Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma.

PURPOSE: An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. METHODS: Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated. RESULTS: Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. CONCLUSIONS: Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.

Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant genetic predisposition syndrome that accounts for 2-7% of all colorectal cancers. Diagnosis of HNPCC is based on family history (defined by Amsterdam or Bethesda Criteria), which often includes a history of multiple synchronous or metachronous cancers. The majority of HNPCC results from germ-line mutations in the DNA mismatch repair (MMR) genes hMSH2 and hMLH1 with rare alterations in hMSH6 and hPMS2 in atypical families. Both HNPCC and sporadic MMR-deficient tumors invariably display high microsatellite instability (MSI-H). Two types of HNPCC families can be distinguished: type I (Lynch I) with tumors exclusively located in the colon; and type II (Lynch II) with tumors found in the endometrium, stomach, ovary, and upper urinary tract in addition to the colon. A proposed association of breast cancer with type II HNPCC is controversial. To address this important clinical question, we examined MSI in a series of 27 female patients who presented with synchronous or metachronous breast plus colorectal cancer. Although MSI-H was found in 5 of 27 (18.5%) of the colon cancers, in all cases the matched breast cancer was microsatellite stable. We also examined the breast tumors from three women who were carriers of MMR gene mutations from HNPCC families. None of these three breast tumors displayed MSI nor was the expression of MMR proteins altered in these tumors. We conclude that breast cancer largely arises sporadically in HNPCC patients and is rarely associated with the HNPCC syndrome.