Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal interval tumor reductive surgery for advanced ovarian cancer.

OBJECTIVES: Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. METHODS: In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). RESULTS: There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024-3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042-2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414-0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. CONCLUSIONS: IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

Correlation of the in situ detection of polymerase chain reaction-amplified metalloproteinase complementary DNAs and their inhibitors with prognosis in cervical carcinoma.

The purpose of this study was to correlate the presence of matrix metalloproteinase (MMP)-9 and MMP-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 mRNAs, detected in serial sections using the reverse transcriptase in situ PCR technique, with prognosis in 23 cases of cervical carcinoma. PCR-amplified MMP and TIMP cDNA were restricted to the invasive cancers cells and the surrounding stromal cells. The ratios of cancer and stromal cells expressing MMP-9 and MMP-2 to those expressing TIMP-1 and TIMP-2 were approximately 1 in those cancers with a good prognosis. This MMP:TIMP ratio in the cancer and stromal cells with a poor prognosis was significantly increased to 5.4 and 3.4 (P < 0.0001), respectively, reflecting a marked reduction in the TIMP detection rate in cancers with a poor prognosis. In cervical cancer cell lines SiHa and HeLa, the MMP:TIMP ratio was also close to 1 and, interestingly, these cell lines are invasive but rarely metastatic in nude mice. These data suggest that the balance of MMP-9 and MMP-2 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of cervical cancer.

A randomized controlled trial of postoperative nasogastric tube decompression in gynecologic oncology patients undergoing intra-abdominal surgery.

OBJECTIVE: To evaluate the effect of nasogastric decompression after extensive intra-abdominal surgery in gynecologic oncology patients. METHODS: Over a 1-year period, 110 gynecologic oncology patients undergoing extensive intra-abdominal surgery were enrolled in a randomized controlled trial of postoperative nasogastric tube versus intra-operative orogastric tube decompression. RESULTS: The nasogastric and orogastric groups were similar in age, case distribution, surgery length, and blood loss. The nasogastric group had significantly longer times to first passage of flatus and tolerance of a clear liquid diet than did the orogastric group. However, both groups were similar in time to tolerance of a regular diet and hospital stay. On average, the nasogastric tube was maintained for 3.2 +/- 2.1 days (range 1-8) after surgery. The average daily nasogastric output was 440 +/- 283 mL (range 68-1565). No patient in the orogastric group required a nasogastric tube postoperatively, but one patient in the nasogastric group had a nasogastric tube reinserted for recurrent nausea and vomiting. Use of a nasogastric tube led to significantly more subjective complaints, eg, ear pain, painful swallowing, and nasal soreness, but did not significantly reduce the incidence of abdominal distention or nausea and vomiting. Major complications, eg, pneumonia, atelectasis, gastrointestinal bleeding, and wound breakdown or infection, occurred equally in both groups. However, the incidence of febrile morbidity was significantly greater in the nasogastric group. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematological indices and electrolytes were comparable in both groups. CONCLUSION: Postoperative nasogastric tube decompression in gynecologic oncology patients undergoing extensive intra-abdominal surgery does not appear to provide any substantial benefit but significantly increases patient discomfort. As a result of this study, we have eliminated postoperative nasogastric decompression except in highly selected circumstances, such as extensive bowel surgery in patients with prior irradiation or substantial edema from bowel obstruction.

Accuracy of ultrasonic weight prediction in the fetus with preterm premature rupture of membranes.

The accuracy of ultrasonic fetal weight prediction in the low birth weight fetus was evaluated, comparing measurement errors in 86 fetuses with premature rupture of membranes with 112 fetuses with intact membranes. Using two ultrasonic formulas for estimation of fetal weight, we found no significant differences in the mean error of ultrasonic weight measurement between these groups. In both groups, the mean measurement error was approximately 9%, with a standard deviation of 7%. It appears that ultrasonic methods for estimation of fetal birth weight are equally applicable to preterm fetuses with or without ruptured membranes.

A randomized controlled trial of early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery.

OBJECTIVE: To evaluate the safety and efficacy of early oral feeding after intra-abdominal surgery in gynecologic oncology patients. METHODS: During a 1-year period, 200 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a randomized controlled trial of early compared with traditional oral postoperative feeding. Patients allocated to early postoperative oral feeding began a clear liquid diet on the first postoperative day and then advanced to a regular diet as tolerated. Patients allocated to traditional postoperative oral feeding received nothing by mouth until return of bowel function (defined as the passage of flatus in the absence of vomiting or abdominal distention), then began a clear liquid diet, and advanced to a regular diet as tolerated. RESULTS: Age, case distribution, surgery length, blood loss, and first passage of flatus were similar in the early and traditional feeding groups. Significantly more patients in the early group developed nausea. Despite this, the incidence of vomiting, abdominal distention, incidence and duration of nasogastric tube use, and percentage of patients who tolerated clear liquid and regular diets on the first attempt were comparable in both groups. Time to development of bowel sounds, time to initiation of clear liquid and regular diets, and hospital stay were significantly longer in the traditional group. Major complications (eg, pneumonia, atelectasis, and wound complications) and febrile morbidity occurred equally in both groups. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematologic indices and electrolytes were comparable in both groups. CONCLUSION: Early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery is safe and well tolerated.

Panniculectomy and supraumbilical vertical midline incisions in morbidly obese gynecologic oncology patients.

BACKGROUND: We reviewed the outcomes of panniculectomy and supraumbilical vertical midline incisions in morbidly obese women undergoing gynecologic operations. STUDY DESIGN: Medical records were reviewed for 62 morbidly obese women with a large dependent pannus who underwent gynecologic operations on the Gynecologic Oncology Service at the State University of New York at Stony Brook between May 1990 and July 1997. Thirty-five patients underwent panniculectomy and 27 had a supraumbilical vertical midline incision, forming the study groups. The patient charts were abstracted for demographic, perioperative, and postoperative data. RESULTS: For the entire study population, the average age was 56 years, the mean body mass was 128.6 kg, and the mean Quetelet Index was 48.3 kg/m2. The mean operative time and estimated blood loss were similar for both groups. Eight percent of the patients had urologic injuries, evenly distributed between the groups. Postoperative infections, wound breakdowns, and hospital stay were greater for the panniculectomy group than for the supraumbilical vertical midline incision group (p < 0.05). Uniform use of subcutaneous closed-suction drains (since 1995) was associated with a significant reduction in the incidence of wound breakdowns and a shorter hospital stay in the panniculectomy group. CONCLUSIONS: Panniculectomy and supraumbilical vertical midline incision provide reasonable peritoneal access with acceptable rates of postoperative complications for morbidly obese women undergoing gynecologic operations.

Transcutaneous electrical nerve stimulation as an adjunct for controlling chemotherapy-induced nausea and vomiting in gynecologic oncology patients.

BACKGROUND: To evaluate the efficacy of a miniaturized portable transcutaneous electrical nerve stimulation (TENS) unit (ReliefBand) as an adjunct to standard antiemetic therapy for controlling nausea and vomiting induced by cisplatin-based chemotherapy in gynecologic oncology patients. METHODS: Forty-two patients were enrolled in a randomized, double-blind, placebo-controlled parallel-subjects trial with a follow-up crossover trial. All patients received a standardized antiemetic protocol, then wore the ReliefBand continuously for 7 days. RESULTS: Thirty-two patients were evaluable for the parallel-subjects component, 16 in each group. The percentage of patients with absent or minimal nausea was 59% overall, which was similar to that for both the active (56%) and placebo (62%) groups. The incidence and severity of nausea and vomiting was similar for each group. Eighteen patients completed two consecutive cycles and were evaluable for the crossover component. The average age of the crossover patients and their dose intensity were comparable with those of the overall study population (56.3 versus 58.6 years and 22.7 versus 22.7 mg/m2/week, respectively). The percentage of cycles with absent or minimal nausea was 47% overall, which was similar to that of the active (50%) and placebo (44%) cycles. However, the severity of nausea was significantly lower in the active cycles during days 2 to 4. Patients averaged less than one episode of vomiting daily in each cycle. CONCLUSIONS: The ReliefBand is an effective adjunct to standard antiemetic agents for controlling nausea induced by cisplatin-based chemotherapy in gynecologic oncology patients.

The gynecologist and surgical procedures for breast disease.

Patients with a palpable mass often benefit most from aspiration. As the clinician tries to aspirate, fluid may be obtained if the lesion is cystic. A solid lesion can be assessed with FNA biopsy with a very high degree of accuracy. Excisional biopsy should be used when a cystic lesion recurs, the mass does not disappear after the cyst is aspirated, or if the fluid obtained is bloody. A solid lesion may need to be excised if the aspirate is negative. The overall detection rate of breast cancer is approximately 20% for excisional biopsies. Mammographically detected lesions can be evaluated with needle-localization biopsies and stereotactic biopsies. The detection rates for breast carcinoma averages approximately 30%, with at least 20% of these lesions being noninvasive. The role of core needle biopsy of palpable lesions is limited; however, histologic confirmation of positive cytologic results from aspirate is possible with this approach. Stereotactic needle biopsy appears to correlate well with the specimen obtained at incisional biopsy and may decrease the need for needle-localized excisional biopsy.

Primary retroperitoneal mucinous cystadenocarcinoma of low malignant potential: a case report and literature review.

A case of primary retroperitoneal mucinous cystadenocarcinoma of low malignant potential in the presence of normal ovaries is reported. The precise etiology of these neoplasms has not been defined; however, they may arise from heterotopic ovarian tissue, monodermal teratomas, embryonal urogenital remnants, intestinal duplication, or coelomic metaplasia. Although minimal data exist to define the appropriate management, it seems reasonable to extrapolate from the treatment of analogous ovarian neoplasms.

Sonographic evaluation of growth discordance and chorionicity in twin gestation.

Ninety-four twin gestations had serial ultrasound examinations for evaluation of fetal growth, with special attention to prediction of weight discordance and chorionicity. Fetal weight estimations were made a mean of 3.2 days before birth and then compared to actual birthweights. The average error in intertwin discordance prediction was 1 +/- 9%. In 56 patients ultrasonic detection of membrane thickness was compared with placental pathologic conditions. If a membrane was seen between twins, it was confirmed by placental pathologic study in all cases. No membrane was seen in four twin pairs, but only one of these actually had monochorionic monoamniotic membranes. The three cases with false-positive diagnoses of monoamniotic twin gestation were initially seen late in pregnancy. If clinical decisions in twin gestations are based on ultrasound determination of discordance and chorionicity, the level of accuracy demonstrated by these data must be considered.

Role of p53 alteration in primary peritoneal carcinoma.

Although the clinicopathologic features of primary peritoneal carcinoma (PPC) in women are relatively well defined, the molecular pathogenesis of the disease has not been examined. The object of this study was to assess the biological significance of p53 alterations in PPC. Twenty-nine PPCs studied for p53 protein accumulation with monoclonal antibody DO-7 consisted of 26 serous carcinomas, one clear cell carcinoma, one tumor with endometrioid features, and one malignant mixed müllerian tumor. P53 was overexpressed in 83% of all PPCs and in 81% of the serous PPCs. Among eight immunopositive tumors with at least two distinct anatomic sites sampled, six tumors showed concordance, whereas two tumors showed discordance for p53 immunopositivity. The latter two tumors support the concept of a multifocal origin of PPC. This is the first report to suggest that loss of p53 function plays an important role in the development of PPC and might contribute to the poor prognosis of this disease. Parallels to serous papillary carcinomas of the uterus and ovary are discussed.

Panniculectomy in morbidly obese gynecologic oncology patients.

BACKGROUND: It is clear that morbid obesity presents a serious risk to women undergoing major intra-abdominal gynecologic surgery. Unfortunately, many gynecologic malignancies and benign conditions are best treated surgically. Thus, the gynecologic surgeon must choose an incision that permits adequate exposure with acceptables rates of complications. Panniculectomy as an approach to the peritoneal cavity is becoming increasingly popular. Recent reports suggest that panniculectomy is reasonably straightforward to perform, provides adequate exposure and is associated with an acceptable rate of manageable complications. In these circumstances, panniculectomy is not a cosmetic procedure, but medically necessary to perform indicated major gynecologic intra-abdominal surgery. AIMS: To present our experience with panniculectomy in morbidly obese women undergoing major intra-abdominal surgery on a gynecologic oncology service. METHODS: The medical records of 48 morbidly obese women (Quetelet Index > 40 kg/m2) with a large dependent pannus who underwent major intra-abdominal surgery via a panniculectomy between May 1990 and October 1999 were reviewed. Data regarding demographics, concomitant medical conditions, operative indications and results, and postoperative outcomes were abstracted for analysis. RESULTS: The mean age was 54.9 years, the mean body mass was 130.2 kg, the mean height was 1.63 m and the mean Quetelet Index was 49.3 kg/m2. The mean operating time was 188 min and the mean estimated blood loss was 615 ml. Two patients suffered intraoperative urologic injuries which were repaired without sequelae; there were no bowel, vascular or neurologic injuries. Eighteen patients had a suprafascial wound breakdown (3 complete and 15 superficial) and 15 patients developed an infection. There were no documented deep venous thromboses, pulmonary emboli or fascial dehiscences. Two patients died in the postoperative period; one from a myocardial infarction on Day 2 and one from overwhelming sepsis on Day 76. CONCLUSIONS: Morbid obesity is associated with substantial operative and postoperative risks. Panniculectomy provides operative exposure with acceptable risks of complications.

Hexamethylmelamine/altretamine as second-line therapy for epithelial ovarian carcinoma.

The purpose of this report was to review second-line hexamethylmelamine (HMM) chemotherapy of epithelial ovarian cancer to determine if HMM was active in cisplatin-resistant disease. Forty-four women with measurable disease received 100-300 mg/day HMM for 14 days, courses repeated every 4 weeks. There were 6 complete and 3 partial responses for an objective response rate of 20%. Among responding patients disease-free survival was 55% and overall survival was 88% at 3 years. Five of the 6 patients with a complete response remained disease-free at 10-117 months. Only 7/35 (20%) nonresponding patients were alive with mean follow-up of 16 months, and all had persistent cancer. Five women manifesting disease progression during cisplatin or carboplatin were subsequently treated with HMM, and none responded. Seventeen patients developing progressive cancer while receiving HMM were subsequently treated with cisplatin or carboplatin and objective responses occurred in 5 (29%). HMM was an active drug against epithelial ovarian cancer previously treated with cisplatin, but further study is needed to determine its activity against cisplatin-resistant ovarian cancer.

A new method and apparatus that prevents the rebreathing of expired carbon dioxide of sleeping neonates and infants.

This study was done to measure the effect on inspiratory carbon dioxide (CO2) levels of infants exposed to the infant Crib Air (ICA) apparatus, a novel device which circulates room air within the infant's crib. Twenty-one healthy, sleeping infants and neonates (mean age = 14.7 weeks) were studied in a prospective crossover trial. All infants were studied lying face down or with the face placed passively to the side in their cribs. Inspiratory CO2 levels were recorded over a 30 minute period by measuring the concentration of CO2 immediately adjacent to the infants' nose and mouth. During the first 15 minute period, the baseline concentration of inspiratory CO2 was recorded. The infants were then exposed to the ICA apparatus in their cribs for 15 minutes and the concentrations of inspiratory CO2 were measured. Mean inspiratory CO2 levels in infants lying face down decreased from 8.5 to 1.4 mm Hg after ICA exposure (P < 0.001). Infants studied with their face placed passively to the side experienced a similar decrease in inspired CO2 concentrations. We conclude that the level of inspired CO2 by sleeping infants can be significantly reduced by the ICA regardless of the position of the infant's head.

Immunohistochemical analysis of alpha 1-integrins in cervical cancer.

OBJECTIVE: The purpose of this study was to determine and compare the expression of the alpha 2-, alpha 3-, alpha 4- and alpha 5-subunits of the beta 1-family of integrins in both the normal and the carcinomatous cervix. STUDY DESIGN: A total of 22 solid tissue specimens (18 cancer and 4 normal) were analyzed immunohistochemically. The double-stain technique used an avidin-biotin complex kit to identify the various integrins and alkaline phosphatase-anti-alkaline phosphatase kit to identify the epithelial cells. Staining intensity, the main outcome measured, was graded as absent, weak, moderate, or strong. Statistical analysis was performed with the Wilcoxon rank sum test for nonparametric data. RESULTS: The alpha 2- and alpha 3-integrins stained the normal cervix epithelium more intensely than the stroma (p = 0.03). The alpha 4- and alpha 5-integrins stained both the stroma and the normal epithelium similarly. The alpha 2-integrin was absent in the stroma of all 18 cancer specimens despite being present in the epithelial regions of 14 to 18 cancers. The alpha 3-integrin had a greater staining intensity in the stroma of the cancers than in the epithelial regions (p = 0.002). Both alpha 4- and alpha 5-integrins were absent in the epithelial regions of the cancers but present in the stroma. CONCLUSIONS: The distribution and intensity of integrin expression in cervical cancer differ from their expression in the normal cervix. In particular, the fibronectin receptors, alpha 4 and alpha 5, were absent in the epithelial regions of the cervical cancers, and alpha 3 also had diminished expression in the malignant epithelium. These changes correlate well with the changes expected in malignant transformation.

Phase II trial of etoposide in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study.

Twenty-eight patients with advanced, persistent or recurrent leiomyosarcoma of the uterus not previously exposed to cytotoxic drugs were entered into a study of single-agent intravenous etoposide 100 mg/m2 daily for 3 days every 3 weeks. No complete or partial responses were observed. Thirteen patients demonstrated stable disease, while 15 exhibited increasing disease. Median progression-free interval was 2.1 months, median survival 9.2+ months. The most frequent and severe adverse effects were the result of myelosuppression and manifested primarily as leukopenia and neutropenia. Based on the absence of activity, no further study of intravenous etoposide in leiomyosarcoma of the uterus at the dose and schedule tested is planned.

Flow cytometric versus immunohistochemical analysis of ovarian cancer class I antigen expression: differences may represent a defect in antigen expression.

Class I antigen expression by ovarian epithelial neoplasms was determined by flow cytometric analysis and an immunoperoxidase technique for each specimen. The numbers of class I positive tumors determined by the methods were compared. The more subjective immunohistochemical analysis and the more objective flow cytometric technique revealed similar results as long as strict criteria for the interpretation of results was applied. Most of the tumor specimens revealed a homogeneous Gaussian distribution of green fluorescence, class I antigen expression, by flow cytometry. There were two specimens that exhibited a less than characteristic type of membrane staining. The antigen-antibody reaction product was expressed in the extracellular matrix, as well as on the cell membrane of certain cells. This may represent a defect in antigen expression and, if so, might alter the immune response to these tumors.

The utility of pretreatment barium enema in women with endometrial carcinoma.

OBJECTIVE: The objective of this study was to assess the clinical utility of a pretreatment barium enema in women with endometrial cancer. METHODS: The medical records of 249 patients with endometrial cancer who underwent a pretreatment barium enema were retrospectively reviewed. The patients' charts were abstracted for demographic information, stage, grade, histology, current disease status, and barium enema results. RESULTS: The pretreatment barium enema was normal in 122 (49%) patients. Diverticulosis was the most common abnormality, reported in 112 (45%) patients. Apparent intraluminal abnormalities were found in 15 (6.0%) patients. Each of these patients underwent colonoscopy prior to treatment for endometrial carcinoma. During colonoscopy, benign colonic polyps were removed from 11 (4.4%) patients. Primary colonic adenocarcinoma was discovered in polypoid lesions removed from 2 (0.8%) patients. Significant luminal narrowing from extrinsic lesions was noted in 2 (0.8%) patients, one at the rectosigmoid and the other at the cecum. No patient was found to have colonic mucosal involvement by endometrial cancer. CONCLUSION: The results of this study do not justify routine pretreatment barium enema to assess the colonic mucosa for metastatic involvement by endometrial cancer or as a screening tool for colorectal cancer in women with endometrial cancer.

A phase I study of intraperitoneal interferon-alpha 2b and intravenous cis-platinum plus cyclophosphamide chemotherapy in patients with untreated stage III epithelial ovarian cancer: a Gynecologic Oncology Group pilot study.

Previous clinical investigations using interferons (IFNs) have shown activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-alpha 2b which could be administered in combination with intravenous (iv) cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-alpha 2b (5-30 x 10(6) units) was administered ip on Day 1 (+/- Day 8). cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and anti-emetics. Courses were repeated every 3 weeks for 8 cycles. Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales. Fifteen patients with mean age 56 years (range 43-73) were entered and received a combined total of 100 treatment cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2-3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. Myelosuppression was the dose-limiting toxicity with grade 3-4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1-5, respectively. No patient completed planned treatment without interruption or dose reduction. Planned cis-platinum dose intensity was most compromised at the fifth IFN-alpha 2b dose level. The maximum tolerated dose of IFN-alpha 2b was determined to be 20 x 10(6) units repeated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamide chemotherapy cycle.

Nifedipine enhances the cardiac toxicity of magnesium sulfate in the isolated perfused Sprague-Dawley rat heart.

Magnesium sulfate is commonly used in tocolytic regimens and as prophylaxis against seizures. Nifedipine may be used simultaneously in either situation. With the isolated perfused rat heart model (Sprague-Dawley rats), we investigated the effects of these agents on cardiac function. Whereas each agent alone depressed cardiac performance, the two drugs together had maximal depressive effects on the heart.