23 superficial lesions to discriminate between these groups. RESULTS: There were 17 visible and 20 non-visible lesions. The lesion visibility was significantly higher in the larger (≥40 mm), non-flat type, more deeply invaded, positive vascular invasion (P < 0.001 each), positive nodal metastasis (P = 0.04) and higher Glut-1 score (P = 0.005) tumour groups. When the visible and non-visible lesions indicated a need for oesophagectomy and ESD respectively, the sensitivity, specificity and accuracy of oesophagectomy were 94% (17/18), 100% (19/19) and 97% (36/37) and those of EUS were 75% (3/4), 79% (15/19) and 78% (18/23) respectively. CONCLUSIONS: Primary lesion FDG visibility can be one of the indicators for choosing between oesophagectomy and ESD for resectable oesophageal SCCs.

[A case of eosinophilic gastroenteritis with ring-like discoloration in the lower end of the esophagus].

We report the case of a 15-year-old Japanese boy with eosinophilic gastroenteritis. The patient complained of abdominal pain and watery diarrhea and had a history of allergic rhinitis. Laboratory data on admission showed leukocytosis with remarkable eosinophilia. Microscopic examination of the biopsied specimens taken from the esophagus, stomach, duodenum, lower ileum and colon showed eosinophilic infiltration. Especially in the lower esophagus, there was a ring-like discoloration with remarkable eosinophil infiltration. We diagnosed eosinophilic gastroenteritis and his clinical symptoms and eosinophilia improved following starting corticosteroid therapy. After 5 months therapy with prednisolone, discoloration of upper digestive tract disappeared. There have been no reports describing discoloration in the lower end of the esophagus seen by gastroscopy.

Minute carcinoma of the pancreas presenting as pancreatic pleural effusion.

A 70-year-old Japanese man with no history of pancreatitis visited his local practitioner, complaining of dyspnea on effort. Left massive pleural effusion was detected and he was then referred to our hospital. A plain chest film showed marked left pleural effusion. Thoracentesis yielded 2000 ml of bloody fluid with high amylase content (22,665 IU/l). Endoscopic retrograde pancreatography revealed a tapered occlusion of the main pancreatic duct. Pancreatic cancer was suspected, and a distal pancreatectomy and a splenectomy were performed. Histologically, the diagnosis was ductal adenocarcinoma of the pancreas, 5 x 6 mm in size, with regional lymph node metastasis. He has experienced no recurrence of cancer or pleural effusion since the operation.

Signet-ring cell carcinoma of the colon 7mm in size with peritonitis carcinomatosa.

A 72-year-old woman was admitted with a complaint of a sensation of abdominal fullness. Cytologic examination of ascites revealed many poorly differentiated adenocarcinoma cells. Barium enema study and colonoscopy revealed IIa+IIc-type carcinoma of the descending colon. Endoscopic mucosal resection was performed to determine the histological type and the depth of invasion. The resected tumor was 7 x 6 mm in size, and an amorphous pit pattern was observed in the depressed area by stereomicroscopy. Poorly differentiated adenocarcinoma with signet-ring cells had diffusely infiltrated into the deeper part of the submucosal layer. Immunohistochemical findings showed this tumor to have mucin derived from gastric foveolar epithelium, suggesting that the signet-ring cell carcinoma of the colon showed gastric differentiation. Primary signet-ring cell carcinoma of the colon and rectum is a rare form of adenocarcinoma of the large intestine and shows more malignant biological behavior than ordinary colorectal carcinoma. Early diagnosis and curative operation are important.

Thymidine phosphorylase activates NFκB and stimulates the expression of angiogenic and metastatic factors in human cancer cells.

Thymidine phosphorylase (TP) promotes angiogenesis and metastasis, and confers resistance to anticancer agents in some cancer cell types. We previously reported that TP stimulates the expression of interleukin (IL)-8 in human KB cancer cells by an unknown mechanism. A mutation in the nuclear factor (NF)κB binding site of the IL-8 promoter suppressed promoter activity in KB/TP cells that overexpress TP. Specifically inhibiting NFκB by using BY11-7082 also suppressed TP-induced IL-8 promoter activity and IL-8 expression. Moreover, TP overexpression led to the activation of NFκB and an upregulation in the expression of its target genes, and increased phosphorylated IKKα/ß protein levels, while promoting IκBα degradation as well as p65 phosphorylation and nuclear localization. The activation of NFκB in KB/TP cells was suppressed by the antioxidants N-acetylcysteine and EUK-8. In addition, in gastric cancer tissue samples, the expression of the NFκB-regulated genes, including IL-8, IL-6, and fibronectin-1 was positively correlated with TP expression. These findings indicate that reactive oxygen species mediated NFκB activation by TP increases the expression of genes that promote angiogenesis and metastasis in gastric cancer.

Frequent expression of thymidine phosphorylase in Epstein-Barr virus-associated gastric carcinoma of diffuse type.

UNLABELLED: The aim of the present study was to elucidate the etiological roles of Epstein-Barr virus (EBV) in the development of EBV-associated GC (EBV-GC), EBV-GCs and non EBV-GCs were compared with regard to the expression of thymidine phosphorylase (TP), which is known to have angiogenic activity in various tumor tissues. PATIENTS AND METHODS: TP expression was examined by immunohistochemistry assay among 156 gastric carcinoma cases (21 EBV-GC cases and 135 non EBV-GC cases). RESULTS: The frequency of tumors with TP expression was nearly twice as high in EBV-GCs (71%) than in non EBV-GCs (37%) (p=0.005). However, such an association was only observed in Lauren's diffuse-type tumors. CONCLUSION: Our finding suggests that the mechanism involved in TP expression of gastric carcinoma appears to be different in intestinal- and diffuse-type tumors.

The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression.

Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). TP is overexpressed in various tumors and plays an important role in angiogenesis, tumor growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP. A novel, specific TP inhibitor, TPI, inhibits angiogenesis induced by overexpression of TP in KB/TP cells (human KB epidermoid carcinoma cells transfected with TP cDNA), as well as the growth and metastasis of KB/TP cells in vivo. 2-deoxy-D-ribose, the degradation product of thymidine generated by TP activity, has both angiogenic and chemotactic activity. Both 2-deoxy-D-ribose and TP inhibit a hypoxia-induced apoptotic pathway. These findings suggest that 2-deoxy-D-ribose is a downstream mediator of TP function. 2-deoxy-L-ribose, a stereoisomer of 2-deoxy-D-ribose, inhibits the promotion of angiogenesis, tumor growth and metastasis by TP. Although the mechanism of the action of 2-deoxy-D-ribose is still unknown, 2-deoxy-L-ribose may inhibit the physiological activities of 2-deoxy-D-ribose, and consequently those of TP. Inhibition of TP activity and function appears to be a promising approach for the chemotherapy of various tumors.