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Biomedical subjects

M S Piver

Publications and source records attributed to M S Piver.

At least 163 records · Page 9Linked to original sources

Progesterone therapy for malignant peritoneal cytology surgical stage I endometrial adenocarcinoma.

Twenty-five patients with surgical stage I endometrial adenocarcinoma and malignant peritoneal cytologic washings were treated with progesterone therapy. Twenty-two patients have undergone a second-look laparoscopy and repeat cytologic washings, one of whom also underwent a third-look laparoscopy. Two patients refused second-look laparoscopy, and in a third patient, a laparoscopy was medically contraindicated; the three patients have no evidence of disease at 15, 46, and 64 months, respectively, and are off therapy. Of the 22 patients who underwent second-look laparoscopy, 21 (95%) had no evidence of recurrent endometrial carcinoma and repeat peritoneal results of cytology were negative for malignant cells; one patient (5%) had persistent malignant peritoneal cytology at second-look laparoscopy but had no evidence of disease at third-look laparoscopy after an additional year of progesterone therapy. All 25 patients (100%) are off progesterone therapy and remain clinically free of disease from 12 to 64 months after discontinuation of therapy.

Adenocarcinoma↗

Tumor-infiltrating lymphocytes: in vitro characterization of morphological and phenotypical changes.

Mononuclear cells (tumor-infiltrating lymphocytes [TIL]) that invade tumor tissue in fresh surgical specimens were examined and characterized. Such cells were seen in virtually all 52 tumor specimens analyzed and were found to be physically attached to the tumor cells. The morphology of these cells is described with scanning and transmission electron microscopy. Phenotype analysis of these tumor-infiltrating lymphocytes was also performed. In the fresh surgical specimens, while the tumor cells are viable, TIL cells are mostly null cells (except for weak positivity for Leu-1 antigen). As the culture ages in vitro, the TIL phenotype changes drastically to a wide variety of both T and B cells as well as monocyte-macrophage lineage. While these phenotype changes occur, the tumor cells to which the TIL are attached display progressive signs of necrosis and cell death. Tumor cells without attached TIL cells are not affected by necrotic changes. It is speculated that these described changes in the phenotype and morphology of TIL may be related to acquiring cytotoxic activity against the tumor cells. An attempt to control these changes may possibly be useful for clinical application in cancer immunotherapy.

B-Lymphocytes↗

Long-term follow-up and complications of infants with vulvovaginal embryonal rhabdomyosarcoma treated with surgery, radiation therapy, and chemotherapy.

The long-term follow-up is presented of three infants with vulvovaginal rhabdomyosarcoma treated at 10, 11, and 15 months of age by radical surgery, pelvic radiation therapy, and chemotherapy. Two patients developed colonic stricture requiring operative repair. One of these two patients also has urinary incontinence secondary to severe bladder contraction. Pelvic radiation did not significantly affect stature. Lateral transposition of the ovaries at the time of surgery preserved endocrine function in one patient with a normal puberty. The other two patients developed normal secondary sexual characteristics with hormonal replacement therapy. These patients perform well academically and socially. They have adapted 14, 14, and 16.5 years after their therapy.

Adolescent↗

Advanced uterine sarcoma; response to chemotherapy.

A 15 year retrospective study of chemotherapy response to multiple regimens employed in 78 evaluable patients with advanced uterine sarcoma was performed. Single agent activity was noted with doxorubicin, methotrexate, and cisplatin (5-11% response rate). Effective multigent regimens included cyclophosphamide, vincristine, doxorubicin, dacarbazine (CYVADIC) (23% response), cisplatin and dacarbazine (21% response) and vincristine, dactinomycin, and cyclophosphamide (VAC) (18% response). There was no difference in response rate among different histologies. More active agents or combinations are needed.

Adult↗

Cervical and vaginal cancer detection at a regional diethylstilbestrol (DES) screening clinic.

From 1979 to 1986, 500 women were enrolled in a New York State regional diethylstilbestrol (DES) clinic for the early detection of DES-associated adenocarcinoma of the cervix or vagina. Only 66 DES-exposed females were seen at Roswell Park Memorial Institute in the 6-year period prior to the establishment of the DES screening clinic. Most (40%) learned of the DES screening clinic through television public service announcements. Documentation by physician, pharmacy, or hospital records of intrauterine DES exposure was possible in only 15.2% of the cases. Because of a mean age of 24 years of the DES-exposed patients, most physician, pharmacy, and hospital records were not readily available from that time period. In 5.2% of the patients enrolled in the DES clinic, review documented that the mother had not taken DES or other synthetic estrogen analogs. Among the 474 evaluable DES patients, gross vaginal or cervical abnormalities were present in 13.5% and DES-associated adenosis was seen in 16.0%. Sixteen (3.4%) developed squamous dysplasia, one developed squamous in situ carcinoma of the cervix, and one developed invasive squamous cell carcinoma of the cervix. During the 6-year period of the DES screening clinic, no patient developed DES-associated adenocarcinoma of the cervix or vagina. The utility of such specialized clinics is discussed.

Adenocarcinoma↗

Malignant peritoneal cytology in stage I endometrial adenocarcinoma: the effect of progesterone therapy (a preliminary report).

From February 1982-June 1986, 25 consecutive patients with surgical stage I endometrial adenocarcinoma (no evidence of metastasis at surgery or occult cervical or adnexal involvement on histopathologic review) and malignant peritoneal cytologic washings were treated with progesterone therapy. Twenty-two patients have undergone a second look laparoscopy and repeat cytologic washings, one of those also underwent a third look laparoscopy. Two patients refused second look laparoscopy, and in a third patient laparoscopy was medically contraindicated; all three have no evidence of disease (NED) at 15, 46, and 64 months respectively and are off therapy. Of the 22 patients who underwent second look laparoscopy, 21 (95%) had no macroscopic evidence of recurrent endometrial carcinoma and repeat negative peritoneal cytology; 1 patient (5%) had persistent malignant peritoneal cytology but was NED at third look laparoscopy one year later. All 25 patients are off progesterone therapy and remain clinically NED from 12-64 months. Although progesterone therapy for malignant peritoneal cytology resulted in a 100% reversal of malignant peritoneal cytology to normal in the 22 patients who underwent second or third look laparoscopy and all 25 patients remain clinically NED, the true value of progesterone therapy can only be ascertained by a randomized trial of progesterone versus no therapy.

Adenocarcinoma↗

Hydroxyurea plus pelvic radiation versus placebo plus pelvic radiation in surgically staged stage IIIB cervical cancer.

Forty-five evaluable patients with stage IIIB carcinoma of the uterine cervix were entered into a prospective, double-blind, randomized study to evaluate the possible radiation-potentiating properties of hydroxyurea. All patients were documented to be without para-aortic lymph node metastasis by pretherapy staging para-aortic lymphadenectomy. The original plan of therapy was for continuous therapy (200 rads/day) of 6,000 rads of pelvic radiation for 6 weeks plus intrauterine radium. However, 16 patients received 6,000 rads in 8 weeks by split-course therapy (2-week rest after 3,000 rads) plus radium. Twenty-nine patients received the planned continuous therapy. The median dose of pelvic radiation for patients who received continuous therapy or split-course radiation was 6,000 rads. Leukopenia (WBC less than 2,500/mm3) was significantly increased in the patients given hydroxyurea as compared to those given placebo (P less than .001). There was no statistically significant difference relative to anemia, thrombocytopenia, radiation skin reaction, diarrhea, or radiation-induced complications requiring surgical correction. The estimated 5-year progression-free survival rate for the combined, continuous, and split-course radiation therapy hydroxyurea patients was 60%, and its was 52% for the corresponding placebo patients (P = .49). However, the estimated 5-year progression free survival rate for the correctly treated patients (continuous therapy) was 91% for the hydroxyurea group and 60% for the placebo group (P less than .06).

Adult↗

Plasminogen activator content of gynecological tumors and their metastases.

The plasminogen activator content of surgically excised gynecological tumors was measured with an azocaseinolytic assay. Ovarian (10 primary, 18 metastases) and uterine (5 primary and 6 metastases) tumors showed similar mean activator activities (21 CTA units/g tissue) mainly of the urokinase type with similar wide variations in each group. About 44% (14 of 32) of the tissues placed in short term organ culture were shown to produce and secrete urokinase activity. Results of the plasminogen activator activity found in the patient tumors or produced by the tumors during culture in the absence or presence of some drugs indicate a wide range of individual variations in sensitivity to these agents.

Aged↗

cis-Diamminedichloroplatinum II based combination chemotherapy for the control of extensive paraaortic lymph node metastasis in cervical cancer.

A prospective study was carried out in nine consecutive patients with extensive paraaortic lymph node metastasis from locally advanced cervical cancer. Patients were treated with pelvic radiation and weekly cis-platinum during radiation followed by cis-platinum based combination chemotherapy given on a monthly basis. Three weeks after completion of pelvic radiation and weekly cis-platinum, and prior to monthly combination chemotherapy, pelvic examination confirmed a 100% local response rate: 78% complete and 32% partial response. All patients have been followed for greater than or equal to 1 year or until death and only 22% (2) are alive NED while 56% (5) are dead of cervical cancer and 22% (2) are alive with cervical cancer. Although there was a significant response to local pelvic tumor by pelvic radiation and weekly cis-platinum, it is concluded that this protocol would not result in a significant increase in 5-year survival for patients with extensive paraaortic lymph node metastasis, because of the inability to control disease outside of the radiated area.

Adult↗

1.5-5 years of uninterrupted cis-diamminedichloroplatinum II chemotherapy for metastatic cervical cancer.

In an attempt to prolong remission duration in patients with metastatic cervical cancer to cis-platinum based chemotherapy, patients were treated on an every other month basis after a minimum of 1 year of cis-platinum based chemotherapy. To date, five patients have received 5, 4.5, 2.3, 2.3, and 1.5 years, respectively, of uninterrupted cis-platinum based chemotherapy. All remain in complete remission after receiving a total dose of cis-platinum of 2523 mg (1530 mg/m2), 2.408 mg (1655 mg/m2), 1496 mg (880 mg/m2), 1325 mg (970 mg/m2), and 1640 mg (950 mg/m2), respectively. The only apparent toxicity has been asymptomatic hypomagnesemia. In contrast, three other patients in complete remission on cis-platinum based chemotherapy voluntarily discontinued such therapy and have subsequently developed uncontrolled recurrent cervical cancer. It is concluded that patients in complete remission from cis-platinum chemotherapy for metastatic cervical cancer can receive long-term cis-platinum based chemotherapy and that such therapy appears to be without significant toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Serum beta-(1----4)-galactosyltransferase activity with synthetic low molecular weight acceptor in human ovarian cancer.

A modified procedure was developed for the determination of UDP-galactose: 2-acetamido-2-deoxy-glucopyranoside beta-(1----4)-galactosyltransferase (GT) in human serum which employed the synthetic substrates p-nitrophenyl 6-0-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-beta-D-galactopyranoside and p-nitrophenyl 6-0-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-alpha-D- mannopyranoside as acceptors. The enzyme products were identified by thin layer chromatography with authentic reference compounds, and the galactosyl linkage was characterized by hydrolysis with beta-D-galactosidase from jack beans. The diagnostic value of this GT for ovarian cancer was tested by measuring the serum enzyme activity in 28 ovarian cancer patients with disease, 20 ovarian cancer patients with no clinical evidence of disease, and 22 healthy females. Although the level of the enzyme activity was significantly higher (P less than 0.002) in the serum of patients with active disease when compared to healthy controls, an appreciable overlap of enzyme activity was found between them. Also, no correlation was found between enzyme activity and tumor size. Differences in methodology and selection of patients makes it difficult to compare results from other reports. However, based on our improved assay procedure, we suggest caution should be exercised in evaluating the merits of GT as a diagnostic marker for ovarian cancer.

Chromatography↗

Cisplatin plus VP16-213 in refractory ovarian carcinoma.

Twenty-five patients with FIGO stage III and IV ovarian carcinoma were treated with cisplatin plus VP16-213 chemotherapy as the second, third, or fourth line of therapy. There were two (8%) partial responses, 18 with stable disease and five with progression of disease. Neurotoxicity was observed in all patients, with two patients developing severe paresthesias and difficulty in walking.

Antineoplastic Combined Chemotherapy Protocols↗

Isolation and morphologic characterization of human ovarian carcinoma cell clusters present in effusions.

Serous, mucinous, endometrioid and clear cell human ovarian carcinoma cells were isolated as multicellular aggregates from patient effusions by filtration on nylon mesh of defined porosity and examined by light microscopy. The cell clusters ranged from compact to loosely adherent groups of cells to spheroids with a central lumen surrounded by a cell monolayer. There was considerable variation in cluster morphology between effusions from different patients as well as within effusion from the same patient. Apparent budding of clusters was observed as well as different stages of cluster growth and development. This was observed for all histologic types studied. Electron microscopy of serous, mucinous and clear cell types showed that cells forming clusters were attached to each other by desmosomes, demonstrating that cluster formation did not result from a nonspecific stickiness of cells. Irregular microvilli were present on the external periphery of the various carcinoma cells and a prominent glycocalyx was present on the surface of mucinous carcinoma cells. Extensive interdigitation of cytoplasmic extensions and extended villi was present in mucinous and serous clusters which appeared to strengthen cluster cohesiveness. Nuclei were irregular with prominent nucleoli frequently present. The cell clusters usually remained intact and viable in culture but generally did not attach to glass or plastic substrata, whereas mesothelial cells and nonactivated histiocytes rapidly attached. When carcinoma cell clusters did attach, they were resistant to detachment by trypsin-EDTA treatment, in contrast to the nonmalignant cells.

Adenocarcinoma↗

Galactoside-binding lectin in human tissues.

Lactose-inhibitable lectin activity has been analyzed by hemagglutination assay in a variety of human tissues and cells obtained at surgery and autopsy. The lectin activity was detected in surgically removed melanoma, sarcoma, colon carcinoma, breast carcinoma, adjacent non-malignant tissues, non-malignant tissues obtained at autopsy and in cells isolated from malignant effusions. Although, on average, malignant tissue had a higher hemagglutinating titer than non-malignant tissue, similar tissues from different individuals varied widely in their apparent lectin content. The lectin was isolated from lung by affinity chromatography and was found to have a native molecular mass of 31,000 daltons and a subunit molecular mass of 14,000 daltons. Utilizing rabbit anti-lung lectin serum in an immunohistochemical assay, the lectin was found to be distributed throughout the cytoplasm of lung epithelial cells. Ouchterlony immunodiffusion analysis confirmed the presence of this lectin in a variety of tissues and in some body fluids. In vitro metabolic radiolabelling experiments showed that the presence of lectin in tissues was most likely due to endogenous synthesis rather than absorption from body fluids. Lectin isolated from several tissues was found to bind to human buffy coat cell receptors.

Electrophoresis, Polyacrylamide Gel↗

Ovarian cancer in children.

Gynecologic malignancies account for approximately 2% of all childhood cancers, 60-70% of which are ovarian in origin. New therapeutic modalities have resulted in a significant increase in survival rates for these young patients. Recent advances in the management of germ cell and sex cord tumors of the ovary have resulted not only in an increase in cure rates but also in simultaneous preservation of future fertility. The recent advent of surgical staging has elucidated the early sites of subclinical or occult metastases that accounted for the high mortality in patients who were previously presumed to have localized ovarian cancer. Treatment options are discussed for the various classes of ovarian tumors in children, at the hand of experience at the authors' institution, and of others.

Adolescent↗

The potential for optimal (less than or equal to 2 cm) cytoreductive surgery in advanced ovarian carcinoma at a tertiary medical center: a prospective study.

From November 1980 to April 1985, 50 consecutive previously untreated patients with FIGO Stage III and IV ovarian cancer were entered into a prospective trial to evaluate what percentage of such patients could have their tumors optimally cytoreduced (residual cancer less than or equal to 2 cm), what operation is required to achieve this goal, and what is the associated morbidity. Optimal cytoreduction was achieved in 76% of the 50 cases and in 77% of 18 cases referred as "inoperable." To achieve this goal, the six most common operations performed in descending order of frequency were bilateral salpingo-oophorectomy (100%), hysterectomy (98%), omental resection (86%), peritoneal tumor resection (40%), intestinal resection (36%), and gastrocolic ligament resection (16%). Fifty-eight percent of the patients had no major complications. The most significant complications were congestive heart failure in 4% and pulmonary embolus in 4%. Ninety-four percent of the patients had chemotherapy initiated in less than or equal to 14 postoperative days. It is concluded that approximately three-fourths of patients with advanced Stage III and IV ovarian carcinoma can have their tumors resected to less than or equal to 2 cm in greatest diameter. The value of such therapy on ultimate response to chemotherapy and survival will have to await longer follow-up, and will be the subject of a subsequent report.

Adenocarcinoma↗