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Biomedical subjects

D S Kapp

Publications and source records attributed to D S Kapp.

At least 73 records · Page 4Linked to original sources
PubMed1989

Development and decay of systemic thermotolerance in rats.

The development and decay of thermotolerance to the lethal effect of systemic hyperthermia was investigated in Sprague-Dawley rats. Systemic hyperthermia was induced by partial submersion of gas-anesthetized rats into a temperature-controlled water bath. Survival was determined in rats challenged for periods of 10 to 90 min at 42.5 C, 24 to 144 h after a sublethal conditioning exposure of 41.8 C for 1 h. Survival curves of various exposure times at 42.5 C lethal to 50% of the animals (LD50) were determined for the conditioned animals and compared with those obtained for simultaneously treated control (unconditioned) rats. The thermotolerance ratios (TTR-LD50 for conditioned animals at various times after sublethal conditioning exposure divided by the LD50 for the control animals) were calculated and compared with the ratios reported in the literature for cells heated in vitro and for tissues heated locally in vivo. Pretreatment of rats at 41.8 C for 1 h resulted in an increase in the LD50 when rats were challenged 24 to 96 h later, with a maximum increased noted at 48 h (56.5 vs. 25.0 min for control; TTR = 2.3). The animals remained relatively resistant to the second heat treatment at 96 h and returned to control levels of heat sensitivity by 120 h. The development and kinetics of thermotolerance to lethality induced by whole-body hyperthermia need to be considered when multiple-fraction hyperthermia treatment plans are designed.

Adaptation, Physiological↗
PubMed1988

Hyperthermia and radiation therapy in the treatment of recurrent Merkel cell tumors.

A high incidence of local recurrence, spread to regional lymph nodes, and distant metastases has been reported after surgical excision of Merkel cell tumors (MCT). The use of postoperative radiation therapy and/or chemotherapy is reviewed from the literature. Despite adjuvant treatment, local tumor recurrences frequently develop. Two patients are presented with metastatic MCT recurrent in previously irradiated sites who had excellent clinical responses and local control following retreatment with local hyperthermia in conjunction with low to moderate dose radiation therapy. These patients represent the first reported use of hyperthermia in the management of MCT. The encouraging local responses described suggest a potential role for the use of hyperthermia and concomitant radiation therapy in the treatment of recurrent MCT.

Adult↗
PubMed1988

Important prognostic factors influencing outcome of combined radiation and hyperthermia.

Clinical experience with combined local-regional hyperthermia and radiation therapy has been rapidly accumulating over the past few decades. Its superior efficacy to the use of radiation alone has been demonstrated in several retrospective and prospective reports in the literature. It is evident now that there are several important factors that will influence the final outcome of the treated patients. The parameters that will be discussed in this paper include: I. Pretreatments factors: 1. tumor dimension 2. tumor histology 3. tumor site. II. Treatment factors: 1. radiation therapy dose 2. hyperthermia parameters: (a) thermal variables (b) number of heat treatments (c) sequence of hyperthermia and radiation treatments (d) hyperthermic device. Finally, evaluation of response and complications will also be discussed. The importance of abiding by an accepted reporting system will be emphasized, and clarification of times at which response assessments were made will also be discussed. With the availability of longer term follow-up, use of an actuarial method of reporting becomes more important. The future of hyperthermia and radiation remains very promising but a lot of questions still need to be answered by well-conducted and reported clinical trials.

Combined Modality Therapy↗
PubMed1988

Bladder cooling in patients treated with regional hyperthermia of the pelvis using an annular phased array.

Regional hyperthermia for the treatment of deep seated tumors is often limited by excessive heating of normal tissues, usually with associated patient pain and/or discomfort. The use of bladder cooling via perfusion of distilled water through a modified tri-lumen irrigation catheter as an aid to circumventing this problem in one anatomical region is described. This relatively simple technique provided rapid pain relief and permitted completion of the hyperthermia treatment in a satisfactory manner. Modifications of this technique may permit selective heating and/or cooling of the bladder during regional hyperthermia treatments in the pelvis.

Adult↗
PubMed1988

A predictive assay for human tumor cellular response to hyperthermia using dansyl lysine staining and flow cytometry.

The heat response of five human tumor biopsies has been examined using the fluorescent probe dansyl lysine and multiparameter flow cytometry. Dansyl lysine has previously been shown to possess specificity for heat killed mammalian cells. The human tumors tested included a cervical squamous cell carcinoma, malignant melanoma, colon adenocarcinoma, ovarian carcinoma, and a mesothelioma. The samples were excised, mechanically disrupted into single cell suspensions and heated in vitro for various lengths of time at 45 degrees C. The cells were returned to 37 degrees C incubation for 12 to 15 hours prior to staining with dansyl lysine. The fraction of cells staining dansyl lysine was quantitated by flow cytometry after gating on high forward angle light scatter and 90 degrees C light scatter. This gate excluded much of the normal cell contamination within the tumor sample. The data show that the heat response of human tumor biopsies varied significantly, with cervical carcinoma and malignant melanoma being the most resistant and the mesothelioma and ovarian carcinoma the most heat sensitive. Finally, evidence is presented for the expression of thermotolerance in ovarian carcinoma and mesothelioma biopsies pre-heated in vitro. Dansyl lysine appears to be useful in measuring the intrinsic cellular heat sensitivity of human tumors and in determining the kinetics of decay of thermotolerance following an initial heat exposure.

Biopsy↗
PubMed1988

Successful management of malignant pericardial effusion in metastatic squamous cell carcinoma of the uterine cervix.

Malignant pericardial effusion secondary to pericardial metastases from gynecological malignancies represents an infrequent but potentially life threatening problem. A patient with recurrent squamous cell carcinoma of the cervix causing symptomatic pericardial effusion is presented, and the incidence, mechanism, pathophysiology, treatment, and outcomes of malignant pericardial effusion in patients with gynecologic malignancies are reviewed. This case represents only the fourth reported patient with metastatic carcinoma of the cervix in whom the diagnosis of malignant pericardial effusion was made antemortem, and is the longest survivor of treatment. Gratifying results, in terms of improved quality and length of survival, can be obtained in what is often perceived as a preterminal complication. Recommendations for management are presented, stressing radiation therapy and other local measures following initial pericardiocentesis.

Carcinoma, Squamous Cell↗
PubMed1988

Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.

Adult↗
PubMed1987

Therapeutic approaches to uterine papillary serous carcinoma: a preliminary report.

Uterine papillary serous carcinoma (UPSC) is a recently identified and characterized unique histopathologic subtype of endometrial cancer. Unlike the more common types of endometrial cancer, UPSC has a high likelihood of transperitoneal seeding and upper abdominal recurrence. Since our initial report of 26 patients with UPSC, an additional 10 patients with FIGO stage I disease have been diagnosed, operatively staged, and managed by an individualized approach. Operative staging revealed 5 of the 10 patients to have more advanced disease than had been determined clinically. Adjuvant postoperative abdominopelvic radiation was administered to 6 patients, 4 of whom remain free of disease within the treated area. Two patients received adjunctive hormonal and chemotherapy; neither has recurred. Two patients received no adjunctive therapy. One of these failed initially in the vagina with subsequent recurrence in the lungs and supraclavicular nodes. The value of operative staging and selection of appropriate adjunctive therapy awaits additional patient accrual and follow-up.

Aged↗
PubMed1987

Prognostic factors and sites of failure in FIGO Stage I, Grade 3 endometrial carcinoma.

The results of therapy and patterns of failure were analyzed for 60 patients with Stage I, Grade 3 endometrial cancer seen at Yale-New Haven Hospital between 1960 and 1980. Fifty-eight patients were treated with a combination of surgery and radiation; one was treated with surgery only; and one received radiation only. The overall absolute 5-year survival rate was 72.9% with poorer prognosis noted for patients greater than 65 years of age, older at time of their menopause, and with Stage IA disease. Of the 14 patients who recurred, distant sites were involved in 93% (13/14), with the lung the most common site of distant failure (5/14), followed by the upper abdomen (4/14). Pelvic sites were involved in 43% (6/14) of the treatment failures. The use of pelvic external beam radiation resulted in a reduction in pelvic recurrences, but did not improve overall survival. The predominance of distant failures despite pelvic radiation suggests the possibility of early vascular and transcoelomic spread in Stage I, Grade 3 endometrial adenocarcinomas. Thorough exploration of the upper abdomen, paraaortic nodes, and the obtaining of pelvic washings for cytology at the time of initial surgery, are recommended in addition to chest CT scans to help identify those patients with occult metastases. Prospective randomized trials in Stage I, Grade 3 patients employing adjuvant cytotoxic chemotherapy, hormonal therapy, and/or whole abdominal-pelvic radiation, should be considered in an attempt to improve survival in high-risk patients.

Carcinoma↗
PubMed1987

Correlations of thermal washout rate, steady state temperatures, and tissue type in deep seated recurrent or metastatic tumors.

The rates of cooling ("thermal washout") in selected sites in tumor and adjacent normal tissues following the completion of clinical hyperthermia sessions were analyzed in ten patients treated with combined radiation and hyperthermia for deep seated recurrent or metastatic tumors. The temperatures were recorded at 10 second intervals for at least 2 minutes after the cessation of microwave power at the end of the 30-60 minute duration hyperthermia treatments. These thermal washouts were characterized by the slope of a log-linear relation between temperature elevation above the oral baseline temperature and time. Washout rates (expressed as a perfusion rate in ml/100g-min) significantly correlated with tissue categories as noted on CAT scan (i.e., tumor, normal tissue, tumor/normal tissue interface, hypodense tumor areas). Relationships between thermal washout rate and steady-state temperature elevation were tested and also showed significant correlations in general and for some specific tissue categories. The implications of these findings in explaining inhomogeneities in heating patterns, and in hyperthermia treatment modeling will be presented.

Combined Modality Therapy↗
PubMed1987

Heating deep seated eccentrically located tumors with an annular phased array system: a comparative clinical study using two annular array operating configurations.

Regional heating administered with an annular array to 12 patients with deep-seated advanced malignant disease eccentrically located in the lower abdomen and pelvis is compared based on the annular array operating configuration. One configuration (4 quadrants active) delivers radiofrequency power with relative uniformity throughout the patient cross-section. The other (2 quadrants active) allows the radiofrequency power deposition to be shifted preferentially into the eccentrically located treatment volume. Phantom measurements have been made to demonstrate the redistribution of radiofrequency power that results when the annular array is operated in these respective configurations. Systemic responses (i.e. oral temperature rise, changes in blood pressure, and heart rate) to these regional hyperthermia applications are compared and are not significantly different with respect to these heating configurations. Temperature data obtained during treatment sessions using these two annular array operating configurations are analyzed based on the fraction of measured tumor and normal tissue temperatures exceeding or equal to a given index temperature. Although the two quadrant configuration is more efficient in delivering power to the treatment volume, this analysis does not indicate a significant gain in therapeutic heating as a result of this preferential power deposition. Treatment tolerance and heterogeneity with respect to tissue type and blood flow remained the dominant limiting factors with regard to temperatures achieved.

Abdominal Neoplasms↗
PubMed1987

Radiotherapy with curative intent: an option in selected patients relapsing after chemotherapy for advanced Hodgkin's disease.

Thirteen patients who had relapsed or failed to obtain a complete remission after combination chemotherapy for the treatment of advanced Hodgkin's disease were treated with subtotal or total lymphoid irradiation with curative intent. Twelve of the 13 patients achieved a complete response (CR). Five of the 12 CRs subsequently relapsed at 3, 9, 9, 12, and 19 months. One patient died of leukemia 11 months following radiotherapy. The actuarial relapse-free survival at 1 year was 60%, and six patients (50%) remain disease-free with a median follow-up of 34 months (range, 10 to 115 months) following the completion of radiotherapy. Patients who failed to obtain a CR to their initial chemotherapy, whose chemotherapy CR was of short duration, or who relapsed initially in extranodal sites, tended to have a worse outcome with radiotherapy. Patients who had long disease-free intervals after initial chemotherapy or relapsed only in nodal sites tended to do relatively well. Radiation therapy was well tolerated with no major toxicity. Potentially curative radiation therapy should be considered an option in the management of selected patients who relapse following combination chemotherapy for advanced Hodgkin's disease.

Actuarial Analysis↗
PubMed1986

Stage IIIA carcinoma of the uterine cervix.

Carcinoma of the uterine cervix presenting with extension to the lower third of the vagina but without hydronephrosis or fixation to the pelvic sidewall is uncommon. It is classified as stage IIIA by the criteria of the International Federation of Gynecology and Obstetrics (FIGO) and accounts for less than 2% of all cervical cancer cases seen in our institution. Because of the paucity of such cases, the results of treatment of FIGO stage IIIA cervical cancer are generally not reported separately. The radiation therapy treatment program at Yale--New Haven Hospital for stage IIIA patients includes intracavitary and vaginal brachytherapy plus external beam radiation therapy, with a strong emphasis on individualization of treatment. The results of treatment in 17 stage IIIA patients were reviewed. Local--regional tumor control was achieved in 12 of the 17 patients (71%) treated. The actuarial 5-year disease-free survival rate was 58%. Our results suggest that FIGO stage IIIA carcinoma of the cervix has a much better prognosis than FIGO stage IIIB cervical cancer, and we recommend that the results of treatment for FIGO stage IIIA be reported separately.

Adenocarcinoma↗
PubMed1986

Adjuvant therapy in mixed mullerian tumors of the uterus.

We report 54 patients with mixed mullerian tumors of the uterus treated at Yale-New Haven Hospital from 1962 to 1983. Seven had previous pelvic irradiation. Twenty-five neoplasms were homologous and 29 were heterologous. The mainstay of therapy was surgery and radiation. By FIGO criteria 9 patients had stage IA disease, 31 stage IB, 6 stage II, and 8 patients had clinical extrauterine disease. Ten of forty-six patients (23%) with FIGO stage I and II disease had extrauterine disease found at surgery. No patient with extrauterine disease had prolonged survival. The 2-year disease-free survival with stage IA was 66%, with stage IB surgically confirmed 32%, and for stage II 33%. Surgically advanced disease in clinical stage I and II patients and recurrence were associated more frequently with a heterologous histology (67%). The small uterus with a less than 10-cm cavity had a better prognosis. Among 29 surgically confirmed stage I and II patients, 83% of recurrences appeared within 2 years (mean 16 months +/- 7 months). Patients who received both intracavitary radiation and external beam developed only 17.6% pelvic recurrence but this reduction in local recurrence was not associated with significant improved long-term survival. Six of eight patients treated with cis-platinum, Adriamycin, and dimethyl triazeno imidazole carboximide for persistent disease or for recurrence showed response for 4 to 24 months, none complete. Five patients were treated by radiation, surgery, and adjuvant chemotherapy (4 with Adriamycin-Cytoxan, 1 with Adriamycin-platinum). Four of the five (80%) are disease free from 36 to 60 months. These data and the experience of others support the need for a clinical trial with adjuvant platinum and Adriamycin in this disease.

Adult↗
PubMed1986

Axillary-subclavian vein thrombosis following combination chemotherapy and radiation therapy in lymphoma.

Four patients with deep venous thrombosis of the upper extremity (DVTUE) following combined modality therapy (mantle radiotherapy and chemotherapy) for either Hodgkin's disease or non-Hodgkin's lymphoma were seen at Stanford University Medical Center between March 1980 and April 1984. A total of 235 patients had received similar combined modality therapy during this time period. Three patients presented with acute onset of DVTUE and were anticoagulated. One patient who was referred with a several month history of DVTUE was observed closely after diagnostic evaluation revealed no evidence of recurrent Hodgkin's disease. All patients remained without evidence of their original lymphoma and had developed adequate venous collateralization. These cases of DVTUE were felt to be treatment related, a previously unreported late complication of combined irradiation and chemotherapy. Methods of diagnosis and therapeutic options are discussed.

Adolescent↗
PubMed1986

Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience.

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.

Actuarial Analysis↗