Search PubMed⌕ Search

Biomedical subjects

T J Saclarides

Publications and source records attributed to T J Saclarides.

At least 37 records · Page 2Linked to original sources
PubMed1996

Brain metastases from colorectal cancer.

PURPOSE: We wished to determine the time interval before diagnosis of brain metastases from a colorectal origin, typical neurologic presentation, overall survival, and impact of type of treatment and metastatic growth patterns (solitary, location, etc.) on prognosis. METHODS: Between 1980 and 1994 we retrospectively identified 19 patients with metastatic colorectal cancer to the brain. Data were collected with regard to patient characteristics, location and stage of primary tumor, and extent and location of metastatic disease. Statistical analyses were performed with STATISTICA for Windows. RESULTS: Mean patient age was 66 (43-87) years. Primary tumor location was distributed throughout the colon; 58 percent had disseminated disease when first diagnosed. All patients were symptomatic. Lesions were solitary in 63 percent, unilateral in 89 percent, and cerebral in 53 percent. Overall median survival was 2.8 months; 1-year survival was 0 percent. Survival was longer following craniotomy (4.1 months) compared with radiation (2.8 months); however, survival was not affected by number or location of metastatic lesions or whether the brain was the sole site of metastatic disease. CONCLUSIONS: Brain metastases from colorectal cancer are infrequently the sole site of metastatic disease, and because survival is dismal regardless of form of therapy chosen, craniotomy is rarely indicated. Exception is the rare patient who has minimum neurologic impairment, a long disease-free interval, a solitary metastasis, and no extracranial disease.

Adult↗
PubMed1996

Formalin instillation for refractory radiation-induced hemorrhagic proctitis. Report of 16 patients.

PURPOSE: Our goal was to evaluate use of topical (4 percent) formalin in management of radiation-induced hemorrhagic proctitis, refractory to other methods of treatment. Specifically, we wished to determine its safety, ability to stop bleeding, and complications associated with therapy. METHODS: Sixteen patients with radiation-induced hemorrhagic proctitis were treated with topical (4 percent) formalin. All had been previously treated with conservative regimens such as cautery, topical steroids, or laser, but these had failed. Five-hundred milliliters (ml) of a 4 percent formalin solution was instilled into the rectum in 50-ml aliquots. Each aliquot was kept in contact with rectal mucosa for approximately 30 seconds. Treatments were performed under local anesthesia in nine patients, sedation only in four, spinal in two, and general in one patient. RESULTS: In 12 patients, bleeding stopped after a single formalin instillation; in 3, bleeding was considerably reduced but continued sporadically. One patient required three treatments before bleeding stopped. Four patients developed postoperative anal pain, of which one also had significant tenesmus and reduced capacity. Of these four patients, only two had significant anal pain and fissures that lasted longer than one month. CONCLUSIONS: Topical (4 percent) formalin is safe and effective in treatment of radiation-induced hemorrhagic proctitis. A single treatment will stop bleeding in 75 percent of patients.

Administration, Rectal↗
PubMed1996

WR-1065 and radioprotection of vascular endothelial cells. II. Morphology.

Although the aminothiol WR-1065 protects normal tissues, its direct effect on the damage and restoration of the vascular endothelium is not clear. In endothelial cells, WR-1065 attenuates both the DNA damage and the G1-phase arrest induced by radiation. After the destruction of nearby endothelial cells, the survivors rearrange their cytoskeleton, migrate and replicate. To determine the effect of radiation on morphology and migration, portions of bovine aortic endothelial cell cultures were denuded with a pipette tip and irradiated (137Cs gamma rays). The following observations were noted after 5 Gy: within 10 min, there was increased formation of protein-mixed disulfides including actin-mixed disulfide; after 30-min, alpha 5 beta 1, the integrin receptor for fibronectin, was up-regulated on the apical membrane surface. Within 5 h, actin-containing stress fibers reorganized, although there was no change in the total filamentous (F-)actin content within the cells. Compared to controls after 24 h, the irradiated cells had migrated 15% farther (P < 0.01), and at the leading edge covered twice the surface area (P < 0.0001). The addition of 2 mM WR-1065 for 2 h before 5 Gy inhibited the increased expression of alpha 5 beta 1, promoted retention of stress fibers and prevented the enhanced cell migration and spreading. These results indicate that WR-1065 prevents radiation-induced morphological responses. This effect appears to be mediated by an impact on both adhesion molecule expression and cytoskeletal reorganization.

Actin Cytoskeleton↗
PubMed1995

Four-contrast defecography: pelvic "floor-oscopy".

PURPOSE: This study was designed to determine the accuracy of physical examination (as judged by four-contrast defecography) for women with pelvic floor relaxation disorders. METHODS: Sixty-two women (mean age, 59 years) who had obstructed defecation or constipation, vaginal prolapse, urinary difficulty, or pelvic pain underwent four-contrast defecography. Oral, vaginal, bladder, and rectal contrast were administered selectively and fluoroscopy was performed. Radiographic findings were compared with physical examination diagnosis. RESULTS: Four-contrast defecography changed the diagnosis in 46 patients (75 percent); 26 percent of presumed cystoceles, 36 percent of enteroceles, and 25 percent of rectoceles were not present on defecography. Defecography also revealed unsuspected coexisting defects in addition to known abnormalities detected on physical examination. In contrast, when physical examination was negative for these defects, 63 percent of patients were found to have cystoceles, 46 percent to have enteroceles, and 73 percent to have rectoceles on four-contrast defecography. The discovery of Grade 2 or 3 unsuspected abnormalities was significant, especially so for enteroceles. For posterior vaginal eversions extending to or past the introitus, physical examination was accurate in only 61 percent. Physical examination of large anterior defects was more accurate, with 74 percent of patients being correctly diagnosed. CONCLUSIONS: Physical examination diagnosis of pelvic floor relaxation disorders is frequently inaccurate, especially for large vaginal eversions. Four-contrast defecography improves diagnostic accuracy, helps to identify all pelvic floor defects before surgery, and can assist with planning the correct operative approach.

Defecation↗
PubMed1995

Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer.

OBJECTIVE: The authors' objective was to quantitatively assess angiogenesis or neovascularity within node-negative colon cancers and to determine if increased angiogenesis correlated with higher recurrence and lower survival rates. SUMMARY BACKGROUND DATA: Neovascularization promotes rapid tumor growth by facilitating nutrient and metabolite exchange. Recent work with breast and nonsmall cell lung cancers has shown that low angiogenic activity imparts a lower risk of recurrence and metastasis. Although adjuvant therapy is beneficial for patients with node-positive colon cancers, no such benefit has been demonstrated for patients with node-negative lesions. Nevertheless, up to 30% of this latter group will experience recurrence. We sought to identify a subset of patients with node-negative colon cancers at high risk for recurrence who might benefit from such therapy. METHODS: One hundred five node-negative colon cancers were immunostained for endothelial cell factor VIII-related antigen. Blood vessels within three microscopic fields at 100X magnification were counted, the mean calculated, and an angiogenesis score assigned. A subjective angiogenesis grade (1-4) was assigned after each slide was surveyed in its entirety. Score and grade were then assessed with respect to cancer recurrence and patient survival. RESULTS: Mean patient age was 71 years (range, 41-90 years) and mean tumor size, 5.6 cm (range, 2-12 cm). Mean follow-up was 6.5 years; mean angiogenesis score, 27.9 (range, 4-50); and mean grade, 2.0 (range, 1-4). Patients living 5 years had significantly lower angiogenesis scores than did nonsurvivors (22.8 vs. 43.2, p = 0.0004). Each 10-vessel increase in score imparted a 2.0-fold greater hazard of death and a 2.7-fold greater hazard of recurrence. The probability of surviving 5 years is estimated by: [formula: see text] and the probability of recurrence is estimated by: [formula: see text] CONCLUSIONS: Angiogenesis within colon cancer is an important predictor of tumor behavior and may identify patients at higher risk for recurrence and early death.

Adenocarcinoma↗
PubMed1994

Predicting lymph node metastases in rectal cancer.

UNLABELLED: For properly selected rectal cancers, local excision is a sphincter-saving alternative to abdominoperineal resection. If histologic assessment of a locally excised tumor reveals ominous features, further treatment with radical resection or irradiation may be necessary to treat potential lymph node metastases. PURPOSE: We wished to determine which features, if any, were predictors of nodal metastases. METHODS: Nine histologic and morphologic features of 62 radically excised rectal cancers were reviewed to determine which factors, if any, were associated with nodal disease. RESULTS: Using a chi-squared analysis, we found worsening differentiation (P = 0.0001), increasing depth of penetration (P = 0.026), a microtubular configuration of 20 percent or more (P = 0.023), and the presence of venous (P = 0.001) or perineural invasion (P = 0.002) to significantly influence nodal disease. Lymphatic invasion was witnessed too infrequently to determine significance but, when present, was associated with nodal metastases in every case. Exophytic tumor morphology, mitotic count, and tumor size were not significant predictors. An analysis of variables determined that, of all factors or combination of factors examined, Broder's classification was the strongest predictor of nodal disease. CONCLUSIONS: If a rectal cancer is accessible and of small size to facilitate local excision, an in-depth histologic assessment is needed to determine if nodal metastases are likely on a statistical basis.

Humans↗
PubMed1994

Tumor angiogenesis and rectal carcinoma.

PURPOSE: This study was designed to determine whether those rectal cancers that demonstrated increased vessel ingrowth or angiogenesis behave in a different fashion. METHODS: The paraffin blocks of 48 rectal cancers removed by low anterior or abdominoperineal resection were recalled and immunostained with a monoclonal antibody specific for endothelial cell Factor VIII. The intense reddish brown color imparted to blood vessels facilitated their quantification which was undertaken at x100 and x200 magnification. Vessel counts within three microscopic fields were averaged and the relationships between angiogenesis score and tumor size, depth of invasion, incidence of lymph node or distant metastases, and survival were assessed. RESULTS: Significantly higher angiogenesis scores were seen in tumors with transmural penetration (at x100, P = 0.002; at x200, P = 0.002) and in patients dying before five years (at x100, P = 0.013; at x200, P = 0.034). Although higher angiogenesis scores were seen in patients with larger tumors and metastases, these trends were not statistically significant. CONCLUSIONS: Our results suggest that the growth of rectal cancer is dependent on the ingrowth of new blood vessels, and that increased vascularity promotes dissemination and adversely affects survival.

Adenocarcinoma↗
PubMed1994

Neuroendocrine cancers of the colon and rectum. Results of a ten-year experience.

PURPOSE: Our goal was to define the incidence of neuroendocrine carcinomas of the colon and rectum, the patterns of neuroendocrine expression, and the cellular subtype within neuroendocrine tumors. We attempted to determine whether differences in neuroendocrine expression or specific cell type influenced survival. METHODS: Over a ten-year period, 988 patients had resections for colorectal cancer. Using immunohistochemical staining methods specific for neuroendocrine markers, 39 (3.9 percent) neuroendocrine cancers were identified retrospectively. Tumors were also stained with monoclonal antibody A-80 which is specific for exocrine differentiation. In this way we were able to determine the extent of neuroendocrine differentiation such as pure neuroendocrine, predominant neuroendocrine, and equal neuroendocrine-exocrine expression. RESULTS: Average patient age was 65.5 (range, 28-89) years; there were 25 males and 14 females. Nineteen tumors were located in the right colon, 11 in the left, and 9 were in the rectum. Three histopathologic patterns were identified: pure neuroendocrine (n = 11), predominantly neuroendocrine (n = 17), and cancers with equal exocrine and neuroendocrine differentiation (n = 7). Three cellular subtypes were seen: small-cell (n = 15), intermediate-cell (n = 15), and well-differentiated neuroendocrine cancers (n = 5). There was one Dukes A cancer, 7 Dukes B, 16 Dukes C, and 15 patients had metastases to distant sites at the time of diagnosis. As a group, neuroendocrine tumors have a poor prognosis: six-month survival was 58 percent, three-year survival was 15 percent, and five-year survival was 6 percent. Survival statistically correlated with tumor stage (P = 0.01) but not with age, sex, tumor location, histopathologic pattern, or neuroendocrine subtypes. Median survival for pure neuroendocrine carcinomas was seven months and for predominantly neuroendocrine carcinomas was five months. Tumors with equal neuroendocrine and exocrine differentiation had a median survival of 22 months (P = 0.3). Small-cell neuroendocrine carcinomas had a median survival of five months, intermediate-cell had 11 months, and well-differentiated had a median survival of 22 months (P = 0.1). CONCLUSIONS: Neuroendocrine differentiation is found in at least 3.9 percent of colon and rectal cancers. Many of these tumors were initially diagnosed as "carcinoids," the diagnosis was changed to "neuroendocrine carcinoma" after immunohistochemical staining. Overall survival is poor especially for small-cell and pure neuroendocrine carcinomas.

Adult↗
PubMed1994

Peritoneovenous shunts for palliation of the patient with malignant ascites.

METHODS: This study evaluated the effectiveness and morbidity associated with 116 peritoneovenous shunts inserted into 89 patients for symptomatic malignant ascites between 1981 and 1991. All patients had previously failed standard medical therapy of salt and fluid restriction, diuretics, and intermittent peritoneal aspirations. RESULTS: Symptoms from the ascites included discomfort, impaired mobility, early satiety, and dyspnea. The study population was composed of 31 men and 58 women whose ages ranged from 24 to 81 years (mean 56). Primary tumors originated from the following sites: breast, 17; ovary, 17; pancreas, 13; gastrointestinal or related organs, 21; and other sites, 21. Mean shunt patency was 83 days; however, only 31% of the patients studied maintained a patent shunt and lived for > 2 months. Symptomatic relief was achieved in only 57 patients (62%). Forty-four patients (49%) developed one or more complications related to shunt placement. The deaths of 12 patients (13%) within 30 days of surgery were directly related to a complication of shunt placement. Overall, 30- and 60-day mortality rates were 43% and 61%, respectively. CONCLUSIONS: Due to the brief and only fair relief of symptoms with a high associated morbidity and mortality, we believe peritoneovenous shunts are of very limited usefulness in the palliation of malignant ascites and suggest that alternate methods should be considered to manage these patients.

Adult↗
PubMed1993

Immunohistochemical detection of mutant P53 protein and human papillomavirus-related E6 protein in anal cancers.

PURPOSE: The wild-type P53 protein, a product of the P53 gene, is a normal growth controlling protein. Mutation of the P53 gene generates a mutant P53 protein which promotes tumor formation through loss of growth suppression. Some of the agents responsible for P53 gene mutation are known, one of which may be tumorigenic human papillomavirus (HPV) infection. Anal cancers are demonstrating a changing trend in the affected population, from older females in the older reported series to younger males more recently. This may be a reflection of infection with tumorigenic HPV types 16 and 18. The E6 oncoprotein of these viruses inactivates the growth-controlling wild-type P53 protein. In this study, our purpose was to determine the incidence of mutant P53 and HPV-16 and 18-related E6 protein and their coexpression in anal cancers. METHODS: We examined 29 anal cancers immunohistochemically for mutant P53 protein, HPV 16 and 18 E6 protein, and coexpression of the two. RESULTS: Mutant P53 protein was present in 58.6 percent of anal cancers overall and in 85.7 percent of anal adenocarcinomas. E6 oncoprotein was present in five cases (17.2 percent), all of which were squamous-cell carcinomas. Coexpression of both mutant P53 and E6 proteins was seen in only three cases (10.3 percent). CONCLUSION: Although tumorigenic HPV may be an important cause for P53 gene mutation in anal cancers, perhaps other mutagenic factors play a predominant role.

Adenocarcinoma↗
PubMed1993

Thoracotomy for colon and rectal cancer metastases.

Between 1978 and 1990, 23 patients underwent 35 thoracotomies for metastatic colorectal cancer. The pulmonary disease was diagnosed within an interval of 0 to 105 (average, 33.4) months after colon resection. Fifteen patients underwent a single thoracotomy; 12 patients had solitary lesions, and three patients had multiple nodules. Eight patients underwent multiple thoracotomies. The median survival following thoracotomy was 28 months; three-year survival was 45 percent, and five-year survival was 16 percent. Factors that had no significant bearing on survival included origin and stage of the primary tumor and patient age and sex. An interval before thoracotomy of three years had an impact on survival approaching statistical significance (P = 0.17). Patients who underwent multiple thoracotomies had a significantly prolonged survival (P = 0.04). Patients who underwent a single thoracotomy for a solitary lesion had a significantly prolonged survival compared with patients who had a single thoracotomy for multiple metastases. After thoracotomy, 14 patients eventually developed recurrent disease, which was confined to the lung in only four patients. Of these 14 patients, 11 subsequently died of cancer. We conclude that thoracotomy for metastatic disease should be considered when the primary tumor is controlled, the lungs are the only site of metastatic disease, and there is adequate lung reserve to withstand surgery. Survival following thoracotomy may be influenced by the interval before diagnosis, the number of pulmonary nodules, and the number of thoracotomies performed.

Adult↗
PubMed1992

Variable expression of P-glycoprotein in normal, inflamed, and dysplastic areas in ulcerative colitis.

Screening programs for the detection of cancer in ulcerative colitis are inexact and not always successful in finding early, curable cancers. P-glycoprotein is a membrane-based, energy-dependent protein found in varying degrees within normal human tissue. P-glycoprotein is overexpressed in malignant tumors, particularly colorectal cancer, and is known to convey resistance to certain anticancer drugs by acting as a membrane "pump." The purpose of this study was to determine the expression of this protein in inflamed and premalignant colonic epithelium, compare its expression with normal controls, and assess its potential use as a screening tool for high-risk patients with ulcerative colitis. Using immunohistochemical techniques, the colons of 21 patients (10 with dysplasia) with ulcerative colitis were stained with monoclonal antibody C-219 (MAbC219) specific for P-glycoprotein. P-glycoprotein was expressed in 38 percent of normal areas, 71 percent of inflamed areas (P = 0.0156), and 70 percent of dysplastic areas. Comparing the level of expression when progressing from normal to inflamed areas within a given patient, 11 patients (52 percent) showed increased expression, 8 (38 percent) showed equal expression, and only 2 (10 percent) showed decreased expression (P = 0.0225). Comparing expression when progressing from inflamed to dysplastic areas (10 patients), 7 showed equal expression and 3 showed increased expression (P = 0.25). Increasing duration of disease was associated with a significant increase in P-glycoprotein expression, but only in histologically normal areas. Duration of disease had no effect on P-glycoprotein expression in inflamed or dysplastic areas. Similarly, when surgery was performed for elective reasons, there was a significant overexpression of P-glycoprotein, but only in histologically normal areas. Our findings suggest that the increase in P-glycoprotein expression from normal to inflamed and dysplastic areas reflects the premalignant nature of ulcerative colitis and occurs early in the course of the disease. Further research needs to be done to determine its role in cancer surveillance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Effect of intraoperative radiation on the tensile strength of small bowel anastomoses.

Increasing interest in the use of preoperative or intraoperative radiation therapy for cancer has led to concerns regarding tissue healing and integrity subsequent to treatment. This is especially so for intestinal anastomoses incorporating irradiated bowel, where poor healing may lead to anastomotic disruption and sepsis. One hundred thirty Sprague-Dawley rats were randomized into five groups as follows: both limbs, one limb, or neither limb of an anastomosis received 2,000 R of radiation intraoperatively. A fourth group had a segment of small bowel irradiated, with no anastomosis; a fifth group had the gut exposed by celiotomy. The control groups and all anastomoses underwent tensile strength measurements on the seventh postoperative day, with findings as follows: no anastomosis, no irradiation, 143.75 g; no anastomosis, irradiated, 114.50 g; anastomosis, no irradiation, 85.273 g; anastomosis, one limb irradiated, 78.100 g; anastomosis, both limbs irradiated, 59.00 g. There was no statistical difference in tensile strength of the anastomosis between when neither limb and when just one limb was irradiated. However, when both limbs were irradiated, the loss of strength was statistically significant (P = 0.002). Irradiation damage scores were assigned using Black et al.'s histologic scoring system. These scores were not significantly different between the irradiated segments. Inflammation and fibrosis scores for the anastomoses were also not significantly different. These results indicate that, in rats, anastomotic healing is impaired only when both limbs of the anastomosed intestine are irradiated. The normal strength of the anastomosis with only one limb irradiated cannot be explained by differences in inflammation, fibrosis, or radiation damage and is caused by an undetermined factor.

Anastomosis, Surgical↗
PubMed1992

Fibrin glue improves the healing of irradiated bowel anastomoses.

Many surgeons are reluctant to construct a bowel anastomosis with irradiated intestine. Previous studies have demonstrated diminished tensile strength of rat small bowel anastomoses that have been irradiated intraoperatively. To determine whether fibrin glue, a known tissue adhesive, improves the healing of these anastomoses, 69 male Sprague-Dawley rats were randomized into three anastomotic groups: Group 1, sutured ileal anastomosis without radiation or fibrin glue; Group 2, irradiated sutured ileal anastomosis without fibrin glue; and Group 3, irradiated ileal anastomosis with fibrin glue added to the suture line. Groups 2 and 3 received a single dose of 2,000 R intraoperatively. At seven days, the rats were sacrificed and the anastomotic segment was tested for breaking (tensile) strength. Anastomotic collagen content was evaluated using a hydroxyproline assay. Tensile strength results demonstrated that Group 2 was significantly weaker than Groups 1 and 3 (P = 0.001) and that the hydroxyproline content of Group 3 was significantly greater than that of Group 2 (P = 0.015). These results show that the addition of fibrin glue to an intraoperatively irradiated small bowel anastomosis improves healing, as demonstrated by both tensile strength and hydroxyproline content studies.

Anastomosis, Surgical↗
PubMed1992

Transanal endoscopic microsurgery.

Transanal endoscopic microsurgery (TEM) has emerged as a minimally invasive means of resecting rectal tumors. Developed in Germany and now being used with increasing frequency in the United States, TEM utilizes a 40-mm operating rectoscope, which is sealed with an airtight facepiece. Carbon dioxide is constantly infused, thereby distending the rectum and maintaining visibility. A variety of instruments, such as tissue graspers, a high-frequency knife, suction, and needle holders, are inserted through the facepiece. Adenomas that are small, large, or even circumferential, as well as selected carcinomas up to 24 cm, can be removed with TEM instrumentation. The optics provide sixfold magnification, and this, combined with the constantly distended operative field, allows for a precise excision of the tumor as well as closure of the wound. For lesions in the mid and upper rectum, TEM is an alternative to a transsacral or transabdominal approach, with subsequently shorter hospital stay and fewer complications.

Adenoma↗