Tumor board in gynecologic oncology.

OBJECTIVE: This study evaluates the influence of a weekly tumor conference on the management of patient care in a gynecologic oncology service. METHODS: The study utilizes all patients discussed in the gyncologic oncology tumor conference at the University of Texas Medical Branch (UTMB) from January 1, 1998, to January 1, 2001. Patient's information (age, race, cancer site, stage, new cancer versus recurrent) was abstracted from the minutes and attendant log of the tumor board. We compared the pathology and diagnosis for each patient as stated both before and after presentation at the tumor board. A discrepancy is defined as a change in tumor site, stage, or treatment, resulting from findings discussed at tumor board meetings. Major discrepancy is defined as changes that affect patient care. Minor discrepancy is defined as changes that do not affect patient care. RESULTS: During the study period, a total of 459 cases were discussed (391 new cancer, 68 recurrent cancer). At each tumor conference, we discussed a mean of 3.7 cases (range 1-9, standard deviation 1.68). Thirty-two cases (6.9%) showed discrepancies with 23 major discrepancies and nine minor discrepancies. As a result of the tumor board, the two most common therapeutic changes were the addition of chemotherapy and surgery. CONCLUSIONS: In this study, a gynecologic oncology tumor board added clinical information available to pathologists, thereby alters final diagnosis and affects patient medical care.

Subjective versus objective nutritional assessment study in women with gynecological cancer: a prospective cohort trial.

OBJECTIVE: Nutritional evaluation of cancer patients may lead to treatment intervention that reduces morbidity and mortality. This evaluation can be done subjectively or objectively. We studied the correlation between subjective and objective nutritional assessment in gynecological oncology patients. METHODS: Sixty-seven consecutive patients admitted to the gynecological oncology service were prospectively evaluated by laboratory criteria using a standardized formula. The prognostic nutritional index (PNI) consists of tests measuring albumin, transferrin, triceps skin fold, and skin sensitivity reaction to common antigens. The patients were also subjectively evaluated using a standardized questionnaire and physical examination, known as the subjective global assessment, by two clinicians who were blinded from the PNI results. Both scores were categorized as normal, mild malnutrition, or severe malnutrition. Reproducibility of the subjective testers and consistency between the subjective and the objective evaluations were assessed with a weighted kappa statistic. RESULTS: Cancer distribution consisted of 39 (58%) cervical, 16 (24%) endometrial, 11 (16%) ovarian, and one (2%) vulvar carcinomas. There was a high level of agreement between the two subjective raters (weighted kappa = 0.797; 95% CI 0.67-0.92). Furthermore, there were no cases in which the ratings differed by two points on the three-point ordered scale of nutritional status. Agreement between the two evaluation methods was only fair to moderate (weighted kappa = 0.435; 95% CI 0.28-0.59). Agreement was exact in 38 of 67 patients (57%). There were eight patients (12%) where the difference in ratings differed by two points on the ordinal scale, all with the subjective scored as normal, but the objective rated as severe malnourishment. CONCLUSION: In assessing nutritional status of gynecological patients, subjective assessment differs with objective/laboratory measurement.

Effect of hemodilution on tissue perfusion and blood coagulation during radical hysterectomy.

OBJECTIVE: The goal of this study was to evaluate the safety of hemodilution on global and splanchnic perfusion and blood coagulation during radical hysterectomy. METHODS: A pulmonary artery catheter and a gastric tonometry catheter were placed in 16 patients with cervical carcinoma. Global perfusion indices, splanchnic perfusion index, and coagulation tests were obtained. Blood was removed to achieve a hemoglobin measurement of 8-9 9 g/dL. Three more measurements were repeated after hemodilution, at the end of surgery, and after the retransfusion of blood. Analysis of variance was used to determine statistical significance. RESULTS: Sixteen patients with cervical carcinoma had 1.0 +/- 0.3 L (mean +/- SD) of blood removed and had a blood loss of 0.8 +/- 0.7 L. Hemodiluted preoperative hemoglobin was 8.7 +/- 1 g/dL. All of the global perfusion indices, except for arterial pH and oxygen consumption, decreased after hemodilution and recovered with the retransfusion of blood (P < or = 0.004). Splanchnic perfusion and coagulation tests were unchanged (P > or = 0.1). Major complication was pulmonary edema in one patient. CONCLUSION: Hemodilution during radical hysterectomy, in this select group of patients, does not appear to compromise tissue perfusion or coagulation.

Surgical blood loss in abdominal hysterectomy.

OBJECTIVE: The aim of this study was to evaluate additional error in estimating red cell loss during abdominal hysterectomy. METHODS: Eighty patients admitted consecutively for abdominal hysterectomy were recruited. The surgeries were done after heparinizing the suction tubing system to prevent clotting and reducing the vacuum pressure to reduce red cell lysis. At the end of the surgery, hematocrit was measured and compared with the patient's venous blood and the blood from the suction container. The Mann-Whitney test evaluated statistical significance. RESULTS: Eight patients were excluded for having a hemolyzed blood sample, receiving a blood transfusion, and having incomplete data. The study cohort consisted of 72 patients: 54 had a simple hysterectomy and 18 had a radical hysterectomy with pelvic and periaortic lymphadenectomy. The hematocrit (mean +/- standard deviation) in the suction container (19.8 +/- 8.8%) was lower than the hematocrit from the venous blood sample (32.4 +/- 6%) (P < 0.001). The hematocrit in the suction container decreased as the duration of the surgeries increased. Although the volume of blood in the suction container was used to estimate blood loss, the concentration of red cells in the container was consistently lower than those in the venous blood sample. The magnitude of dilution increased as the length and radical nature of the surgery increased. CONCLUSIONS: These findings suggest that other fluid, probably lymph, contributes to the dilution of red cells in the container and increases the estimated blood volume loss during surgery. Estimation of red cell surgical blood loss becomes less accurate as the length and radical nature of the surgery increase.

p53 Adenovirus as Gene Therapy for Ovarian Cancer.

Ovarian cancer arises from the accumulation of mutations in multiple combinations of genes (1). The most extensively studied tumor suppressor gene in solid tumors is p53, a 53-kD nuclear phosphoprotein that binds DNA. The p53 gene product plays a role in normal cellular proliferation by regulating gene transcription, cell cycle control, and apoptosis (2). Mutations of p53 are the most common molecular genetic abnormality to be described in human cancer, and have been identified in malignancies of the breast, colon, lung, esophagus, head and neck, and hematopoietic system (3). Mutations of the p53 gene have been identified in 30 to 79% of epithelial ovarian cancers (4,5). Most of the mutations identified in p53 are distributed throughout the open reading frame as missense mutations. We have identified a missense mutation in the p53 gene in the 2774 ovarian cancer cell line that converts an arginine residue in the DNA binding region of the protein to a histidine residue (6). The mutation in codon 273 we found in 2774 cells is one of the six major hotspots identified for p53 missense mutations (7).

Prognostic nutritional index in relation to hospital stay in women with gynecologic cancer.

OBJECTIVE: To estimate the prevalence of malnutrition, correlate it with length of hospital stay, and evaluate laboratory tools to define it in gynecologic oncology. METHODS: Sixty-seven consecutive hospitalized gynecologic oncology patients were evaluated prospectively using the standardized Prognostic Nutritional Index method, based on serum albumin, transferrin, triceps skin fold and skin sensitivity tests, which defines criteria for malnourished and nourished patients. It was correlated with length of hospital stay. The Mann-Whitney test and Pearson's correlation coefficient were used to evaluate statistical relationships. RESULTS: Cancer distribution among study subjects was 39 cervical (58%), 16 uterine (24%), 11 ovarian (16%), and one vulvar (2%). Malnutrition was found in 36 of 67 women (54%; 95% confidence interval [CI] 41%, 66%). The median (interquartile range) hospital stays of nourished women (n = 31) and malnourished women (n = 36) were 6 (range 4-7) days and 8 (range 6-16) days, respectively (two-sided P =.004). That difference remained after controlling for age, extent of metastases, and cancer sites. Albumin correlated well with Prognostic Nutritional Index (R = -.78; 95% CI -.86, -.66; P <.001). Albumin also correlated with length of hospital stay R = -.41; 95% CI -.56, -.25; P <.001). CONCLUSION: Malnutrition is common in gynecologic oncology patients and contributes to longer hospital stays. Albumin is a good substitute for the Prognostic Nutritional Index laboratory test for assessing malnutrition.

Vulvar carcinoma.

Carcinoma of the vulva is an uncommon gynecologic malignancy primarily affecting postmenopausal women. The lesion is most commonly associated with HPV DNA, although, for many, a defined preinvasive to invasive connection is not readily apparent. Most patients experience symptoms of pruritus, irritation, and even pain for weeks or months before the diagnostic biopsy is performed. Patient embarrassment and unfamiliarity and reluctance on the part of the physician to fully evaluate these symptoms add to the delay. Vulvar carcinoma is staged surgically following resection. A concerted effort to conserve as much normal tissue as possible has been the focus of recent investigation. Separate incision resection of the vulvar mass and groin has improved wound healing and quality of life for many patients. The effect these conservative procedures have on long-term survival is currently being evaluated. Increased use of radiation therapy or chemoradiation has allowed organ preservation in many otherwise exenterative cases. In some instances, this neoadjuvant therapy has provided an opportunity to surgically clear otherwise unresectable lesions. Current radiotherapy techniques might also be as effective as groin dissection in certain low-risk patients. Adjuvant radiation and chemoradiation improve local control and reduce groin recurrence risk. In addition, patients with histologically positive groins enjoy longer survival when the pelvis is also treated. Selected use of multimodality therapy will likely extend the lives of women with vulvar cancer.

Postpartum regression rates of antepartum cervical intraepithelial neoplasia II and III lesions.

OBJECTIVE: To study the histologic regression and progression rates of cervical intraepithelial neoplasia (CIN) II and III after delivery and the effect the route of delivery has on the regression rates of CIN. METHODS: Pregnant patients with satisfactory colposcopic examinations and biopsy-proven CIN II and III were identified. Delivery information and postpartum biopsy results were obtained by chart review. RESULTS: Two hundred seventy-nine patients had antepartum biopsies of CIN II or CIN III. Of these, 126 women were excluded for the following reasons: lost to follow-up (75), human immunodeficiency virus positive (two), cesarean hysterectomy (four), and inadequate postpartum follow-up (45). This yielded a study group of 153 patients consisting of 82 with CIN II and 71 with CIN III. The regression rates were 68% and 70% among CIN II and CIN III patients (P = .78), respectively. Seven percent of patients with CIN II progressed to CIN III on postpartum evaluation. Twenty-five percent of those patients with CIN II and 30% of those with CIN III remained the same postpartum. No CIN lesions progressed to invasive carcinoma. There were no differences in regression rates or progression rates among the women who had vaginal deliveries (130), women who labored and then underwent cesarean (17), or women who proceeded to a cesarean without laboring (six). CONCLUSION: We found similar high postpartum regression rates despite the route of delivery. We recommend conservative antepartum management with postpartum colposcopic evaluation regardless of route of delivery because we are unable to predict which of these lesions are more likely to regress.

Comparison of gastric mucosal pH and clinical judgement in critically ill patients.

OBJECTIVES: To compare gastric tonometry (pHi) with estimates of pHi in ill injured patients, and to correlate pHi with haemodynamic variables. DESIGN: Prospective, non-interventional study. SETTING: ICU of Level I trauma centre, USA. MAIN OUTCOME MEASURES: 154 gastric tonometry measurements were compared with physicians' estimates of adequacy of resuscitation. Resuscitation was categorised as inadequate (pHi < 7.35) or adequate (pHi> or = 7.35). Measured and estimated pHi were also compared with oxygen delivery, oxygen consumption, cardiac index, mixed venous O2 saturation, and critical illness scores. RESULTS: Estimated pHi was often higher than measured pHi in the judgement of all four surgical intensive care physicians. Measured pHi correlated positively with mixed venous O2 tension (r = 0.21). There were significant negative correlations between measured pHi and both oxygen delivery (r = -0.25) and oxygen consumption (r = 0.28). Estimated pHi correlated positively with mean arterial pressure (r = 0.21) and hospital day (r = 0.26); it correlated negatively with pulmonary arterial elastance (r = -0.35). CONCLUSION: Experienced intensive care physicians tended to overestimate visceral perfusion, which suggests that gastric tonometry adds useful information over and above routine haemodynamic indices. Arterial blood pressure and mixed venous oxygen saturation correlated better with measured pHi than with other indices of perfusion.

In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer.

OBJECTIVES: To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (i.p.) 2774 human ovarian cancer cell line that contains a p53 mutation. STUDY DESIGN: An initial study of adenovirus tolerance was determined in nude mice by a single i.p. injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD100 dose of 1 x 10(7) cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-beta gal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 x 10(8) pfu of Ad-CMV-p53. RESULTS: The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 x 10(8) pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P = 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-beta gal-treated mice. CONCLUSIONS: These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibition in vivo. Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.

Pathology slide review in gynecologic oncology.

OBJECTIVE: To analyze the diagnostic accuracy and alteration in treatment planning from interinstitution (different institution) pathologic consultation. METHODS: We reviewed pathologic reports from 720 referred patients. The diagnosis rendered from a gynecologic pathologist was compared with the original diagnosis. Discrepancies were coded as none, minor, or major. A discrepancy was major if it led to treatment alteration. A discrepancy was minor if it did not lead to treatment alteration. The judgment to declare a discrepancy was made by a gynecologic pathologist, a gynecologist, and three gynecologic oncologists. The review cost was $150 per case. The Cochran-Mantel-Haenszel test evaluated any systematic pattern in discrepancies. RESULTS: Seven hundred twenty specimens consisted of 113 vulvar, 170 uterine, 289 cervical, 105 ovarian, and 43 vaginal tissues. Six hundred one (84%) pathologic diagnoses showed no discrepancy. There were 104 (14%) minor and 15 (2%) major discrepancies. After reviewing 15 major discrepancies, six surgeries were canceled, two surgeries were modified, one adjuvant radiation treatment was added, one chemotherapy treatment was modified, and five adjuvant chemotherapy treatments were cancelled. No systematic error was identified with regard to the sources (tissue origin) or methods of obtaining the specimen (P = .675). The cost of reviewing 720 specimens was $108,000. The cost of identifying each major discrepancy was $7200. CONCLUSION: Reviewing pathology slides before definitive treatment reveals notable discrepancies in diagnoses. The cost of pathology review is globally expensive but has consequential impact on proper treatment planning for the individual patient.

Does glutamine supplementation increase radioresistance in squamous cell carcinoma of the cervix?

OBJECTIVE: Glutamine is proposed to protect bowel from radiation. However, glutamine may decrease cancer's radiosensitivity. We evaluate glutamine's effect on the growth rate and radiosensitivity of two cervical carcinoma cell lines in vitro. METHODS: HeLa and CaSki cells were seeded at 3000 cells/well in glutamine-free medium. An increasing amount of glutamine (0.4, 10, and 20 mM) was added to the respective plates, incubated, and irradiated with a single fraction of 0.5, 1, 3, and 6 Gy. Using a growth inhibition assay and photometric analysis, the viable cells were counted on day 8. Cell counts represent a mean +/- standard deviation from six experiments and are expressed in 10(3) cells. Analysis of variance was performed. RESULTS: In nonirradiated HeLa plates, absence of glutamine results in 5.7 +/- 1.2 cells/well. Addition of glutamine at 0.4, 10, and 20 mM to nonirradiated cells significantly (P < 0.0001) increased growth to 79.1 +/- 10.0, 122.5 +/- 9.0, and 114.3 +/- 13.9 cells/well, respectively. In culture plates irradiated with 6 Gy, HeLa cells supplemented with 0.4, 10, and 20 mM of glutamine showed lower cell counts (P < 0.008). A similar significant growth suppression at 6 Gy in comparison to 0.5, 1, and 3 Gy was observed (P < 0.01). CaSki cells showed similar patterns. CONCLUSIONS: Growth of HeLa and CaSki cells in vitro requires a minimum of 0.4 mM of glutamine in the medium. Supraphysiologic glutamine concentration does not increase tumor growth or radioresistance. Glutamine should be evaluated further as a potential bowel radioprotector.

Adenovirus-based p53 gene therapy in ovarian cancer.

Mutations of the p53 tumor suppressor gene are the most common molecular genetic abnormality to be described in ovarian cancer. To determine the feasibility of mutant p53 as a molecular target for gene therapy in ovarian cancer, we constructed an adenovirus vector containing the wild-type p53 gene. The ability of this adenovirus construct (Ad-CMV-p53) to express p53 protein was examined by Western blot analysis in the H358 lung cancer cell line, which has a homozygous deletion of the p53 gene. The ability of the adenovirus vector system to infect ovarian cancer cells was tested using an adenovirus containing the beta-galactosidase reporter gene under the control of the CMV promoter (Ad-CMV-beta gal). The ovarian cancer cell line 2774, which contains an Arg273His p53 mutation, was infected with Ad-CMV-beta gal, and the infected cells were assayed for beta-galactosidase activity after 24 hr. To test the ability of wild-type p53 to inhibit cell growth, the 2774 cell line was infected with Ad-CMV-p53 or Ad-CMV-beta gal, and the effect of these agents on the growth of 2774 cells was determined using an in vitro growth inhibition assay. Western blot analysis of lysates from H358 cells infected with Ad-CMV-p53 showed expression of wild-type p53 protein. When 2774 cells were infected with Ad-CMV-beta gal at a multiplicity of infection (m.o.i.) of 10 PFU/cell, > 90% of cells showed beta-galactosidase activity, demonstrating that these cells are capable of efficient infection by the adenovirus vector. Growth of 2774 cells infected with Ad-CMV-p53 was inhibited by > 90% compared to noninfected cells. The ability of the adenovirus vector to mediate high-level expression of infected genes and the inhibitory effect of Ad-CMV-p53 on the 2774 cell line suggests that the Ad-CMV-p53 could be further developed into a therapeutic agent for ovarian cancer.

Primary malignant melanoma of the uterine cervix: two case reports and a century's review.

Primary malignant cervical melanoma is diagnosed by the presence of junctional melanocytic abnormality and the absence of distant metastasis. Amelanotic and poorly differentiated tumors can often be diagnosed with the HMB-45 immunoperoxidase stain which is very specific for melanoma. Early reported cases were treated with simple excision followed many times by radiation therapy. Radical hysterectomy, pelvic lymphadenectomy, and partial vaginectomy have been advocated by some contemporary investigators. Radiation can be used as adjuvant or palliative treatment; its efficacy is not well established. Few patients have been treated with modern chemotherapy. No patient has been treated with immunotherapy. Primary malignant cervical melanoma carries a very poor prognosis. Most patients succumb from their disease within 2 years. One patient has survived 14 years. The small number of reported cases makes it difficult to evaluate the efficacy of any treatment modality.