Shigeru Yamagishi

Amphiregulin Is a Promising Prognostic Marker for Liver Metastases of Colorectal Cancer

Purpose: Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors. The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer. Experimental Design: The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner. Results: Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217). Conclusions: AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis.

Allergic Reactions to Oxaliplatin in a Single Institute in Japan

Allergic reactions to oxaliplatin can be severe and are an important cause of discontinuation of treatment. A retrospective review was performed for 105 patients who received FOLFOX regimens between May 2005 and June 2007. Twenty-five cases (23.8%) of allergic reactions were identified, including 9 late onset reactions (8.6%) and 16 immediate reactions (15.2%). Severe allergy (Grades 3 and 4) occurred in seven patients (6.7%). Re-introduction of FOLFOX was attempted for seven immediate onset patients with a severity grade of 1 or 2, and three of these patients (42.9%) showed relapse of allergy. In approximately 10% of the patients, FOLFOX had to be discontinued due to allergy before the disease became refractory to the regimen. Our experience indicates that allergy to oxaliplatin may be a significant concern and that methods are required for suppression of this allergy.

Evaluation of intraperitoneal lavage cytology before colorectal cancer resection

PurposeThe aim of this study was to assess the usefulness of intraperitoneal lavage cytology (lavage Cy) status before the resection of colorectal cancer as a predictive factor of peritoneal recurrence.Materials and methodsThe lavage Cy-positive [lavage Cy (+)] rate, peritoneal recurrence rate, and 5-year survival rate were examined in 298 cases of colorectal cancer in relation to various clinicopathological factors.ResultsThe overall lavage Cy (+) rate was 6.0%. The lavage Cy (+) rate within the group with peritoneal and hepatic metastases was significantly higher than that in the group without metastases (46.7% vs. 3.9% and 26.9% vs. 4.0%, respectively). The lavage Cy (+) rate was not significantly associated with any of the clinicopathological factors examined. The peritoneal recurrence rate was higher in the lavage Cy (+) group than in the lavage Cy-negative [lavage Cy (−)] group, although the difference was not statistically significant. There was no significant difference in survival, regardless of the lavage Cy status, among the 263 patients who underwent curative resection.ConclusionThe lavage Cy status before resection was not a useful predictive factor of peritoneal recurrence in cases of colorectal cancer.

Laparoscopic colorectal cancer surgery by a colon lifting-up technique that decreases the number of access ports: comparison by propensity scoring of short-term and long-term outcomes with standard multiport laparoscopic surgery.

Background: Laparoscopic colectomy for colorectal cancer has become established as a minimally invasive surgical approach. However, many disposable instruments are required, and there is an associated disadvantage of cost. We have developed a new technique, which uses a suture string to lift up the colon. This method is expected to reduce the number of access ports required without compromising the radical cure. Operative Procedure: A suture string piercing the abdominal wall is passed through the mesocolon. The colon is retracted anteriorly and is fixed at the abdominal wall. The main mesenteric vessels are under tension, and lymph node dissection is performed easily by a medial approach. The working space is more stable because the colon is fixed to the abdominal wall. Methods: This study examined the short-term and long-term surgical outcomes of laparoscopic resection for colorectal cancer using our colon lifting-up technique (CLT), compared with the standard multiport technique. The study design was a case-matched control by propensity scoring. Analyzed variables were sex, age, American Society of Anesthesiologists score, cancer in a different organ, multiple colorectal cancer, operator, operative year, tumor location, operative procedure, adjuvant chemotherapy, and International Union Against Cancer TNM stage. Results: From 2000 to 2010, 301 patients underwent CLT and 436 standard multiport technique, 148 patients were matched by propensity score and analyzed. Regarding short-term outcomes, there was no difference between the 2 groups. The mean number of ports needed was 3.37±0.48 for CLT (93 with 3 ports, 55 with 4). There were no differences in recurrence-free survival and overall survival in long-term follow-up results for each stage. There were neither recurrences nor complications due to CLT. Conclusions: The CLT facilitated laparoscopic colectomy without compromising cure rates. It is a useful method to keep a stable view and to conserve medical resources.

Abstract 830: Clinical significance of measuring serum p53 antibodies in synchronous multiple colorectal cancer and double cancer patients

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Aims: The clinical significance of measuring serum p53 antibodies in colorectal cancer patients was evaluated. Patients and Methods: Preoperative serum tumor markers including CEA, CA19-9 and p53 antibody were examined in 264 patients (stage I: 68, II: 73, III; 81) who were given diagnoses of colon and/or rectal cancer in Yokohama City University Hospital from 2007 to 2008. Correlativity of tumor markers to clinical findings was investigated. Results: In the overall patients, range, median and positive ratio of each tumor marker are shown in Table [1][1]. Positive ratio of CEA and CA19-9 gradually increased according to clinical stage of the tumor, however, those of p53 showed almost the same concentration in any stage. Then, in stage I patients, positive ratio of p53 was higher than CEA and CA19-9 (p=0.0005). Thirty five cases (13.3%) of patients had synchronous or metachronous double or triple colorectal cancers. In that group, positive ratio of p53 was 48.3%, and median serum concentration of p53 was 0.915U/ml (0.15-295). Positive ratio and serum concentration of p53 of double or triple colorectal cancer patients were significantly higher than that of single cancer patients (p=0.0375). Conclusions: Serum concentration of p53 is sensitive, especially in early stage of colorectal cancer compared with other tumor markers. Colorectal cancer patients who showed high concentration of p53 have to be carefully checked for occult 2nd gastrointestinal tumor. View this table: 1 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 830. [1]: #T1

Abstract 5176: Expression of the atypical protein kinase C combined with expression of other factors is important for determination of structures in lateral spreading type tumors of the colon or the rectum

Background: LSTs grow superficially along the colonic wall but are short in height despite diameters larger than 10 mm. In our investigation, LSTs maintain cell polarity in spite of neoplasms comparing with polypoid-type tumor. In the present study, we examined the microscopic morphologies and functional characteristics of LSTs using immunohistochemical studies. Material and Methods: 30 LSTs and 20 polypoid-type colorectal tumors resected endoscopically or surgically in the department of Gastroenterological Surgery of Yokohama City University Hospital from 1998 to 2007, were examined. Localization of beta-catenin or E-cadherin, conservation of basement membrane and aPKCl/i were investigated by immunohistochemistry. Results: The expression of beta-catenin was of the preserved type in 7 (87.5%) of the LST adenomas, 11 (100%) of the polypoid-type adenomas and 7 (77.8%) of the LST intramucosal cancers. The expression of beta-catenin was of the nucleic type in 5 (55.6%) and the preserved type in only 2 (22.2%) of the polypoid-type cancers in adenoma. The expression of E-cadherin was also of the cytoplasmic or preserved type in all cases of the LST adenomas and polypoid-type adenomas and 8 (88.9%) of the LST intramucosal cancers. The expression of E-cadherin was of the lost type in none (0%) of the LST adenomas and polypoid-type adenomas while it was of the lost type in 5 (55.6%) of the polypoid-type cancers in adenoma. The expression of type IV collagen was of the continuous type in 8 (100%) of the LST adenomas and 6 (66.7%) of the LST intramucosal cancers. The expression of type IV collagen was discontinuous in 8 (72.7%) of [the] polypoid-type adenomas and lost in 7 (77.8%) of the polypoid-type cancers in adenoma. The expression of type IV collagen was of the lost type in all cases of LST invasive cancers with adenoma. Conclusion: In aPKC lambda/iota e xpression, >90% of adenoma was 1+ or 2+. 87% of LST adenomas were 1+ and 45% of polypoid-type adenomas were 2+. About 70% of cancer in polypoid-type adenoma and invasive cancer of LSTs were 3+. On the other hands, about 60% of LST intramucosal cancers were 1+. LST adenomas or LST cancer in situ showed weaker expression of aPKC than polypoid-type adenomas or cancers. In the site of strong expression of aPKCl ambda/iotab eta-catenin was expressed in nucleus and in the site of weak expression of aPKC lambda/iota, beta-catenin was expressed in cytoplasm and cell membrane Conclusions: In the present study, we showed that in LSTs, not only adenomatous lesions, but also intramucosal cancerous lesions, maintained the characteristics of normal epithelial cells in the expression of beta-catenin, E-cadherin and Type IV collagen. They also showed weak expression of aPKC lambda/iota. (Supported by the grants of Japanese Ministry of Education, Culture, Sports and Science) Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5176.