Robert M. Beazley

Results of a phase I trial of a recombinant vaccinia virus that expresses carcinoembryonic antigen in patients with advanced colorectal cancer

AbstractBackground: The inadequacy of systemic treatments of advanced colorectal cancer has aroused interest in biologic therapy. Recent animal models have demonstrated the efficacy and safety of a recombinant vaccine that contains vaccinia and the gene for carcinoembryonic antigen (rV-CEA). Methods: A phase I clinical trial of rV-CEA was conducted to assess vaccine toxicities, the maximum tolerated dosage, resulting immune activities, and tumor responses. A dose-escalation protocol was devised for three concentrations. Six patients per dosage were each to receive three vaccinations. Results: Seventeen patients with advanced colorectal cancer received a total of 44 vaccinations. Mild local and systemic reactions—comparable to those seen with vaccinia alone—were observed and were typically associated with the first vaccination. No significant complications or deaths were caused by the rV-CEA. In particular, no autoimmune colitis developed, nor did leukopenia occur, despite some homology between CEA and leukocyte antigens. All three vaccine concentrations were equally well tolerated. Most patients demonstrated tumor progression by clinical and radiographic parameters and by CEA levels. Immune assays are pending. Conclusions: This phase I trial demonstrated the safety of rV-CEA in patients with advanced colorectal cancer. Future clinical studies are warranted and will likely be influenced by investigations of the immune responses to the vaccine.

Reoperative parathyroid surgery

Reoperative parathyroid surgery is associated with a high mortality and morbidity. Morbidity consists of uncorrected hypercalcemia, hypoparathyroidism, and recurrent nerve injury. Initial operative failure is most frequently a result of not identifying four parathyroid glands. On reoperation, parathyroid glands are most often found in the neck and are usually hyperplastic. It is recommended that before attempting rexploration for parathyroid disease, all the patients records especially the operative note and the previous pathology material should be reviewed. Preoperative localization by selective venous catheterization is of great use in the management of this type of patient.

Is splenectomy more dangerous for massive spleens

BACKGROUND Reports vary about whether risks are greater for removal of massive (> or = 1500 g) spleens than for smaller (< 1500 g) spleens. We sought to determine the hazards of splenectomy. METHODS We reviewed 223 consecutive adults with elective splenectomies for hematologic diseases. Morbidity and mortality rates were combined with published data to create a meta-analysis. RESULTS Patients with massive spleens are more likely to have postoperative complications (relative risk [RR] 2.1, 95% confidence interval [CI] 1.3 to 3.4; P = 0.003) and death (RR 4.7, 95% CI, 1.5 to 15.1; P = 0.01). However, when the investigation is restricted to comparable diagnoses, patients with massive spleens do not differ from those with smaller spleens regarding complications (RR 1.4, 95% CI, 0.8 to 2.7; P = 0.3) or mortality (RR 2.1, 95% CI, 0.5 to 9.7; P = 0.4). These observations are confirmed by metaanalysis. Furthermore, multivariate analysis indicts age as a critical risk of complications and death. CONCLUSIONS Increased age and underlying illness are the predominant factors associated with morbidity and mortality following splenectomy for hematologic disease. Adjusting for age and diagnosis, spleen size is not a hazard.

Estrogen receptor functional status in human breast cancer.

Estrogen receptors (ER) are detected in 50-85% of all breast tumors, and are clinically important because they tend to identify patients with a higher probability of responding to hormonal or endocrine manipulations. However, approximately 30-40% of all ER+ patients do not respond to hormonal manipulations. The lack of response to hormonal manipulations in ER+ patients could be the result of nonfunctional ER, as determined by its inability to recognize and bind to specific DNA-responsive elements and/or its inability to recruit other transcriptional activation factors. The functional status of ER in 34 human breast tumors was assessed determining the structural integrity of the ER DNA-binding domain using site-directed monoclonal anti-estrogen receptor antibody and sucrose density gradient analysis. Based on the fraction of ER containing an intact DNA-binding domain, the tumors were classified into three groups: group I with > 65% of intact ER, group II with > 30% of intact ER, group III with < 30% of intact ER. Clinical and pathologic data were obtained only for patients who were treated with the anti-estrogen tamoxifen and correlated with ER functional status. In group I, 11 of 13 (84.6%) patients were responsive to hormonal therapy with favorable clinical outcome; two patients had unfavorable clinical outcome. In group II, 13 of 15 patients (86.7%) had favourable clinical outcome, and two patients 13.3% had unfavorable outcome. In group III, three of six patients appeared to be hormone responsive with favorable clinical outcome, and three of the patients in this group had unfavorable response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytogenetic studies of an adrenal cortical carcinoma

Cytogenetic findings in the third reported case of adrenal cortical carcinoma are described. In contrast to the two previous cases, hypodiploidy characterized almost all cells, which had as many as eight abnormal chromosomes in each cell analyzed.

Carcinoma of the right colon

Abstract A review of eighty-nine consecutive patients with cancer of the right colon has been undertaken as a medical audit and to determine those factors supporting long-term survival and those which make early detection difficult. The most important factor in indefinite survival without recurrent disease has been and still remains the absence of involved regional lymph nodes. In this series, when regional nodes were uninvolved and the patient survived the operative period, the chance for survival was 80 per cent at five years and 64 per cent at ten years. Twenty per cent of the patients with positive nodes in this series survived five years; death from carcinoma had occurred by the four year mark in those patients who were to die of the disease. The duration of disease in these patients, as ascertained by history taking, sheds little light on their prognosis. Patients with lesions of the right transverse colon seemed to have the same prognosis as patients with lesions of the cecum and ascending colon. Family incidence of carcinoma may be significant in raising an early suspicion of disease by either patient or family physician. It seems to have no further significance in determining longevity. Diverticulosis of the colon and colonic polyps should be viewed as associated lesions which may obscure awareness and the urgency of early precise diagnosis in the presence of colonic cancer. In this series 40 per cent of the patients were treated by resident surgeons. These patients fared as well as did those operated on by their more experienced colleagues.

Vitamin D, Sunlight and Colon Cancer: The Implications for the Presence of the 1α-Hydroxylase in Normal and Malignant Colon Cancer Tissue

Vitamin D deficiency has been implicated as a possible factor in the development of many cancers including cancer of the prostate, breast and colon 1, 2. Garland & Garland reported that mortality rates due to colorectal cancer in the United States are highest in areas with the least amount of solar radiation 3. Countries with the lowest prevalence of colon cancer are located within 20 degrees of the equator 4. Increasing latitude increases the risk of developing colon cancer with the exception of Japan where the diet is high in vitamin D from ingestion of fatty fish 5. A prospective cohort study of 1954 men determined that men who ingested more than 150 IU of vitamin D had a 50% lower incidence of colon cancer than those who consumed less than 150 IU of vitamin D 6. A twelve-year prospective study of over 89,000 female nurses found that the highest quintile of vitamin D intake was associated with a relative risk of 0.42 (95% CI 0.19 – 0.91) of developing colon cancer when compared to the lowest quintile of vitamin D intake 7. A 6 year prospective study of almost 48,000 men revealed that men in the highest quintile of vitamin D intake had half the incidence rate of colon cancer than men in the lowest quintile of vitamin D intake 8. A case-control study of 25,620 adults revealed that individuals with 25(OH)D levels greater than 20 ng/ml had one-third the risk of colon cancer compared to subjects who were vitamin D insufficient9.