Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.     

SURVEILLANCE OF SMALL INTESTINAL ABNORMALITIES IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: A PROSPECTIVE CAPSULE ENDOSCOPY STUDY

Background: Patients with hepatocellular carcinoma (HCC) sometimes suffer from obscure gastrointestinal bleeding. Portal hypertension (PH), common in cirrhosis, induces esophagogastric varices. Because of the location, PH also may influence mucosal abnormalities in the small intestine. The objective of this study is to estimate the prevalence of small intestinal mucosal abnormalities in HCC patients using capsule endoscopy (CE). Patients and Methods: We prospectively conducted CE in HCC patients, and analyzed the findings in relation to hepatic function, the number and size of HCC tumor and findings obtained by conventional endoscopy. Results: Thirty‐six patients (aged 66.7 ± 7.5 years, 29 men) underwent CE. Abnormal findings in the small bowel were found in 16 patients (44%), angioectasias in eight patients (22%), erosions in five (14%), varices in four (11%), polyps in four (11%), and submucosal tumor in one (3%). The patients with angioectasia had a larger spleen index than the no abnormal lesions group (85.4 ± 15.8 vs 59.0 ± 24.4, P = 0.02). The former group had been more frequently treated for esophageal varices endoscopically (62% vs 15%, P = 0.02). Large HCC nodules seemed more common in the patients with angioectasia than subjects without abnormal lesions (38% vs 5%, P = 0.06). Small intestinal varices also seemed to have a positive association with large HCC. During the follow up after CE, one patient with small intestinal polyps suffered from obscure gastrointestinal bleeding. Conclusions: CE revealed that HCC patients frequently have small intestinal mucosal lesions. In particular, small intestinal angioectasia, which may cause obscure gastrointestinal bleeding, seems to be associated with portal hypertension.     

Combination chemotherapy with cisplatin and irinotecan in patients with adenocarcinoma of the small intestine

Background  Small-bowel adenocarcinoma (SBA) is a rare tumor that has a poor response to chemotherapy and a poor prognosis. Treatment strategies for SBA have not been clearly established. Methods  All patients with SBA treated using a combination of cisplatin and irinotecan (IP) as first-line chemotherapy at the National Cancer Center Hospital in Japan between January 1999 and February 2007 were studied retrospectively. Results  Eight patients received IP as first-line chemotherapy. The median follow-up was 9.5 months (range, 4.2–37.5 months). The median number of cycles of IP was three (range, 1–5). The overall response rate (complete or partial response) was 12.5% (complete response, n = 0; partial response, n = 1). The disease control rate (complete or partial response or stable disease) was 75%. The median time to treatment failure was 4.5 months (95% confidence interval, 0.9–5.8 months), and overall survival was 17.3 months (range, 1.9–21.3 months). The most common adverse events were neutropenia and anorexia. Conclusion  IP combination chemotherapy may be an acceptable option for patients with SBA. Further studies are warranted to determine the optimal chemotherapeutic regimen for SBA.     

Enema reduction of intussusception with a small dose of iopamidol may have advantages over barium

Barium enema (B-enema) has been the standard method for hydrostatic reduction of intussusception, although recently air enema has been used due to the lower risk when perforation occurs. Recently, we have administered a small dose of iopamidol during enema reduction (I-enema) in children with intussusception. From November 1989 to December 1993, we treated 50 children with intussusception at Kiyama Hospital. Barium was used in the first half of the period, and iopamidol in the second half. Reduction was successful in 22 of 24 patients with barium (92%) and 23 of 26 with iopamidol (88%); 25 children had the ileocolic type and 25 the ileoileocolic (-cecal) type of intussusception. Operations were carried out in 3 patients from each group. I-enema avoids some of the drawbacks of barium and air enemas. It is a new method of enema reduction, as a contrast medium is injected first. It is possible to obtain a good image of the advanced portion with a small dose of contrast medium, which is important for treatment. For institutions performing B-enemas, I-enemas can be performed easily with the same equipment and technique. It causes less contamination upon leakage than a B-enema, and also has less influence on the intestinal membrane with very few risks if perforation occurs. Better images are obtained than with air. A large dose of contrast medium is not needed, thereby reducing medical expenses to a minimum. Iopamidol can be used safely for enema reduction of intussusception with an expected high success rate.     

A Solitary Peutz-Jeghers-type Hamartomatous Polyp of the Rectum: Report of a Case and Review of the Literature

A solitary Peutz-Jeghers-type polyp of the rectum in a 64-year-oldJapanese man is reported. Barium enema and endoscopic examinationrevealed a solitary polypoid lesion in the rectum. The polypwas pedunculated, and measured 2 x 1.5 x 1.5 cm. The patienthad neither mucocutaneous pigmentation nor a family historyof gastrointestinal polyposis. Histopathologically, this polyphad an arborizing muscular network originating from the muscularismucosa, and was covered by well organized mucosa with epithelialhyperplasia. The smooth muscle bundles in the polyp were thickerthan those seen in Peutz-Jeghers syndrome, but their networkwas not as complex.     

Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate

The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), isknown to induce oxidative stress and the subsequent formationof a type of oxidative DNA damage, 8-hydroxygu-anine (8-OH-Gua),in the rat kidney (Umemura et al., 1990). Using an improvedDNA isolation method (Nakae et al., 1995), which reduces thebackground level of 8-OH-Gua, we found a five-fold increasein the 8-OH-Gua level in kidney DNA after a single i.p. injectionof Fe-NTA. On the basis of the report that 8-OH-Gua repair activityis enhanced after cells are exposed to oxidative stress dueto ionizing radiation (Bases et al., 1992), the measurementof 8-OH-Gua repair activity will also be useful to assess cellularoxidative stress. The 8-OH-Gua repair enzyme activity was determinedwith an endonuclease assay using a 22 mer DNA that contains8-OH-Gua at a specific position. A five-fold increase in the8-OH-Gua repair activity as compared with the control, was observedin the target organ, the rat kidney, 120 h after Fe-NTA administration.In the non-target organ, the liver, the increase was not aslarge (two-fold). This simple assay of oxidative DNA damagerepair will be useful for evaluating the carcinogenicity ofoxygen radical forming chemicals, in addition to chemical analysesof oxidative DNA damage.