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Biomedical subjects

W F Sindelar

Publications and source records attributed to W F Sindelar.

At least 73 records · Page 4Linked to original sources
PubMed1986

Experiments evaluating antitumor immunity induced by cholesterol hemisuccinate-treated syngeneic cell vaccines.

Evaluation of the efficiency of immunizations with syngeneic tumor vaccines prepared from cells treated with cholesterol hemisuccinate (CHS) was performed in five animal models: P815 mastocytoma in DBA/2 mice, MCA-103 fibrosarcoma in C57BL/6N mice, L1210 leukemia in DBA/2 mice, Ehrlich ascites carcinoma in C57BL/6N mice, and CBP pancreatic cancer in CB/SsLak hamsters. Animals received two to four weekly intraperitoneal immunizations with 10(6) or 10(7) tumor cells, followed by challenges with syngeneic viable tumor cells. Survival and tumor growth rates were observed. No significant differences were observed among animals immunized with CHS-treated irradiated tumor vaccines, nontreated irradiated tumor vaccines, and nonimmunized controls in the P815, MCA-103, L1210, and CBP models. Mice immunized with nontreated irradiated Ehrlich ascites cell vaccines showed longer survival than those immunized with CHS-treated irradiated cell vaccines and nonimmunized controls. Results indicated that CHS-treated tumor cell vaccines were not effective in protecting against tumor challenges in five different syngeneic tumor models.

Animals↗
PubMed1986

Comparison of the sensitivity and specificity of the CA19-9 and carcinoembryonic antigen assays in detecting cancer of the pancreas.

In this study, we determined the sensitivity and specificity of the new serum assay CA19-9 in detecting adenocarcinoma of the pancreas and compared the results with those of the serum assay to carcinoembryonic antigen (CEA). Thirty-seven patients with biopsy-proven adenocarcinoma (14 patients with resectable disease and 23 patients with unresectable disease) were compared with 157 controls (48 patients with benign pancreatic disease, 34 patients with nonpancreatic sources of abdominal pain, 58 patients with benign jaundice, 7 patients with nonpancreatic malabsorption, and 10 patients with renal failure on dialysis). It was determined that a cutoff of 75 U/ml enhanced the diagnostic efficiency (sensitivity + specificity) of CA19-9 over the manufacturer's recommended cutoff of 37 U/ml. The sensitivity of CA19-9 (greater than 75 U/ml) in detecting cancer was greater than that of CEA (greater than 5 ng/ml) (86.5% vs. 48.4%) (p less than 0.01, McNemar test). The sensitivity of CA19-9 was 78.6% in resectable and 91.3% in unresectable disease. The specificity of CA19-9 was also greater than CEA (92.5% vs. 87.3%), although this difference was not statistically significant. The higher the CA19-9 or CEA level, the greater the specificity of either assay; at CA19-9 levels greater than 600 U/ml and CEA levels greater than 20 ng/ml the specificity is approximately 99%. The combination of an elevated CA19-9 level (greater than 75 U/ml) and an elevated CEA level (greater than 5 ng/ml) also enhanced specificity to 99%. It is concluded that CA19-9 used alone is superior to CEA used alone in detecting cancer of the pancreas and that the combination of mild elevations of both assays improves their specificity. Although the CA19-9 marker can be elevated with other intraabdominal adenocarcinomas (e.g., gastric, biliary, or colonic), CA19-9, together with CEA, will be useful to the clinician in differentiating benign from malignant pancreatic processes and in alerting the clinician to the possible presence of an intraabdominal neoplasm in the proper clinical setting.

Adenocarcinoma↗
PubMed1986

Depression and carcinoma of the pancreas.

A systematic psychiatric evaluation of 21 subjects with intraabdominal malignancy (pancreatic or gastric carcinoma) was performed. Depression was frequently associated with and often the presenting symptom complex of patients with carcinoma of the pancreas. This finding was not observed in patients with gastric carcinoma. Clinical and theoretical implications of these findings are discussed.

Adjustment Disorders↗
PubMed1986

Quality control parameters of intraoperative radiation therapy.

We have tried to outline many of the factors which must be considered in the technical delivery of IORT and in subsequent evaluation of these patients. Unless careful attention is given to details of patient selection, surgery, pathology, radiation therapy and follow-up, it is likely that a vast morass of data will be obtained which will be very difficult to interpret. It is the hope of the IORT Working Group that other institutions using IORT will employ our recommendations with regard to dosimetry, follow-up, and the general technical approach. This will likely lead to an earlier understanding of the exact role of this modality in cancer therapy today.

Combined Modality Therapy↗
PubMed1986

Gastrointestinal carcinoma-associated antigen defined by a murine monoclonal antibody.

A murine monoclonal antibody, CHIP, has been prepared against a human pancreatic carcinoma cell line, SHAW. With the use of the avidin-biotin immunoperoxidase technique, the CHIP antibody detected an antigen found in 11 of 20 fixed tissue sections of tumors obtained from patients with pancreatic carcinoma. The antibody also detected the antigen in 25 of 26 colon carcinoma specimens, 4 of 6 gastric carcinoma specimens, and 1 of 2 esophageal adenocarcinoma specimens. The antigen was also found in normal proximal jejunum and colon and in small amounts in pancreatic islets and parathyroid. There was no reactivity with normal pancreatic ductal or acinar cells or with mesenchymal tissues.

Adenocarcinoma↗
PubMed1986

Pathological tissue changes following intraoperative radiotherapy.

Ninety patients with a variety of advanced-stage malignancies were treated with surgical resection, when feasible, and with intraoperative radiotherapy. Certain patients received additional external beam radiotherapy. During clinical follow-up, 45 patients died. Twenty-two patients (49% of deaths) underwent detailed autopsies between 1 and 18 months after treatment, with special attention directed towards assessing radiation damage to various tissues. Histological changes related to radiation were generally manifested as fibrosis. Mild fibrotic changes in retroperitoneal soft tissues and mild hypocellularity in vertebral bone marrow were consistently present in patients treated for pancreatic carcinoma, gastric carcinoma, and retroperitoneal or pelvic sarcomas. Fibrosis of the soft tissues of the porta hepatis without narrowing of the bile duct was present in patients treated for pancreatic or gastric cancer. perineural fibrosis was present in retroperitoneal and pelvic nerve trunks in patients treated for abdominal or pelvic sarcomas and in patients treated for unresectable carcinoma of the pancreas. Significant radiation-related changes were generally not observed in major blood vessels, intestine, or ureter. Intact irradiated primary tumors consistently displayed necrosis.

Autopsy↗
PubMed1986

The spectrum of sonographic findings in pancreatic carcinoma.

The ultrasound studies of 59 patients with cancer of the pancreas were reviewed and the findings grouped into two categories: intrapancreatic, which included the appearance of the primary tumor and the pancreatic duct; and extrapancreatic, which included biliary obstruction, hepatic metastases, regional lymph node involvement, ascites, spleen enlargement and invasion, and alteration of the upper abdominal veins. Pancreatic duct dilatation was more evident with smaller tumors of the pancreatic head, while inferior vena cava compression was found not to be a constant finding even with large tumors of the head of the pancreas. Tumor extension to regional lymph nodes was difficult to detect and consequently underestimated. Nonvisualization, occlusion with or without collaterals, and displacement or deformity of the major branches of the portal venous system were detectable sonographically. The liver metastases of pancreatic carcinoma tended to be small and hypoechoic. This is a different pattern from that typically described for other gastrointestinal adenocarcinomas and, in particular, markedly different and distinguishable from the metastatic pattern seen with malignant pancreatic islet cell tumors. The significance of the intra- and extrapancreatic changes seen sonographically in cancer of the pancreas by ultrasound is discussed in relationship to clinical staging and prognosis.

Adenocarcinoma↗
PubMed1986

Trial of therapy with monoclonal antibody 17-1A in pancreatic carcinoma: preliminary results.

Monoclonal antibody 17-1A was administered to 25 patients with advanced unresectable carcinoma of the pancreas. Ten patients received 17-1A alone in 400 mg doses delivered intravenously, while 15 patients received 400 mg 17-1A absorbed on to autologous peripheral blood mononuclear cells collected by leukapheresis (usual yield greater than 10(9) cells). No toxicity was observed. Twenty-three patients developed circulating anti-murine immunoglobulin within three weeks of treatment, and 11 patients developed circulating anti-idiotypic immunoglobulin. Four out of 19 clinically evaluable patients (21%) showed objective regressions of tumor. Response did not correlate with the presence or absence of anti-idiotypic antibody and did not correlate with the method of treatment with 17-1A alone or 17-1A and mononuclear cells, at the time of current analysis.

Antibodies, Monoclonal↗
PubMed1985

An enzymatic method for the consistent production of monodispersed viable cell suspensions from human solid tumors.

An enzymatic method is described for disaggregation of viable tumor cells from human solid tumors. The enzymatic cocktail consists of 0.1% collagenase, 0.01% hyaluronidase, and 0.002% deoxyribonuclease. After mechanical mincing of the tumor tissue, tumor specimens are dissociated by incubation in the enzymatic cocktail for 12-18 hours at room temperature. In 17 cases of sarcoma, the mean yield was 5 X 10(6) viable cells per gram tumor tissue. Yield was 1 X 10(7) viable cells per gram tumor tissue in 23 cases of gastrointestinal carcinoma. The viabilities of tumor cell suspensions ranged from 50 to 98%, except for low viabilities in four specimens that were grossly composed almost entirely of necrotic tissue. The dissociation procedure is simple and the viable cell yield is sufficient for applications in studies of human cancer immunobiology.

Cell Survival↗
PubMed1985

Tolerance of peripheral nerve to intraoperative radiotherapy (IORT): clinical and experimental studies.

In our clinical experience combining wide excision and intraoperative radiotherapy (IORT), five patients have developed clinical signs of lumbosacral or sciatic neuropathy within 9 months of receiving IORT to a dose of 20-25 Gy. Three patients showed recovery of nerve function over several months while two patients have shown no recovery and have near complete loss of extremity function. In an attempt to investigate this clinical observation further, the lumbosacral plexus and sciatic nerve of American foxhounds were surgically exposed and received a single dose of IORT ranging from 20-75 Gy. An approximate linear relationship between radiation dose and time to onset of hind limb paresis is found with 19 of 21 irradiated dogs showing clinical signs of nerve injury within an interval of 1-19 months. No recovery of nerve function is seen in these dogs. Histological study of the irradiated nerves demonstrates a loss of nerve fibers, particularly those of the large myelinated type without evidence of vascular occlusion or thrombosis. These studies suggest that peripheral nerve may be a dose-limiting normal tissue in clinical studies of IORT.

Adult↗
PubMed1985

Intraoperative radiation therapy at the National Cancer Institute: technical innovations and dosimetry.

The technical complexity of intraoperative radiotherapy (IORT) requires modification of the standard physical and dosimetric methods used in external electron beam therapy. At the National Cancer Institute, a number of technical innovations have been integrated into ongoing clinical studies of IORT. These include: (1) an electron beam applicator system that is significantly different from other IORT systems and includes customized "squircle" applicators; (2) peripheral dose shields; (3) a modified surgical table replacing the standard radiation treatment couch; and (4) routine use of multiple IORT fields that necessitates field matching. The IORT applicator system and related devices and techniques are dosimetrically characterized in detail both for use in the IORT program and in order to illustrate many useful facets of electron dosimetry.

Electrons↗
PubMed1985

Randomised trial of intraperitoneal irrigation with low molecular weight povidone-iodine solution to reduce intra-abdominal infectious complications.

A prospective randomized trial was performed comparing the efficacy of intraperitoneal irrigation with low molecular weight povidone-iodine solution ('Betadine LMW') (PVP-I LMW) in reducing the risk of intra-abdominal infectious complications. Seventy-five patients who were undergoing surgical procedures in the face of bacterial contamination were studied. Patients were intra-operatively randomized to receive intraperitoneal irrigation prior to abdominal closure with PVP-I LMW or with saline. Patients were maintained on peri-operative systemic antibiotics, and surgical incisions were drained and were closed primarily or left open according to the practice of the surgeon responsible. If incisions were closed, the subcutaneous tissue was irrigated prior to skin closure with the same irrigant as used intraperitoneally, PVP-I LMW or saline. Patients were followed for abnormal wound healing, peritonitis, intra-abdominal abscesses, or other infectious complications. Serum iodine levels were monitored in some patients. Intra-abdominal infectious complications developed in two of 37 patients receiving PVP-I LMW irrigation as compared to complications in nine of 38 patients receiving saline irrigation (P less than 0.05). When infectious complications were excluded that were possibly due to surgical technical failures (such as anastomotic leakage), peritonitis or intra-abdominal abscesses were observed in one of 37 PVP-I LMW patients and in seven of 38 saline control patients (P less than 0.05). Wound infections developed in one of 37 PVP-I LMW patients and in three of 38 control patients. A broad range of serum iodine levels were observed in control patients preoperatively and at 24 h and 7 days postoperatively. Serum iodine levels in 'Betadine LMW' patients rose approximately nine-fold by 24 h postoperatively and returned to pre-operative levels by 7 days. It was concluded that PVP-I LMW solution can reduce the incidence of intra-abdominal infectious complications when used as an intraperitoneal irrigant in patients undergoing bacterially-contaminated surgical procedures.

Abdomen↗
PubMed1985

Isolation-perfusion of the liver with 5-fluorouracil.

Isolation-perfusion of the liver was performed in ten pigs using 5-fluorouracil administered in the perfusion circuit at doses of 100, 250, 500, and 1000 mg/kg body weight. Perfusion was performed for 60 minutes at normothermic (37 C) or hyperthermic (41 C) temperatures. One animal died shortly after perfusion. Incomplete isolation of the hepatic vasculature in two animals resulted in significant drug leakage into the systemic circulation with resulting hematologic toxicity. Perfusion with 5-fluorouracil at 1000 mg/kg produced hepatic necrosis. Perfusion with 5-fluorouracil at doses of 100, 250, or 500 mg/kg produced no hepatic toxicity except for transient elevations of hepatic enzymes and resulted in no systemic drug toxicity. Levels of 5-fluorouracil tolerated by the liver in the isolation-perfusion system were more than 1000-fold greater than the maximum drug levels achievable by routine systemic, intra-arterial, or intraperitoneal administration.

Animals↗
PubMed1985

Interruption of the inferior vena cava for the prevention of recurrent pulmonary embolism.

Pulmonary embolism in high-risk patients may be minimized by inferior vena caval interruption by ligation, plication, intraluminal filters, or intraluminal balloons. Vena caval filter implantation is the least traumatic of all surgical methods of preventing pulmonary embolism. These nonocclusive methods are preferred to minimize the possible sequelae of venous insufficiency. The prevention of septic emboli requires complete ligation of the inferior vena cava. The transvenous approach to caval interruption by intraluminal filters is particularly useful in severely ill patients. When major surgical procedures are performed for the purpose of caval interruption, the intra-abdominal approach has greater associated mortality and morbidity than does the retroperitoneal approach. The Mobin-Uddin and Kim-Ray Greenfield filters are at present the most frequently used modalities for prevention of fatal pulmonary embolism when intervention is required. In large series of patients where intraluminal caval filters have been utilized, there has been an operative mortality of under 1 per cent, with an incidence of recurrent emboli of under 2 per cent, and an incidence of venous stasis sequelae of approximately 20 per cent. Some clinicians prefer the Greenfield filter over the Mobin-Uddin umbrella because of greater ease and flexibility of placement. In general, however, both transvenous intraluminal filters have been used effectively with acceptable mortality and morbidity, and the device used might properly be determined by the experience of the surgeon.

Anticoagulants↗
PubMed1985

Results of multimodality therapy of resectable soft-tissue sarcomas of the retroperitoneum.

Thirty-seven patients with resectable retroperitoneal sarcomas were studied prospectively to determine the efficacy of aggressive multimodality treatments. No patients was lost to follow-up, which ranged from 11 to 85 months (median 29 months). All patients received radiotherapy and some received postoperative chemotherapy (doxorubicin, cyclophosphamide, and high-dose methotrexate). A subset of 15 patients were entered into a prospective, randomized study testing the efficacy of adjuvant chemotherapy (eight received chemotherapy; seven did not). Two-year actuarial survival rates were inferior in the chemotherapy arm (100% versus 47%; p = 0.06), but the small number of patients precluded drawing definitive conclusions from this randomized study alone. Among the entire 37 patients (21 received chemotherapy; 16 did not) the actuarial 3-year survival rate was 43% and appeared unaffected by chemotherapy. Two patients suffered doxorubicin infiltration, three sustained cardiac toxicity, two developed cyclophosphamide-induced cystitis, and three withstood transient, severe bone marrow suppression. Eight patients suffered severe radiation enteritis, and one patient died after bowel resection for this problem. Thus the chemotherapy regimen we administered did not appear to improve survival but was associated with major morbidity. Radiotherapy was also associated with major complications, and since all patients received radiotherapy, it remains to be established if this modality is beneficial in improving survival.

Actuarial Analysis↗
PubMed1984

A method of supporting venous tubing in the neck to prevent occlusion of peritoneovenous shunts.

Mechanical occlusion of the cervical venous tubing segment of a peritoneojugular shunt may occur because of kinking or angulation. This may be associated with partial or complete shunt failure. In four patients with inadequate palliation of ascites after shunt placement, restricted flow in the cervical tubing was diagnosed as the cause. When a stainless steel helical support was passed over the end of the tubing, angulation was eliminated and extended shunt patency was restored in all four patients. The helical support is recommended for use in patients who have or are at risk for the development of occlusion in the cervical venous tubing portion of the peritoneovenous shunt.

Ascites↗
PubMed1984

Inhibition of growth and metastases in mice by immunization with cholesterol hemisuccinate-enriched tumor cells.

Incorporation of cholesterol hemisuccinate (CHS) into the membrane of tumor cell rigidifies the lipid layer, exposes cryptic antigens, and enhances immunogenicity. The local growth and metastatic spread of the 3LL Lewis lung carcinoma were studied in conjunction with immunizations by CHS-enriched 3LL cells. C57BL/6J mice received 2 consecutive immunizations with 10(7) CHS-treated, irradiated (10,000 rad) 3LL cells. Two control groups were immunized with MCA-102 sarcoma cells or CHS-enriched syngeneic spleen cells. All groups were challenged with viable 3LL cells after immunizations. Mice pre-immunized with CHS-enriched 3LL cells showed a delayed tumor growth after subsequent challenge with 3LL. Effect of immunization on the growth of established tumors was examined in 3LL-bearing mice which were treated with 10(7) CHS-enriched tumor cells on days 1-12 after initial tumor implantation. A second identical immunotherapy was given 6 days after the first immunization. Tumor growth was significantly inhibited in mice which received the first immunization 1 day after tumor implantation, while immunization on day 3 or after inhibited the growth rate to a lesser extent. Suppression of pulmonary metastases was assessed after excision of a primary 3LL tumor growing in the foot pad which had reached 8 mm in diameter. Immunization consisted of intraperitoneal injection of 10(7) irradiated CHS-enriched tumor cells following excision and repeated after 6 days. This immunization resulted in a significant decrease in pulmonary metastasis as scored by direct counts of metastatic nodules, by [125I]iododeoxyuridine (125IUdR) incorporation, and by lung weight. Metastatic 3LL cells from nodules which survived immune elimination were isolated and implanted into mice which were pre-immunized with primary 3LL cells enriched with CHS. For comparison, a group of mice was immunized and challenged with primary 3LL cells. Inhibition of tumor growth and pulmonary metastasis formation was observed only in the mice which were challenged with the primary tumor.

Animals↗