Colonoscopic polypectomy resulted in a lower-than-expected incidence of colorectal cancer. These results support the view that colorectal adenomas progress to adenocarcinomas, as well as the current practice of searching for and removing adenomatous polyps to prevent colorectal cancer.

Patterns of local and distant recurrences following resections for rectal cancer provide clinical perspective for multidisciplinary prevention and follow‐up programs. From 1968 to 1976 at Memorial Hospital, 412 patients with potentially curable rectal cancer were treated by anterior (AR) or abdominoperineal (APR) resections. First sites of recurrences were categorized as pelvis, liver, distant viscera, and intraabdominal/ retroperitoneal sites. Pelvic recurrences were further evaluated according to the location of the tumor, type of resection, and stage of disease. Among the 412 cases, 182 (44.2%) patients developed recurrence, of which 105 (57.6%) were pelvic. Pelvic recurrence was the predominating site either alone (55 of 103) or with concomitant extra‐pelvic sites (50/79). In instances of single‐site first recurrence, pelvic failure was recognized earliest at 19.1 months, which was significantly earlier than single‐distant visceral sites at 34.9 months. Pelvic recurrence was selectively related to various categories of the Dukes and modified Dukes staging systems. Dukes stage significantly predicted pelvic recurrence rates for Dukes A versus B. Astler‐Coller stages of B2 and C1 were associated with significantly lower rates of pelvic recurrence (29.7% and 22.1%, respectively) than C2 cancers. The incidence of pelvic recurrence was significantly increased for low and mid rectal cancers as compared with cancers at or above 12 cm. The type of resection utilized (APR versus AR) was associated with no difference in the rate of pelvic recurrence, except for the few patients in whom AR was performed for low rectal Dukes C cancers. Patients with pelvic recurrence had an ultimate disease‐free survival of only 3.8% as compared with patients with no pelvic recurrence of whom 77% remained alive without disease or went on to die of other causes. The timing and predominance of pelvic failure in rectal cancer with its own treatment‐related morbidity and overall dismal survival outcome justifies organized multidisciplinary efforts to prevent such failure and prospective trials of comprehensive follow‐up programs to evaluate improved cure rates or palliation. Cancer 53:1354‐1362, 1984.

Siblings and parents of patients with adenomatous polyps are at increased risk for colorectal cancer, particularly when the adenoma is diagnosed before the age of 60 or--in the case of siblings--when a parent has had colorectal cancer.

Several laboratories have reported that overexpression of the multidrug resistance (MDR) protein is associated with intracellular alkalinization, and several investigators have reported that cells induced to undergo programmed cell death (apoptosis) acidify quite significantly. Because it is difficult to fully explain the resistance to apoptosis-inducing chemotherapeutic drugs that is exhibited by MDR tumor cells solely via altered drug transport alone [Hoffman et al. (1996) J. Gen. Physiol. 108, 295-313], we have investigated whether overexpression of the hu MDR 1 protein alters progression of the apoptotic cascade. LR73 fibroblasts induced to undergo apoptosis either via treatment with the chemotherapeutic drug colchicine or by serum withdrawal exhibit cellular volume changes, intracellular acidification, nuclear condensation, and chromosomal digestion ("ladder formation"), characteristic of apoptosis, in a temporally well-defined pattern. However, multidrug resistant LR73/20E or LR73/27 hu MDR 1 transfectants recently created in our laboratory without selection on chemotherapeutic drug are significantly delayed in the onset of apoptosis as defined by the above criteria, regardless of whether apoptosis is induced by colchicine treatment or by serum withdrawal. Thus, the delay cannot simply be due to the well-known ability of MDR protein overexpression to lower chemotherapeutic drug accumulation in MDR cells. LR73/27V500 "selectants", exhibiting similar levels of MDR protein overexpression but higher multidrug resistance due to selection with the chemotherapeutic drug vincristine, exhibit a slightly longer delay in the progression of apoptosis. Normal apoptotic cascade kinetics are partially restored by pre-treatment of the MDR cells with the MDR protein inhibitor verapamil. Untransfected LR73 cells not expressing MDR protein but elevated in pHi via manipulation of CO2/HCO3- as described [Hoffman et al. (1996) J. Gen. Physiol. 108, 295-313] are inhibited in DNA ladder formation, similar to LR73/hu MDR 1 transfectants. These results uncover an additional mechanism whereby MDR protein overexpression may promote the survival of tumor cells and further support the notion that in some systems intracellular acidification may be either causal or permissive for proper progression of the apoptotic cascade.