[Sacral nerve modulation in coloproctology]. / Sakrale Nervenmodulation in der Koloproktologie.

Sacral nerve modulation and stimulation (SNM/SNS) is a minimally invasive treatment for fecal incontinence, which has become widely established in recent years. Modulation of sacral nerve roots occurs through an electrode which is placed in the sacral foramina S2-4. By complex spinal and supraspinal mechanisms, rectal compliance is improved and anal incontinence episodes are reduced. The use of SNM is a suitable therapeutic option for nearly all causes of fecal incontinence refractory to conservative treatment. In the majority of patients, a significant reduction of incontinence episodes or a complete relief of symptoms is achieved. These results are also observed in long-term follow-up. Although the efficacy of SNM in constipation is less well established, it may be considered in patients who fail to respond to conservative measures. The role of further potential indications for SNM/SNS in coloproctological disorders is discussed in the present review.

[Can an online risk assessment tool for identification of hereditary colorectal cancer reach the at-risk population and influence screening compliance?]. / Kann mit einem Online-Risikotest die Risikopopulation für familiären und erblichen Darmkrebs erreicht und ihr Vorsorgeverhalten positiv beeinflusst werden?

BACKGROUND AND AIM: Lynch syndrome is a frequent autosomal dominant cancer predisposition leading to an estimated incidence of 3000-4000 new cancer diagnoses of colorectal and endometrial cancer in Germany per year. The underlying hereditary condition is largely underestimated and underrecognized by physicians. The usually young at-risk population, feeling insecure about their personal risk assessment, seeks information online. The aim of this study was to evaluate whether this online risk assessment tool for identification of increased risk for hereditary cancer predisposition reaches the target population and whether it succeeds in positively influencing intensified screening compliance. METHODS: The underlying algorithm for the test is based on the Bethesda and Amsterdam criteria and recent literature on polyposis syndromes. In the context of interrogating family and personal history, a total of five risk categories were defined. In addition to the cancers as defined in the above mentioned criteria, precursor lesions (polyps) were integrated into the risk estimate. Prior to launching, the algorithm was validated in family pedigrees of 102 mutation carriers with identified MLH-1 or MSH-2 mutations. RESULTS: During the time interval analysed, which was between October 2008 and April 2011 a total of 656 participants were included. Among these 19.1 % (125/656) belonged to the target population at increased familial or hereditary risk. 72.8 % (91/125) were yet healthy with known cancer-affected relatives. Merely 34.4 % (11/32) of the high-risk population were currently participating in a risk adjusted screening program. After completion of the online test 62.5 % (20/32) felt motivated to reconsider and adjust accordingly with increased surveillance. The test received an overall "good" evaluation (83 %) based on handling, performance and information content. CONCLUSION: This online risk-assessment tool was mainly completed by healthy (not cancer-affected) individuals with an increased risk for familial or hereditary colorectal cancer predisposition. The family pedigrees were comparable to these of known mutation carriers. The at-risk population was positively motivated to intensify screening strategies and the test received an overall positive evaluation.

Factors influencing lymph node harvest in colorectal surgery.

BACKGROUND AND AIMS: Lymphadenectomy in colorectal cancer is a critical component concerning prognosis and survival of patients. Several variables influence the number of harvested lymph nodes (LN). However, results of studies are contradictory, and influencing factors remain to be identified. The aim of the present study was to identify factors that have a significant influence on the number of assessed LN in oncologic colorectal cancer resection. MATERIALS AND METHODS: Three hundred and forty-one patients (190 men and 151 women), who underwent a colorectal cancer resection in a curative intention in the years 2000-2005, were analysed retrospectively. All specimens were histologically examined by two pathologists. RESULTS: In a median, 15.1 LN per operation were resected. Early tumour stage (p<0.01), length of resected bowel segment (p<0.05) and right-sided location (p<0.001) had a significant influence on the number of resected LN. Age, gender, surgeon volume, differentiation of the tumour, LN metastases, lymphatic invasion and depth of tumour invasion had no significant association with harvested LN number. Furthermore, the presence or absence of the vermiform appendix and the length of the resected ileum segment in right-sided resections did not significantly affect the assessed LN. CONCLUSION: The question arises whether for colorectal cancers of all locations the same amount of resected and analysed LNs should be lasting to fulfill oncologic criteria, as the number of harvested LNs depends on several parameters.

Differential gene expression in colon carcinoma cells and tissues detected with a cDNA array.

Expression of selected genes coding for proteins with defined cellular functions was analysed in human cell lines derived from normal colonic mucosa, non-mucinous colonic carcinomas and mucinous colonic carcinomas. Altered expression of 10 genes in colon carcinoma cells was found by using a cDNA array; 6 of these alterations (60%) were confirmed by Northern blotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Among these 6 genes, 3 transcription factors as well as the topoisomerase II alpha and the mitosis inhibitor WEE1Hu gene were significantly suppressed in the tumour cell lines. In addition, the gene coding for the cell cycle inhibitor p21 was overexpressed only in cell lines derived from mucinous carcinomas. The significant suppression of the kinase WEE1Hu gene in carcinoma cells of both phenotypes and the tendency of the mucinous phenotype to overexpress p21 protein were confirmed in human colon carcinoma tissues. Our data show that the cDNA array method permits a correct identification of changes in gene expression with a relatively high accuracy. The different expression of the p21 gene in the non-mucinous and mucinous carcinoma cells supports the hypothesis that these phenotypes may develop along different genetic pathways. The detection of WEE1Hu gene suppression in colon carcinoma cells and tissues suggests its potential role in tumourigenesis.

Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas.

Mutations in the adenomatous polyposis coli or beta-catenin gene lead to cytosolic accumulation of beta-catenin and, subsequently, to increased transcriptional activity of the beta-catenin-T cell-factor/lymphoid-enhancer-factor complex. This process seems to play an essential role in the development of most colorectal carcinomas. To identify genes activated by beta-catenin overexpression, we used colorectal cell lines for transfection with the beta-catenin gene and searched for genes differentially expressed in the transfectants. There are four genes affected by beta-catenin overexpression; three overexpressed genes code for two components of the AP-1 transcription complex, c-jun and fra-1, and for the urokinase-type plasminogen activator receptor (uPAR), whose transcription is activated by AP-1. The direct interaction of the beta-catenin-T cell-factor/lymphoid-enhancer-factor complex with the promoter region of c-jun and fra-1 was shown in a gel shift assay. The concomitant increase in beta-catenin expression and the amount of uPAR was confirmed in primary colon carcinomas and their liver metastases at both the mRNA and the protein levels. High expression of beta-catenin in transfectants, as well as in additionally analyzed colorectal cell lines, was associated with decreased expression of ZO-1, which is involved in epithelial polarization. Thus, accumulation of beta-catenin indirectly affects the expression of uPAR in vitro and in vivo. Together with the other alterations, beta-catenin accumulation may contribute to the development and progression of colon carcinoma both by dedifferentiation and through proteolytic activity.