Photodynamic therapy of colorectal cancer using a new light source: from in vitro studies to a patient treatment.

PURPOSE: Photodynamic therapy (PDT) is a relatively new alternative modality for palliation of rectal cancer. Current source of light for PDT are laser systems that are expensive and not necessarily needed for PDT. We evaluated a new nonlaser light source for PDT, Versa-Light. METHODS AND RESULTS: In vitro PDT--CT26 murine colon carcinoma cells were incubated with aluminum phthalocyanine (AlPcS4) for 48 hours and subjected to photoradiation using Versa-Light, and viability was assessed. There was a significant decrease in viability of treated cells compared with controls. In vivo PDT--BALB/c mice were injected either subcutaneously or intrarectally with CT26 cancer cells. IP AlPcS4 (2.5 mg/kg) was injected when tumors were visible. After 24 hours, mice were subjected to photoradiation. Massive tumor necrosis in response to PDT was observed. PDT also prolonged survival of treated mice. Patient treatment--A 70-year-old woman with recurrent local rectal carcinoma received intravenous Photofrin II (2 mg/kg). After 48 and 96 hours, she was subjected to direct photoradiation. After the first light session, there was complete macroscopic disappearance of the tumor. Biopsies up to 10 weeks after the treatment showed no cancer cells in the treated area. Sixteen weeks later, a randomized biopsy from previous tumor site showed carcinoma cells. CONCLUSIONS: We believe that Versa-Light, is a good light source for PDT. It was effective in both in vitro and animal studies. It can also be safely used for clinical PDT.

Traumatic rupture of the intestine in patients with inflammatory bowel disease.

Three young patients suffering from inflammatory bowel disease were admitted to our hospital during the past year for extensive intestinal rupture caused by disproportionately minor trauma. There was almost no concomitant intra-abdominal injury. We believe that a minimal direct or acceleration/deceleration trauma to a preexisting diseased intestine might have caused extensive damage that was not apparent on admission. It was concluded that these patients should be carefully monitored and that their relative intestinal vulnerability should be borne in mind during diagnosis of and therapeutic planning for their condition.

Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.

The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.