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Biomedical subjects

S Groshen

Publications and source records attributed to S Groshen.

At least 109 records · Page 6Linked to original sources
PubMed1993

Impact of autologous blood transfusions on patients undergoing radical prostatectomy using hypotensive anesthesia.

We report on a retrospective study consisting of 71 consecutive patients who underwent radical retropublic prostatectomy under controlled hypotensive anesthesia, examining the impact of a preoperative autologous blood collection program on perioperative blood requirements. The population consisted of 34 patients who elected not to use autologous blood (group 1) and 37 patients who underwent radical prostatectomy after storing 1 to 3 units of their own blood (group 2). Median operative time and estimated blood loss were not statistically different. In group 1, 20 homologous blood units were used by 7 patients (21%). In group 2, 37 of 41 units transfused were autologous units and only 3 patients (8%) received homologous blood. However, for every unit of autologous blood deposited preoperatively there was a corresponding decrease in admission blood concentrations and 21 of 37 patients were anemic at hospitalization. In addition, the study suggests that in many patients the anemia produced by preoperative phlebotomy does not resolve preoperatively. In response, the effectiveness of preoperative autologous blood collection is decreased by this preoperative anemia. Although inefficient, we nevertheless conclude that an autologous blood collection program decreases homologous transfusion exposure and efforts should be directed to increase the erythropoietin response to the anemia produced by preoperative phlebotomy. Presently, it is an expensive program that offers only a modest benefit for patients undergoing radical retropubic prostatectomy.

Adenocarcinoma↗
PubMed1993

Radical retropubic prostatectomy and postoperative adjuvant radiation for pathological stage C (PcN0) prostate cancer from 1976 to 1989: intermediate findings.

Between 1976 and 1989, 114 patients undergoing radical retropubic prostatectomy and bilateral pelvic lymph node dissection for prostatic adenocarcinoma were found to have stage PcN0 lesions. Postoperative adjuvant radiation therapy without hormonal treatment was given to 95 of these patients (83%): 26 (27%) with stage C1, 37 (39%) with stage C2 and 32 (34%) with stage C3 disease. The median radiation dose was 45 Gy. given at 180 cGy. daily. Median followup was 4.4 years (range 1.4 to 13.3). The overall 5 and 10-year actuarial rates for the patients were 94% and 70%, respectively. Disease-specific 5 and 10-year actuarial survival rates were 99% and 78%, respectively. At 5 and 10 years the chance of clinical recurrence was estimated as 6% and 13%, respectively, and the chance of recurrence (clinical or indicated by prostate specific antigen levels) was estimated to be 34% and 46%, respectively. Patients with high Gleason scores (8 to 10) and seminal vesicle involvement (stage C3) fared worst. There were 5 patients with clinical distant metastases, 1 with a clinical local recurrence and 1 with both conditions. Detectable elevation of prostate specific antigen without clinically evident recurrence was noted in 25 patients. Radiation therapy was well tolerated with minimal morbidity. Disease-specific survival and survival without clinical recurrence were improved over historical control in patients with stage PcN0 prostate cancer treated by radical prostatectomy alone. These data support a role for adjuvant radiation therapy in stage PcN0 prostate adenocarcinoma following radical prostatectomy.

Adenocarcinoma↗
PubMed1993

Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.

PURPOSE: This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS: Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS: Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma < or = 1.0 cm in diameter or special tumor types < or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION: Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.

Breast Neoplasms↗
PubMed1993

Peripheral blood stem cells harvested during marrow recovery from disease-specific chemotherapy shorten duration of neutropenia in patients undergoing autologous bone marrow transplantation.

A total of 41 patients who underwent autologous bone marrow transplantation without the use of granulocyte-macrophage colony-stimulating factor were retrospectively evaluated to determine whether the infusion of peripheral blood stem cells collected during the period of recovery of bone marrow from previous disease-specific chemotherapy could shorten the time to bone marrow engraftment after transplantation. Of the 41 patients, 24 patients received bone marrow only (group 1), 8 patients received bone marrow plus steady-state peripheral blood stem cells (group 2) and 9 patients received bone marrow plus rebound peripheral blood stem cells collected during the period of recovery from disease-specific chemotherapy (group 3). Infusion of rebound peripheral blood stem cells (group 3) accelerated recovery of white blood cells and neutrophils and resulted in a white blood cell count of > 10(9)/L by day 15 compared with day 25 in group 1 (P < 0.001), and a neutrophil count of > 0.5 x 10(9)/L by day 16 versus day 26 in group 1 (P = 0.0034). Addition of steady-state peripheral blood stem cells (group 2) did not hasten myeloid engraftment, and recovery of platelets was not improved in either group given peripheral blood stem cells. Compared with patients in group 1, patients in group 3 required 7 fewer days of parenteral antibiotics (25 days versus 18 days, respectively; P = 0.0072) and were discharged about 3 weeks earlier than patients in group 1 (day + 41 verus day +21; P = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer.

Seventy-three transitional cell carcinomas of the bladder were analyzed by immunohistochemistry for p53 nuclear accumulation, and the results were compared to mutations detected in the p53 gene by single strand conformational polymorphism analysis (SSCP) and DNA sequence analysis. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections. A highly significant association between the presence of p53 mutations and p53 nuclear reactivity as detected by immunohistochemistry was found (P = 0.0001). Of 32 tumors that demonstrated p53 mutations by SSCP, 27 (84%) showed p53 nuclear reactivity. Of the five cases that did not demonstrate p53 nuclear reactivity, four had mutations in exon 5. However, of 41 tumors with no evidence of p53 mutation by molecular analysis, 12 (29%) showed p53 immunoreactivity. This indicates that immunohistochemical methods may be more sensitive than SSCP in detecting p53 mutations or that discordant cases represent tumors with accumulation of wild type p53 protein, without mutations at the p53 locus. Of the 15 tumors that were found to have mutations at exon 8, 13 demonstrated high-intensity homogeneous p53 nuclear reactivity by immunohistochemistry, and all mutations located at codon 280 demonstrated high-intensity homogeneous immunoreactivity. However, three of three tumors with exon 6 mutations demonstrated low-level p53 immunoreactivity, and four of six tumors with mutations in exon 5 showed no detectable p53 nuclear reactivity. This indicates that the heterogeneity of immunoreactivity observed when analyzing p53 nuclear accumulation may be related to the site of the p53 gene mutation. Information on tumor grade, stage, lymph node status, disease-free interval, and overall survival were available in 54 patients who had undergone cystectomy. A significant association was observed between p53 alterations (detected by immunohistochemistry and SSCP) and histological tumor grade (P = 0.003) and stage (P = 0.01). We conclude that the immunohistochemical detection of p53 nuclear accumulation in formalin-fixed, paraffin-embedded tissue is highly associated with mutations in the p53 gene; this association has now been demonstrated in a large number of tumors. The heterogeneity of p53 nuclear reactivity seems to be related to the site of mutation in the p53 gene. A small proportion of tumors with a p53 gene mutation do not demonstrate immunohistochemically detectable p53 nuclear accumulation. Furthermore, a small but substantial proportion of tumors demonstrate p53 nuclear reactivity but do not show detectable mutations in the p53 gene by SSCP. Finally, both grade and stage of bladder cancer are related to p53 alterations, detected by immunohistochemistry or molecular methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Transitional Cell↗
PubMed1992

Association of HLA phenotype with response to active specific immunotherapy of melanoma.

PURPOSE: Only a proportion of patients with disseminated melanoma who were immunized successfully with a therapeutic melanoma vaccine (theraccine) had a major clinical response. We investigated whether there was a correlation between their HLA phenotypes and the likelihood of a clinical response. PATIENTS AND METHODS: Seventy patients with disseminated melanoma who were treated with melanoma theraccine were HLA-typed serologically. The two melanoma cell lines used in the theraccine also were typed by serology and cDNA probes (for class II). Results were analyzed to see whether any alleles were present or absent in responders consistently. RESULTS: The HLA class I alleles A2 (and the cross-reacting A28), B12 (and its split B44 and B45), and C3 were found to be associated with clinical remission. The effects of these alleles on response were apparent when two or more of the alleles were analyzed together. There was a 38% response rate in those 24 patients with two or three of the alleles compared with 20% in the group as a whole. CONCLUSIONS: These data support two distinct possibilities between which we cannot yet distinguish. Responses may be more likely when there is a close match between the HLA molecules in the theraccine and the patients' own molecules. Alternatively, certain types of HLA class I molecules present in the patients may facilitate rejection of autochthonous melanomas by efficiently presenting melanoma-associated antigens to cytotoxic T cells.

Adult↗
PubMed1992

Survival and prognostic factors in node-negative breast cancer: results of long-term follow-up studies.

Seven hundred sixty-seven patients treated at the Memorial Sloan-Kettering Cancer Center from 1964 through 1970 by mastectomy and axillary dissection have now been followed for a median of 18 years. This unusual database consists of a consecutive series of women cared for by physicians specialized in the treatment of breast cancer in one institution. The data suggest that patients with T1, N0, M0 tumors of 1 cm or less may be "cured" by mastectomy and axillary dissection, the estimated proportion of "cured" patients being 89%. The data also suggest that node-negative patients can be placed in categories of risk for recurrence on the basis of primary tumor size.

Breast Neoplasms↗
PubMed1992

Interleukin-2 (IL-2) and IL-2-activated bone marrow in transplantation: evaluation from a clinical perspective.

Incubation of bone marrow (BM) with interleukin-2 (IL-2) in vitro results in generation of killer cells providing a tool for enhancing the graft-versus-tumor effect in transplantation. We have evaluated the influence of IL-2 on the progenitor cell activity (PCA), homing pattern of BM and hemopoiesis in a syngeneic bone marrow transplantation (BMT) model in mice. The PCA index and homing pattern of BM activated with IL-2 in vitro for 24 h (ABM) were similar to those of fresh bone marrow (FBM). In vitro culture of BM for more than 1 day resulted in progressive decline in its PCA index; this was not related to the presence or absence of IL-2 in the culture medium. Toxicity of IL-2 was related to the dose and not the time of institution of IL-2 therapy after BMT. Maximum tolerated dose of IL-2 instituted immediately after BMT was 10 times higher than the dose in a non-BMT setting. The pattern of marrow reconstitution following BMT with ABM was comparable to that with FBM. This study shows that BMT with BM activated with IL-2 for 24 h results in normal hemopoiesis, and IL-2 therapy instituted immediately after BMT with ABM does not cause additional toxicity.

Animals↗
PubMed1991

Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin.

Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy.

Adolescent↗
PubMed1991

Induction of graft versus leukemia effect in bone marrow transplantation: dosage and time schedule dependency of interleukin 2 therapy.

The present work is a continuation of our studies to improve the graft versus leukemia (GVL) effect in autologous bone marrow transplantation. We have recently shown that the GVL effect of bone marrow transplantation (BMT) with interleukin 2 (IL-2)-activated bone marrow (ABM) followed by IL-2 therapy immediately after BMT is superior to the GVL effect of BMT with fresh, syngeneic bone marrow, with or without IL-2 therapy, in mice with acute myeloid leukemia. The present studies show that institution of IL-2 treatment 1, 2, or 3 weeks after BMT with ABM resulted in shortening of survival and fall in cure rate as compared to IL-2 therapy instituted immediately after BMT with ABM. Increasing the dose of IL-2 did not improve results. However, reducing the frequency of IL-2 administration to once a day instead of twice a day affected the results adversely. Commencing IL-2 therapy 1, 2, or 3 weeks after BMT with fresh, syngeneic bone marrow did not improve the GVL effect as compared to IL-2 therapy started immediately after BMT with fresh, syngeneic bone marrow. Cryopreserved bone marrow was effectively activated with IL-2 and used successfully for BMT after thawing. The animals cured of leukemia by BMT with ABM and and IL-2 therapy were not resistant to leukemia and died when reinfused with leukemic cells. Our findings suggest that for optimum GVL effect, activation of bone marrow is necessary and IL-2 therapy should be started immediately after BMT with ABM.

Acute Disease↗
PubMed1991

Intravenous immunoglobulin in the treatment of human immunodeficiency virus-related thrombocytopenia.

Fourteen patients with sexually transmitted human immunodeficiency virus (HIV)-related immune thrombocytopenia were treated with intravenous gammaglobulin (IVIG). The patients were treated with a uniform program consisting of 1 g/kg of IVIG on day 1 and day 2, followed by 1 g/kg on day 15. Most patients had pretreatment bleeding symptoms, which included petechiae, spontaneous and traumatic ecchymoses, gum bleeding, and epistaxis. Median baseline platelet count was 17,000/mm3 (range 3-61,000/mm3). After the infusion of the IGIV, all patients had a resolution of their bleeding by day 8. The median maximum platelet count achieved with the IGIV was 220,000/mm3 (range 76-426,000/mm3). No patient achieved either a sustained complete or partial remission after the conclusion of the IVIG therapy. Toxicities were minimal with the majority being headache and nausea. In conclusion, patients with sexually transmitted HIV infection and immune thrombocytopenia respond favorably to IVIG. This treatment should be considered as first-line therapy for patients with HIV-related immune thrombocytopenia who require immediate but temporary increase in their platelet count, attributable to symptoms or signs of clinical bleeding or because of the need for an invasive procedure.

Adult↗
PubMed1991

Phase II trial of carboplatin or iproplatin in cervical cancer.

From July 1984 to November 1987, 89 patients with recurrent measurable squamous-cell cancer of the uterine cervix were randomized in a single institution to receive treatment with either carboplatin (CBDCA) or iproplatin (CHIP). Objective response rates were similar: 2 complete regressions (CRs) and 10 partial regressions (PRs) were recorded both in the 46 evaluable patients treated with CBDCA (response rate, 26.1%; 95% confidence interval, 15-41%) and in the 40 evaluable patients treated with CHIP (response rate, 30%; 95% confidence interval, 17-47%). The median duration of response was 5.5 months for CBDCA and 6 months for CHIP; the median survival was 7.5 and 7.6 months, respectively. Both drugs were given in an outpatient setting and myelosuppression (thrombocytopenia) was the predominant toxicity. Analysis of all toxic events yielded additional interesting observations: the occurrence of moderate to severe platelet nadirs beyond cycle 1 was confined to CHIP, a higher incidence of gastrointestinal toxicity during treatment with CHIP, and five moderate to severe complaints of asthenia (recorded as neurologic events) during CHIP therapy versus only one during treatment with CBDCA. Because of its antitumor activity and its toxicologic advantage, a future role for CBDCA in the treatment of cervical cancer appears likely.

Antineoplastic Agents↗
PubMed1991

The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.

We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study.

In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients.

Adult↗
PubMed1991

Serum erythropoietin titers in patients with human immunodeficiency virus (HIV) infection and anemia.

The pathophysiology of anemia in patients with human immunodeficiency virus (HIV) infection is multifactorial. In order to determine the role of erythropoietin (EPO) response as a cause of the anemia, serum levels were determined by direct radioimmunoassay in 110 symptomatic patients with various stages of HIV infection. Symptomatic patients (ARC and AIDS) not receiving zidovudine (ZDV) therapy demonstrated a strong inverse relationship between serum EPO and hemoglobin levels (p = 0.01 and p less than 0.001, respectively). Patients with AIDS who were anemic while receiving ZDV demonstrated serum EPO levels that ranged from normal to markedly elevated (9-3,390 mU/ml). The diversity of serum EPO levels in patients with HIV infection and anemia suggests that the etiology of anemia in these patients and their potential response to recombinant human EPO may not be uniform.

AIDS-Related Complex↗