Margaret M. Steinhoff

Herceptin and Gemcitabine for Metastatic Pancreatic Cancers That Overexpress HER-2/neu

Purpose: To determine the response rate and toxicities of Herceptin and gemcitabine for patients with metastatic pancreatic adenocarcinomas that overexpress HER-2/neu. Methods and Materials: Patients with metastatic pancreatic cancer with 2 +/3 + HER-2/neu expression by immunohistochemistry were eligible. Patients received gemcitabine, 1 g/m2/week, for 7 of 8 weeks followed by 3 of every 4 weeks, and Herceptin, 4 mg/kg loading dose, followed by 2 mg/kg/week. Results: Screening logs demonstrated the rate of HER-2/neu overexpression was 16%. Thirty-four patients were enrolled. Thirty patients (88%) had pancreatic cancers with 2 + overexpression and 4 patients (12%) had 3 + overexpression. Toxicity was similar to gemcitabine alone. Confirmed partial responses were observed in 2 of 32 patients (6%). Thirteen of 32 patients (41%) had either a partial response or a > 50% reduction in CA 19–9. The median survival for all 34 patients was 7 months, and the 1-year survival was 19%. Conclusion: The response rate of Herceptin and gemcitabine is similar to gemcitabine alone. The 7-month median survival in patients with metastatic pancreatic cancer suggests there may be a modest benefit for some patients. Infrequent HER-2/neu overexpression limits the role of targeting the HER-2/neu gene and prevents definitive conclusions on the addition of Herceptin to gemcibine for patients with pancreatic cancer.

Clinical axillary recurrence in breast cancer patients after a negative sentinel node biopsy

BACKGROUND The purpose of this study was to determine the axillary recurrence rate in breast cancer patients with a negative sentinel lymph node who did not have an axillary node dissection. METHODS Sentinel lymphadenectomy for breast cancer patients, without axillary node dissection if the node was negative, was introduced in 1998 at our institution. This study includes those women with a negative sentinel lymph node. Adjuvant chemotherapy was administered based on primary tumor characteristics. If breast radiotherapy was used, no attempt was made to include the axilla. RESULTS From January 1998 to December 2001, 206 patients (208 breast cancers) had a negative sentinel lymph node. The median age at diagnosis was 56 years and median tumor size was 1.2 cm. With a median follow-up of 26 months, there have been 3 axillary recurrences with a clinical sentinel lymph node false negative rate of 1.4%. CONCLUSIONS In this study, the clinical false negative rate of a sentinel lymph node biopsy is 1.4%. Our study provides further evidence supporting the use of sentinel lymphadenectomy in women with breast cancer.

The value of breast lumpectomy margin assessment as a predictor of residual tumor burden in ductal carcinoma in situ of the breast

Margin width is considered the most important risk factor for local recurrence in ductal carcinoma in situ (DCIS) of the breast. The purpose of this report is to assess the predictive utility of lumpectomy specimen margin assessment for the presence and extent of residual DCIS.

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

A study was undertaken to use the 2‐tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3‐tier system and determine the progression‐free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158.

Sentinel node identification and the ability to detect metastatic tumor to inguinal lymph nodes in squamous cell cancer of the vulva

OBJECTIVES The goal of this study was to identify one or more inguinal sentinel nodes in patients with primary squamous cell carcinoma of the vulva and to determine the ability of the sentinel node to predict metastasis to the inguinal lymphatic basin. METHODS Techniques employing technetium-99m (Tc-99m) sulfur colloid and isosulfan blue dye were utilized to identify sentinel nodes in the inguinal lymphatic beds. Technetium-99m sulfur colloid was injected intradermally at the tumor margins 90-180 min preoperatively followed by a similar injection of isosulfan blue dye 5-10 min before the groin dissection. A handheld collimated gamma counter was employed to identify Tc-99m-labeled sentinel nodes. Lymphatic tracts that had taken up blue dye and their corresponding sentinel node were also identified and retrieved. A completion inguinal dissection was then performed. Each sentinel node was labeled as hot and blue, hot and nonblue, or cold and blue. The sentinel nodes were subjected to pathologic examination with step sections and nonsentinel nodes were evaluated in the standard fashion. RESULTS Twenty-one patients with a median age of 79 were entered onto protocol and a total of 31 inguinal node dissections were performed. A sentinel node was identified in 31/31 (100%) groin dissections with the use of Tc-99m. Isosulfan blue dye identified a sentinel node in 19/31 (61%) groin dissections. Surgical staging revealed 7 patients with stage I disease, 5 with stage II disease, 5 with stage III disease, and 4 with stage IV disease. Lymph nodes in 9 groin dissections were found to have metastatic disease, and in 4 of these dissections, the sentinel node was the only positive node. Lymph nodes in 22 groin dissections had no evidence of metastasis. No false-negative sentinel lymph nodes were obtained (sentinel node negative and a nonsentinel node positive). CONCLUSION Tc-99m sulfur colloid is superior to isosulfan blue dye in the detection of sentinel nodes in inguinal dissections of patients with vulvar cancer. A sentinel node dissection utilizing Tc-99m alone can identify a sentinel node in all inguinal dissections. Pathologic examination with step sections has shown the sentinel node to be an accurate predictor of metastatic disease to the inguinal nodal chain.

Axillary staging using ultrasound-guided fine needle aspiration biopsy in locally advanced breast cancer

BACKGROUND Axillary lymph node status is important for staging and planning therapy prior to neoadjuvant chemotherapy in patients with locally advanced breast cancers (LABC). The objective of this study was to evaluate the use of axillary ultrasonography coupled with fine needle aspiration biopsy (US-FNAB) to determine lymph node status prior to initiation of neoadjuvant chemotherapy. METHODS Patients with a LABC, defined as a breast cancer clinically larger than 3.0 cm or a cytology positive axillary lymph node, were evaluated by clinical examination followed by ultrasonographic evaluation. Lymph nodes were categorized as suspicious for malignancy based on size >1.0 cm, decrease in the fatty hilum, or parenchymal echogenicity. US-FNAB was performed on all patients. Most patients received neoadjuvant chemotherapy followed by definitive surgery. Axillary surgery consisted of axillary lymph node dissection. Axillary status by clinical examination and US-FNAB was compared with that obtained by axillary node dissection. RESULTS From January 1998 to May 2001, 26 patients (27 axillae) presented with LABC to our institution. The median age of these patients was 48 years. The sensitivity and specificity of US-FNAB for evaluating axillary metastatic disease in patients with LABC were 100% and 100%, respectively. CONCLUSIONS In patients with locally advanced breast cancer, axillary ultrasonography coupled with fine needle aspiration biopsy can accurately stage the axilla. It is particularly useful and should be used more frequently in patients undergoing neoadjuvant chemotherapy. The use of ultrasonography to stage the axilla in patients who present with small breast cancers should be explored.

α and β subunits of inhibin/activin as sex cord-stromal differentiation markers

Inhibins (α and β heterodimers) and activins (β homodimers) are related peptides with opposing biologic action on gonadotropin regulation. They serve as components of the pituitary-gonadal feedback system. Although sexcord stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. A total of 28 sex cord-stromal tumors of the ovary and 43 non-sex cord-stromal tumors were immunohistochemically evaluated for the presence of α and β subunits of inhibin and activin. For comparison, 10 normal adult gonads including seven ovaries with hilar regions and three testes also were examined. Immunoreactivity for both α and β subunits of inhibin/activin was identified in both non-neoplastic and neoplastic granulosa, Sertoli, Leydig, hilar and luteinized theca cells, with the strongest immunoreactivity in Leydig and hilar cells. One of three Sertoli-Leydig cell tumors that showed a sarcomatoid growth pattern and one sex-cord tumor with annular tubules also were immunoreactive for both subunits. For non-sex cord stromal-derived ovarian tumors, α subunit immunoreactivity was negative in all but two of five ovarian mucinous tumors. Weak immunoreactivity for β subunit was found in most ovarian surface epithelial carcinomas, two of four colonic, and one of three pancreatic carcinomas. No immunostaining was found in nonspecialized gonadal stromal or interstitial cells, thecal cells, germ cells, ovarian small cell carcinomas, carcinoid tumors, dysgerminomas, or leiomyosarcomas. Immunostaining of α subunit (inhibin α), but not of β subunit could serve as a sex cord-stromal differentiation marker because α subunit alone is largely confined to sex cord-stromal lesions with the exception of some ovarian mucinous tumors. Further studies are needed to define the usefulness of this sex cord-stromal differentiation marker in the practice of surgical pathology. Coexpression of α and β subunits in sex cord-stromal elements suggests that dimeric inhibin is expressed in these cells.

Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders

OBJECTIVE The human epididymis protein 4 (HE4) is a novel biomarker for ovarian cancer. This study measured the HE4 and CA125 levels in women with benign gynecological disorders. STUDY DESIGN Sera were obtained from women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with elevated biomarker levels were compared. RESULTS There were 1042 women with benign disease. HE4 levels were less often elevated than CA125 (8% vs 29%, P < .001). A marked difference was observed in patients with endometriosis in which HE4 was elevated in 3% of patients and CA125 in 67% (P < .0001). Serous ovarian tumors were associated with elevated levels of HE4 in 8% of patients and CA125 in 20% (P = .0002); uterine fibroids in 8% vs 26% (P = .0083); dermoids in 1% vs 21% (P = .0004); and inflammatory disease in 10% vs 37% (P = .014). CONCLUSION HE4 is elevated less frequently than CA125 in benign disease, particularly in premenopausal patients.

Absence of estrogen and progesterone receptors in glassy cell carcinoma of the cervix

Objective To review available evidence about the effectiveness of alternative therapies for nausea and vomiting of pregnancy. Data Sources MEDLINE and 13 additional US and international data bases were searched in 1996–1997 for papers that described use of alternative medicine in the treatment of pregnancy and pregnancy complications, specifically those addressing nausea, vomiting, and hyperemesis. Bibliographies of retrieved papers were reviewed to identify additional sources. Methods of Study Selection All relevant English language clinical research papers were reviewed. Randomized clinical trials addressing specifically the use of nonpharmaceutical and nondietary interventions were chosen for detailed review. Tabulation, Integration, and Results Ten randomized trials studying the effects of acupressure, ginger, and pyridoxine on nausea and vomiting of pregnancy were reviewed. Evidence of beneficial effects was found for these three interventions, although the data on acupressure are equivocal. Insufficient evidence was found for the benefits of hypnosis. Other interventions have not been studied. Conclusion There is a dearth of research to support or to refute the efficacy of a number of common remedies for nausea and vomiting of pregnancy. The best-studied alter-native remedy is acupressure, which may afford relief to many women; ginger and vitamin B6 also may be beneficial.

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.