Biomedical subjects

M L Berman

Publications and source records attributed to M L Berman.

At least 91 records · Page 5Linked to original sources

PubMed1990

In vitro cytotoxicity of human recombinant tumor necrosis factor alpha in association with radiotherapy in a human ovarian carcinoma cell line.

It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors.

Carcinoma↗

PubMed1990

Whole-abdominal radiotherapy for patients with minimal residual epithelial ovarian cancer.

Sixteen patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery followed by multiagent chemotherapy were found to have residual tumor masses less than 2 cm in greatest diameter at reexploration and were treated with whole-abdominal radiation (19-31 Gy). Thirteen patients also received pelvic boosts to a total pelvic dose of 41-53.7 Gy. Radiotherapy was completed in all but 2 patients after treatment delays in 7 patients. Early treatment complications included myelosuppression in 11 patients, diarrhea in 3, and a self-limited small bowel obstruction in one. Delayed complications were severe and included 9 patients with radiation enterocolitis, 8 of whom required intestinal resection or diversion. One additional patient with radiation cystitis required instillation of formalin to control bleeding. Two patients are without evidence of disease 28 and 30 months following radiotherapy, while the remaining 14 patients have recurred after a median progression-free interval of 9 months (range 1-30 months). All patients who recurred failed within the treatment field and died of cancer after a median interval of 19 months following radiotherapy and 9 months after documentation of progression. These data suggest that few patients with persistent ovarian cancer following surgery and chemotherapy will be salvaged with radiotherapy.

Abdomen↗

PubMed1990

Influence of histological features and treatment on the prognosis of patients with cervical cancer metastatic to pelvic lymph nodes.

Ninety-seven patients with stage IB through IIB cervical cancer metastatic to pelvic lymph nodes treated at Magee-Womens Hospital, Pittsburgh, Pennsylvania, between 1955 and 1979 were analyzed retrospectively to determine histological factors which might predict treatment failure. All patients were treated by radical hysterectomy with a pelvic lymphadenectomy (S) or in combination with radiation therapy (S + RT) (27 and 73%, respectively) and were followed for a minimum of 5 years or until death. There were no significant differences between the two treatment groups when compared for patient age at diagnosis, distribution of disease stages, cell type, and tumor differentiation. The groups were dissimilar only with respect to the number of lymph nodes found to contain metastatic carcinoma. Significantly more patients treated by S + RT than by S alone were found to have metastasis to more than one node. Of patients treated with S alone, 65% recurred within 5 years compared with 51% with the addition of RT (P less than 0.16). The extent of both lymphocytic and polymorphonuclear infiltration of the tumor did not influence the probability of recurrence following treatment; however, tumors with a marked eosinophilic infiltration recurred significantly more frequently than those without (P less than 0.05).

Combined Modality Therapy↗

PubMed1990

Hemolytic-uremic syndrome associated with neoadjuvant chemotherapy in the treatment of advanced cervical cancer.

Hemolytic-uremic syndrome (HUS) is a rare but severe complication of neoplastic disease as well as some of its treatments. The pathophysiology of HUS is poorly understood, but it affects multiple organ systems and carries a high mortality rate. The diagnosis of HUS is based on a clinical triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal failure, for which no proven therapies exist. This report describes a case of HUS developing in a patient with stage IVA squamous cell carcinoma of the uterine cervix following treatment with cisplatin/bleomycin/vincristine neoadjuvant chemotherapy prior to radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

The use of molecular probes to distinguish new primary tumors from recurrent tumors in gynecologic malignancies.

This is the first report using DNA molecular probe technology to distinguish between recurrent tumor and a second primary malignancy in a patient. Tumor DNA was extracted from squamous cell carcinoma of the cervix at the time of radical hysterectomy. Eighteen months later a squamous cell cancer was found in a vaginal apex biopsy from which DNA was extracted. Tumor DNA from both lesions was subjected to restriction enzyme digestion and DNA molecular hybridization with human papillomavirus (HPV) probes. Although both lesions were positive for HPV 16, their respective restriction enzyme patterns had different HPV genetic arrangements, thereby demonstrating their distinctness.

Adult↗

PubMed1990

Gynecologic Oncology Group experience with ifosfamide.

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Primary invasive carcinoma of the vagina.

A retrospective review was conducted of 53 women with invasive carcinoma of the vagina and without documented exposure to diethylstilbestrol who were seen at the University of California Irvine Medical Center, Long Beach Memorial Medical Center, and Saddleback Memorial Medical Center from 1976-1988. Forty-seven (89%) had squamous cell carcinoma and six (11%) adenocarcinoma. Thirty-seven (70%) were treated with whole-pelvis irradiation and brachytherapy, nine with surgery alone, and the other seven with a combination of treatments. The crude and corrected 2-year survival rates for the entire group were 47 and 69%, respectively. Those with previous pelvic surgery were more likely to develop serious treatment-related complications. There was a statistically significant correlation between previous hysterectomy and the diagnosis of primary invasive carcinoma of the vagina after the onset of symptoms. Women diagnosed during routine examination, before symptom onset, tended to have a survival advantage. All women, including those who have had hysterectomy, should be counseled to continue gynecologic cancer surveillance regardless of age.

Adenocarcinoma↗

PubMed1990

The influence of endometriosis on the staging of cervical cancer.

Pelvic endometriosis often presents as nodularity of the uterosacral and broad ligaments. Therefore, the presence of unrecognized pelvic endometriosis in cervical cancer patients can masquerade as parametrial spread of tumor, preventing correct assessment of stage of disease. A review of three cases in which these disease processes coexisted demonstrates that endometriosis can easily be mistaken for tumor extension on pelvic examination, computed tomography, and even gross inspection at laparotomy, resulting in incorrect staging and inappropriate management decisions. Because clinical staging often is inaccurate in cervical cancer patients with a history of endometriosis, pre-treatment operative assessment should be considered and frozen sections are recommended to assist with intraoperative management whenever the diagnosis of endometriosis could be entertained.

Adenocarcinoma↗

PubMed1990

Management of endometrial cancer with suspected cervical involvement.

The 1989 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer cells for operative assessment of the extent of uterine disease, grade, and sites of metastasis before assigning a stage to the cancer. In the current study, 70 endometrial cancer patients with suspected cervical involvement based on a positive endocervical curettage or punch biopsy were treated with initial surgery followed by tailored radiation or chemotherapy. Only 37% of the patients had operative findings consistent with the preoperative suspicion of stage II disease. Postoperative therapy was determined by the extent of cervical involvement, depth of myometrial invasion, cell type, tumor grade, and the presence and location of extra-uterine disease. Based upon these parameters, 21 patients were believed to have low risk for pelvic recurrence and received no adjuvant therapy (90% 5-year survival); 38 patients received postoperative pelvic radiation because of high-risk factors for pelvic recurrence or pelvic nodal involvement (65% 5-year survival); and 11 patients received chemotherapy and/or extended radiation because of extrapelvic disease (no 5-year survivors). The approach outlined supports initial surgery for cases of endometrial cancer with suspected cervical involvement. This approach permits accurate surgical staging under the new FIGO system, avoids radiotherapy in many patients whose disease is less extensive than suspected preoperatively, and can accomplish good local control with limited morbidity.

Combined Modality Therapy↗

PubMed1989

Phase II study of esorubicin (4'-deoxydoxorubicin) in advanced epithelial carcinoma of the ovary: a Gynecologic Oncology Group study.

Twenty-six patients with advanced, measurable epithelial carcinoma of the ovary were treated with 76 courses of esorubicin at doses ranging from 20-30 mg/m2 every 3 weeks. All patients are evaluable for toxicity and response. All patients had received prior therapy including radiation therapy in 9, non-anthracycline chemotherapy in 25, and surgery in 25. All patients were GOG performance status 0, 1 or 2. Two partial responses were seen. Severe (grade 3 or 4) leukopenia, thrombocytopenia, and anemia were seen in 13, 1 and 4 patients, respectively. Moderate gastrointestinal toxicity was also noted. Alopecia and mucositis were rare. Phlebitis was not seen. Neither clinical congestive cardiomyopathy nor decrement in left ventricular ejection fraction was observed. We conclude that using this dose and schedule of esorubicin as second-line chemotherapy in ovarian epithelial neoplasms lacks significant activity and is associated with moderate toxicity.

Adult↗

PubMed1989

Conservative surgical management of superficially invasive stage I vulvar carcinoma.

Fifty patients with stage I squamous cell carcinoma of the vulva were treated by means of wide local excision and either unilateral or bilateral superficial inguinal lymphadenectomy. Depth of invasion per se was not an exclusionary criterion; however, 36 of 37 patients for whom depth of invasion could be assessed had tumors invasive to a maximum depth of 5 mm. Factors investigated included recurrences and survival in addition to the early and delayed morbidity associated with this operative approach. Recurrent intraepithelial or minimally invasive cancer was documented in six patients, five of whom were treated successfully by a subsequent wide local excision following initial surgery. Only one patient died of recurrent carcinoma 16 months following surgery. The morbidity with this operation was appreciably less than that generally reported with more extensive operations commonly employed in the management of vulvar cancer and is recommended for management of patients with early invasive disease.

Adult↗

PubMed1989

Conservative management of extramammary Paget's disease of the vulva.

Patients with extramammary Paget's disease of the vulva at the University of California--Irvine Medical Center and the Memorial Medical Center of Long Beach Women's Hospital between 1976 and 1986 were treated with nonradical surgery. These 14 patients were analyzed in a retrospective fashion to determine if conservative management was successful in eradicating the disease process while preserving appearance and sexual function. All patients were treated with nonradical surgery: skinning vulvectomy with split-thickness skin graft (86%), hemivulvectomy (7%), and simple vulvectomy (7%). In all cases intraoperative frozen-section analysis of surgical margins was performed to determine the extent of disease and outline the margins of resection. No patients had Paget's disease associated with an underlying adenocarcinoma. Three patients developed recurrent Paget's disease. Two of these patients recurred at the site of a positive margin and thus represent persistent disease. Only one patient (7%) had recurrent disease in the face of negative margins. The median duration of follow-up was 50 months. All patients are presently free of disease. The rationale for this conservative management is discussed.

Adult↗

PubMed1989

Treatment of advanced and recurrent endometrial carcinoma: correlation of patient response to hormonal and cytotoxic chemotherapy and the response predicted by the subrenal capsule chemosensitivity assay.

The tumors from 38 patients with advanced or recurrent endometrial carcinoma were assayed by the subrenal capsule xenograft assay (SRCA) for sensitivity to hormonal and cytotoxic chemotherapy. Three patients initially received radiation therapy. All other patients received maximal surgical debulking followed by treatment with radiation therapy (5), and/or hormonal (19), and cytotoxic (30) chemotherapy. All the patients who received hormonal chemotherapy had progression of disease. There were 2 complete responses, 5 partial responses, and 26 disease progressions with cytotoxic chemotherapy; and 2 complete responses, 2 partial responses, and 5 disease progressions with radiation therapy. The SRCA was 100% predictive of the response of the tumors to hormonal therapy and had 75% sensitivity, 65% specificity, and 66% efficiency of the response of the tumors to cytotoxic chemotherapy. Laboratory assays of tumor response to radiation therapy were not measured. Those patients with early stage, well-differentiated tumors with no residual disease had the longest survival times. Absence of residual disease after the first surgery was the most important delineator of survival for all categories of patients.

Actuarial Analysis↗

PubMed1989

Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a Gynecologic Oncology Group Study.

Ifosfamide (isophosphamide) and mesna (2-mercaptoethane sodium sulfonate) were administered intravenously at monthly intervals to 46 patients with advanced epithelial ovarian carcinoma refractory to or recurrent after cisplatin-containing combination chemotherapy. Initially, ifosfamide was given as 1.5 g/m2/d x 5 days and mesna as 300 mg/m2 every 4 hours for three doses following ifosfamide, but the initial dose of ifosfamide was reduced to 1.2 g/m2 because of toxicity. Four of the patients initially entered were found to be ineligible: two who had had more than one prior chemotherapy regimen and two who did not have ovarian primaries. One patient received an inadequate trial and four patients had discontinuation of therapy because of toxicity, leaving 41 evaluable for response. Three patients (7.0%) had complete responses and five (13.0%) had partial responses for an overall response rate of 20.0%. Response duration ranged from 2.1 to 20.3 + months with a median of 6.9 + months. Two patients died of renal failure, one of whom had no known renal disease and received 1.5 g/m2/d x 5 days ifosfamide. The second patient received the 1.2 g/m2 dose and was found to have chronic pyelonephritis and pyonephrosis at autopsy. Gynecologic Oncology Group (GOG) grade 3 or 4 granulocytopenia was seen in eight (19.5%), grade 3 or 4 thrombocytopenia in four (9.8%), and grade 3 or 4 neurotoxicity in six (14.6%) of the 41 patients evaluable for toxicity. Ifosfamide/mesna is active in epithelial ovarian cancer. GOG trials in untreated patients are being initiated and toxicity is being evaluated.

Carcinoma↗

PubMed1989

Phase II experience with ifosfamide/mesna in gynecologic malignancies: preliminary report of Gynecologic Oncology Group studies.

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Pseudocholinesterase activity in human cerebrospinal fluid.

Pseudocholinesterase (PCHE) activity and dibucaine numbers (DN) in the cerebrospinal fluid (CSF) and plasma of 10 ASA physical status 1 and 2 patients were measured using a kinetic method. CSF had a mean PCHE activity of 0.018 +/- 0.013 unit/ml with a DN of 59 +/- 4. Whereas, PCHE activity and DN in the plasma were 0.960 +/- 0.12 units/ml and 84 +/- 3, respectively. We also measured PCHE activity and DN in the CSF and plasma of 4 patients in whom there was a recent history of intraventricular bleeding. These patients had a CSF PCHE activity of 0.340 +/- 0.07 units/ml (DN = 78 +/- 3) and a plasma PCHE activity of 0.950 +/- 0.10 units/ml (DN = 82 +/- 2). Our data show that there is a low activity of PCHE in CSF, 1/20-1/100th that of plasma. Our data also show that PCHE activity increased to 1/4 to 1/2 that of plasma in CSF of patients with bleeding into CSF.

Adult↗

PubMed1988

Concordance of combination and single agent chemosensitivity prediction in ovarian carcinoma using the subrenal capsule xenograft assay (SRCA).

The tumors from 62 patients with advanced ovarian adenocarcinoma were assayed by the subrenal capsule xenograft assay (SRCA) for sensitivity to doxorubicin (A), cis-platinum (P), and cyclophosphamide (C), individually and in combination. In some instances only one or two of the individual drugs were assayed; however, the combination, CAP, was always tested. All patients received an optimal surgical debulking (absence of any residual tumor masses greater than or equal to 2 cm) followed by chemotherapy with CAP. Forty-two tumors were predicted to be sensitive to CAP by the SRCA; 51 of 71 (72%) individually tested drugs agreed with this determination. Twenty-one tumors were predicted to be resistant to CAP and 32 of 36 (89%) individually tested drugs agreed with this determination. In this preliminary study, 11 patients had surgically documented partial responses to CAP chemotherapy. All of these patients had tumors which prospectively tested as sensitive to CAP in the SRCA: 13 of 18 (72%) of separately tested drugs were in concordance with this sensitivity. Fourteen patients failed CAP therapy and three of these failures were predicted prospectively by the SRCA: 9 of 9 (100%) of separately tested drugs were in concordance. Thus, there is an overall concordance of 82% (22/27) between the individual components of a combination chemotherapy and the combination therapy itself. It would seem that extrapolations of sensitivity or resistance can be made from the individual components.

Adenocarcinoma↗

PubMed1988

Stepwise detoxification from cocaine. A promising regimen.

Cocaine dependence may not respond to behavioral and self-help treatment because of alterations in neurochemistry, particularly the catecholamine system. Thus, medical detoxification using a stepwise approach and several different therapeutic agents is often needed to assist the patient in achieving a cocaine-free state. An outpatient regimen includes regular clinic attendance, urine testing, education of patient and family, psychological evaluation, and a three- to four-week counseling program. Continued use of medication may be advisable for four to six months. Re-treatment is encouraged if relapse occurs.

Adolescent↗