The molecular pathology of ovarian serous borderline tumors.

Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.

[NEMS: a new predictor of mortality in the critical patient?]. / NEMS: ¿nuevo predictor de mortalidad en el paciente crítico?

Numerical scales are commonly used in intensive care units to predict hospital mortality and to assess the therapeutic effort and care that critically ill patients require. The aim of this work was to study whether the NEMS value can be used as a predictor of mortality, comparing it with the APACHE II. A prospective study in a 24 intensive care unit beds was conducted. The APACHE II and NEMS values were stratified into three levels. Demographic data and the first 24 hours values of APACHE II and NEMS scales were collected. A total of 1257 patients were included, 16.4% of whom died. 69.6% were surgical; median stay was 2 days (1-4). Median age was 66 years (50-77), 59.3% were men. The median APACHE II and NEMS for the living and the dead in the subsequent course was 10 (6-20) versus 22.5 (17.25 to 29) (p <0.001) and 24 (18-29) versus 34 (25 to 39.7) (p<0.001) respectively. The correlation between both scales was rho=0.457 (p<0.01). Logistic regression controlled for age, sex and APACHE II showed an OR of 3.1 (95% CI: 1.5-6.6) only for high NEMS, compared to the lowest level. According to the results NEMS should not be used as a predictor of mortality, although the risk of death increases by three times with high NEMS.

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): cardiac patient]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: paciente cardíaco.

Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hyperglycemia in the first 24 hours in patients admitted for acute coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30-day mortality. In critically-ill cardiac patients with stable hemodynamic failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining adequate nutritional status. Protein intake should be 1.2*-1.5 g/kg/day. Routine polymeric or high protein formulae should be used, according to the patient's prior nutritional status, with sodium and volume restriction according to the patient's clinical situation. The major energy source for myocytes is glutamine, through conversion to glutamate, which also protects the myocardial cell from ischemia in critical situations. Administration of 1 g/ day of omega-3 (EPA+DHA) in the form of fish oil can prevent sudden death in the treatment of acute coronary syndrome and can also help to reduce hospital admission for cardiovascular events in patients with chronic heart failure.

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): patient with polytrauma]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: paciente politraumatizado.

Patients with polytrauma can be viewed as paradigmatic of the critically-ill patient. These previously healthy patients undergo a life-threatening aggression leading to an organic response that is no different from that in other types of patients. The profile of trauma patients has changed and currently corresponds to patients who are somewhat older, with a higher body mass index and greater comorbidity. Severe injuries lead to intense metabolic stress, posing a risk of malnutrition. Therefore, early nutritional support, preferentially through the enteral route, with appropriate protein intake and glutamine supplementation, provides advantages over other routes and types of nutritional formula. To avoid overnutrition, reduced daily calorie intake can be considered in obese patients and in those with medullary lesions. However, little information on this topic is available in patients with medullary lesions.

Polypoid or non-polypoid? A novel dichotomous approach to uterine carcinosarcoma.

OBJECTIVE: To examine the impact of the polypoid morphology of uterine carcinosarcoma on clinical outcome, as well as its relationship to well-established prognostic factors. METHODS: In a retrospective study of fifty eight patients with uterine carcinosarcoma treated with hysterectomy, we correlated the polypoid status of tumors with stage, lymphatic vascular invasion, myometrial invasion, size, carcinoma to sarcoma ratio, type of carcinomatous and sarcomatous components, disease free survival and overall survival. RESULTS: By multivariate analysis, the polypoid status had no impact on disease free survival (p=0.8958), but approached significance as a positive predictor for overall survival (p=0.0569); patients in the polypoid group lived on average 14.9 months longer than those with non-polypoid tumors. Polypoid neoplasms had a smaller average size and grew to a smaller maximum size than the non-polypoid tumors. While non-polypoid tumors were either carcinoma or sarcoma predominant, polypoid tumors were mostly sarcoma predominant (p=0.0348). Polypoid carcinosarcomas also demonstrated an appreciably lesser extent of myometrial invasion (p=0.0019), a markedly lower rate of lymphatic vascular invasion (p=0.0002), and tended to present as early stage tumors (p=0.0265). Carcinomatous component in polypoid tumors tended to have pure or nearly pure (>or=90%) endometrioid histology (p=0.1608). There was no relationship between polypoid status and type of sarcomatous component (p=0.5299). CONCLUSIONS: Polypoid carcinosarcomas differ from their non-polypoid counterparts in key histological parameters such as the carcinoma to sarcoma ratio, myometrial and lymphatic vascular invasion, stage and type of carcinomatous component. Patients with polypoid tumors may have a better survival outcome than those with non-polypoid tumors.

Epidermal growth factor receptor expression in cervical intraepithelial neoplasia and its modulation during an alpha-difluoromethylornithine chemoprevention trial.

Chemoprevention trials designed to prevent progression to invasive cervical cancer will benefit from the identification of biomarkers that assess the risk of developing tumors, predict likelihood of response to treatment, and measure biological response to intervention. The purpose of this study was to examine expression of epidermal growth factor receptor (EGFR) as a marker for progression of cervical intraepithelial neoplasia (CIN) and as a surrogate end point biomarker in a chemoprevention trial with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. To evaluate quantitative and spatial changes in EGFR expression during cervical tumorigenesis, paraffin sections from 42 archival cervical cone biopsies, each containing multiple stages of CIN, were immunohistochemically stained for EGFR, and the level and spatial expression of EGFR were quantitated by image analysis. In the progression from normal epithelium to CIN 1 to CIN 2 to CIN 3 to invasive cancer, EGFR expression showed two types of changes. Normal control epithelium showed EGFR expression predominantly confined to the basal layer, while histologically normal epithelium in specimens containing CIN showed relatively increased EGFR expression in the basal layer and the extension of EGFR expression away from the basal layer. The total EGFR relative staining intensity (RSI) of epithelium increased with the degree of CIN, predominantly due to a progressive expansion of EGFR-expressing cells away from the basal layer rather than an increase in the level of EGFR expression per cell. To determine whether EGFR expression would be modulated by a 1-month chemopreventive intervention with DFMO, pretreatment and posttreatment cervical biopsy specimens from 25 patients (22 evaluable) were examined for EGFR expression. Although the overall levels of EGFR expression were not modulated in either histological responders or nonresponders, responders showed a prominent down-regulation of EGFR expression away from the basal layer after DFMO treatment. Interestingly, pretreatment EGFR expression levels predicted for DFMO response [i.e., eight responses (72.7%) for 11 cases with RSI levels below 0.35 versus one response (9.1%) for 11 cases with RSI levels above 0.35 (P < 0.01)]. These results suggest that CIN progression is associated with a spatial dysregulation of EGFR expression that can be reversed by DFMO treatment, especially in patients whose pretreatment CIN 3 lesions exhibit relatively low EGFR expression.

A randomized clinical trial of 4-hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the cervix.

PURPOSE: Previous trials of topical trans-retinoic acid treatment of cervical intraepithelial neoplasia (CIN) grades 2 and 3 led to a statistically significant regression of CIN 2, but not CIN 3. We tested N-(4-hydroxyphenyl)retinamide (4-HPR), a promising oral retinoid that has been shown to induce apoptosis through nonretinoic receptor acid-mediated pathways, for its toxicity and efficacy against CIN 2/3. EXPERIMENTAL DESIGN: In a blinded randomized trial, 4-HPR at 200 mg/day for 6 months (with a 3-day/month drug holiday) was compared with placebo in patients with biopsy-proven CIN-2/3 [high-grade squamous intraepithelial lesions (HGSILs)]. Patients were treated with placebo or 4-HPR for 6 months, biopsied, and then followed for an additional 6 months. At the 12-month end point, they underwent either loop excision if a histological lesion was present or a biopsy from the original area of the lesion if no lesion was present. RESULTS: An interim analysis of blinded data showed a significantly worse prognosis at 12 months for one group. When the code was broken because of the poorer outcomes, we discovered that the 4-HPR treatment arm was performing more poorly than was the placebo at 6 and 12 months (25 versus 44% response rates at 6 months; 14 versus 50% at 12 months). Toxicity was not significant in either arm. CONCLUSIONS: 4-HPR at 200 mg/day with a 3-day/month drug holiday is not active compared with placebo in the treatment of HGSIL. Because 4-HPR is active in the laboratory, the lack of effect in our trial may indicate that higher doses are needed in patients to achieve comparable results.

[Nutritional support in sepsis]. / Nutrición artificial en la sepsis.

Although it is considered that metabolic and nutritional support must be part of the management of septic patients, it has not been conclusively shown that nutritional support will improve survival or complications from sepsis. Specific data on this issue are scarce since there are few studies that have investigated specialized nutritional support in septic patients. Thus, most of the recommendations are based on outcomes obtained in severely ill patients with different pathologies. It is assumed that nutritional support should be carried out through the enteral route whenever possible, as in other critically ill patients. The energetic waste in these patients is highly variable, although in general terms the hypermetabolic situation may be classified as moderate. An adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation to calculate the caloric intake. Septic patients should receive a hyperproteic intake. The amount of glucose administered should not exceed 70% of non-protein calories, and lipids intake should not exceed 40%. With regards to micronutrients, it is recommended to increase the supply of those with antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are data to consider that the use of diets enriched with pharmaco-nutrients (both with parenteral and enteral routes) may be beneficial in septic patients, although there is some controversy when interpreting the outcomes.

[Nutritional support in the critically ill patient: to whom, how, and when?]. / Soporte nutricional del paciente crítico: a quién, cómo y cuándo?

Existing data about indication and time of onset of nutritional support are not homogeneous. However, the presence of a deterioration of the nutritional status is accompanied by harmful effects so that, broadly speaking, specialized nutritional support onset would be advisable if a fasting period longer than 5-7 days is foreseen. Parenteral nutrition routinely administered to critically ill patients may increase their morbidity and mortality. Whenever possible, enteral nutrition should be the preferred route of nutrients intake since it has been shown to have a favorable effect on infectious complications rates. Enteral nutrition should be started early on (within the first 36 hours of admission). Although transpyloric nutrients administration may however reduce bronchoaspiration and increase the diet effective volume received by patients, there are no data for recommending routinary usage of the transpyloric route for nutritional support in the critically ill patients.

[Recommendations for nutritional assessment and specialized nutritional support of critically ill patients]. / Recomendaciones para la valoración nutricional y el soporte nutricional especializado de los pacientes críticos.

Due to the characteristics of critically ill patients, elaborating recommendations on nutritional support for these patients is difficult. Usually the time of onset of nutritional support or its features are not well established, so that its application is based on experts' opinion. In the present document, recommendations formulated by the Metabolism and Nutrition Working Group of the Spanish Society of Intensive and Critical Medicine and Coronary Units (SEMICYUC) are presented. Recommendations are based on the literature analysis and further discussion by the working group members in order to define, consensually, the more relevant issues of metabolic and nutritional support of patients in a critical condition. Several clinical situations have been considered which are developed in the following articles of this publication. The present recommendations aim at providing a guideline for the less experienced clinicians when considering the metabolic and nutritional issues of critically ill patients.

Progressive dysregulation of proliferation during cervical carcinogenesis as measured by MPM-2 antibody staining.

To better characterize the amount and location of loss of proliferation control during cervical carcinogenesis, 44 cervical cone biopsy specimens containing various grades of premalignant and malignant lesions and 12 normal cervix specimens were immunohistochemically examined using MPM-2. This antibody recognizes a phosphorylated epitope on a group of proteins that are preferentially phosphorylated at mitosis. The spatial organization of mitotic figures was determined using a computer-assisted image analysis system. The mitotic figure frequencies/unit of epithelial area were found to increase as the histological type progressed; the numbers of mitoses/square millimeter was 1.7 +/- 0.5 (mean +/- SE) for control normal epithelium (n = 12), 3.1 +/- 1.7 for normal epithelium adjacent to cervical intraepithelial neoplasia (CIN) and cancer (n = 28), 7.9 +/- 1.3 for CIN1 (n = 24), 75.8 +/- 16.3 for CIN2 (n = 11), 127.2 +/- 9.7 for CIN3 (n = 22), 196.9 +/- 33.2 for carcinoma in situ (n = 9), and 156.2 +/- 31.0 for cervical carcinoma (n = 8). The MPM-2 index was higher in high-risk premalignant lesions (i.e., those adjacent to areas of high-grade CIN and carcinoma) than it was in lower risk premalignant lesions (i.e., those with no adjacent higher grade CIN or cervical cancer), even if they exhibited the same histological grade. Moreover, the mean relative distance of the mitotic cells from the basement membrane (i.e., the distance from the basal layer to the surface) also increased as the histological grade progressed. These results suggest that proliferation becomes sequentially dysregulated both quantitatively and spatially during cervical carcinogenesis and that the MPM-2 antibody might be useful as a proliferation biomarker.

DNA image cytometric measurement as a surrogate end point biomarker in a phase I trial of alpha-difluoromethylornithine for cervical intraepithelial neoplasia.

Cervical intraepithelial neoplasia grade 3 (CIN 3) is considered a high-risk precursor of invasive cervical cancer. alpha-Difluoromethylornithine (DFMO) is a promising antiproliferative chemopreventive agent. The purpose of this study was to evaluate image cytometric measurement of nuclear DNA (ICM-DNA) as a surrogate end point biomarker (SEB) in a Phase I trial of DFMO for CIN. Thirty patients with CIN 3 were treated with DFMO at five doses, ranging from 0.0625 to 1.0 g/m2/day, for 1 month. Half of the patients had histological responses. Twenty-five pre- and posttreatment cervical biopsy specimens (from 11 responders and 14 nonresponders) were available for this analysis. ICM-DNA was performed on 4-micron sections cut from formalin-fixed tissue blocks and stained with a thionin-SO2 Feulgen reaction. ICM-DNAs for each case were expressed as normalized measurements (against the nuclear modal absorbance of lymphocytes) of the absorbance of each cell of interest and were presented in bar histograms. The mean normalized summed absorbance (sigma ODn) was obtained as a mean histogram of the cell population of interest. Nineteen (76%) of 25 patients had a significant decrease in sigma ODn after DFMO treatment. Posttreatment values were significantly lower than pretreatment values in a paired analysis, and responders had significantly lower values than nonresponders. Analyses of different ICM-DNA references, including percentile values of sigma ODn distribution, DNA malignancy grade, and 5c exceeding rate, showed a decrease of mean sigma ODn during DFMO treatment. In addition, the summed posttreatment sigma ODn histograms also showed progressively shorter right shoulders compared with pretreatment histograms in both responders and nonresponders. We concluded that the modulation of sigma ODn reflected the chemoprevention effect of DFMO even before morphological changes appeared, and thus, ICM-DNA may be useful as a SEB in chemoprevention trials of DFMO. Additional reasons for using ICM-DNA as a SEB are the relative simplicity of its use, the high accuracy of the results, the low cost of the reagents, the ability to use small tissue samples, and the objectivity and reproducibility of the procedure.

Low-stage clear-cell carcinoma of the endometrium.

Clear-cell carcinoma (CCC) of the endometrium is a relatively rare malignancy that is considered to be one of the most aggressive types of endometrial carcinoma. To evaluate the behavior of low-stage (stages I and II) CCC of the endometrium, we retrospectively reviewed 17 such cases seen at The University of Texas M.D. Anderson Cancer Center from 1963 to 1990. Patients' ages ranged from 52 to 81 years. Fifteen cases were pure CCC, and two cases were predominantly CCC with a focus of endometrioid adenocarcinoma FIGO grade I. All patients have been followed-up for at least 3 years. At the time of the study, six patients were alive without disease, one patient was alive with disease, five had died of other causes, and five had died of disease. The estimated survival rate was 71%. Estimated 5-year survival rates for endometrioid adenocarcinoma FIGO grade III and uterine papillary serous carcinoma are 73 and 39%, respectively. We conclude that patients with low-stage CCC of the endometrium have a survival rate similar to that of patients with endometrioid adenocarcinoma FIGO grade III and better than that of patients with uterine papillary serous carcinoma of similar stages.

Serous tumors involving extra-abdominal/extra-pelvic sites after the diagnosis of an ovarian serous neoplasm of low malignant potential.

The involvement of extra-abdominal/extra-pelvic sites by serous tumors after the diagnosis of an ovarian serous neoplasm of low malignant potential is extremely rare. In this study we present the clinicopathologic features of 12 such cases seen at our institution during a period of 19 years (1980-1999). The patients' age ranged from 19 to 50 years (mean 33 years). By FIGO staging the original ovarian tumors were distributed as follows: stage I, 4; stage II, 2; stage III, 5; unknown stage, 1. All patients were treated surgically. Ten patients also received adjuvant therapy (radiotherapy, 2; chemotherapy and radiotherapy, 4; chemotherapy, 3; intraperitoneal 32P, 1). The interval between the diagnosis of the ovarian neoplasm and the subsequent tumor involving an extra-abdominal/extra-pelvic site ranged from 4 to 240 months (mean 124 months). Sites of extra-abdominal/extra-pelvic involvement and the number of cases were as follows: left neck lymph nodes (LNs), 4; left and right neck LNs, 1; pleura, 2; lung, 1; mediastinum, 1; chest wall, 1; axillary and chest LNs, 1; and vertebral body, 1. Eight patients were treated with chemotherapy, 1 with radiotherapy, 2 with chemotherapy and radiotherapy, and 1 with surgery alone. Follow-up ranging from 5 months to 18 years was available in 11 patients. Six patients died of disease and 5 patients were alive with no evidence of disease. In this small series of cases, no definitive clinical or pathologic feature related to the occurrence of extra-abdominal/extra-pelvic serous tumors was found. Based on the LN involvement and the endosalpingiosis seen in some cases, these tumors might develop from circulating neoplastic serous cells or from areas of endosalpingiosis involving extra-abdominal/extra-pelvic sites.

Vessels within vessels in the myometrium.

We have encountered a peculiar vascular architecture in the myometrium wherein arteries are found free-floating within cleft-like spaces. Using different colored dye injections in the uterine arteries and veins, we demonstrated that these spaces are venous channels. This was confirmed by immunoperoxidase staining for CD34, which enhanced the cells lining these spaces. A review of 81 hysterectomy specimens showed that this vascular architecture was present in 42 cases (52%), while it was identified in the parenchyma of only two mastectomy specimens among the 45 specimens from different organs studied. A strong association existed between the presence of this architecture and history of menorrhagia (p = 0.0116). This peculiar vascular architecture might be important in the pathogenesis of menorrhagia and the development of intravenous leiomyomatosis. Pathologists should also be able to recognize these spaces as vascular channels in the event that malignant cells are identified within them.

Near real time confocal microscopy of amelanotic tissue: dynamics of aceto-whitening enable nuclear segmentation.

High resolution, in vivo confocal imaging of amelanotic epithelial tissue may offer a clinically useful adjunct to standard histopathologic techniques. Application of acetic acid has been shown to enhance contrast in confocal images of these tissues. In this study, we record the time course of aceto-whitening at the cellular level and determine whether the contrast provided enables quantitative feature analysis. Confocal images and videos of cervical specimens were obtained throughout the epithelium before, during and post-acetic acid after the application of 6% acetic acid. Aceto-whitening occurs within seconds after the application. The confocal imaging system resolved sub-cellular detail throughout the entire epithelial thickness and provided sufficient contrast to enable quantitative feature analysis.

Nephrogenic adenoma of the prostatic urethra involving the prostate gland: a clinicopathologic and immunohistochemical study of eight cases.

Nephrogenic adenoma (NA) of the prostatic urethra with involvement of the prostate gland can mimic other small-gland proliferations of the prostate, particularly adenocarcinoma of the prostate. To further characterize this lesion and refine diagnostic criteria we retrospectively reviewed the clinicopathologic features and immunohistochemical findings of eight cases of NA involving the prostate gland seen at The University of Texas M.D. Anderson Cancer Center from 1987 to 1992. The patients' ages ranged from 44 to 76 years (average age, 65 years). Six patients had lower genitourinary tract operations. Follow-up information was available for six patients (follow-up period, 5 to 38 months); only one patient had clinical evidence of recurrence (5 months after surgery). The remaining patients were alive and well with no evidence of disease. Histologically, NA was characterized by a proliferation of small tubules lined by a single layer of cuboidal or flattened cells with clear or eosinophilic cytoplasm. The nuclei were round with fine chromatin and there was no mitotic activity. Nucleoli were generally small, but occasionally prominent. All NA extended into the prostatic parenchyma, raising the possibility that these lesions may represent prostatic small-gland proliferations, particularly prostate adenocarcinoma. However, all cases tested were negative for prostate-specific antigen and prostatic acid phosphatase. Our findings indicate that the histologic features and the use of prostate-specific antigen and prostatic acid phosphatase immunostains will help to distinguish NA of the urethra involving the prostate from other small-gland proliferations (eg, small-acinar adenocarcinoma of the prostate, clear cell adenocarcinoma of the urethra, sclerosing adenosis, atypical adenomatous hyperplasia, florid hyperplasia of mesonephric remnants, simple lobular atrophy, and incomplete basal cell hyperplasia).

Immunohistochemical localization of human immunodeficiency virus p24 antigen in placental tissue.

As human immunodeficiency virus (HIV) infection spreads into the heterosexual population, perinatally acquired HIV infection will increase in incidence, and knowledge of the mechanism of this transfer is important. We have used immunoperoxidase techniques to detect HIV p24 antigen in formalin-fixed, paraffin-embedded placental tissue from nine known HIV serologically positive mothers. In four of these cases we have detected evidence or viral antigen in placental Hofbauer cells, vascular endothelium, or intermediate trophoblast. The implications for understanding the mode of transfer of infection to the fetus are discussed.

Intraoperative lymphatic mapping for vulvar cancer.

OBJECTIVE: To determine the feasibility of intraoperative lymphatic mapping in patients with vulvar cancer. METHODS: Isosulfan blue was injected intradermally at the junction of tumor and normal skin in nine patients. We then attempted to identify the dye in the superficial lymphatic channels and in a superficial groin lymph node. RESULTS: The sentinel node was identified in seven of 12 groins in seven of the nine subjects studied. Six of the successful cases had unilateral lesions. The cases in which a sentinel node was not identified were both patients with midline lesions, including one whose scar was injected following a prior wide local excision of a perineal tumor and one who appeared to have direct drainage to the deep pelvic nodes. There were no technique-related complications. In no case was there a positive non-sentinel node in the presence of a negative sentinel node. CONCLUSION: Intraoperative lymphatic mapping is technically feasible in patients with vulvar cancer, particularly those with unilateral disease. Further experience is needed to evaluate the reliability of the technique in identification of groin node metastases.