Down-regulation of µ-protocadherin expression is a common event in colorectal carcinogenesis.

We have previously reported that treatment of colorectal cancer cells with mesalazine results in the up-regulated expression of a novel member of the cadherin protein superfamily, named µ-protocadherin, which is able to sequester ß-catenin on plasmatic membrane of treated cells inhibiting its proliferation signalling pathway. This finding suggests that µ-protocadherin could exert an oncosuppressive effect on colorectal epithelium. The purpose of our study was to assess whether µ-protocadherin expression is down-regulated during colorectal carcinogenesis. This issue was addressed by analyzing the messenger RNA and protein expression of µ-protocadherin in normal and tumor colorectal cell samples using a combination of quantitative real-time polymerase chain reaction, microarray analysis, and immunohistochemical examination. To better contextualize the role played by µ-protocadherin in the pathogenesis of colorectal cancer, this last assay was also extended to ß-catenin, E-cadherin, and Ki-67 proteins. The results obtained evidenced that (1) levels of µ-protocadherin transcript were down-regulated in all the analyzed colorectal cancer samples as compared with normal mucosa; (2) expression of µ-protocadherin protein was completely lost in most analyzed colorectal cancer samples (71%); (3) µ-protocadherin retains ß-catenin on the plasmatic membrane of normal colon enterocytes, which implies that ß-catenin is released from this site and translocated to the nucleus in colorectal cancer cells. Our data consequently suggest that down-regulation of µ-protocadherin expression is a common event in colorectal carcinogenesis and might therefore play an important role in this pathologic process.

Preoperative therapy for lower rectal cancer and modifications in distance from anal sphincter.

PURPOSE: To assess the frequency and magnitude of changes in lower rectal cancer resulting from preoperative therapy and its impact on sphincter-saving surgery. Preoperative therapy can increase the rate of preserving surgery by shrinking the tumor and enhancing its distance from the anal sphincter. However, reliable data concerning these modifications are not yet available in published reports. METHODS AND MATERIALS: A total of 98 cases of locally advanced cancer of the lower rectum (90 Stage uT3-T4N0-N+ and 8 uT2N+M0) that had undergone preoperative therapy were studied by endorectal ultrasonography. The maximal size of the tumor and its distance from the anal sphincter were measured in millimeters before and after preoperative therapy. Surgery was performed 6-8 weeks after therapy, and the histopathologic margins were compared with the endorectal ultrasound data. RESULTS: Of the 90 cases, 82.5% showed tumor downsizing, varying from one-third to two-thirds or more of the original tumor mass. The distance between the tumor and the anal sphincter increased in 60.2% of cases. The median increase was 0.73 cm (range, 0.2-2.5). Downsizing was not always associated with an increase in distance. Preserving surgery was performed in 60.6% of cases. It was possible in nearly 30% of patients in whom the cancer had reached the anal sphincter before the preoperative therapy. The distal margin was tumor free in these cases. CONCLUSION: The results of our study have shown that in very low rectal cancer, preoperative therapy causes tumor downsizing in >80% of cases and in more than one-half enhances the distance between the tumor and anal sphincter. These modifications affect the primary surgical options, facilitating or making sphincter-saving surgery possible.

Incidence and clinical impact of sterilized disease and minimal residual disease after preoperative radiochemotherapy for rectal cancer.

PURPOSE: In advanced rectal cancer, chemoradiation can induce downstaging until complete disappearance of the tumor or its persistence in minimal form. The complete sterilized and the minimal residual disease often are considered similar. We evaluated the specific incidence of these two conditions and analyzed their impact in terms of local recurrence, distant metastasis, and survival. METHODS: We studied 139 uT3/T4 N0/N+ rectal cancers, treated with preoperative chemoradiation and curative surgery after six to eight weeks. We evaluated ypTNM stage and tumoral regression, according to the five degrees proposed by Dworak, with special attention to 4 and 3 (sterilized and minimal residual disease). RESULTS: Tumor downstaging occurred in 65 patients (46.7 percent), including 25 sterilized lesions (17.9 percent) and 24 minimal residual disease (17.2 percent). In median follow-up of 30 months, none of the patients with sterilized disease developed local or distant recurrence. Among patients with minimal residual disease, none developed local recurrence, whereas two (8.3 percent) developed distant metastasis, and one died from disease. In patients with gross residual disease (Grade 2, 1, 0) the percentage of local recurrence was 8.8 percent, distant recurrence 26.6 percent, and 13.3 percent died from disease. The difference between three groups is statistically significant as regards local and distant recurrence. CONCLUSIONS: After preoperative therapy, the sterilized disease shows an excellent prognosis. The minimal residual disease has an important numeric incidence. Its outcome is different, with a not-negligible risk of distant recurrence. The minimal residual disease has a much better prognosis in comparison with the gross residual disease.

Late complication of open inguinal hernia repair: small bowel obstruction caused by intraperitoneal mesh migration.

We describe a case of small bowel obstruction due to prosthetic mesh migration. A 67-year-old male, who had undergone prosthetic repair of inguinal hernia 3 years before, was admitted for a mechanical small bowel obstruction. Laparotomy revealed the penultimate ileal loop choked by an adhesion drawing it towards a polypropylene mesh, firmly attached to the parietal peritoneum of the inguinal region. The intestinal loop was released; the mesh was embedded deep with continuous whip suture after folding the parietal peritoneum. The patient was dismissed on the 11th postoperative day surgically healed. The "tension-free" technique is undoubtedly the gold standard for hernia repair. However, it is not free of complications, mostly due to technical errors, of which the surgeon must be aware, both when he is responsible for correcting defects in the wall, as well as when he has to face an occlusion in a patient who has undergone plastic surgery for inguinal hernia.