PubMed Health⌕ Search

Biomedical subjects

D S Kaufman

Publications and source records attributed to D S Kaufman.

54 records · Page 3Linked to original sources
PubMed1992

Deoxyribonucleic acid flow cytometry in invasive bladder carcinoma: a possible predictor for successful bladder preservation following transurethral surgery and chemotherapy-radiotherapy.

Tumor deoxyribonucleic acid (DNA) ploidy was evaluated as an objective parameter that may correlate better with the responsiveness of bladder cancer to chemotherapy plus radiotherapy than do clinical features or histopathological subtypes. A total of 40 patients with localized muscle-invading bladder cancer (clinical stages T2 to T4) underwent prospective treatment on a potential bladder preserving protocol. Tumors of 37 of the 40 patients were analyzed by DNA flow cytometry of multiple paraffin embedded specimens. Transurethral resection, neoadjuvant chemotherapy and 40 Gy. radiotherapy plus cisplatin were followed by urological reevaluation of the tumor (a complete response required a negative biopsy and a negative urine cytology study). A total of 7 noncomplete response patients underwent immediate radical cystectomy whereas the full bladder sparing treatment (radiotherapy to 64.80 Gy. plus cisplatin) was given to 23 complete response patients and 7 noncomplete response patients who were unsuited for surgery. Of the tumors 22 (59%) were purely aneuploid and 10 (27%) were purely diploid. Five tumors contained aneuploid and diploid patterns in different tumor specimens (partly diploid). Current status with a 30-month median followup in surviving patients includes an 82% overall survival rate in the aneuploid group versus 47% in the diploid/partly diploid group. Of all the patients 68% are free of invasive tumor: 82% in the aneuploid group versus 47% in the diploid/partly diploid group. By multivariate analysis pure aneuploidy was significantly (p = 0.05) correlated with freedom from invasive tumor in the bladder (either as persistence or as recurrence) and approached significance (p = 0.08) in correlation with overall patient survival. A longer observation time will be required to confirm this unexpectedly good outcome for patients with pure aneuploid tumors. We hypothesize that pretreatment DNA ploidy status may become a clinically useful prognostic factor in selecting patients for successful treatment with transurethral surgery and neoadjuvant chemotherapy plus radiotherapy.

Clinical Protocols↗
PubMed1992

Adjuvant postoperative radiation therapy for rectal adenocarcinoma.

From October 1975 to August 1988, 261 patients at high risk for local recurrence after curative resection of rectal carcinoma underwent high-dose postoperative irradiation. Patients received 45 Gy by a 4-field box usually followed by a boost to 50.4 Gy or higher when small bowel could be excluded from the reduced field. Since January 1986, patients also received 5-fluorouracil (5-FU) for 3 consecutive days during the first and last week of radiotherapy. Five-year actuarial local control and disease-free survival decreased with increasing stage of disease; patients with Stage B2 and B3 disease had local control rates of 83% and 87% and disease-free survivals of 55% and 74%, respectively. In patients with Stage C1 through C3 tumors, local control rates ranged from 76% to 23%, and disease-free survivals ranged from 62% to 10%, respectively. For patients with Stage C disease, disease-free survival decreased progressively with increasing lymph node involvement, but local control was independent of the extent of lymph node involvement. For each stage of disease, local control and disease-free survival did not correlate with the dose of pelvic irradiation. Preliminary data from this study suggest a trend toward improved local control for patients with Stage B2, C1, and C2 tumors who receive 5-FU for 3 consecutive days during the first and last weeks of irradiation compared with patients who do not receive 5-FU. Current prospective randomized studies are addressing questions regarding the optimum administration of chemotherapy with pelvic irradiation for patients following resection of rectal carcinoma.

Adenocarcinoma↗
PubMed1992

Radiotherapy and chemotherapy in invasive bladder cancer with potential bladder sparing.

The standard treatment in the United States for patients with muscle infiltrating tumors is radical cystectomy with or without radiation treatment. The results of such treatment have been generally unsatisfactory, with 40% or more patients developing systemic disease with a 5-year survival rate of less than 50%. Combination chemotherapy employing both cisplatin and methotrexate can produce a 30% to 50% clinical complete response rate (negative biopsy, negative urinary cytology) of the primary tumor. Although the optimal combination of chemotherapeutic agents has not yet been determined, it is unlikely that combination chemotherapy alone, even in completely responding patients, will be adequate to rid the bladder of a primary invasive transitional cell carcinoma. Additional therapy by either surgery or external beam radiotherapy seems warranted owing to the high likelihood that there will be residual microscopic tumor in the bladder. Concomitant systemic chemotherapy and external beam radiotherapy produces complete remissions in 65% to 90% of patients. Follow-up of from 3 to 5 years following full chemoradiotherapy will be necessary to be certain that the bladder has been sterilized of cancer. Combined cisplatin and external beam radiation (using a boost technique that spares the section of the bladder uninvolved with tumor) does not seem to enhance local soft-tissue toxicity (relative to the radiotherapy alone) with the exception of the neurotoxicity seen with intra-arterial cisplatin. Debulking TURB tumor appears to improve the local success rate for patients being considered for bladder preservation with the use of the combination of systemic chemotherapy and/or radiotherapy. Not all patients respond to concomitant chemotherapy and radiation therapy. Our current approach is that the selection process must be carried on at several points during the treatment. Only patients who respond completely to the initial courses of chemotherapy and radiation should be carried to a full radiation dose. In the absence of a complete response following upfront chemotherapy and 4000 cGy in combination with additional cisplatin courses, cystectomy at that point is the recommended treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Cisplatin↗
PubMed1991

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Adult↗
PubMed1991

Interval report of a phase I-II study utilizing multiple modalities in the treatment of invasive bladder cancer. A bladder-sparing trial.

Clinicians at the Massachusetts General Hospital have used two cycles of methotrexate, cisplatin, and vinblastine (MCV) before radiotherapy and cisplatin in 53 patients with muscle-invasive bladder cancer. Eleven patients did not complete the protocol, but overall, the toxicity was not formidable. Of the total patients accessioned, 34 are alive. Of the 34 patients in the series who completed the full treatment protocol, the estimated survival rate at 54 months is 77%. This interim analysis suggests that the treatment is achieving at least limited success in saving lives and bladders.

Adult↗
PubMed1990

Bladder cancer. Advances in laboratory innovations and clinical management, with emphasis on innovations allowing bladder-sparing approaches for patients with invasive tumors.

In the present decade important progress has been made in the understanding of the biology and management of bladder cancer. Experimental laboratory models and new investigative tools have revealed potentially important prognostic markers and have led to an improved understanding of the histogenesis of the disease. Advances in the management of superficial bladder cancer (intravesical chemotherapy or immunotherapy, improved urinary cytology, laser technology, flexible fiberoptic cystoscopy, and photodynamic therapy) have, in some subgroups, improved tumor control while decreasing patient complications. For invasive bladder cancer (invasive of bladder muscle or beyond) improved techniques of cystectomy and radiotherapy have reduced the complications of treatment and may have contributed small but important improvements in cure. A major improvement in the last decade has occurred in objective remission rates with chemotherapy for patients with metastatic bladder cancer. From 20% to 40% of patients achieve a complete remission, and 10% to 20% may survive for more than 3 years. Randomized Phase III trials are currently in progress and must be completed to define the true role of multidrug chemotherapy in patients with metastatic disease and to validate data from the regimens of cyclophosphamide, methotrexate, and vincristine (CMV) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) before any of these approaches to treatment can be considered of proven benefit. Preliminary data from the Massachusetts General Hospital are presented of a potentially effective approach to select patients with invasive tumor for successful bladder preservation. In this approach transurethral debulking surgery is combined with upfront CMV chemotherapy plus cisplatin and 4000 cGy. If tumor is found on cystoscopic reevaluation with biopsy and cytology immediately following cisplatin and 4000 cGy, cystectomy is performed; if not, consolidation by a radiation boost to 6480 cGy plus cisplatin is given. The approach is fairly well tolerated, allows cystectomy without undue complications, has yielded a 88% complete response rate in patients selected for bladder preservation, and resulted in 90% of patients free of distant metastases with follow-up ranging from 6 to 30 months. A randomized Phase III trial with and without neoadjuvant MCV chemotherapy for selective bladder preservation is now under way and accruing well.

Actuarial Analysis↗
PubMed1990

Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.

Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.

Aged↗
PubMed1990

Angiogenic activity is defective in monocytes from patients with alopecia universalis.

Monocyte/macrophages are important components of cell-mediated immune responses in presentation of antigen, as regulators of lymphocyte function, and as sources of cytokines that modulate functions of cells other than those of the immune system. Their role in the pathogenesis of alopecia areata (AA) and universalis (AU) has not been explored. This study is an investigation of the function of peripheral blood monocytes from normal subjects and patients with AA, AU, and alopecia totalis (AT), with respect to the principal macrophage-derived angiogenic factor, tumor necrosis factor alpha (TNF alpha). Because neovascularization is a necessary component in the anagen phase of hair growth and may play a role in the pathology of these disorders, we asked whether monocyte/macrophage angiogenic activity was compromised in these alopecias. Purified preparations of monocytes were activated in culture. Conditioned media were assessed for angiogenic activity on the chick chorioallantoic membrane and for concentration of TNF alpha by enzyme-linked immunosorbent assay (ELISA). Both angiogenic and the TNF concentration were significantly diminished in conditioned media from AU monocytes when compared to those from normal subjects and patients with AA. These results show that the function of AU monocytes may be abnormal and that the abnormality may distinguish AU from AA. Defective monocyte/macrophage function could also play a pathogenic role via effects on neovascularization and/or modulation of the immune response.

Adult↗
PubMed1990

Can chemo-radiotherapy plus transurethral tumor resection make cystectomy unnecessary for invasive bladder cancer?

The standard treatment for muscle-invading bladder tumors is, in the US, radical cystectomy +/- radiation; in Europe, it is radical radiotherapy. Neither of these therapies alone is wholly satisfactory. Suggested improvements in the complete response rates of the primary tumor have been reported with combination chemotherapy and with chemo-radiotherapy. Selecting for full chemo-radiotherapy only patients having a biopsy-proven CR to initial chemotherapy and/or to 4,000-4,500 cGy of radiation may further increase the success of bladder-preserving programs and not compromise survival (relative to immediate cystectomy), but this has not yet been proven. Randomized trials of neoadjuvant chemotherapy must be finished before its efficacy in subclinical systemic disease will be known. Likewise, proof of the efficacy of neoadjuvant chemotherapy in improving bladder preservation by chemo-radiotherapy must await completion of randomized trials. Three to five years of follow-up will be necessary before chemo-radiotherapy can be recommended as curing the bladder of cancer.

Combined Modality Therapy↗
PubMed1988

Use of anti-L3T4 and anti-Ia treatments for prolongation of xenogeneic islet transplants.

The effects of T helper lymphocyte and Ia+ cell depletion were examined for their ability to independently and synergistically achieve prolongation of xenogeneic (rat-to-mouse) islet transplants. Recipient mice were depleted of T helper lymphocytes by short-term treatment with the anti-L3T4 monoclonal antibody GK1.5. Donor rat islets were treated prior to transplantation with a concentration of anti-Ia immunotoxin (13.4 x RT) that selectively depleted Ia+ cells within the islets while leaving functional insulin-secreting beta-cells unaffected. Anti-L3T4 treatment alone allowed transplants to be prolonged compared with untreated controls; however, all such treated mice rejected their xenogeneic transplant within 22 days. Although 13.4 x RT treatment of donor islets alone did not prolong engraftment, when donor rat islets were pretreated with the anti-Ia immunotoxin and grafted into L3T4-depleted mice, normoglycemia was maintained for greater than 50 days in 56% of transplants. These results suggest that neither L3T4 depletion nor anti-Ia immunotoxin treatment alone is enough to achieve indefinite survival of xenogeneic islets. However, decreasing the immunogenicity of the transplanted islets by anti-Ia immunotoxin treatment prior to transplantation into anti-L3T4 treated mice can allow greatly prolonged xenogeneic graft survival.

Animals↗
PubMed1987

The effects of human immunodeficiency virus recombinant envelope glycoprotein on immune cell functions in vitro.

The effect of human immunodeficiency virus (HIV) recombinant envelope glycoprotein 120 (rgp 120) on the functions of peripheral blood mononuclear cells (PBMC) in vitro was investigated. The results demonstrate that rgp 120 used at concentrations less than 1 microgram/ml has no significant effects on PBMC function in vitro. However, the addition of 1-20 micrograms/ml of rgp 120 significantly inhibits the tetanus toxoid-induced PBMC proliferative response in a dose-related manner as determined by [3H]thymidine incorporation. The data also show that rgp 120 (5 micrograms/ml) causes up to 70% reduction in the number of immunoglobulin G-secreting cells in pokeweed mitogen-stimulated PBMC cultures. Further, rgp 120 can selectively interact with the CD4a epitope of the CD4 helper cell membrane receptor. These results indicate that microgram per milliliter levels of rgp 120 can depress certain immune functions in vitro. The significance of these findings to the pathogenesis of immunodeficiency in HIV infection remains to be determined.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Malignant lymphoma of the thyroid gland: a clinical and pathologic study of twenty cases.

Among 20 patients with malignant lymphoma of the thyroid gland, the mean age at diagnosis was 63 years and the male to female ratio was 1:6. All patients had a firm, rapidly enlarging neck mass. In 90% of the patients the mass had been present for less than 1 year; in 40%, for less than 1 month. Approximately half of the patients tested had hypothyroidism; three fourths had elevated antithyroid antibodies. There was one nodular lymphoma. The remaining 17 cases available for review were diffuse. Thyroid lobectomy was performed in seven patients, limited excision in eight, and needle biopsy alone in five. External irradiation was administered in 11 cases (55%). Chemotherapy was used alone in one patient (5%) and in combination with radiotherapy in eight (40%). Six patients (30%) were alive without evidence of recurrent disease at follow-up ranging from 1 to 12 years. Eleven patients had died of lymphoma, all but one dying within 1 year. One patient died of other causes and two were lost to follow-up study. There was no appreciable effect of patient age or sex, lymphoma histology, or extent of surgical resection on survival. Treatment of choice for primary lymphoma of the thyroid gland appears to be external irradiation or chemotherapy, alone or in combination. The role of surgery is limited to making a tissue diagnosis of lymphoma, unless the tumor is completely intrathyroidal.

Adolescent↗
PubMedDate not supplied

Treatment strategies using transurethral surgery, chemotherapy, and radiation therapy with selection that safely allows bladder conservation for invasive bladder cancer.

Combined modality therapy with the goal of effecting cure and achieving organ preservation has become the standard oncological approach in many malignancies. Although radical cystectomy has been considered the standard treatment for invasive carcinoma of the bladder, equivalent results have been achieved using combined modality treatment in selected patients, particularly those with T2 and T3a disease without obstructed ureters. Effective combined modality treatment consists of three treatment modalities: (1) transurethral resection of the bladder tumor (TURBT), followed by concurrent (2) chemotherapy, and (3) radiation. Following induction therapy, histologic response is evaluated by cystoscopy and biopsy. Clinical complete responders continue with concurrent chemotherapy and irradiation. Those patients not achieving a clinical complete response are advised to undergo cystectomy. Individually the local monotherapies of radiation, TURBT, or systemic chemotherapy each achieve a local control rate of 20% to 40%. When they are combined, complete response rates of 70-80% are achieved and 85% of these will remain free of invasive recurrence in the bladder. Bladder preservation trials using combined modality treatment approaches with selection for organ conservation by response to initial treatment report an overall 5-year survival rate of approximately 50%, and they have achieved a 40% to 45% 5-year survival rate with the bladder intact. Modern multi-modality bladder preservation approaches offer survival rates similar to radical cystectomy, for patients of similar clinical stage and age, and an improved quality of life by allowing a majority of patients to retain their own fully functional bladder. Bladder conservation therapy may be offered to selected patients with bladder cancer as one alternative to radical cystectomy, and its use should be by experienced multi-modality teams of urologic oncologists.

Age Factors↗
PubMedDate not supplied

Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer?

PURPOSE: This study analyzes the long-term outcome of patients with stage T4 colon cancer who receive postoperative irradiation. The purpose of the study is to define the potential role of this modality with current systemic therapies. PATIENTS AND METHODS: A retrospective analysis was performed of 152 patients undergoing resection of T4 colon cancer followed by moderate- to high-dose postoperative tumor bed irradiation with and without 5-fluorouracil-based chemotherapy. Of the 152 patients, 110 patients (T4N0 or T4N+) were treated adjuvantly, whereas 42 patients received irradiation for the control of gross or microscopic residual local tumor. RESULTS: For 79 adjuvantly treated patients with stage T4N0 or T4N+ cancer with one lymph node metastasis, the 10-year actuarial rates of local control and recurrence-free survival were 88% and 58%, respectively. Results were less satisfactory for patients with more extensive nodal involvement. The 10-year actuarial rates of local control and recurrence-free survival of 39 patients with T4 tumors complicated by perforation or fistulas were 81% and 53%, respectively. For 42 patients with incompletely resected tumors, the 10-year actuarial recurrence-free survival was 19%. CONCLUSIONS: In comparison with historical controls, postoperative tumor bed irradiation improves local control for some subsets of patients. In addition to standard 5-fluorouracil-based chemotherapy, adjuvant tumor bed irradiation should be considered when colon cancers invade adjoining structures, when they are complicated by perforation or fistulas, or when they are incompletely excised at the primary site.

Adult↗
PubMedDate not supplied

Combined modality treatment with selective bladder conservation for invasive bladder cancer: long-term tolerance in the female patient.

PURPOSE: To assess the physical, psychological, social, and organ-specific long-term treatment sequelae occurring in women with muscle-invading bladder carcinoma treated with combined modality therapy that allowed for bladder conservation in 67% of patients. PATIENTS AND METHODS: Patients with muscle-invading (T2-4a,Nx,M0) bladder cancer were treated with maximal transurethral resection followed by induction chemoradiotherapy (cisplatin x 2 plus 40 Gy pelvic irradiation or the same preceded by 2 cycles of methotrexate, cisplatin, and vinblastine) between the years 1986 and 1994. Women who had a complete response and all those who were not candidates for cystectomy received consolidation therapy of additional cisplatin and tumor boost to 64.8 Gy. Women who were incomplete responders and those who developed recurrent invasive tumor underwent immediate radical cystectomy. Forty-two women were treated with this approach, 21 of whom (median age, 69 years; median follow-up time, 56 months) were available for and underwent a structured interview of treatment and health-related issues using a quantitative symptom score. RESULTS: All 21 patients have full urinary continence and no dysuria. Nineteen report unchanged or improved bladder capacity and function. No patient reported loss of bowel continence. Of the five women who were sexually active, two report an increase in intercourse frequency and one noted a decrease. There is no decrease in intercourse satisfaction or orgasm, and no dyspareunia or vaginal bleeding was noted. Eleven patients reported high levels of anxiety related to their bladder cancer before treatment. This was significantly reduced or absent in 9 of 11 after treatment. Actuarial overall survival for all 42 women was 58% at 5 years. Actuarial overall survival with an intact bladder was 47% at 5 years. DISCUSSION: This study shows that overall survival is high when chemoradiation and transurethral resection are used in potential bladder-sparing protocols for muscle-invading transitional cell carcinoma of the bladder in women. Furthermore, 67% of the women, including most long-term survivors, retain their bladders. The functional quality of the conserved organ, the rectum, and the vagina, as reported by the patients, was excellent.

Adult↗