Endothelial nitric oxide synthase: correlation with histologic grade, lymph node status and estrogen receptor expression in human breast cancer.

Nitric oxide is produced by several isoenzymes which are present in many different tissues. We have recently reported the presence of inducible nitric oxide synthase in a breast cancer cell line. The purpose of this study was to examine the distribution of endothelial nitric oxide synthase (eNOS) in a series of human breast tumours. Immunohistochemical investigations demonstrated immunolabelling of tumour cells with the primary antibody, bovine endothelial anti-nitric oxide synthase. Although there was no correlation between eNOS staining and tumour size, there was a significant (p < 0.005) negative correlation (rho = -0.65) between the percentage of tumour cells staining positive for eNOS and the histologic grade of the tumour; there was also a significant (p < 0.05) negative correlation (rho = -0.40) between the percentage of tumour cells staining positive for eNOS and the number of positive lymph nodes. A significant (p < 0.005) positive correlation (rho = 0.63) between the percentage of tumour cells staining positive for eNOS and estrogen receptor (ER) expression by the tumour was also observed. In conclusion, our results demonstrate that eNOS is expressed by human breast tumours and that its presence negatively correlates with histologic grade and lymph node status and positively correlates with ER expression.

Chondroid lipoma: a rare but diagnostically important lesion.

Chondroid lipoma is a rare benign fatty tumour that has been confused with liposarcoma and chondrosarcoma. We present a case in a 44-year-old man and highlight the features that differentiate this benign lesion from the more aggressive ones.

Absence of prolactin gene expression in colorectal cancer.

AIMS: Previous studies documenting hyperprolactinaemia in patients with colorectal cancer have suggested that the tumour is the source of hormone production. The aim of this study was to determine the frequency of hyperprolactinaemia in patients with colorectal cancer before, during, and after surgery, and also to determine whether prolactin is produced by these tumours. METHODS: Serum prolactin concentrations were measured in 20 patients with colorectal cancer before, during, and after surgical resection of their tumours. Samples taken during surgery included peripheral venous blood and blood taken from the main veins draining the tumour. To determine whether the tumour was responsible for the production of prolactin in these patients, paraffin wax embedded sections of tumour specimens were subjected to immunohistochemistry and western blotting using a monoclonal antibody to prolactin. RESULTS: Five patients (three women, two men) had preoperative prolactin concentrations above the normal reference range, although this increase was of clinical importance in only two. After surgical resection of their tumours, prolactin concentrations remained high in both patients. All 20 patients had greatly raised prolactin values at the time of surgery, irrespective of whether this was measured in peripheral blood or in blood taken from veins draining the tumour. All 20 colorectal cancer tissue samples, including those with raised preoperative and/or postoperative prolactin concentrations, were negative for prolactin staining. Frozen tissue was also available in four cases. The absence of prolactin gene expression in these four tumours was confirmed both by repeat immunohistochemistry and by western blotting. A further 50 colorectal cancer cases examined by immunohistochemistry alone were also unreactive for prolactin. CONCLUSIONS: The results of this study suggest that serum prolactin concentrations may occasionally be raised in colorectal cancer patients, but that the tumour is not the source of hormone production.

Increased hematopoietic toxicity following administration of interferon-a with combination dideoxynucleoside therapy (zidovudine plus ddI) administered in normal mice.

Because of the urgency to develop drugs which will effectively combat HIV infection, many combination therapies which have proved effective against HIV in vitro have undergone, or are undergoing clinical trial. Unfortunately many of drugs are being used without rigorous and exhaustive preclinical evaluation to assess their potential to develop hematopoietic toxicity. We report here the results of two in vivo studies performed to analyze the effect of combined zidovudine (AZT) plus didanosine (ddI) therapy, either with or without interferon-a (IFN-a), on murine hematopoiesis. Normal C57BL/6 female mice were administered AZT (1.0 mg/ml) plus dose-escalation ddI (0.1, 1.0 and 2.5 mg/ml) placed in their drinking water. Control mice received IFN-å (100 units/ml) alone. Mice were serially bled and sacrificed over a six-week period for assessment of hematopoietic toxicity measured by peripheral blood indices and assays of hematopoietic progenitors, i.e., erythroid (BFU-E), myeloid (CFU-GM), and megakaryocyte (CFU-Meg) cultured from bone marrow and spleen. AZT plus dose-escalation ddI decreased the hematocrit and white blood cell count when administered to normal mice compared to untreated controls during the six-week examination period. Marrow derived BFU-E, CFU-GM, and CFU-Meg were all reduced, however an increase was observed from the spleen for all three progenitor cell types. Use of IFN-a, in addition to combination AZT plus ddI further decreased the hematocrit, white blood cells and platelets. Marrow derived CFU-GM and CFU-Meg were increased slightly and only marginally for BFU-E with a similar response observed from the spleen. These results demonstrate that combination AZT plus ddI when used in vivo may produce synergistic hematopoietic toxicity, and that the addition of IFN-a to this treatment regimen increases this toxicity. These data indicate caution when this therapeutic approach is suggested for patients infected with HIV. If used, these patients will require careful monitoring for blood cell toxicity.

Five-year follow-up study of the fat clearance technique in colorectal carcinoma.

PURPOSE: The aim of our study was to determine the five-year survival of patients with colorectal carcinoma whose Dukes classification had changed following fat clearance of the mesocolon or mesorectum. METHODS: One hundred three patients with colorectal carcinoma were followed up at a special clinic for at least five years after surgery. The tumors from these patients had previously been given a Dukes classification before and after fat clearance. RESULTS: Four of the five patients whose Dukes status changed from B to C as a result of fat clearance died of malignant disease during the five-year follow-up period. After fat clearance it was apparent that Dukes B patients survived, on average, 11 months longer than Dukes C patients. A significantly increased mean number of positive nodes was found after fat clearance in Dukes C cases, both in those who were alive at five years and those who died of their malignant disease. CONCLUSIONS: The fat clearance technique is a useful aid to improving the accuracy of the Dukes classification and has prognostic significance. It should be used in specimens of colorectal carcinoma, which on initial examination appear to be Dukes B cases.

The relationship between tumour volume and the extent of spread in colorectal carcinoma.

115 colorectal carcinomas were measured in three dimensions. To compare the tumour volume, greatest linear dimension and the maximum thickness of colorectal carcinomas with the extent of spread. A formula was devised for estimating tumour volume based on the oval shape of most carcinomas. Dukes staging was performed after xylene/alcohol fat clearance. The mean tumour volume of Dukes B tumours was greater than A tumours. The mean volume of C tumours was greater than that of A tumours. The mean volume of Dukes B tumours was greater than that of C tumours. The greatest linear dimension and the tumour thickness measurements also showed differences but were not as discriminating as the tumour volume. Using the Astler and Coller modification of Dukes staging, the mean tumour volume of C2 tumours was significantly greater than that of C1 tumours. Both C1 and C2 tumour volumes when considered separately were smaller than those of the B tumours. There was a significant positive correlation coefficient between tumour volume and the greatest linear dimension and also between tumour volume and the tumour thickness. There was no significant correlation within the C tumours between tumour volume and the number of lymph nodes with metastatic deposits. Colorectal carcinomas differ from other solid tumours in their growth pattern and metastatic behaviour. There is no direct relationship between increasing tumour size and progression in the Dukes staging. Some tumours appear to metastasize to lymph nodes while still small (C1 tumours); other tumours appear not to metastasize to lymph nodes regardless of size (B tumours).(ABSTRACT TRUNCATED AT 250 WORDS)

Mixed adenocarcinoma/carcinoid tumour of large bowel in a patient with Crohn's disease.

A 50 year old woman with a 20 year history of Crohn's disease underwent laparotomy which revealed extensive disease in the small and large bowel, and this was resected. Gross examination of the resected bowel showed features of Crohn's disease as well as a polypoid tumour in the caecum. Histopathological examination of the tumour showed it to be an infiltrating mixed adenocarcinoma/carcinoid tumour arising in a tubulovillous adenoma. Random sampling of the rest of the bowel affected by Crohn's disease also showed a focus of dysplasia and adenomatous change. It is suggested that Crohn's disease may have played a part in the pathogenesis of the tumour.

Detection of lymph node metastases in colorectal carcinoma before and after fat clearance.

One hundred and three colorectal carcinoma specimens were examined to determine the value of the xylene and alcohol fat clearance technique in detecting lymph node metastases. The mesocolon or mesorectum was dissected initially by the traditional method and all the lymph nodes identified were examined histologically. After fat clearance the specimen was dissected again and further lymph nodes were examined. Forty-one specimens were obtained from the rectum and 62 from the colon. Traditional dissection produced a mean of 6.2 lymph nodes per specimen, but following fat clearance a further mean of 12.4 nodes per specimen were found. The total number of lymph nodes recovered varied from two to 69 with a mean of 18.5 per specimen. Traditional dissection showed 45 specimens (43.7 per cent) to have lymph node metastases but after fat clearance a further five specimens (4.8 per cent) were found to be lymph node positive. Therefore, of the 58 specimens graded initially as Dukes' B, five (8.6 per cent) were shown after fat clearance to be Dukes' C tumours. In the Dukes' C cases the mean (s.d.) number of involved lymph nodes per specimen was 2.7 (2.1) by traditional dissection and 4.2 (3.9) after fat clearance. Forty-seven (94.0 per cent) of the Dukes' C tumours were correctly identified after examination of specimens containing up to 13 lymph nodes. Fat clearance of the mesocolon or mesorectum should be used when traditional dissection has failed to identify at least 13 nodes and the tumour has been classified as Dukes' B.

Cellobiose/mannitol sugar absorption test in patients with dermatitis herpetiformis: a preliminary report.

An abnormal cellobiose/mannitol ratio is present in new patients presenting with dermatitis herpetiformis and in patients who have never adhered to a strict gluten-free diet. In patients with dermatitis herpetiformis in remission on a strict gluten-free diet, small bowel absorption as measured by the cellobiose/mannitol ratio is normal. It is suggested that cellobiose/mannitol ratio absorption is a useful screening test for the intestinal abnormality associated with dermatitis herpetiformis and failure of the test to return to normal could suggest poor dietary compliance.

A case of polyorchidism with testicular teratoma.

A patient with duplication of the testis who presented initially with torsion of a right inguinal testis is described. Subsequently, a malignant teratoma of the trophoblastic type (choriocarcinoma) developed in the scortal testis on the right side. This scrotal testis was impalpable initially but a normal testis was present on the left side. The patient died of cerebral and pulmonary metastases of the teratoma.