PubMed Health⌕ Search

Biomedical subjects

S C Rubin

Publications and source records attributed to S C Rubin.

At least 109 records · Page 6Linked to original sources

Paget's disease of the vulva.

Thirty-six patients with Paget's disease of the vulva were reviewed. Median age of the patients at diagnosis was 64 years (range 41-84 years). Five patients (14%) had an associated invasive adenocarcinoma of the vulva at the time of diagnosis. Of 31 patients with superficial noninvasive Paget's disease, 28 were available for follow-up. Treatment of patients with superficial Paget's disease was surgical and based on the extent of disease. Procedures performed included total vulvectomy (25), wide local excision (4), and skinning vulvectomy with skin graft (1). The median follow-up was 108 months (range 6-266 months). Twenty-two of twenty-eight patients remained free of disease. Six patients have required multiple procedures for recurrent superficial Paget's disease. Treatment of Paget's disease of the vulva is surgical. Radical surgery is the preferred treatment of patients with an associated invasive adenocarcinoma; three of five patients with an invasive adenocarcinoma were long-term survivors. Patients with superficial Paget's disease of the vulva should be treated by local excision utilizing frozen-section margin evaluation as a guide to extent of excision. Only one patient with an initial diagnosis of superficial Paget's disease of the vulva developed invasive adenocarcinoma.

Adenocarcinoma↗

Expression of P-glycoprotein in epithelial ovarian cancer: evaluation as a marker of multidrug resistance.

The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein that mediates active cellular efflux of certain chemotherapeutic agents. P-Glycoprotein expression was evaluated in 98 frozen tumor specimens from 57 patients with epithelial ovarian cancer by the indirect immunoperoxidase technique with monoclonal antibodies C219 and JSB-1 used for detection. Tumor specimens were further characterized antigenically with a panel of monoclonal antibodies representing a variety of epithelial cell antigens. Included were 57 specimens from 33 previously untreated patients; 11 specimens were also available from eight patients in this group after chemotherapy. An additional 30 specimens were studied from 24 other patients after chemotherapy. In only four of the 57 patients with ovarian cancer (7%) did one or more of the specimens express P-glycoprotein. Two of these patients had tumors that were considered clinically drug resistant. No increase in P-glycoprotein expression was noted after exposure to chemotherapy, including the eight individuals for whom specimens were available both before and after treatment. Although drug resistance is a major problem in treatment of ovarian cancer, resistance to the drugs most active against these tumors probably occurs through a mechanism other than expression of the MDR1 gene product.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Anticipatory immune suppression and nausea in women receiving cyclic chemotherapy for ovarian cancer.

Nausea and immune function were assessed in 20 cancer patients in the hospital prior to chemotherapy and compared with assessments conducted at home. Proliferative responses to T-cell mitogens were lower for cells isolated from hospital blood samples than for home samples obtained several days earlier. Patients also experienced increased nausea in the hospital. Hierarchical multiple regression analyses indicated that decreased immune function in the hospital was not related to increased anxiety. The observed anticipatory immune suppression is consistent with the hypothesis that chemotherapy patients may develop conditioned immune suppression as well as conditioned nausea after repeated pairings of hospital stimuli with the emetic and immunosuppressive effects of chemotherapy.

Adult↗

Immunohistochemical localization of P-glycoprotein in adult human ovary and female genital tract of patients with benign gynecological conditions.

The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein, which mediates active cellular efflux of certain cytotoxic agents. Two mouse monoclonal antibodies (MAb), C219 and JSB-1, were used to identify P-glycoprotein in frozen tissue from the female genital tract of 14 women with benign gynecological conditions; multiple samples from several sites in the genital tract were available from seven patients. P-glycoprotein was detected in the ovarian surface epithelium in four of 14 cases, in the Fallopian tube in three of five cases, in occasional epithelial cells of the endometrial glands in two of five cases, in some endocervical glandular epithelium in three of five cases, in ectocervical squamous epithelium in one of the two cases, and in luteinized cells of the eight cases in which a corpus luteum was present in the specimen. Positive staining with these two MAb was also observed in some endothelial cells in the cortex of the ovary and in the stromal tissue of the myometrium, endometrium, and endocervix. These studies suggest that, if epithelial ovarian cancers are derived from the surface epithelial cells of the ovary, a small proportion of the cancers might be expected to retain the phenotype found in non-cancerous cells and to express P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Palliative surgery for intestinal obstruction in advanced ovarian cancer.

Intestinal obstruction in ovarian cancer patients is a major complication which frequently affects survival and quality of life. After a reasonable trial of conservative management fails, surgery is the only hope for relief of obstruction. In an effort to evaluate the success of such surgery we have reviewed the outcome of 54 operations (52 patients) for relief of intestinal obstruction performed over the 3-year period 1983-1985. Possible predictive factors for success and survival following surgery were analyzed. The sites of intestinal obstruction in the 54 procedures were as follows: small intestine 24 (44%); large intestine 18 (33%); combined small and large intestine 12 (22%). In 11 operations no surgical correction of the obstruction was possible. In 43, major intestinal procedures were performed, including 14 bypasses, 13 resections, and 20 colostomies. Of the 43 instances in which intestinal procedures were performed, 4 patients expired without leaving the hospital. At the time of discharge from the hospital the remaining 34 of these 43 patients were eating a regular or low-residue diet. Successful palliation of intestinal obstruction was thus achieved in 79% of the 43 instances in which a definitive procedure could be performed, and in 63% of the total of 54 operations. Mean survival following surgery was 6.8 months for the group undergoing a definitive procedure, and 1.8 months for the group undergoing exploration only. There was no significant difference between the two groups with regard to age, time from diagnosis, prior radiotherapy, number of prior laparotomies, site of obstruction, or use of total parenteral nutrition. None of the multiple clinical variables analyzed correlated with survival following definitive surgery. Most patients explored for intestinal obstruction due to advanced ovarian cancer can have their obstruction relieved and be discharged from the hospital. We were not able to define criteria that would allow selection of patients unlikely to benefit from surgery.

Adult↗

Intestinal surgery in gynecologic oncology.

Intestinal surgery is frequently required in the management of patients with gynecologic malignancies. During a recent 3-year period 10.4% of all laparotomies performed on the Gynecology Service at Memorial Sloan-Kettering Cancer Center included major intestinal surgery. A total of 215 separate intestinal procedures were performed during 171 operations on 158 patients. The majority of operations were performed in patients with ovarian (42.7%), cervical (24%), and endometrial (12.3%) malignancies. Seventy-nine of 171 (46.2%) of operations were performed on previously irradiated patients. The most frequent indications for intestinal surgery were intestinal obstruction (43.2%) and intestinal fistula (21%). Procedures performed included 87 intestinal resections, 26 intestinal bypasses, 82 colostomies, and 20 intestinal conduit urinary diversions. Hand suturing was used in 71% of anastomoses; automatic stapling instruments were used in 29%. There was a single surgical mortality. Complications including infections, obstruction, and fistula formation were infrequent. These difficult intestinal procedures can be performed safely in the context of a fellowship training program. Since a significant proportion of all laparotomies done in gynecologic cancer patients will include major intestinal surgery, physicians managing patients with these diseases should have both the technical skills necessary to perform these procedures, as well as a thorough understanding of the diseases themselves.

Female↗

Synergistic activity of tumor necrosis factor and interferon in a nude mouse model of human ovarian cancer.

In vitro and in vivo studies suggest a synergistic inhibition of tumor growth by the combination of certain interferons and tumor necrosis factors. We have examined the activity of two of these agents in an animal model of human ovarian cancer. The human ovarian cancer cell line SK-OV3 was grown subcutaneously in immunodeficient mice. Mean relative tumor volume was determined weekly by external tumor measurements and a standard formula. Animals were treated by intraperitoneal injection with (1) recombinant human tumor necrosis factor alpha (rHTNF) 5 or 10 micrograms/day; (2) recombinant murine interferon gamma (rMIFN) 5 x 10(4) units per day; or (3) a combination of rHTNF 5 micrograms/day and rMIFN 5 x 10(4) units/day. Simultaneous control groups were run for all experiments. Administration of rHTNF alone in either dose had no effect on rate of tumor growth. Administration of rMIFN at a dose of 5 x 10(4) units/day produced a marginal decrease in rate of tumor growth. Animals receiving both rHTNF 5 micrograms/day and rMIFN 5 x 10(4) units daily showed marked inhibition of tumor growth, with the mean relative tumor volume after 4 weeks of treatment measuring 0.75 +/- 0.91 in the treatment group and 11.06 +/- 2.96 in the control group. rHTNF and rMIFN demonstrate a synergistic inhibition of tumor growth in this animal model of human ovarian cancer.

Animals↗

Influence of secondary cytoreduction at the time of second-look laparotomy on the survival of patients with epithelial ovarian carcinoma.

The value of secondary cytoreductive surgery at the time of second-look laparotomy in patients with epithelial ovarian carcinoma is not established. Sixty-seven patients with residual carcinoma found at the time of second-look laparotomy performed at Memorial Sloan-Kettering Cancer Center between December 1, 1978, and May 30, 1986, were evaluated for survival relative to the success of secondary cytoreductive surgery. At second-look laparotomy, 17 patients had microscopic disease, 28 patients had disease less than 2 cm and 22 patients had disease greater than 2 cm. After secondary cytoreductive surgery 33 patients had microscopic disease, 26 patients had disease less than 2 cm, and 7 patients had disease greater than 2 cm (1 unknown). Five-year survival by Kaplan-Meier calculation was 62% for patients found to have microscopic disease at second-look laparotomy and 51% for patients whose disease was rendered microscopic by secondary cytoreductive surgery (P = 0.55). Patients left with gross disease (either less than or greater than 2 cm) had 5-year survivals of less than 10% (P = 0.013 compared with microscopic residual). Secondary cytoreductive surgery at the time of second-look laparotomy in patients with epithelial ovarian carcinoma may result in improved survival of patients who are reduced to microscopic residual disease.

Adult↗

A longitudinal study of antigen expression in epithelial ovarian cancer.

The extent to which the antigenic phenotype of human epithelial ovarian cancer changes during the course of the disease is an issue that must be addressed in order to maximize the potential of antibody-directed imaging and therapy. We have obtained tumor specimens at two separate operations from ten patients with epithelial ovarian cancer and typed these specimens with a panel of 19 monoclonal antibodies to cell surface glycoprotein and carbohydrate antigens including blood group antigens. Antibodies with relatively high specificity for malignant cells as well as those detecting more widely distributed epithelial antigens were used in the study. Mean time between the two operations was 8.5 months. Five patients received intraperitoneal therapy during the interval between the two operations, including platinum-based regimens (four patients) and tumor necrosis factor (one patient). Four patients received intravenous platinum-based chemotherapy; one received no treatment. Frozen sections of specimens were stained with the antibodies by the indirect immunoperoxidase technique. Antigenic phenotypes were found to be unrelated to the patient's age, stage, tumor grade, histologic cell type, prior chemotherapy, and interval between operations. Most significantly, little difference was seen in antigenic expression between tumors obtained at the two operations for either the cell surface or blood group markers. Variations in the staining pattern were seen with antibody B72.3 and, to some extent, with the anti-blood group antibodies, which are known for producing heterogeneous staining. The antigenic phenotype of the tumor specimens in a given patient as determined immunohistochemically by our panel of antibodies showed only minor variation between operations, even under the selective pressures of chemotherapy and immunotherapy.

Adenocarcinoma↗

Long-term access to the peritoneal cavity in ovarian cancer patients.

One hundred thirty-six totally implanted peritoneal catheter systems were placed in 130 patients. No complications occurred at catheter placement. A total of 629 courses of intraperitoneal therapy were administered. The average catheter has remained in place for 4.5 months (range 1-19 months). Seven catheters (5.1%) were removed for infection. An additional 7 catheters were removed because of blockage, for a total removal rate due to complications of 10.2%. Catheters were not used for drainage of the peritoneal cavity. The totally implanted peritoneal catheter system provides a reliable means for long-term access to the peritoneal cavity in patients with ovarian cancer.

Antineoplastic Agents↗

Serum CA 125 levels and surgical findings in patients undergoing secondary operations for epithelial ovarian cancer.

Serum CA 125 levels and surgical findings were prospectively compared in 96 secondary laparotomies performed on patients with epithelial ovarian cancer. All patients had documentation of an elevated CA 125 level (greater than 35 U/ml) at a time when ovarian cancer was present, and thus the tumors were known to be "marker positive." Operation was performed in 45 patients who were clinically free of disease and in 51 patients in whom there was clinical evidence of disease. At the time of operation, 29 patients had normal CA 125 levels; persistent disease was documented in 18 (62%) of these. Of the patients with normal CA 125 levels at the time of operation, those with persistent disease had a significantly higher mean CA 125 level (16.9) than those with no disease detected (8.8, p = 0.001). At exploration, cancer was found in 84 patients. There was a correlation between the maximum diameter of the largest residual tumor mass and the accuracy of the CA 125 level as follows: microscopic to 1 cm disease, 55% accuracy; greater than 1 to 5 cm disease, 80% accuracy; greater than 5 cm disease, 92% accuracy (p = 0.013). There was no correlation of CA 125 accuracy with the patient's age, number of months from initial diagnosis, tumor stage, grade, or cell type, or the highest-ever level of CA 125. Of the 84 patients with tumor found at exploration, 66 had elevated CA 125 levels, yielding a sensitivity of 78.5%. There were 12 patients with no tumor found at exploration; 11 of these had normal CA 125 levels. The one patient who had an elevated CA 125 level subsequently had a recurrence; the corrected specificity is thus 100%. An elevated CA 125 level is an accurate predictor of persistent disease. Most of these patients will have gross tumor present. The accuracy of the CA 125 level in detecting disease is related to the amount of tumor present. In our population, the predictive value of an elevated CA 125 level was 100%; the predictive value of a normal CA 125 level was 38%.

Adult↗

Second-look laparotomy in endodermal sinus tumor: a report of two patients with normal levels of alpha-fetoprotein and residual tumor at reexploration.

The role of second-look laparotomy in the management of patients with endodermal sinus tumor of the ovary is controversial. We report two women who converted to a normal alpha-fetoprotein (AFP) level during treatment with combination chemotherapy, yet were found to have residual endodermal sinus tumor at second-look laparotomy. In view of the limited experience with this rare disease, we continue to recommend second-look laparotomy for patients who have completed chemotherapy for endodermal sinus tumor of the ovary, regardless of the serum AFP level.

Adolescent↗

Recurrence after negative second-look laparotomy for ovarian cancer: analysis of risk factors.

To determine the long-term rate of recurrence and define risk factors for recurrence, we have analyzed clinical information on 83 patients followed up for a minimum of 4 years (median, 69 months) after negative second-look laparotomy. Overall, 21 of 83 patients (25.3%) had a recurrence. Median interval to recurrence was 14 months. Stage, grade, and type of chemotherapy were significantly related to risk of recurrence. In patients with stage I disease only one of 27 (3.7%) had a recurrence. Patients with stage I disease were not included in further analysis of risk factors. In stages II, III, and IV, 20 of 56 patients (35.7%) had a recurrence. Recurrence rates by grade (excluding stage I) are as follows: grade 1, three of 21 (14.3%); grade 2, six of 17 (35.5%), and grade 3, 11 of 17 (64.7%). Platinum-treated patients in stages II, III, and IV had a 50% (12/24) recurrence rate compared with 25% in nonplatinum-treated patients (8/32) (p = 0.05). Differences in disease-free survival between platinum- and nonplatinum-treated patients were significant at the p = 0.02 level. When treated with platinum-based regimens, more patients will achieve complete clinical remission and subsequently negative second-look laparotomy. However, the recurrence rate in these patients is considerably higher than that in patients treated for longer durations with nonplatinum regimens.

Antineoplastic Agents↗

Treatment of uterine leiomyosarcoma.

We reviewed 46 cases treated at the Gynecology Service of Memorial Sloan-Kettering Cancer Center from 1970-1984 to evaluate the impact of modern multimodal therapy on survival of patients with uterine leiomyosarcoma. Eighteen patients had their primary treatment at Memorial Hospital, whereas the remaining 28 patients were referred either after primary surgery (ten) or after the development of recurrent disease (18). Thirty-four patients initially had disease confined to the uterus. Twelve of these patients received various adjuvant treatment regimens after hysterectomy, and 83.3% developed recurrent disease; 68.2% of 22 patients who received no adjuvant therapy developed recurrent disease. Twelve patients who presented with extrauterine disease all died within two years of initial treatment. Thirty-seven patients were treated for persistent or recurrent disease after primary treatment. No objective responses to radiation therapy were seen in these patients. Doxorubicin used alone or in combination produced a 16.7% response rate (average duration four months), whereas there were no responses to chemotherapeutic regimens not containing doxorubicin. The disease-free survival rate for all patients in this study was 22%; those patients who presented with stage I and II disease had a 29% survival rate.

Adult↗

Peritoneal cytology as an indicator of disease in patients with residual ovarian carcinoma.

Cytologic assessment of peritoneal washings or ascites in ovarian cancer patients has been suggested as a method of evaluating response to therapy or disease status, although the accuracy of this technique has not been clearly established. Ascitic fluid or peritoneal washings were obtained during 96 reassessment laparotomies that were biopsy-positive for residual intraperitoneal ovarian cancer. Cytologic studies done on these samples failed to detect malignant cells in 66% of the cases with gross residual disease and 78% of the cases with only microscopic residual disease on biopsy. The accuracy of peritoneal cytology in detecting residual ovarian cancer was unrelated to residual tumor size, original clinical stage, histologic tumor grade, and tumor cell type. Examination of ascitic fluid found at the time of surgery was somewhat more reliable than assessment of peritoneal washings, although this difference was of borderline statistical significance. Peritoneal cytology cannot reliably detect residual ovarian cancer after initial treatment with surgery and chemotherapy. Negative peritoneal cytology is frequently seen in the presence of gross residual tumor.

Ascitic Fluid↗

Radical hysterectomy for recurrent cervical cancer following radiation therapy.

In patients with small central recurrences following radiation therapy for cervical cancer the surgeon may have to make a judgment as to when radical hysterectomy is preferable to exenteration. During the years 1968-1984 there were 21 radical hysterectomies performed at Memorial Sloan-Kettering Cancer Center for recurrent cervical cancer. The original clinical stage distribution is as follows: IB-4, IIA-4, IIB-11, IIIB-1, IVA-1. The median interval from initial diagnosis to recurrence was 10 months. There were two operative deaths; both were from sepsis. Ten of the 21 patients developed postoperative fistulas, with 9 requiring surgical diversion of the urinary or both urinary and intestinal tracts. Thirteen of 21 patients (62%) have survived with a median follow-up of 73 months. Seven patients suffered recurrences following radical hysterectomy. All developed recurrence in the central pelvis. Four had sidewall disease as well, but none had distant disease at the time recurrence was diagnosed. Of 11 patients with cervical tumors of 2 cm or less in size at the time of radical hysterectomy, none experienced recurrence, while among 10 patients with tumor size of greater than 2 cm, 7 had recurrence. All patients whose initial clinical stage was IB or IIA have survived without recurrence. There was only 1 survivor among 5 patients with positive parametrial or vaginal margins. Six of the 13 survivors required urinary diversion, and 2 required colostomy as well. Radical hysterectomy for this indication is a morbid procedure which should be undertaken only by the most experienced of pelvic surgeons and limited to patients of early clinical stage with central recurrences of less than 2 cm in size.

Adult↗