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Background. Somatostatin has been shown to inhibit in vitro and xenograft growth of human colon cancer. The kinetic index, proliferating cell nuclear antigen (PCNA), has previously been used to measure the effects of manipulation of growth of normal rectal epithelium. Methods. Twenty-five patients with distal colorectal cancer were considered for entry in a presurgical study of Sandostatin (Sandoz, East Hanover, NJ) 1 mg every 8 hours. Biopsies were performed pretreatment, during treatment (14 days), and day of surgical resection (2 days off treatment). A control series of 16 patients underwent endoscopic and subsequent surgical biopsy. A kinetic index was created called PCNA-maximum proliferative index (PCNA-MPI), which was reproducible within one biopsy and between two separate biopsies. Multiple biopsies were taken from the growing edge of tumors, the most cellular and best-stained fields selected, and the highest 6 of 10 separate counted fields were used to produce PCNA-MPI. Results. A significant decline in PCNA-MPI was observed in 6 of the 10 treated patients for whom all three biopsies were available, followed by a significant elevation on withdrawal of treatment. Changes in PCNA-MPI in the control group were less frequent and smaller. Conclusions. Sandostatin causes a reduction in PCNA-MPI in patients with human colorectal cancer. Cancer 1995; 76:572-8. Key words: colorectal cancer, proliferating cell nuclear antigen, somatostatin, clinical trial.

Background. Liver metastases from neuroendocrine tumors often present with disabling symptoms due to syndromes of hormonal excess. A locally destructive technique such as hepatic cryotherapy not only alleviates symptoms but may improve survival in this group of patients. Methods. Six patients with metastatic neuroendocrine tumors were treated with hepatic cryotherapy. Four patients were symptomatic and three of these had elevated tumor markers from ectopic hormone production. Results. All patients are alive and asymptomatic, with a median follow-up of 24 months (range, 6 months to 6 years). All have had a complete radiologic response. All with elevated preoperative markers have had a greater than 89%, decrease in tumor markers. Coagulopathy occurred in two patients necessitating additional surgery, but there was no other morbidity attributable to the cryotherapy. Conclusion. To the authors' knowledge, this study demonstrates for the first time that hepatic cryotherapy offers supportive treatment for patients with neuroendocrine tumors metastatic to the liver. Cryotherapy alleviates symptoms and may improve survival. Cancer 1995; 76:501-9.

Gastrin is a hormone that influences cells of the gastrointestinal system. In addition to its normal function, gastrin may also help to stimulate the growth of malignant cells. In one study, more than half the specimens of colorectal cancer tested were found to have high-affinity receptors for gastrin on their cell surfaces. Only 33 percent had no gastrin receptors at all. This raises the possibility that antagonists of the gastrin receptors might be used to slow the growth of cancers. A preliminary study to evaluate the feasibility of this approach was conducted using laboratory cultures of colorectal cancer cells. An experimental antagonist of the gastrin receptor, known only as L-365,260, was added to growing specimens of two different human colorectal cancer cell cultures. The growth of one cell line was inhibited by 44 percent, while the growth of the other was inhibited by 64 percent. A related series of experiments utilized nude mice. These laboratory mice have a seriously impaired cellular immune system, and therefore cannot destroy experimentally injected cancer cells as easily as normal mice. The experimenters injected the mice with cells from a rat pancreatic cancer that was known to have gastrin receptors. The administration of G17, a form of gastrin, hastened the growth of the cancers in these animals. However, if L-365,260 was given to the mice, the G17 no longer stimulated the progression of the cancer. Since many human cancers of the gastrointestinal tract have gastrin receptors, the authors hope that gastrin receptor antagonists may find application in the treatment of these cancers. (Consumer Summary produced by Reliance Medical Information, Inc.)