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Background:Two strategies to interrogate the insulin growth factor 1 receptor (IGF-1R) pathway were investigated: vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation, angiogenesis, and stem cell propagation.Methods:A phase I, multi-cohort dose escalation study was conducted in patients with advanced solid tumours. Patients received dalotuzumab (10 mg kg-1) and escalating doses of MK-2206 (90-200 mg) or escalating doses of dalotuzumab (7.5-10 mg kg-1) and MK-0752 (1800 mg) weekly. Upon maximum tolerated dose determination, patients with low-RAS signature, high-IGF1 expression ovarian cancer were randomised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus, whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752.Results:A total of 47 patients were enrolled: 29 in part A (18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm) and 18 in part B (6 in each arm). Dose-limiting toxicities (DLTs) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction, maculopapular rash, and gastrointestinal inflammation. For dalotuzumab/MK-0752, DLTs included grade 3 dehydration, rash, and diarrhoea. Seven patients remained on study for >4 cycles.Conclusions:Dalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable. Further developments of prospectively validated predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed. [ABSTRACT FROM AUTHOR]

Numerous studies have documented increased breast cancer risks with hormone replacement therapy (HRT), but these do not give a woman her specific absolute risk for the remainder of her life. This article estimates the magnitude of the effect of HRT on breast cancer incidence in California and calculates a woman's cumulative risk of breast cancer with different formulations and durations of HRT use. The effects of HRT on the underlying breast cancer incidence were estimated using the attributable fraction method, applying HRT prevalence data from the 2001 California Health Interview Survey and published rates of higher relative risk (RR) from HRT use from the Women's Health Initiative (WHI) study and Million Women's Survey (MWS). The annual number of breast cancers potentially attributable to HRT in California was estimated, along with individual cumulative risk of breast cancer for various ages to 79 years according to HRT use, duration, and formulation. Using the WHI data, 829 of 19,000 breast cancers (4.3%) in California may be attributable to HRT. This figure increases to 3401 (17.4%) when the MWS RRs are applied. Use of estrogen-only HRT or short-term (approximately 5 years) use of combined HRT has a minimal effect on the cumulative risk calculated to the age of 79 years; application of the MWS data to a Californian woman commencing HRT at the age of 50 years (no HRT, 8.5%; estrogen only, 8.6%; combined, 9.1%). Prolonged (approximately 10 years) use of combined HRT increases the cumulative risk to 10.3%. This article demonstrates that HRT will generate a small additional risk of breast cancer in an individual. The reduction in perimenopausal symptoms may be considered sufficient to warrant this extra risk. However, this view needs to be balanced because the small increases in individual risk will be magnified, producing a noticeable change in population cancer caseload where HRT use is high. [ABSTRACT FROM AUTHOR]

From July 1, 1955 to March 31, 1989 24 patients with locally advanced vulvar cancer underwent ultraradical resection. Three patients had received prior radiotherapy. Seventeen of the 24 patients underwent posterior exenteration, four underwent anterior exenteration, and the remaining three required a total pelvic exenteration. One patient died 3 months postoperatively of fulminating infection considered to be a complication of the operation. Three other patients experienced serious complications, including postoperative hemorrhage, severe urinary sepsis, and colostomy stoma necrosis. Eleven (46%) of the 24 patients have remained alive without evidence of recurrent cancer for at least 3 years. Of the 10 patients known to have died of recurrent cancer, nine had positive lymph nodes at the time of surgery. It may be reasonable to utilize ultraradical surgery in patients with clearly resectable lesions who have negative or perhaps 1 or 2 microscopically positive regional lymph nodes. [ABSTRACT FROM AUTHOR]

The feasibility of achieving curative resection of perianal pre-invasive and invasive lesions with preservation of fecal continence was studied prospectively. Resection of these lesions involved excision of as much as the anterior third of the external anal sphincter. Twenty-two patients had invasive cancer and nine had extensive carcinoma in situ suspicious for invasive disease on preoperative assessment. Anal reconstruction consisted of plication of the external anal sphincter and plication of the puborectalis muscles. The perianal/perineal defects were closed using bilateral rhomboid flaps in 21 patients, unilateral rhomboid flaps in five patients and local advancement flaps in five patients. Twenty-eight patients were ultimately continent of feces, although two required further surgery for incontinence. Two of the three incontinent patients had fecal incontinence before surgery. Two patients had recurrence of invasive cancer, neither of which was perineal or perianal. Curative surgery of selected perianal lesions with preservation of fecal continence can be achieved with local resection and reconstruction with the use of local full thickness skin flaps. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the effects of coliform endotoxin on the circulating levels of atrial natriuretic factor and renal function. To understand the direct effects of endotoxin in the release of atrial natriuretic factor by cardiac tissue, studies in isolated rat atria were performed.Study Design: In vivo studies were used. Anesthetized dogs were studied, with one group receiving isotonic saline solution (n = 6) and the other group receiving 50 microg/kg of coliform endotoxin (n = 7) as a continuous infusion over a 4-hour period. Cardiovascular parameters, renal function, and circulating levels of atrial natriuretic factor were measured at specified time intervals. In another set of experiments with in vitro studies left atria from Sprague-Dawley rats were isolated and perfused. In the control group (n = 9) the standard Krebs perfusate was used. In the endotoxin group (n = 9) coliform endotoxin was added at a concentration of 250 microg/mL to the standard perfusate. Atrial pressure was used as an index of stretch, and atrial natriuretic factor was measured from the perfusate.Results: Administration of endotoxin resulted in decreased blood pressure (P < .05) with a concomitant increase in heart rate. Renal artery flow, however, showed an increase (P < .05) initially followed by a return to its baseline value, with a sustained increase occurring in the saline solution control group. A significant (P < .05) and sustained increase in the circulating levels of atrial natriuretic factor after endotoxin infusion did not prevent the decrease in fractional sodium excretion (P < .05) and creatinine clearance despite an increase in the urinary output. Serum sodium, serum potassium, and osmolalities, however, remained relatively stable. The study pertaining to isolated atria showed that in the presence of low atrial pressures, addition of endotoxin had no significant effect on the release of atrial natriuretic factor. With the increase in atrial pressure atrial natriuretic factor release was significantly higher in the group directly exposed to endotoxin compared with the control group.Conclusions: These studies demonstrate that the slow infusion of coliform endotoxin results in increased circulating levels of atrial natriuretic factor. This increase is in part due to the direct effect of endotoxin on the heart as indicated by studies in isolated atria. Our data suggest that atrial natriuretic factor in endotoxemia acts in an integrative manner with other hormones on a variety of target organs to modulate cardiovascular function and fluid balance. [ABSTRACT FROM AUTHOR]

On January 30, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic a worldwide emergency. Worldwide there have been 170 million cases of the resulting disease coronavirus 2019 (COVID-19), of those, 3.53 million have resulted in death. The Food and Drug Administration (FDA) with Mayo Clinic as the lead institution authorized COVID-19 convalescent plasma (CCP) for treatment of SARS-CoV-2 infection. Effective therapeutic window for CCP administration had yet to be defined. We addressed this gap by characterizing longitudinal biologic response and clinical outcomes of COVID-19 patients treated with CCP. Primary outcome was discharged to home/home health., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Lattanzio et al.)

Objective: This phase 1b/2 clinical trial (NCT01663857) evaluated the efficacy of ralimetinib in combination with gemcitabine (G) and carboplatin (C), followed by maintenance ralimetinib, for patients with recurrent platinum-sensitive epithelial ovarian cancer., Methods: Phase 1b was to determine the recommended phase 2 dose (RP2D) of ralimetinib administered Q12H on Days 1-10 (q21d) in combination with G (1000 mg/m 2 , Days 3 and 10) and C (AUC 4, Day 3) for six cycles. In phase 2, patients were randomized double-blind 1:1 to ralimetinib (R)+GC or placebo (P)+GC, for six cycles, followed by ralimetinib 300 mg Q12H or placebo on Days 1-14, q28d., Results: 118 patients received at least one dose of ralimetinib or placebo; eight in phase 1b and 110 in phase 2 (R+GC, N = 58; P+GC, N = 52). The RP2D for R+GC was 200 mg Q12H. The study met its primary objective of a statistically significant difference in PFS (median: R+GC, 10.3 mo vs. P+GC, 7.9 mo; hazard ratio [HR] = 0.773, P = 0.2464, against a two-sided false positive rate of 0.4). Secondary objectives were not statistically significant for median overall survival (R+GC, 29.2 mo vs. P+GC, 25.1 mo; HR = 0.827, P = 0.4686) or overall response rate (R+GC 46.6% vs. P+GC, 46.2%; P = 0.9667). The safety profile of R+GC therapy was mainly consistent with safety of the chemotherapy backbone alone. Grade 3/4 elevated alanine aminotransferase was more common in the ralimetinib arm., Conclusions: Addition of ralimetinib to GC resulted in a modest improvement in PFS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose There is a growing demand for BRCA1/ 2 mutation ( BRCAm) testing in patients with ovarian cancer; however, the limited number of genetic counselors presents a potential barrier. To facilitate more widespread BRCAm testing in ovarian cancer, pretest counseling by the oncology team could shorten testing turnaround times and ease the pressure on genetic counselors. Patients and Methods The prospective, observational Evaluating a Streamlined Onco-genetic BRCA Testing and Counseling Model Among Patients With Ovarian Cancer (ENGAGE) study evaluated a streamlined, oncologist-led BRCAm testing pathway. The analysis population comprised 700 patients with ovarian cancer at 26 sites in the United States, Italy, and Spain. The primary objectives were to assess turnaround time and, using questionnaires, to evaluate stakeholder satisfaction (patients, oncologists, and geneticists or genetic counselors) with the oncologist-led BRCAm testing pathway. Results The median overall turnaround time was 9.1 weeks (range, 0.9 to 37.1 weeks), with median turnaround times in the United States, Italy, and Spain of 4.1 weeks (range, 0.9 to 37.1 weeks), 20.4 weeks (range, 2.9 to 35.4 weeks), and 12.0 weeks (range, 2.0 to 36.7 weeks), respectively. Patient satisfaction with the oncologist-led BRCAm testing pathway was high, with > 99% of patients expressing satisfaction with pre- and post- BRCAm test counseling. Oncologist satisfaction with the BRCAm testing pathway was also high, with > 80% agreeing that the process for performing BRCAm testing worked well and that counseling patients on BRCAm testing was an efficient use of their time. Oncologists expressed higher levels of satisfaction with the BRCAm testing pathway than did geneticists or genetic counselors. Conclusion The results of the ENGAGE study demonstrate that an oncologist-led BRCAm testing process is feasible in ovarian cancer. Development of local BRCAm testing guidelines similar to the one used in this study could allow faster treatment decisions and better use of resources in the management of patients with ovarian cancer.

Background: While most gynecologic cancers respond to first-line cytotoxic chemotherapy, treatment of recurrent disease is frequently associated with acquired drug resistance. In order to find an in vitro surrogate of this clinical phenomenon, a tumor chemoresponse assay was studied., Methods/materials: Patients who had tissue submitted for repeated chemoresponse testing were identified through a retrospective search. Sixty-three patients met inclusion criteria (chemoresponse testing completed at primary diagnosis and upon recurrence of disease and assays completed ≥90 days apart). The Wilcoxon signed-rank test was used to compare chemoresponse, represented as a response index (RI), between primary and recurrent measurements. In a secondary analysis, response was categorized and coded as Responsive = 3, Intermediately Responsive = 2 and Non-Responsive = 1, and the paired t-test was used to compare chemoresponse between primary and recurrent measurement., Results: Median time between primary and recurrent tumor testing was 309 days (IQR 208-422). Drugs tested included carboplatin, cisplatin, docetaxel, doxorubicin, gemcitabine, paclitaxel, topotecan, and combination carboplatin/gemcitabine and carboplatin/paclitaxel. There were no differences in chemoresponse between primary and recurrent measurement when chemoresponse was represented by RI scores; although a trend toward increased resistance to paclitaxel upon recurrence was noted. When chemoresponse was analyzed as a continuous variable corresponding to categorized response, a significant shift toward increased resistance to paclitaxel at recurrence, and a marginally significant trend toward increased resistance to carboplatin at recurrence, were observed., Conclusions: We observed a trend toward increased chemoresistance at recurrence for paclitaxel, and a marginally significant trend toward increased chemoresistance to carboplatin, but no change in chemoresponsiveness between primary diagnosis and recurrence of disease for other common chemotherapy drugs, including common second-line agents such as doxorubicin, gemcitabine, and topotecan.

Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2)., Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework., Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049)., Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.

Background: It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area., Methods: Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing., Results: Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the "ovarian cancer cluster region" (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation-positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively., Conclusions: The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status., (Copyright 2005 American Cancer Society.)

This study was undertaken to estimate the antitumor activity of tamoxifen in patients with persistent or recurrent nonsquamous cell carcinoma of the cervix. Furthermore, the nature and degree of adverse effects from tamoxifen in this cohort of individuals was examined. Tamoxifen citrate was to be administered at a dose of 10 mg per orally twice a day until disease progression or unacceptable side effects prevented further therapy. A total of 34 patients (median age: 49 years) were registered to this trial; two were declared ineligible. Thirty-two patients were evaluable for adverse effects and 27 were evaluable for response. There were only six grades 3 and 4 adverse effects reported: leukopenia (in one patient), anemia (in two), emesis (in one), gastrointestinal distress (in one), and neuropathy (in one). The objective response rate was 11.1%, with one complete and two partial responses. In conclusion, tamoxifen appears to have minimal activity in nonsquamous cell carcinoma of the cervix.

Objective: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting., Method: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry-based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed., Results: There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels., Conclusion: LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.

Unlabelled: Clinical usefulness of sentinel lymph node (SLN) biopsy has been demonstrated in the management of early vulvar cancer. However, what constitutes a negative SLN has not been well defined. Furthermore, to what extent the SLNs should be sectioned for the greatest likelihood of detection of micrometastases and whether multilevel sectioning will further increase this detection rate in this setting have not been well studied. We analyzed 280 groin lymph nodes (SLNs=45, non-sentinel [NSLNs]=235) in 14 patients with invasive squamous cell carcinoma (ISCC) of the vulva treated with vulvectomy and inguinal SLN and NSLN dissection at the H. Lee Moffitt Cancer Center (HLMCC) between 1996 and 2001. Each SNL was evaluated for micrometastases by H&E and pancytokeratin AE1/3 (CKAE1/3) immunohistochemical staining. All negative SNLs (N=40) were sectioned times 3 (x3) at 50-micron intervals and independently reviewed by two pathologists in order to assess the utility of this inexpensive and logical approach to identifying additional micrometastases. Also, the Wilcoxon Rank Sum Test was used to determine if there was an association between tumor size, depth of invasion and SNL status. The patient age ranged from 35 to 81 years (mean 59 yrs); size of invasive tumor from 1.0 to 7.0 cm (mean 3.4 cm); depth of invasion from 3 to 25 mm (mean 10.8 mm). Of 45 SLNs examined from 14 patients, 11% (5/45) SNLs were positive for micrometastases on initial H&E and/or CKAE1/3 stains. Eighty-nine per cent (40/45) SNLs were negative in the remaining 9 patients. None of the latter 40 SNLs showed micrometastases on additional multilevel sectioning. Instead 3 of 135 NSLNs examined in these 9 patients revealed micrometastases on H&E (skip-micrometastases). Mean tumor size (cm) and depth of invasion (cm) were 4.06 (s.d. 1.89) and 1.20 (s.d. 0.35) for SLN (+) and 3.02 (s.d. 2.12) and 1.01 (s.d. 0.86) for SLN (-) tumor subsets (p values 0.385 and 0.348, respectively)., Conclusion: Following routine H&E and CK AE1/3 stains, multilevel sectioning does not appear to detect additional micrometastases in sentinel lymph nodes in squamous cell carcinoma of the vulva. Even though mean tumor size and depth of invasion were greater in SNL (+) as compared to SLN (-) tumor subsets in our series, this difference did not reach statistical significance.

Background: The human ovarian surface epithelium (HOSE) is the putative source of ovarian epithelial cancer, the most lethal gynecologic malignancy that affects women in the United States. The current study was designed to provide a database of normal HOSE cell features for diagnostic and research applications., Methods: HOSE was harvested from 42 women undergoing laparoscopy or laparotomy for benign gynecologic disorders, infertility problems, or pregnancy. Of the 42 women, 12 were postovulatory and 20 were receiving hormonal regimens. Cells were harvested with a sterile brush inserted through a laparoscopic port or with a sterile cell scraper at laparotomy., Results: Two HOSE populations were identified, ranging in size from 8 to 10 microm and from 15 to 20 microm, respectively. The cells measuring 15-20 microm exhibited slight anisonucleosis, more prominent nucleoli, fine cytoplasmic metachromasia, and an overall reparative or squamoid morphology. Cells were single or arranged in small clusters, sheets, or papillae. They coexpressed cytokeratin and vimentin but did not overexpress p53. Cellularity and proliferation (up to 3.2% +/- 0.8) were higher and papillae more frequent in postovulatory and cyst-bearing ovaries, including polycystic ovaries, suggesting underlying ovarian or hormonal influences. Representative HOSE brushings yielded a mean of 23,133 cells per patient (range, 4250-64,500 cells), equivalent to an estimated 0.58, 0.46, and 0.14 microg of nuclear protein, cell RNA, and nuclear DNA, respectively. Within 7-10 days of explantation, HOSE cells formed confluent monolayers with immunohistochemical and ultrastructural epithelial features., Conclusions: The current study defined baseline features of HOSE cells important to pathologists and clinicians evaluating women at risk for ovarian epithelial cancer and to researchers investigating the pathobiology of this aggressive gynecologic malignancy., (Copyright 2003 American Cancer Society.)

Purpose: To determine the safety of omitting routine interval laboratory assessments, dietary restrictions, and isolation precautions between cycles of chemotherapy for gynecologic malignancies., Methods: Data were retrospectively obtained from the records of women receiving chemotherapy for gynecologic cancer from July 1999-June 2000. Routine nadir determinations were not performed between treatment cycles; social interaction was encouraged, and pathogen-free diet recommendations were not provided., Results: Eighty women received 449 cycles of chemotherapy. Four (5%) patients developed neutropenic fevers, and one of these women succumbed to sepsis. Eighteen (22.5%) women had 29 cycles delayed due to persistent myelosuppression when the ensuing chemotherapy infusion was to be administered. Hematopoietic growth factors overcame these delays during subsequent cycles in all but two patients., Conclusion: Omitting scheduled interval laboratory monitoring, dietary restrictions, and isolation precautions between chemotherapy cycles is convenient for patients, likely cost-effective, and does not increase morbidity in the gynecologic oncology population.

In the new millennium, practitioners who provide primary care for women of all ages must be well educated in the diagnosis and treatment modalities for breast carcinoma. This disease strikes one of eight women. That statistic alone should encourage diligent and persistent efforts to detect this disease early enough to prevent the large number of deaths annually Early detection will reduce the morbidity associated with breast cancer. Strong efforts are ongoing in the fields of genetics and breast cancer research to achieve earlier detection of breast cancer and a reduction in morbidity regardless of the stage of the breast carcinoma. As results of ongoing studies materialize and new studies are funded, it is hoped that more answers will emerge to combat the devastating effects of breast cancer.

Objective: Our objective was to review our experience with carcinoma of Bartholin's gland relative to treatment and oncologic outcome., Methods: Patient names were collected from our vulvar cancer database for the period September 1985 to September 2000. The medical records were retrospectively reviewed, and data were abstracted relative to demographics, presenting symptoms, treatment, and oncologic outcome., Results: We treated 12 women with Bartholin's gland carcinoma, and 11 patients are reported. Seven women presented with a painless vulvar mass, and 8 of 11 had initially been treated for an infectious process before referral to our institution. Squamous histology was most common, and the right gland was more frequently involved. Ten patients were treated with primary surgery, followed by adjuvant radiation in 7 for inadequate resection margins or lymphatic metastases. One patient was treated with primary chemoradiation. Stage I, II, III, IVA, and IVB disease was present in 3, 1, 4, 2, and 1 patient, respectively. Recurrence was suffered by 54.5% during a mean follow-up time of 73.5 months (median, 60; range, 8-180 months). Overall survival is 58.3% to date., Conclusions: Conventional therapy for Bartholin's gland carcinoma yielded a 67% 5-year survival. Seventy-one percent of women receiving adjuvant radiotherapy recurred despite this precaution. Work is needed to identify an effective systemic therapy and to better determine which patients may benefit from pelvic radiotherapy., (Copyright 2001 Academic Press.)

Gynecologic malignancies account for 15% of all cancer diagnosis in women. Primary lymphatic spread is well recognized in vulvar, cervical, uterine, and ovarian carcinomas. Vulvar carcinoma spreads locally to the inguinofemoral lymph nodes in a relatively predictable fashion similar to the local spread of breast carcinoma. Lymphatic mapping using radioactive colloid should provide adequate means to sample these nodal basins while attempting to reduce postoperative morbidity. Methods of vulvar lymphoscintigraphy are described.

Purpose: The aim of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva., Materials and Methods: In the operating room the gross tumor border was marked. The pathologist took a radial section in each quadrant and measured the distance of occult lateral spread of the tumor., Results: From 7/01/93 to 6/30/96, 24 tumors from 21 patients were studied. The mean maximum tumor diameter was 3. 2 cm (0.5-7.0) and the mean depth of invasion was 9.1 mm (1.1-28.0). The gross and microscopic extent correlated in 20 tumors. Maximum lateral microscopic extent of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative and infiltrative and arose from or involved mucosa., Conclusion: The gross and microscopic periphery of most invasive squamous vulvar cancers are approximately the same. Ulcerative tumors with an infiltrative pattern of invasion which involve mucosal epithelium may be more likely to extend beyond what is grossly apparent. Measurement of the tumor-free margin should be included in future studies., (Copyright 1999 Academic Press.)

A prospective, randomized study of patients undergoing radical hysterectomy for gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if ligation of the hypogastric arteries at the time of radical hysterectomy decreases blood loss. Patients were randomized to either ligation of the hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver type III radical hysterectomy. Surgeries were performed by Board certified gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN residents. Patients were analyzed for demographic characteristics and intraoperative and postoperative parameters. Statistical analysis was performed with independent samples t-test, Mann-Whitney rank sum test, Chi square and Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group 2. Groups were similar with respect to demographics and preoperative parameters except for age. There were no differences among the groups with respect to intraoperative and postoperative parameters. The mean estimated blood loss for group 1 was 600 ml and 550 ml for group 2 (P = NS). Hypogastric artery ligation (HAL) at the time of radical hysterectomy for gynecologic malignancy does not reduce blood loss.

Objective: To identify sentinel lymph nodes using intraoperative lymphoscintigraphy., Methods: Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes., Results: Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive., Conclusion: Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique., (Copyright 1997 Academic Press.)

Purpose: On a long-term basis patients with continent urinary diversions may have an acceptable number of complications, such as urinary incontinence. We report on a new surgical technique for treatment of the incompetent anti-incontinence segment., Materials and Methods: Seven patients presented with a large capacity, low pressure reservoir and an incompetent anti-incontinence mechanism. The original anti-incontinence mechanism consisted of an intussuscepted reimplanted appendix (Mitrofanoff) in 2 patients, tapered ileum and reinforced ileocecal valve in 3, and tapered and reimplanted ileal segment in 2. Surgical reconstruction involved 2 stages: stage 1 - lengthening and tubularizing the cecum with the anti-incontinence segment and stage 2 - creation of the flap valve mechanism. Stage 2 required intraoperative modification when abundant peri-reservoir fibrosis, a thin-walled reservoir (cecal wrap) or an excessive thickened mesentery was encountered., Results: After a mean followup of 7 months 6 of 7 patients performed catheterization every 4 hours and were continent. Several patients required a concomitant procedure with the incontinence revision., Conclusions: We describe a 2-stage technique for correction of a variety of untoward anatomical conditions related to a failed anti-incontinence segment with continent urinary reservoirs. Concomitant repair of other coexisting structural abnormalities related to the continent reservoir may also be necessary.