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Biomedical subjects

W F Sindelar

Publications and source records attributed to W F Sindelar.

At least 55 records · Page 3Linked to original sources
PubMed1988

Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis.

Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor.

Adrenal Glands↗
PubMed1988

Tolerance of the canine bladder to intraoperative radiation therapy: an experimental study.

An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram at 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP. We conclude that the bladder trigone will tolerate IORT to 20 Gy without major clinical sequellae. Above 20 Gy, progressive inflammation and fibrosis of the U-V junction resulted in obstructive hydronephrosis in three animals within 1-2 years of IORT. The bladder mucosa remained intact with doses to 40 Gy, although submucosal fibrosis and chronic inflammation were evident and appeared dose-related. However, bladder function as measured by cystometry showed essentially no change with follow-up to 4 years. From this large animal study, IORT for early-stage bladder carcinoma is technically feasible and deserves a careful clinical study.

Animals↗
PubMed1988

Surgery with intraoperative radiotherapy for sarcomas of the pelvic girdle: a pilot experience.

Sarcomas of the pelvic girdle represent difficult treatment problems. Many are not treatable for cure, and among the patients who are technically resectable, there is high risk for local tumor recurrence and distant spread. Intraoperative radiotherapy (IORT) has been used in conjunction with surgical resection in five patients with extensive sarcomas of the pelvic girdle. Patients underwent a hemipelvectomy and IORT (dose 20-30 Gy) to the sacral resection margin and surrounding soft tissues. Three patients developed pulmonary metastases within 3 months and eventually died from metastatic disease (8-38 months). Two patients have remained disease-free (43 and 53 months). Four patients (80%) have remained locally free of tumor with follow-ups of 8-53 months. The only treatment complication was late osteonecrosis of the coccyx which appeared 7 months after treatment. By contrast, six historical control patients with sarcomas of the pelvic girdle treated with resection alone showed a local control rate of only 27% over a 40-month follow-up. On the basis of this preliminary experience, it appears that IORT may substantially help to control local disease in patients with grossly resectable sarcomas of the bony pelvis.

Adolescent↗
PubMed1988

Response of canine esophagus to intraoperative electron beam radiotherapy.

Tolerance of esophagus to intraoperative radiotherapy (IORT) was investigated in dogs. Thirteen adult foxhounds were subjected to right thoractomy, mobilization of the intrathoracic esophagus, and IORT to a 6 cm full-thickness esophageal segment using 9 MeV electrons at doses of 0, 2,000, or 3,000 cGy. Dogs were followed clinically and were evaluated at regular intervals after treatment with fiberoptic esophagoscopy, barium swallows, and postmortem histologic evaluations. One sham-irradiated control dog showed no abnormalities during follow-up of 24 months. Seven dogs receiving 2,000 cGy IORT showed transient mild dysphagia and mild esophagitis, but no clinically or pathologically significant complications. Five dogs receiving 3,000 cGy demonstrated severe ulcerative esophagitis within 6 weeks of treatment which progressed to chronic ulcerative esophagitis with stricture formation by 9 months following IORT. One 3,000 cGy dog died at 13 months from an esophageal perforation. On the basis of a pilot experience using 13 experimental animals, it was concluded that intact canine esophagus tolerates IORT well to doses of 2,000 cGy, but doses of 3,000 cGy pose serious and potentially lethal risks. The clinical application of IORT to the treatment of human intrathoracic neoplasms requiring esophageal irradiation should be approached with caution, particularly at doses exceeding 2,000 cGy.

Animals↗
PubMed1988

Preliminary results of a randomized study of adjuvant radiation therapy in resectable adult retroperitoneal soft tissue sarcomas.

Between January 1980 and September 1985, 35 adult patients with resectable retroperitoneal soft tissue sarcomas were entered on a randomized trial comparing two forms of adjuvant radiation therapy. Fifteen patients received the experimental therapy consisting of intraoperative radiotherapy (IORT) to 20 Gy using high-energy electrons followed by low-dose (35 to 40 Gy) postoperative external beam irradiation. Twenty patients received standard therapy consisting of high-dose (50 to 55 Gy) postoperative external beam irradiation. With a minimum follow-up of 15 months, there is no significant difference in the actuarial disease-free survival (DFS) and overall survival (OS) comparing the two groups (median DFS, 34 months; median OS, 38 months). At 5 years follow-up, approximately 40% of patients are alive and 20% of patients remain disease-free. Although there is a trend towards an improvement in in-field local control in the experimental arm, the predominant pattern of failure in both groups was locoregional within the retroperitoneum and/or peritoneal cavity. Acute and late radiation enteritis were significantly reduced in the experimental group. However, four experimental patients developed late (greater than 6 months following treatment) peripheral neuropathy believed related to the use of IORT; all four recovered. We conclude that there is no difference in the therapeutic effectiveness of the combination of IORT and low-dose external beam radiation compared with conventional high-dose radiation as adjuvant treatment in retroperitoneal sarcomas, although the former appears to be less toxic. Newer combined modality treatment strategies are discussed to improve the prognosis in these patients.

Adult↗
PubMed1988

Evaluation of the utility of a radioimmunoassay for serum CA 19-9 levels in patients before and after treatment of carcinoma of the pancreas.

By radioimmunoassay we determined circulating levels of a tumor-associated antigen, CA 19-9, in 47 patients with pancreatic adenocarcinoma, to learn if serial testing was useful in predicting prognosis or in detecting disease progression. Before treatment, 42 (89%) had an abnormal serum level, and 45 (96%) had an abnormal level at some time during the disease course. A pretreatment value of less than 1,000 U/mL (normal, less than or equal to 37 U/mL) was found in 38 patients; 20 (53%) had resectable disease. One of nine patients (11%) with a pretreatment value greater than 1,000 U/mL had resectable disease (P2 = .05). Among 14 patients who underwent pancreatectomy and were studied serially, the CA 19-9 level normalized in eight; seven (88%) survived greater than or equal to 18 months. Six patients whose levels did not normalize after pancreatectomy all died in less than 12 months (P2 less than .005). Greatly elevated levels occurred in 11 patients after pancreatectomy 1 to 7 months before clinically apparent recurrence. The other three patients without significant elevations remain clinically free of disease. The data suggest that serial determination of serum CA 19-9 levels are useful as a prognostic indicator and in detecting disease recurrence following pancreatectomy. Concurrent determinations of carcinoembryonic antigen (CEA) levels showed abnormal preoperative values in 28 of 46 patients tested (61%). Concurrent serial postoperative determinations of CEA were available in ten patients. Whereas CA 19-9 values clearly indicated eight recurrences, CEA was helpful in only four. In this small group of patients, CA 19-9 was a better predictor of recurrence.

Adenocarcinoma↗
PubMed1988

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Surgical approaches and techniques in intraoperative radiotherapy for intra-abdominal, retroperitoneal, and pelvic neoplasms.

Eighty-five patients with locally advanced intra-abdominal, retroperitoneal, and pelvic malignant diseases have been treated at the National Cancer Institute (NCI) with electron beam intraoperative radiotherapy (IORT). In general, IORT was performed after resection to the tumor bed and to areas of locoregional spread. IORT was delivered directly to some unresectable tumors. The median survival for the entire NCI patient group was 13.9 months, with 34% of the patients projected to achieve local control of disease at 5 years. Multiple abutting IORT fields were used in 76% of the patients; they encompassed treatment areas as large as 569 cm2 and involved as many as five separate IORT applications. Multiple fields were matched along straight edges on the treatment applicators or provided by means of lead shielding strips. Areas of field overlap were prevented by the use of lead shields. Surgical approaches and radiotherapeutic techniques of multiple field matching have been developed and are detailed for carcinoma of the pancreas, carcinoma of the stomach, sarcomas of the retroperitoneum, carcinoma of the rectum, and tumors of the pelvic girdle.

Abdominal Neoplasms↗
PubMed1987

Comparison of angiography and ultrasound in the evaluation of the portal venous system in pancreatic carcinoma.

Detailed images of upper abdominal vascular anatomy can now be obtained by experienced operators using modern real-time ultrasound scanners. To help determine the role of real-time ultrasound in preoperative evaluation of pancreatic carcinoma, ultrasound and angiographic results were compared in a series of 45 patients admitted with documented carcinoma of the pancreas. When surgical results were available, these were compared with the ultrasound and angiographic findings. The main tributaries of the portal system were evaluated with ultrasound and angiography for evidence of compression, displacement, or occlusion. A sensitivity of 90% and specificity of 95% were achieved for splenic vein abnormalities by ultrasound compared to angiography. For portal vein evaluation, sensitivity was 75%, and specificity was 100%, whereas for the superior mesenteric vein a sensitivity of 100% and a specificity of 94% were attained. Ultrasound can make angiography prior to laparotomy unnecessary in many cases if thorough evaluation of the portal venous system is emphasized during the initial ultrasound study.

Humans↗
PubMed1987

History, preliminary results, complications, and future prospects of intraoperative radiotherapy.

Intraoperative electron beam radiotherapy (IORT) is a new combined modality therapy in the treatment of cancer. IORT is delivered during a surgical procedure to a tumor or tumor bed and areas of possible local regional spread, with the ability to shield or physically move normal tissues and organs out of the treatment volume. IORT is feasible for various intraabdominal, retroperitoneal, pelvic, and other malignancies. It is possible to increase the total radiation dose, thereby improving the therapeutic ratio; a better local control without an increasing morbidity. Although the optimum use of IORT is still unknown, it is believed that its greatest value is in combination with maximal surgical resection of the tumor with or without external beam radiotherapy (EBRT). IORT is still an experimental treatment modality combining surgery, EBRT, and if necessary, chemotherapy. Because IORT is an expensive treatment method, it is important to determine which method is the best and most convenient for the patient. The answer can be given only when prospective, randomized clinical IORT trials and cost-effectiveness studies are initiated.

Combined Modality Therapy↗
PubMed1987

Response of the mediastinal and thoracic viscera of the dog to intraoperative radiation therapy (IORT).

IORT may be a potentially useful adjunctive treatment combined with surgery and/or external beam irradiation in treating locally advanced lung and esophageal tumors. To begin investigation of this modality, the tolerance of intact mediastinal structures to IORT was studied using adult American Foxhounds (wt. 25-30 kg). Groups of six animals received IORT to doses of 20, 30, or 40 Gy to two separate intrathoracic ports, using 9 MeV electrons to treat a portion of the collapsed right upper lobe, and 12 MeV electrons to treat the mediastinal structures. A group of three dogs received thoracotomy with sham irradiation. Two dogs from each treatment dose group, as well as one sham-irradiated control, were sacrificed electively at 1, 3, and 12 months following IORT. There were no acute nor late IORT related mortalities. Post-operative weight loss was minimal (average 4.5% of pre-operative weight) for all dogs. Serial esophagrams showed no inflammation or ulceration. No cardiac nor pulmonary changes were noted clinically. At autopsy, the irradiated lung showed evidence of acute pneumonitis at 1 month with progressive fibrosis at 3 months and 1 year. Esophageal reactions were minimal, with only two dogs (one 30 Gy and one 40 Gy) demonstrating histologically confirmed esophagitis at 1 month. Tracheal changes were minimal. Cardiac damage was evident in the right atrial tissues. In several dogs, this cardiac damage ranged from myocardial vascular changes to frank ischemic necrosis noted at 1 and 3 months, and dense fibrosis at 1 year. The phrenic nerves showed normal function, but had evidence of perineural fibrosis. The large vessels demonstrated only mild histologic evidence of irradiation. The results of this large animal study suggest that intact mediastinal structures will tolerate small volume IORT to doses of 20 Gy without significant clinical sequellae. Although the histologic changes in the right atrium and contralateral lung are worrisome, no cardiac nor pulmonary problems arose over the 1 year follow-up. Irradiation of the contralateral lung and other sensitive structures can be reduced by careful selection of electron beam energy and use of custom lead shielding.

Animals↗
PubMed1987

Delivery of intraoperative radiation therapy after pneumonectomy: experimental observations and early clinical results.

Intraoperative radiation therapy (IORT) is capable of delivering high doses of radiation to mediastinal structures while sparing lung parenchyma, heart, and other locoregional tissues. A canine model of pulmonary resection and IORT was investigated by performing a pneumonectomy in 15 adult foxhounds followed by 0 cGy, 2,000 cGy, 3,000 cGy, 4,000 cGy. No clinical complications developed in 4 animals in the 2,000-cGy group. However, 2 of the 8 animals given a high dose died of esophageal hemorrhage or carinal necrosis. Esophagitis occurred in 10 of 12 animals, and none of the animals experienced bronchial stump dehiscence. In a limited Phase I protocol, 4 patients with non-small cell lung cancer were treated with resection and 2,500 cGy of IORT to two separate ports encompassing the superior and inferior mediastinum. Two patients experienced life-threatening bronchopleural fistulas, and 2 patients died as a consequence of esophageal problems. One patients had recurrence with brain metastases, and the 1 long-term survivor is free from disease. As opposed to the animal model of thoracic IORT, the clinical study demonstrated major toxicity with respiratory and esophageal morbidity. The therapeutic usefulness of thoracic IORT in the management of lung cancer must be questioned in view of this small but consistent series of patients. Further carefully designed clinical studies using lower doses of IORT are needed.

Adult↗
PubMed1987

Aberrant peripancreatic arterial anatomy. Considerations in performing pancreatectomy for malignant neoplasms.

One-hundred twenty patients with malignant neoplasms of the pancreas referred to the Surgery Branch of the National Cancer Institute over a 5-year period were prospectively examined with selective celiac and superior mesenteric angiography. Forty-one patients (34%) showed various arterial anomalies in the peripancreatic and hepatic areas. The most common anomalies included the right hepatic artery arising from the superior mesenteric artery (16%) and the left hepatic artery arising from the left gastric (11%). Thirty-two of the 120 patients eventually underwent pancreatic resection, and ten of the 32 resected patients (31%) had aberrant arterial anatomy. Recognition of the arterial anomalies permitted resection with no arterial reconstruction in nine of the patients. One patient required sacrifice of an aberrant right hepatic artery that was reconstructed with an anastomosis to the gastroduodenal artery remnant. Selective angiography should be done routinely before any potential radical resection for malignant neoplasms of the pancreas. Recognition of arterial anomalies generally permits satisfactory resection. Even if arterial segments require sacrifice, reconstruction can generally be accomplished with regional vessels, avoiding major arterial grafts.

Arteries↗
PubMed1987

Iliac arterial-enteric fistulas occurring after pelvic irradiation.

Fistulas from the iliac artery to the bowel constitute a condition that is often lethal. Excluding fistulas related to vascular grafts, a review of previously reported cases shows that they are most often due to atherosclerotic iliac aneurysms. Three unusual cases of this condition that occurred after high-dose pelvic irradiation for treatment of cancer are presented; in no case was recurrent tumor evident. These cases suggest that high-dose pelvic irradiation can predispose to the formation of iliac arterial-enteric fistulas, particularly if sepsis or inflammation develops. The definitive surgical management of these fistulas entails bowel resection, arterial ligation, and extra-anatomic bypass.

Adult↗
PubMed1986

Active immunotherapy of human solid tumor with autologous cells treated with cholesteryl hemisuccinate. A Phase I study.

A marked increase in specific immunogenicity of tumor cells is induced upon incorporation of cholesteryl hemisuccinate (CHS) into the cell membrane, which presumably promotes the expression of latent tumor-associated antigens. Immunotherapy with CHS-treated and irradiated tumor cells as vaccine was found to be very effective in various murine experimental tumors and in eliciting delayed-type hypersensitivity in cancer patients. Based on these findings, we have carried out a Phase I study on 21 patients with solid tumor who had exhausted standard therapeutic options. All participating patients were examined by conventional physical and clinical tests prior and during the study. The immunotherapy regimen for most patients consisted of an intramuscular injection of 2 X 10(7) CHS treated and irradiated autologous tumor cells given at 2-week intervals. Variations on this regimen were mostly due to the lack of sufficient number of cells. None of the patients displayed evidence of toxicity or any other local or systemic adverse effects. In seven patients, regression of tumor mass was observed. In six of nine patients who were tested for delayed-type hypersensitivity against their CHS treated tumor cells, a significant increase in skin reaction was observed after immunotherapy. The lack of any adverse reaction in this treatment, in addition to the observed positive clinical and immunologic response in advanced cancer patients, indicate a safe therapeutic potency which is planned to be investigated in the subsequent clinical studies.

Cholesterol Esters↗
PubMed1986

Inhibition of tumor angiogenesis by hexuronyl hexosaminoglycan sulfate.

The efficacy of heparin (HEP), the heparin analogue hexuronyl hexosaminoglycan sulfate (HHS), and hydrocortisone (HC) was studied in inhibiting the growth of four morphologically distinct pancreatic adenocarcinoma lines (CBP, LHP2, LSP3, and Pour-LVG) in hamsters. Animals were inoculated with LD100 doses of one of the four tumor lines and were randomly allocated to groups of five animals, which received in their drinking water either: HEP (1000 U/ml) alone, HHS (10 mg/ml) alone, HC (0.5 mg/ml) alone, HEP plus HC, HHS plus HC, or no additives (control). Tumors were measured, growth rates calculated, and nonparametric statistical comparisons made among the median growth rates of all of the treatment groups. All four tumors were tested in the rabbit cornea assay for their ability to induce angiogenesis. Extracts of tumors from control animals as well as from animals treated with HHS plus HC were prepared for quantitative testing in vitro by endothelial cell migration assay. All four tumor lines caused angiogenesis as measured in the rabbit cornea assay. A reduction in median tumor growth rates was observed in animals treated with HHS plus HC bearing the CBP, Pour-LVG, and LSP3 tumors. Similarly, in vitro capillary endothelial cell migration was decreased by HHS plus HC treatment in animals bearing CBP, Pour-LVG, and LSP3 tumors. Animals bearing the LHP2 tumor showed no effect of HHS plus HC treatment on tumor growth rate and no effect on endothelial cell migration. HEP alone, HHS alone, HC alone, and HEP plus HC showed no effect on tumor growth rate in any of the four tumors tested.

Animals↗