The possible mechanism of enhanced carcinogenesis induced by genotoxic carcinogens in rasH2 mice

Microarray and RT-PCR analyses were performed for the transgene and Ras-related genes in forestomach squamous cell carcinomas (SCCs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rasH2 mice; these results were compared with our previous molecular data of N-ethyl-N-nitrosourea-induced forestomach SCCs and urethane-induced lung adenomas in rasH2 mice. Overexpression of the transgene was detected in the DMBA-induced SCCs, suggesting that the transgene plays an important role in enhanced carcinogenesis in rasH2 mice. In addition, the mouse endogenous ras genes were up-regulated in the DMBA-induced SCCs, and are probably involved in the tumorigenesis of forestomach SCCs. Genes such as osteopontin, Cks1b, Tpm1, Reck, gelsolin, and amphiregulin that were commonly altered in these three different carcinogen-induced tumors may contribute to the development of tumors in rasH2 mice.     

Three cases of multiple thymoma with a review of the literature

Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II-1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi-centric origin or from intra-thymic metastasis.     

Placement of a metallic stent across the main duodenal papilla may predispose to cholangitis

BACKGROUND: Cholangitis is a major complication after metallic stent placement to treat biliary obstruction, and it may impair quality of life. Whether transpapillary stent placement contributes cholangitis is still controversial. OBJECTIVES: The present study aimed to determine risk factors for acute cholangitis after metallic biliary stent placement. DESIGN: Retrospective cases series. PATIENTS: A total of 108 patients with malignant biliary obstruction were treated with metallic stents, resulting in 12 cases of cholangitis. MAIN OUTCOME MEASUREMENTS: A multiple logistic regression model was performed with clinical parameters, including stent placement across the main duodenal papilla. RESULTS: By multiple logistic regression model, age; lower location; and Wallstent, Ultraflex stent, and covered stent were negatively associated with cholangitis. Restenosis and placement across the main duodenal papilla were positively associated with the occurrence of cholangitis. Transpapillary stent placement was the most significant risk factor. In this logistic model, the area under a receiver operating characteristics curve was computed as 0.92: sensitivity, 0.92 (95% confidential interval (CI), 0.62-1.00); specificity, 0.86 (95% CI, 0.78-0.93); positive predictive value, 0.46 (95% CI, 0.26-0.67); and negative predictive value, 0.99 (95% CI, 0.94-1.00). CONCLUSIONS: Disruption of the sphincter mechanism by transpapillary placement may be the most important etiologic factor in the propensity for cholangitis after metallic stent placement for malignant biliary obstruction.     

Liver biopsy interpretation for causes of late liver allograft dysfunction

Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.     

Abdominal Surgery Affects Small Bowel Transit Time and Completeness of Capsule Endoscopy

The aim of the study was to evaluate bowel dysmotility in patients with a history of abdominal surgery by measuring both gastric transit time and small bowel transit time during capsule endoscopy and assessing the completeness of the examination. The study included 26 patients who had undergone abdominal surgery (postoperative group) and 52 patients who had not (control group). The capsule reached the cecum in 50.0% of the postoperative group and 80.8% of the control group (P = 0.005). While there was no significant difference in gastric transit time between the two groups (P = 0.882), small bowel transit time was significantly longer in the postoperative group (338.3 ± 119.2 min) than in the control group (266.4 ± 110.8 min, P = 0.010). This is the first study to report that the small bowel transit time during capsule endoscopy is prolonged in patients who had a history of abdominal surgery, resulting in a lower frequency of complete examination.     

Interferon-α-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway

Object  The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action. Result  When the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-α, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-α-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-α inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-α inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-α, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-α alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication. Conclusion  IFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes.     

Double-balloon endoscopy: past, present, and future

Double-balloon endoscopy (DBE) was developed as a new technique for visualization of and intervention in the entire small intestine. In DBE, the intestinal walls are held apart by a balloon attached to the distal end of a soft overtube. DBE has been reported worldwide to be very useful for not only diagnosis but also endoscopic therapy. Biopsy samples of small intestinal tumors can be obtained using DBE, and the appropriate treatment can be selected before a surgical procedure. For inflammatory diseases, DBE can reveal the localization of ulcers in the lumen (on the mesenteric or antimesenteric side), which is important for differential diagnosis. Some endoscopic therapies such as hemostatic procedures, polypectomy, and dilation therapy for benign strictures can be performed in the same manner as in the large intestine. DBE may also be suitable for colonoscopy for difficult insertion cases and therapeutic procedures such as endoscopic submucosal dissection. Furthermore, a double-balloon endoscope can be selectively inserted into the afferent loop to perform endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y anastomosis, allowing various kinds of endoscopic treatments for biliary diseases to be successfully performed. Endoscopic therapy in the small intestine, whose wall is very thin, should be performed with special care to avoid complications such as bleeding and perforation. In the future, improvement is expected in terms of maneuverability, therapeutic capability, and imaging technology such as the addition of a magnifying function and flexible spectral imaging color enhancement. We anticipate that DBE will contribute to the establishment of medical science of the small intestine and to research elucidating the mechanisms of small intestinal diseases.