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S C Rubin

Publications and source records attributed to S C Rubin.

At least 73 records · Page 4Linked to original sources
PubMed1994

Management of early-stage epithelial ovarian cancer.

Because ovarian cancer is asymptomatic until the late stages of the disease and because accurate methods of early detection are lacking, only about 40% of these cancers present in stages I and II. As a result, ovarian carcinoma remains the leading cause of death from gynecologic malignancy in the United States. However, proper management of early cases may lead to a good prognosis for long-term survival and, in some cases, may even permit preservation of reproductive capacity. The appropriate management of these early cases includes meticulous and thorough staging at the time of the initial surgery. In women who do not desire further reproduction, total abdominal hysterectomy and bilateral salpingo-oophorectomy should be carried out. In those who eagerly wish to maintain reproductive potential, the uterus and contralateral ovary may be preserved, providing certain criteria have been met. Patients with stage Ia or Ib grade 1 disease can be followed-up without further therapy after definitive surgery; those with Ic or grade 3 tumors should receive adjuvant therapy. Patients with stage I epithelial ovarian cancer who are without evidence of disease after comprehensive staging surgery and primary adjuvant chemotherapy do not require second-look laparotomy. In the future, laparoscopy will play an increasingly important role in the diagnosis and management of early-stage epithelial ovarian cancer.

Combined Modality Therapy↗
PubMed1994

Distribution of intraperitoneal chemotherapy into the pleural cavity.

BACKGROUND: Intraperitoneal chemotherapy is an established treatment for abdominal and pelvic malignancies. Several catheter-related complications have been reported. We report a case of abnormal distribution of intraperitoneal chemotherapy into the pleural cavity. CASE: A patient receiving intraperitoneal cisplatin developed shortness of breath. A pleural effusion was diagnosed and was evacuated by thoracentesis. Abnormal distribution of instilled fluid was responsible for her distress. CONCLUSION: Communications exist between the peritoneal and pleural cavities. The use of intraperitoneal chemotherapy or radioactive material may lead to respiratory complications if abnormal distribution occurs.

Antineoplastic Agents↗
PubMed1993

Monoclonal antibodies in the management of ovarian cancer. A clinical perspective.

Despite recent advances in the conventional management of ovarian cancer, this disease remains the leading cause of death among the gynecologic malignancies, killing more American women each year than all other gynecologic cancers combined. As a tumor arising from a nonessential organ that remains primarily confined to the peritoneal cavity, ovarian cancer makes an attractive target for monoclonal antibodies (MoAb). Several MoAb have been developed that have actual or potential clinical use in the management of ovarian cancer. Serum assays using a MoAb against an ovarian cancer-associated antigen (CA 125) are currently in routine clinical use for monitoring the course of disease in women with known ovarian cancer. Such assays may play a role in multitechnique screening programs. Radiolabeled antibodies are under study for use in external imaging or intraoperative detection of ovarian cancer. Isotope-labeled antibodies also are being evaluated in the treatment of ovarian cancer as are antibodies coupled to drugs or biologic toxins. Some antibodies may have direct antitumor effects through binding to biologically active receptors or through immune effector functions. The use of antibody fragments, chimeric antibodies, human antibodies, and genetically engineered antibodies is under active investigation. MoAb have important potential for improving the diagnosis, monitoring of response to therapy, and treatment of ovarian cancer.

Antibodies, Monoclonal↗
PubMed1993

High-resolution positron emission tomography of human ovarian cancer in nude rats using 124I-labeled monoclonal antibodies.

PET has inherently high resolution and excellent contrast imaging and accurately measures radioactivity concentrations in vivo. When combined with specific immunological targeting it might provide a highly specific and sensitive radioimmunoscintigraphic tool. To investigate this we injected 124I-labeled MAb MX35 or MAb MH99 monoclonal antibodies (doses 200-400 mu Ci) intravenously into nude rats bearing subcutaneous human ovarian cancer xenografts (SK-OV-7 and SK-OV-3 cell lines). A melanoma cell line (SK-MEL-30) was used as a control tumor. These murine monoclonal antibodies react with cell-surface antigens expressed by most ovarian cancer cells, including the ovarian cell line used. Imaging was performed at 1-6 days using a high-resolution positron emission tomograph (PCR-I) with a spatial resolution of 4.5 mm. The slice thicknesses were 0.5 and 1.0 cm. Forty to seventy thousand coincident pulses were obtained per frame. The PET results were compared with those of autopsy and histology. Samples of blood, tumor, and normal tissues were obtained at various time points. PET calculation of isotope uptake ratios demonstrated specific localization of the antibodies in tumor, with ratios of tumor to normal tissue uptake as high as 6:1. Subcutaneous ovarian cancer nodules as small as 7 mm were identified with PET imaging. The results corresponded well with tissue sampling. Our findings suggest that PET imaging of tumors with 124I-labeled monoclonal antibodies may be useful in human diagnostic and therapeutic applications in ovarian cancer as well as other diseases.

Animals↗
PubMed1993

Comparison of antigen expression on fresh and cultured ascites cells and on solid tumors of patients with epithelial ovarian cancer.

The antigenic phenotype of malignant cells from ascites of patients with epithelial ovarian cancers was examined and compared to that of their primary and metastatic sites. Cell-surface antigens on frozen sections of primary and metastatic tumors and frozen cell pellets from ascites were analyzed with a panel of murine monoclonal antibodies using the indirect immunoperoxidase method. In addition, ascites cells cultured with and without autologous cell-free ascitic fluid were evaluated by immunofluorescence. The pattern of antigen expression detected on fresh and cultured ascitic epithelial cells was shown to be identical to the expression in autologous solid tumor tissues. When placed in culture, malignant epithelial cells generally persisted for a minimum of one, but no more than five, passages. Addition of autologous ascitic fluid to cultures of ascites cells did not alter the phenotype of the epithelial tumor cell population and did not enhance the growth of these cells. From one culture of ascites cells a permanent malignant epithelial ovarian cancer cell line (designated SK-OV-8) was established. The demonstration that epithelial tumor cells found in ascites of patients with epithelial ovarian cancer have the identical antigenic phenotype as their solid tumor counterpart, at least for the panel of antigens studied, may be useful in planning imaging and therapeutic trials with monoclonal antibodies.

Adult↗
PubMed1993

Early invasive carcinoma of the cervix.

Ninety-two patients with early invasive carcinoma of the cervix (5 mm or less) treated between July 1977 and June 1990 are reviewed. Eighty patients had squamous cell carcinomas and 12 had adenocarcinomas. The diagnosis was established by conization in 77 of 92 (83.6%) patients. Thirty-six patients (39%) had a depth of stromal invasion of 1 mm or less, 32 patients (35%) between 1 and 3 mm, and 24 patients (26%) between 3 and 5 mm. Forty-four patients were treated with radical hysterectomy and bilateral pelvic lymphadenectomy (RHND). None of these patients had positive lymph nodes. Thirty-three patients were treated with conservative hysterectomy (CH), 4 with modified radical hysterectomy, and 2 with trachelectomy. Six patients received radiotherapy. Three patients were treated by conization only. Two patients developed in situ carcinoma (CIS) of the vagina 12 months after CH for lesions on conization that invaded less than 1 mm. In both cases the cone margins were positive, and in one a microscopic focus of CIS of the cervix was present at the resection margin of the hysterectomy specimen. A third patient developed an invasive lesion of the vagina 25 months after CH for a lesion that invaded 2.5 mm in a cone whose margins were not specified, but the hysterectomy margins were clear. All 3 patients were successfully retreated. The remaining patients are free of disease for a median follow-up of 51 months. The results of the study indicate that CH is adequate therapy for patients in whom the diagnosis of early invasive cervical cancer is established by conization with free margins and the depth of invasion is 3 mm or less. Although only 1 of 24 patients with invasion > 3 mm but < or = 5 mm had a CH, pathologic findings in 18 patients who had RHND suggest that CH would have been sufficient for these since there were no instances of spread to nodes or parametrium.

Adenocarcinoma↗
PubMed1993

Biodistribution and intraoperative evaluation of radiolabeled monoclonal antibody MX35 in patients with epithelial ovarian cancer.

Murine monoclonal antibody (MAb) MX 35 shows strong homogeneous reactivity with more than 90% of epithelial ovarian cancers. Twenty-five patients with advanced ovarian cancer were entered into a clinical trial using 125I- or 131I-labeled MX 35 in doses of 2, 10, or 20 mg administered by intravenous (i.v.) or intraperitoneal injection. All patients underwent laparotomy at 7 to 20 days following MAb injection to assess tumor distribution, obtain biopsies of tumor and normal tissue, and evaluate the use of an intraoperative hand-held gamma-detecting device. Following i.v. injection, serum Mab half-life was 36 hr. Tumor biopsies obtained at surgery showed MAb accumulation of from 6.7 x 10(-3) to 4.0 x 10(-5)% injected dose/g of tissue. There was no correlation between absolute MAb accumulation in tumor and MAb dose administered. Regression analysis showed a correlation between MAb accumulation and the interval between MAb injection and surgery (P = 0.008). Specific localization of MAb in tumor was demonstrated by tumor:normal tissue ratios ranging from 2.3:1 to 34:1 (mean, 10.18:1). The tumor:normal tissue ratios were not significantly related to MAb dose, the level of immunohistochemical antigen expression, or the interval between MAb injection and surgery. Due to the relatively long serum half-life, mean tumor:serum ratios were only 1.53 following IV injection. This ratio did not correlate with MAb dose, days from injection, or antigen expression. There was an excellent correlation (P = 0.001) between MAb uptake, as measured by the intraoperative hand-held gamma counter, and direct gamma counting of excised tissues. MAb MX 35 localizes well to tumor in selected patients with ovarian cancer, and MAb uptake can be reliably quantitated in vivo with the hand-held intraoperative gamma counter.

Antibodies, Monoclonal↗
PubMed1993

Secondary cytoreduction--thoughts on the "pro" side.

The advantages of secondary cytoreduction in the treatment of women with ovarian carcinoma include improved survival and potential improvement in quality of life. To summarize the literature on this topic, patients can be grouped into four distinct clinical settings. Debulking at the time of second-look laparotomy, interval debulking following three to four courses of chemotherapy, and debulking at the time of recurrence following a disease-free interval are scenarios which offer clinical advantages to women with ovarian carcinoma. However, there is little or no evidence to support a survival or quality of life advantage for women who undergo secondary debulking despite progressive disease on primary platin-based chemotherapy. Data on the pro side of the secondary tumor debulking debate are summarized here.

Female↗
PubMed1993

Limited-field radiotherapy as salvage treatment of localized persistent or recurrent epithelial ovarian cancer.

Thirty-five patients with persistent or recurrent epithelial ovarian cancer were treated with salvage pelvic or para-aortic radiotherapy for disease limited to the pelvis (29), para-aortic retroperitoneum (5), or vaginal cuff (1). Prior therapy included a median of 3 chemotherapeutic drugs (range, 1-7) over a median of 12 cycles (range, 5-39); 12 patients had received intraperitoneal chemotherapy. The median number of prior laparotomies was 3 (range, 2-5). Including pelvic boosts, the median dose delivered to the treatment field was 4600 cGy (range 4000-7000); 2 patients received additional treatment with a permanent 125I implant. All patients completed therapy, although 5 (14%) with grade 3 toxicity required a treatment break. Late bowel complications unrelated to recurrence occurred in 3 patients (9%). Median actuarial and progression-free survivals for all patients from start of radiotherapy were 40 and 14 months, respectively. At least 16 of 26 (62%) recurrences involved the treatment field. Multiple prognostic factors were evaluated in terms of recurrence, survival, and acute and chronic complications, but no significant prognosticators were detected. These findings indicate that limited-field salvage radiotherapy has an acceptable complication rate and may prolong the symptom-free survival interval in selected patients.

Adult↗
PubMed1993

Isoflurane versus fentanyl: hemodynamic effects in cancer patients treated with anthracyclines.

Cancer patients treated with anthracycline derivatives are at risk for perioperative cardiovascular decompensation. The authors studied hemodynamic performance before, during, and after laparotomy in 14 anthracycline-treated patients with ovarian carcinoma. General anesthesia was maintained with 70% N2O in O2, and patients were randomized to receive supplementation with either isoflurane, 0.59% end-tidal +/- 0.04 (mean +/- SE), or fentanyl, 2.67 micrograms/kg +/- 0.49 as a loading dose, and a total dose of 7.16 micrograms/kg +/- 0.71. The degree of hemodynamic stability relative to the baseline was assessed. There was no obvious superiority of either technique prior to the skin incision. However, during and immediately after surgery, a clearer tendency for isoflurane-N2O to result in better hemodynamic stability was found. Isoflurane-N2O demonstrated significantly smaller change scores in systemic vascular resistance (SVR) and cardiac index (CI). At the start of surgery, the isoflurane-N2O change in SVR was 228.08 dyne.sec.cm-5 compared to 479.58 for the fentanyl patients, (P = 0.002); at the end of surgery the corresponding means were -12.09 and 703.14 dyne.sec.cm-5, respectively, (P = 0.002). Isoflurane-N2O was associated with significantly greater CI stability in the early postoperative period: the isoflurane-N2O mean change was -0.081 L/min/m2, versus -0.993 for the fentanyl-N2O patients, (P = 0.005). The authors conclude that anthracycline-treated patients who do not have overt evidence of cardiomyopathy can be safely anesthetized with either anesthetic technique. However, during surgery and in the early postoperative period, an isoflurane-N2O technique appears to offer better hemodynamic stability.

Acid-Base Imbalance↗
PubMed1993

Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis.

OBJECTIVE: We tested the hypothesis that there is prognostic significance to the level of expression of the protooncogene HER-2/neu in advanced ovarian cancer, as prior studies have suggested. STUDY DESIGN: We determined expression of HER-2/neu by immunohistochemistry, with monoclonal antibody 9G6 and the indirect immunoperoxidase technique, on frozen tumor specimens from 105 patients with stage III or IV epithelial ovarian cancer. All patients were treated at Memorial Sloan-Kettering Cancer Center, and no patient was lost to follow-up. Median follow-up among surviving patients is 34 months. HER-2/neu expression was scored as negative, weak, 1+, 2+, or 3+. The staining pattern of normal ovarian epithelium was scored negative to 1+. Multivariate analysis was performed to evaluate the prognostic significance of HER-2/neu expression. RESULTS: Twenty-five of the 105 patients (24%) showed strong membrane staining (3+); the other tumor specimens showed weaker membrane staining or no immunoreactivity. There was no correlation of HER-2/neu expression with any of a variety of clinical factors, including stage, grade, cell type, and residual tumor. No significant survival difference was found between patients with levels of staining intensity similar to those of normal ovarian epithelium and those with increased expression (3+). Median survival times were 36 and 27 months, respectively, for the two groups (95% confidence intervals 29 to 45 and 18 to 39 months). Multivariate analysis of possible prognostic factors showed that HER-2/neu overexpression conferred a marginal worsening of survival (p = 0.09) for the subgroup of patients in whom a negative surgical reassessment was not achieved after chemotherapy. CONCLUSION: HER-2/neu expression does not appear to be an important prognostic factor in patients with advanced epithelial ovarian cancer.

Adult↗
PubMed1993

High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer.

Non-haematopoietic malignancies are commonly associated with thrombocytosis. The aetiology of tumour-associated thrombocytosis is still unclear but may be related to tumour-derived thrombopoietin-like factors. Epithelial ovarian tumour cells have been shown to release IL-6 in vitro and high IL-6 levels have been identified in ascites of patients with ovarian cancer. Since IL-6 is a potent stimulator of megakaryocytopoiesis we examined IL-6 production at the tumour site and its relationship to serum IL-6 levels and circulating platelet counts in patients with ovarian cancer. Forty patients undergoing exploratory laparotomy for epithelial ovarian cancer [stage I+II: 6 (15%); stage III: 25 (62.5%); stage IV: 9 (22.5%)] and 24 women with benign ovarian conditions were evaluated. Sera were available from 39 cases with ovarian cancer and from 19 cases with benign ovarian tumours. Ascites was obtained from 35 patients with ovarian cancer. IL-6 activity in serum and ascitic fluid was determined by the standard B9 proliferation assay (detection level: 1 pg/ml). IL-6 bioactivity was detectable in 22 (56%) sera from patients with ovarian cancer, but in only five (26%) of the serum samples obtained from benign cases (P < 0.001). Serum IL-6 levels in patients with ovarian cancer were significantly higher (median 3 pg/ml; range < 1 to 1221 pg/ml) than in patients with benign ovarian conditions (median 0 pg/ml; range < 1 to 4 pg/ml) (P < 0.001). However, much higher concentrations of IL-6 were measured in malignant ascites specimens (median 22,100 pg/ml; range < 1 to 182,600 pg/ml). IL-6 bioactivity in serum and ascites samples was completely inhibited by a neutralizing goat anti-human IL-6 antiserum. Thrombocytosis (platelet counts > 400 x 10(9)/l) occurred in 25 (62.5%) of the 40 patients with ovarian cancer, but in only two (8%) of the 24 cases with benign ovarian tumours. In eight (20%) cases with malignant disease platelet counts ranged between 600 x 10(9)/l and 1060 x 10(9)/l. IL-6 bioactivity in ascitic fluid correlated significantly with circulating platelet counts (r = 0.5916; P < 0.001). Maximum IL-6 bioactivity in ascites and highest platelet counts occurred in patients with undifferentiated ovarian adenocarcinoma or advanced disease. In conclusion, these observations strongly suggest a role for IL-6 in the development of tumour-associated thrombocytosis.

Adult↗
PubMed1993

Second-look laparotomy in carcinoma of the fallopian tube.

OBJECTIVE: To evaluate the role of second-look laparotomy following platinum-based chemotherapy in patients with fallopian tube cancer. METHODS: We conducted a retrospective chart review of 35 patients with tubal cancer who underwent a second-look laparotomy following cytoreductive surgery and platinum-based combination chemotherapy. RESULTS: The distribution by stage was as follows: I, three (9%); II, five (14%); III, 24 (69%); and IV, two (6%); one patient was inadequately staged. The tumor grade was recorded in 31 patients, and 80% of these were grade 2 or 3. Twenty-one of the 35 patients (60%) were found to be free of disease at second-look operation. Neither stage nor grade were predictive of findings at the second-look procedure, although none of the five patients with stage I disease and/or grade 1 tumor had disease found at second-look surgery. The absence of gross residual disease following primary surgery was the strongest predictor of disease-free status at second-look laparotomy (P < .01). With a mean follow-up of 50 months among the survivors, only four (19%) of the patients with no evidence of tumor at reexploration have had a recurrence. CONCLUSION: Second-look laparotomy provides useful prognostic information in patients with tubal cancer; approximately 80% of patients who have a negative second-look following platinum-based chemotherapy will remain disease-free.

Actuarial Analysis↗
PubMed1993

Relationship between saliva and serum CA 125 in women with and without epithelial ovarian cancer.

OBJECTIVE: To determine the distribution of saliva CA 125 levels in women with and without ovarian cancer, and to determine whether there is a correlation between saliva and serum CA 125 levels in either group. METHODS: CA 125 levels were measured by immunoradiometric assay in the serum and saliva of 50 women with epithelial ovarian cancer known to have elevated serum CA 125 levels (above 35 U/mL) and in 50 women seen for benign gynecologic conditions. RESULTS: Serum and saliva CA 125 values followed a log-normal distribution in both groups. The medians for serum and saliva CA 125 levels in cancer patients were 578 and 1379 U/mL, respectively. In the benign group, the median CA 125 value was 11 U/mL in serum and 994 U/mL in saliva. The correlation between saliva and serum CA 125 levels was not statistically significant in either the cancer (r = 0.003) or the benign group (r = 0.025). CONCLUSION: There is no relationship between saliva and serum CA 125 levels in women with either epithelial ovarian cancer or benign gynecologic conditions.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Second-look laparotomy in stage I ovarian cancer following comprehensive surgical staging.

OBJECTIVE: To evaluate the role of second-look laparotomy in patients with comprehensively staged stage I epithelial ovarian cancer. METHODS: We reviewed the medical records and obtained long-term follow-up on 54 stage I patients who had second-look laparotomies following complete surgical staging and chemotherapy. RESULTS: The distribution by stage was as follows: stage IA 18 (33%), stage IB two (4%), and stage IC 34 (63%). Eighteen patients (33%) had endometrioid tumors, 12 (22%) clear cell, 13 (24%) mucinous, eight (15%) serous, and three (6%) undifferentiated. Forty-four patients (82%) had grade 2 or 3 tumors. Thirty-eight (70%) were treated with platinum-based regimens and 16 (30%) received non-platinum regimens. At second-look laparotomy, tumor was identified in three women (5.5%). Stage, cell type, and grade did not predict the second-look laparotomy result, although no patient with a grade 1 tumor had a positive second-look laparotomy. With a mean follow-up of 48 months from second-look laparotomy, 11 women (22%) have had recurrences following negative second looks. Tumor grade was a strong predictor of recurrence following negative second-look laparotomy (P < .0001), with the risk of recurrence being 0% for grades 1 and 2 and 52% for grade 3. Substage, cell type, and chemotherapy type and duration did not predict recurrence. CONCLUSIONS: The likelihood of a positive second-look laparotomy is about 5% in well-staged stage I ovarian cancer. Patients with stage I, grade 3 tumors have a risk of recurrence of approximately 50% following negative second-look laparotomy.

Adult↗
PubMed1993

Platinum-based chemotherapy of high-risk stage I epithelial ovarian cancer following comprehensive surgical staging.

OBJECTIVE: To determine the long-term outcome in patients with high-risk stage I epithelial ovarian cancer treated with adjuvant platinum-based chemotherapy following comprehensive surgical staging. METHODS: We conducted a retrospective review of 62 patients with stage IA and IB (grades 2 or 3) and stage IC (all grades) epithelial ovarian cancer treated with platinum-based chemotherapy following comprehensive surgical staging. Clinicopathologic correlations were performed using disease-free survival as the end point. RESULTS: The mean patient age was 47 years. The distribution by stage was IA in 19 (31%), IB in four (6%), and IC in 39 (63%). Eighty percent of the patients had grade 2 or 3 tumors. The distribution by cell type was as follows: clear-cell 22 (35%), endometrioid 15 (24%), mucinous 11 (18%), serous eight (13%), and undifferentiated six (10%). The patients underwent an average of six cycles of platinum-based therapy. With a median follow-up of 40 months among survivors, 15 patients (24%) have relapsed, at a median interval of 22 months from diagnosis. Relapses occurred primarily in the peritoneal cavity and retroperitoneal lymph nodes. No patient has been rendered free of disease after relapse. Patients with grade 3 tumors had an increased risk of relapse as compared to those with grade 1 or 2 tumors (46 versus 8%; P = .002). Patients with clear-cell tumors had a higher risk of relapse than those with other cell types (41 versus 15%; P = .05). There was no statistically significant relationship between risk of recurrence and substage. None of 11 patients with stage IA, grade 2 disease had recurrence. Actuarial 5-year disease-free survival for the entire group of 62 patients was 73%. CONCLUSION: Platinum-based chemotherapy for high-risk stage I ovarian cancer does not appear to improve survival over that previously reported with non-platinum regimens.

Adolescent↗
PubMed1992

Endoluminal ultrasound staging of cervical cancer.

Clinical staging of cervical cancer is incorrect in approximately one-third of patients who undergo surgical staging. Pretreatment laparotomy is the staging method of choice for patients with cervical cancer at Memorial Sloan-Kettering Cancer Center. We performed transabdominal, transvaginal, and transrectal ultrasound staging on 12 patients. In 5 of 6 patients undergoing radical hysterectomy, clinical ultrasound and surgical staging were consistent. One patient could not tolerate rectal probe sonography. Ultrasound staging was correct in 1 of 6 patients with advanced disease. A new technique of cervical imaging with transrectal ultrasound and vaginal douche is described. We believe it unlikely that ultrasound will improve the accuracy of clinical staging in patients with cervical cancer.

Female↗