Assessing the risk of ovarian malignancy algorithm for the conservative management of women with a pelvic mass.

OBJECTIVE: To evaluate the use of as an aid in the identification of women who can safely undergo conservative, non-surgical management. METHODS: All patients referred to the Program in Women's Oncology for surgery with a pelvic mass are evaluated at a prospective multidisciplinary tumor board (TB) where ROMA and imaging are used for management recommendations. This study evaluated women presented to TB with a pelvic mass between 2009 and 2013 who had either surgical or conservative management. RESULTS: Of the 498 patients assessed, 392 (79%) had benign disease, 22 (4%) had LMP tumors, 28 (6%) had stage I-II epithelial ovarian cancer (EOC), 36 (7%) had stage III-IV EOC and 20 (4%) had non-EOC. Using clinical assessment in conjunction with ROMA, the TB recommended observation in 188 (37.8%) women. All patients diagnosed with an invasive malignancy were recommended for surgery by the TB. In the 315 patients managed surgically, 212 were found to have benign disease and 84 women were diagnosed with an invasive malignancy. The sensitivity for the initial TB recommendations using ROMA in conjunction with clinical judgment for detecting malignancy was 100% with a specificity of 47.7% and a NPV of 100%. When including low malignant potential tumors the sensitivity was 99.1%. For stage I-IV EOC ROMA alone had a sensitivity of 95.3%. CONCLUSIONS: ROMA in conjunction with clinical assessment can safely identify women for conservative management.

Predictive factors for the presence of malignant transformation of pelvic endometriosis.

OBJECTIVES: To determine predictive factors for the presence of malignant transformation in ovarian endometriotic cysts. STUDY DESIGN: This was an IRB approved, case control study analyzing patient data from 2004 to 2013. Pathology database records were searched to identify patients with benign endometrioma and ovarian carcinoma arising in the background of endometriosis. Inclusion criteria required each patient to have a preoperative diagnosis of adnexal mass and no other findings concerning for malignancy. Patient clinical records were queried for preoperative symptoms, serum CA125 levels and radiologic findings. Pathologic data were collected including histology, tumor grade and stage. RESULTS: A total of 138 patients met inclusion criteria; 42 women with ovarian cancer arising in the background of endometriosis and 96 women with benign endometrioma. Women diagnosed with ovarian cancer were significantly older than women with endometriosis (53.6 vs. 39.2 years). There was no difference in presence of symptoms between the two groups. Women with malignant tumors were found to have significantly larger cysts (14 cm vs. 7.5 cm; p<0.0001) that were more often multilocular (45.7% vs. 12.2%; p<0.0001), and contained solid components (77.1% vs. 14.5%; p<0.0001). Among patients that were observed prior to surgery there was a significant difference in the change in size of the mass over time with 4.2 cm increase for cases vs. 1.0 cm increase for controls (p=0.02). Multiple logistic regression analysis indicated that for every 5 years increase in age there was an adjusted OR of 2.17 (p=0.003). An age of 49 years or greater had an 80.6% sensitivity (95% CI: 62.5-92.5%) and an 82.9% specificity (95% CI: 67.9-92.8%) for malignancy, and solid component on imaging had an adjusted OR of 23.7 (p<0.0001). Serum CA125 levels tended to be higher in patients with malignant tumors but did not reach statistical significance with a mean of 204.9 vs. 66.9 (p=0.1). CONCLUSIONS: Significant predictors for malignant transformation of endometriosis include cyst characteristics and age. Women above the age of 49 with multilocular cysts and solid components are at high risk for malignant transformation of endometriosis. Serum CA125 level is not a significant predictor of malignant transformation.

Long-term follow-up of vulvar cancer patients evaluated with sentinel lymph node biopsy alone.

OBJECTIVE: The objective of this study was to examine SLN evaluation alone in women with squamous cell carcinoma (SCC) of the vulva and evaluate the inguinal recurrence and complication rates. METHODS: An IRB approved prospective study enrolled patients with SCC of the vulva. Peritumoral injection of Tc-99 sulfur colloid and blue dye was used to identify SLNs intraoperatively. Patients with negative SLN for metastasis were followed clinically without further treatment. Patients with metastasis to a SLN underwent full groin node dissection followed by standard treatment protocols. RESULTS: A total of 73 women were enrolled onto protocol with 69 patients undergoing SLN dissection. Mean age was 66.9years (range: 29-91) with 47 stage I, 12 stage II, 9 stage III, 2 stage IV and 3 unstaged patients. SLN dissections were successful in 63 patients. Of the 111 groins evaluated with a SLN dissection 93% had a SLN identified with an average of 2 SLN per groin. There were 92 groins with negative SLN and 11 groins with positive SLN. 57 patients had negative SLN and underwent conservative management with the median follow-up of 58.3months. Three patients experienced groin recurrences (2 unilateral, 1 bilateral) for a recurrence rate of 5.2% (3/57). The complication rate for the inguinal incisions was 17.5% (1 cellulitis, 1 abscess, 2 lymphoceles, 5 lymphedema and leg pain). CONCLUSIONS: Isolated SLN dissection alone has a low inguinal recurrence rate with decreased complications and should be considered as an option for women with SCC of the vulva.

Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study.

OBJECTIVES: To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). DESIGN: Prospective randomised trial. SETTING: Breast health centre of a tertiary care centre. PARTICIPANTS: 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. INTERVENTIONS: Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. OUTCOME MEASURES: The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). RESULTS: 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. CONCLUSIONS: Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. TRIAL REGISTRATION: clinicaltrials.gov (NCT00711529).

Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus.

OBJECTIVE: Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus. METHODS: Pre-operative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%. RESULTS: Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125. CONCLUSION: HE4 is elevated in all stages of endometrial can100cer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.

For women receiving chemotherapy for clinically apparent early ovarian cancer, is there a benefit to surgical staging?

BACKGROUND: For women with early stage ovarian cancer (ESOC), comprehensive staging is the standard of care and studies suggest that these patients may not require further treatment. For women with incidentally diagnosed ovarian cancer there is a lack of consensus as to whether surgical staging be performed, particularly if chemotherapy is recommended. OBJECTIVE: We performed this retrospective study to determine the outcomes of women treated with chemotherapy for clinically apparent ESOC, stratified by whether staging was performed or not. METHODS: This study was approved by institutional review board. All patients presenting to the Multidisciplinary Gynecologic Oncology Tumor Board between 1998 and 2005 with a consensus opinion of having clinically apparent ESOC were identified. Staging (partial or complete) was determined by a study pathologist and patients were stratified as being staged or unstaged. Survival was estimated using the Kaplan-Meier method. STATA 8.0 was used for all calculations. RESULTS: Eighty-eight patients were identified: 52 (59%) were staged and 36 (31%) were not. Median follow-up was 50 and 59.5 months, respectively. The majority of patients received carboplatin and paclitaxel in both cohorts with a median of 6 cycles. Five-year Disease Free Survival was 85% versus 80%, respectively (P = 0.54). Five-year Overall Survival was 85% versus 88% (P = 0.688). CONCLUSION: For women presenting with a clinically apparent ESOC in whom chemotherapy is administered, there does not seem to be an additional benefit to surgical staging. A prospective trial of women with clinically apparent ESOC to test this hypothesis should be considered.

Isolated sentinel lymph node dissection with conservative management in patients with squamous cell carcinoma of the vulva: a prospective trial.

OBJECTIVES: Sentinel lymph node (SLN) dissections have a high sensitivity and negative predictive value for the detection of metastatic disease. The objective of this study was to examine the inguinal recurrence rate along with complication rates for patients undergoing inguinal SLN dissection alone for vulvar carcinoma. METHODS: An IRB approved prospective study enrolled patients with biopsy proven squamous cell carcinoma of the vulva. Peritumoral injection of Tc-99 sulfur colloid and methylene blue dye was used to identify SLNs intraoperatively. Patients with SLNs negative for metastatic disease were followed clinically. Patients with metastasis detected in a SLN subsequently underwent a full groin node dissection followed by standard treatment protocols. RESULTS: Thirty-six patients were enrolled onto study with 35 undergoing a SLN dissection. All SNL dissections were successful with a mean of 2 SLN obtained per groin. There were 24 patients with stage I disease, 8 stage II, 3 stage III and 1 stage IV. A total of 56 SLN dissections were performed with 4 patients found to have inguinal metastasis by SLN dissection. There were 31 patients with a total of 46 SLN dissections found to be negative for metastatic disease. The median follow-up has been 29 months (range 8 to 51) with 2 groin recurrences for a groin recurrence rate of 4.3% and a recurrence rate per patient of 6.4%. There have been no reports of groin breakdown, extremity cellulitis or lymphedema. CONCLUSIONS: The recurrence rate for patients undergoing inguinal sentinel node dissection alone is low. These patients did not experience any complications as seen with complete groin node dissections. Sentinel lymph node dissection should be considered as an option for evaluation of inguinal nodes for metastatic disease.

The joint use of LCA and emergy evaluation for the analysis of two Italian wine farms.

The aim of this paper is to evaluate two agroindustrial productive processes in their entirety (one organic and one semi-industrial), focusing on the comparison of impacts derived from the inputs and outputs of the system (life cycle assessment, LCA), integrated with a physical evaluation of the resources and natural services, on a common basis (emergy). Methods based on the joint use of LCA and emergy evaluation are useful, as they measure the contribution of environmental services and products to the productive process thus focusing primarily on the environmental impact of emissions and non-renewable energy inputs. The complementarity of the methods used in this paper contributes important elements and information useful for the comprehension of the organization of agriculture within Siena's territory. The results show important elements and useful information: (1) for the comprehension of the two agroecosystems' organization; (2) for the use of the energy flows that determine their development. Moreover, the combined use of emergy and LCA gives a comparative thermodynamic performance evaluation between organic and semi-industrial farming.

The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass.

OBJECTIVES: The CA125 tumor marker is used to help predict the presence of ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels occur in many benign gynecologic conditions, we set out to identify other novel biomarkers that would increase the sensitivity and specificity of CA125. METHODS: Serum and urine samples were obtained preoperatively from women undergoing surgery for an adnexal mass. The samples were analyzed for levels of CA125, SMRP, HE4, CA72-4, activin, inhibin, osteopontin, epidermal growth factor (EGFR), and ERBB2 (Her2) and were compared to final pathology results. Logistic regression models were estimated for all markers and combinations, with cross-validation analysis performed to obtain the sensitivities at set specificities of 90%, 95%, and 98%. RESULTS: Two hundred and fifty-nine patients with adnexal masses were enrolled. Of these, 233 patients were eligible for analysis with 67 invasive epithelial ovarian cancers and 166 benign ovarian neoplasms. Mean values for all marker levels except Her2 differed significantly between patients with benign masses and cancer. As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%). Comparatively, combined CA125 and HE4 yielded the highest sensitivity at 76.4% (specificity 95%), with additional markers adding minimally to the sensitivity of this combination. HE4 was the best single marker for Stage I disease, with no increase in sensitivity when combined with CA125 or any other marker. CONCLUSIONS: As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially Stage I disease. Combined CA125 and HE4 is a more accurate predictor of malignancy than either alone.

Sex, intimacy, and the gynecologic oncologists: survey results of the New England Association of Gynecologic Oncologists (NEAGO).

Sexuality is an important aspect of life and is often affected in patients diagnosed with cancer. For women, estimates of sexual dysfunction range from 40 to 100%. In light of these statistics, we were interested in determining the comfort level and practice of specialists in gynecologic oncology as it relates to taking a sexual history and addressing related concerns by conducting a survey of the New England Association of Gynecologic Oncologists (NEAGO). Our results show that although nearly all respondents felt comfortable addressing sexual problems in their patients, less than half took a sexual history in new patients and 80% did not feel there was sufficient time to devote to exploring sexual issues. The results of our survey suggest that aspects of sexual dysfunction in women with gynecologic cancer may be neglected by gynecologic oncology providers. This encourages cancer programs to develop formal resources for women with questions regarding sexuality following a diagnosis of cancer.

Lower uterine segment involvement as a predictor for lymph node spread in endometrial carcinoma.

OBJECTIVES: Several predictive factors for lymph node spread in endometrial cancer have been identified including tumor grade, depth of invasion, lymphatic or vascular-space invasion, and histologic subtype. Lower uterine segment involvement may also be predictive of lymph node spread. The objective of this study was to investigate the relationship between lower uterine segment involvement in endometrial carcinoma and lymph node spread. METHODS: This was an IRB approved retrospective study. Data were collected for all patients diagnosed with endometrial cancer from June 1999 to December 2004. The primary end point was the presence of nodal involvement. Subset analysis was performed by histologic subtype. Univariate and multivariate nominal logistic regression was performed. Categorical variables were compared using Chi-square and Fischer's Exact Test. RESULTS: Two-hundred and ninety-nine subjects were eligible for review. One-hundred seventy four (58%) had lower uterine segment involvement. Forty-four (25%) of those with lower uterine segment involvement had positive nodes compared to 10 (8%) of those without (p=0.0001). On univariate analysis, lower uterine segment involvement, lymphovascular-space invasion, and deep invasion predicted nodal disease. On multivariate analysis, lower uterine segment remained predictive of nodal spread for the endometrioid subset. For high-risk histologies, only lymphovascular-space invasion and deep myometrial invasion were predictive of nodal spread. CONCLUSIONS: Lower uterine segment involvement in endometrial carcinoma is an important predictor of lymph node involvement for patients with endometrioid histologies. Tumor within the lower uterine segment may be an important factor to consider in intraoperative decision making regarding staging.

Oral thalidomide as palliative chemotherapy in women with advanced ovarian cancer.

OBJECTIVE: We prospectively evaluated thalidomide, an oral agent with antiangiogenic and immunomodulatory properties, in patients with recurrent ovarian cancer, comparing the drug to standard intravenous chemotherapy and treatment holiday in terms of both progression-free interval and quality of life. METHODS: Eligible patients had recurrent ovarian or primary peritoneal cancer and had received a minimum of two prior therapeutic regimens. Patients were offered one of three arms: (Arm A) any standard intravenous single-agent chemotherapy; (Arm B) oral thalidomide 200 mg daily; (Arm C) treatment holiday. Computed tomography (CT) scans were performed every two cycles until disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CA-125 was measured monthly as was quality of life using the Functional Assessment of Cancer Therapy (FACT-O) questionnaire. RESULTS: Forty patients participated: 18 on Arm A; 18 on Arm B; and 4 on Arm C. The groups were comparable in terms of number of prior regimens and cycles of chemotherapy. The progression- free intervals were similar in Arm A and Arm B (3.7 versus 3.8 months). The PR/SD rate was 6.7%/60% for Arm A, and 7.7%/53.8% in Arm B. Of those treated with thalidomide, 53% had a drop in CA-125 greater than 50%, compared to 13% receiving intravenous chemotherapy. FACT-O scores at baseline and throughout treatment were equivalent. CONCLUSION: The oral chemotherapeutic agent thalidomide appears to be comparable in response and quality of life, compared to single agent intravenous chemotherapy, in our population of heavily pretreated patients with ovarian cancer.

The prognostic significance of lower uterine segment involvement in surgically staged endometrial cancer patients with negative nodes.

OBJECTIVES: Endometrial cancer is the most common female genital malignancy in the United States. Stage is the most important prognostic factor. Other factors include grade, lymph-vascular space invasion (LVI), and myometrial invasion. Tumor location in the lower uterine segment (LUS) may also be important. LUS involvement correlates with nodal involvement, and nodal involvement is an important prognostic indicator. This study investigates the importance of LUS involvement in patients with pathologically negative nodes. METHODS: This was an IRB approved retrospective study. Data were collected for patients diagnosed with endometrial cancer from June 1999 to September 2004. Patients who underwent nodal evaluation with no evidence of nodal disease were eligible for analysis. The primary endpoint was progression-free survival. Secondary endpoints included recurrence rate and overall survival. Analysis was performed with the JMP5.1 statistical program. RESULTS: 285 patients were identified. 85 were excluded because they received postoperative care elsewhere. 3 charts were missing, and 15 pathology reports did not mention LUS. 147 of the remaining 182 subjects had negative nodes and formed the study population. 57% of these subjects had LUS involvement. Follow-up was similar for those with and without LUS involvement at 74 vs. 73 months respectively. PFS was similar at 70 and 63 months in those with and without LUS involvement (p=0.2). Recurrence correlated with LUS involvement on univariate analysis, however, not on multivariate analysis. CONCLUSIONS: In endometrial cancer patients with negative nodes, disease within the lower uterine segment does not imply a worse prognosis. The previously described implications of LUS involvement are likely due to the strong association of LUS disease with lymph node spread.

Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women and Infants' Hospital.

OBJECTIVES: Carboplatin (C) is a standard treatment for gynecologic cancers, but its use in recurrence is associated with an increased risk of hypersensitivity reactions (HSR) in those previously treated with C. However, there is no way to predict those at risk for a C-HSR. We sought to evaluate whether the platinum-free interval (PFI) was predictive of incidence and severity of HSRs. METHODS: Patients treated with C between 1/99 and 12/2005 were identified through our chemotherapy database. Records were reviewed in those receiving multiple C regimens or with C HSR. Severity was defined as mild or severe based on symptoms. RESULTS: 126 patients were identified who had multiple C regimens. 63 (50%) experienced C HSRs of which 36 (29%) were severe. The incidence of C HSR was 25.8% for PFI < 12 months and 56.5% if > or = 12 months (p=0.0023). The incidence of a severe C HSR significantly increased with time as well: 6.5% PFI < 12 months, 23.9% PFI 12-24 months and 47% PFI > or = 24 months (p=0.0091). Of those receiving a 3rd regimen of C, 8/8 had a HSR and these were severe in seven (88%). Of note, 60 patients received > 8 (range 9-19) cycles with the first C regimen, and none of the patients reacted after cycle 8. CONCLUSIONS: A duration of greater than 12 months between C regimens is associated with an increased risk of both any--and severe--HSR. Our data also suggests that upfront treatment with C beyond eight cycles is not associated with an increased risk of HSR.

Elevated body mass index does not increase the risk of palmar-plantar erythrodysesthesia in patients receiving pegylated liposomal doxorubicin.

OBJECTIVES: The dose-limiting toxicity of pegylated liposomal doxorubicin (PLD) is palmar-plantar erythrodysesthesia (PPE). Some physicians are reluctant to use this drug in overweight patients, postulating that larger size increases the likelihood of PPE. We sought to determine whether a correlation exists between body mass index (BMI) and the frequency or severity of skin reactions during PLD chemotherapy. METHODS: The records of all patients receiving PLD chemotherapy for gynecologic malignancy at our institution were reviewed for chemotherapy history, BMI at start of treatment, dose, infusion time, and adverse outcomes. Skin reaction sites, grade, and treatments were recorded. Possible predisposing factors were extracted, as well as the reason for drug discontinuation. RESULTS: Over 7 years, 103 patients were treated with PLD for gynecologic malignancies. 429 cycles were given, and PPE occurred in 36% of patients treated. Of those with PPE, reactions were grades 1, 2, or 3 in 54%, 32%, and 14% of patients, respectively. The BMI of patients with PPE (29.0) was not significantly different from that of patients without PPE (28.8). Analysis using finer subsets of weight also revealed no association. Finally, logistic regression revealed no relationship between BMI and rash grade. CONCLUSIONS: Elevated BMI does not appear to correlate with occurrence of PPE in our population. Of interest, among patients discontinuing PLD due to skin toxicity, 25% had clinical evidence of response. The identification of predisposing risk factors may help guide treatment decisions; however, elevated BMI does not appear to be such a risk factor.

Inguinal sentinel node dissection versus standard inguinal node dissection in patients with vulvar cancer: A comparison of the size of metastasis detected in inguinal lymph nodes.

OBJECTIVE: The emergence of sentinel lymph node (SLN) technology has provided the ability for an in depth pathologic evaluation for the detection of metastasis to lymph nodes through the use of ultra-staging. The SLN has been shown to be predictive of the metastatic status of its nodal basin. More recently, SLN dissections have been employed in the evaluation of the inguinal lymphatic basins in patients with vulvar malignancies. We hypothesize that the average size of metastasis detected in non-palpable inguinal lymph nodes is smaller when detected through the use of SLN dissection and ultra-staging versus complete inguinal node dissection (CND). METHODS: This was an IRB approved retrospective study. The tumor registry database was searched to identify all patients diagnosed with a vulvar malignancy from 1990 to 2004. The records were reviewed to identify patients with inguinal lymph node metastasis. Only patients with non-palpable inguinal lymph nodes (metastasis 1 cm or less) were included in the analysis. All pathology slides were reviewed. The smallest metastatic foci of cells were measured from lymph nodes obtained through the traditional complete inguinal lymph node dissection (CND) and compared with the largest metastatic foci of cells detected in sentinel lymph node dissections. The mean size and standard deviation for each group was calculated and analyzed with a Mann-Whitney test. RESULTS: There were 336 inguinal node dissections performed in patients identified with a vulvar malignancy. SLN dissections were performed in 52 groins and CND in 284 groins. Fifty-eight patients were found to have metastatic disease to the inguinal lymph nodes. Thirty of these patients had no evidence of lymph node metastasis on clinical exam or at the time of their EUA. There were 7 groins with metastasis detected through an SLN and 23 groins through a CND. The mean size of the metastatic foci detected in the SLN group was 2.52 mm (SD 1.55) and in the CND group was 4.35 mm (SD 2.63). This was not statistically significant (P = 0.109). However, when comparing the detection of micrometastasis in each set, there was a significant difference (P = 0.02) in the detection of the size of metastasis detected with smaller cluster of cells detected in the SLN group. CONCLUSION: SLN dissection with ultra-staging allows for a more extensive pathologic examination of lymph nodes and may allow for the detection of smaller tumor foci than the traditional pathological examination of lymph nodes obtained from a CND. The clinical implication of the detection of these micrometastasis and smaller metastasis remains to be determined.

Pathologic evaluation of inguinal sentinel lymph nodes in vulvar cancer patients: a comparison of immunohistochemical staining versus ultrastaging with hematoxylin and eosin staining.

OBJECTIVES: To evaluate the value of immunohistochemical (IHC) staining of inguinal sentinel lymph nodes (SLN) found to be negative for metastatic disease by ultrastaging with hematoxylin and eosin (H&E) staining. METHODS: An IRB approved study identified 29 patients who had undergone an inguinal sentinel lymph node dissection for squamous cell carcinoma of the vulva. All sentinel lymph nodes found to be negative for metastatic disease based on ultrastaging with H&E staining were reevaluated with pancytokeratin antibody (AE1/AE3) immunohistochemical (IHC) staining to detect micrometastasis. RESULTS: Twenty-nine patients with squamous cell carcinoma of the vulva underwent an inguinal sentinel node dissection. Nineteen patients had inguinal dissections negative for metastatic disease, 2 patients had bilateral inguinal metastasis, and 8 patients had unilateral inguinal metastasis. A total of 42 groin dissections with SLN biopsies were performed; 12 groins were positive for metastatic disease and 30 were negative based on ultrastaging with eosin and hematoxylin staining. A total of 107 sentinel lymph nodes (2.5 SLN per groin) were obtained, of which 18 SLN contained metastatic disease identified by ultrastaging and staining with H&E. Two SLN contained micrometastasis less than 0.3mm in size and 16 SLN contained metastasis greater than 2mm in size. Eighty-nine SLN found to be negative for metastasis by ultrastaging with H&E staining were also negative for micrometastasis on evaluation with pancytokeratin antibody AE1/AE3 IHC staining. CONCLUSIONS: The addition of immunohistochemical staining to ultrastaging with H&E staining in the pathologic evaluation of inguinal sentinel lymph nodes does not increase the detection of micrometastasis in patients with primary squamous cell carcinoma of the vulva.

What matters matter? P values, H values, leadership, and us.

Framed by the question "What matters matter?," this essay considers today's physicians' need for leadership, the principled road they embarked on, and the reasons to continue. Taken as a whole, the vast problems of health care seem unsolvable. Approached in small tangible steps, if not cure, could direction, even inspiration, appear? When people are sick, they look to physicians. By actually caring for patients, physicians have earned trust and learned, scientifically and artfully, about life in ways others cannot. Meaningful patient-centered care occurs at the junction of logical science and tenuous human needs: "p values" and "h values." Along with the privileged understanding gained from patients comes the responsibility to stand publicly for the rights of all patients to private moments. Standing up in these ways can never be easy; then again, it never was. It is the continued journey toward historic ideals. It is an imprecise place of struggle, where caring "leadership" has always been most needed, fulfilling and truly defining physicians. Despite today's seemingly insurmountable obstacles, in this place each physician can find ways to reenergize around what matters matter.

Molecular analysis of inhibin A and activin A subunit gene loci in epithelial ovarian cancer.

Inhibin A (alpha-betaA) and activin A (betaA-betaA) are biochemically similar proteins that generally have opposite biologic functions. For example, while inhibin (alpha subunit) is proposed to be a tumor suppressor in some types of ovarian cancer, activin appears to stimulate tumor development. Previous reports suggest that a loss of alpha inhibin subunit expression and elevated serum activin levels are associated with human epithelial ovarian cancer (EOC). Our objective was to examine the alpha inhibin subunit gene locus on chromosome 2q for evidence of loss of heterozygosity (LOH) in cases of EOC and to correlate these results with serum activin A levels measured in the same patients. Ovarian tumor and matched healthy tissue samples were collected from 22 women with EOC. DNA was extracted and subjected to PCR analysis using 10 primers, seven from chromosome 2q (alpha inhibin subunit locus) and, as a control, three from chromosome 7p (inhibin/activin betaA subunit). In addition, each patient had a preoperative serum activin A measurement using an ELISA assay. One (1/22) case of EOC demonstrated LOH for one microsatellite marker at the alpha inhibin gene locus. Thirty-six percent (8/22) of patients had an activin A level that was increased above the normal range. We conclude that loss of heterozygosity at the inhibin/activin alpha subunit locus is not frequently associated with EOC. More direct molecular analyses of the inhibin and activin genes are warranted to rule out mutations in cases of epithelial ovarian cancer.