Faculty Bibliography

OBJECTIVE: To describe sentinel lymph node (SLN) detection rates in endometrial cancer and estimate how many cases are needed to achieve >90% SLN detection. METHODS: We conducted a prospective study of patients undergoing primary surgery for endometrial cancer between September 2005 and March 2009. Lymph node mapping was performed using blue dye injection into the cervix in all cases. Additional injection methods included blue dye injection in the uterine fundus, and cervical injection of Tc99m. SLNs were identified and removed, followed by regional lymph node dissection. The results were analyzed according to two study periods: an "early" phase (September 2005-December 2007) and a "late" phase (January 2008-March 2009). RESULTS: One hundred and fifteen patients with endometrial cancer were included. The cervix was the only site of injection in 82 cases (71%), while a combined cervical and fundal injection was performed in 33 cases (29%). Overall, SLN detection was achieved in 98 (85%) cases. In the initial 27 months of the study, a SLN was identified in 50 of 64 cases (78%), with 2 false negative cases. In the subsequent 15 months, successful mapping was achieved in 48 of 51 cases (94%) with no false negative cases. When examining an individual provider's performance, after the first 30 cases, the rate of successful mapping significantly increased from 77% to 94% (P=0.033). CONCLUSION: Sentinel node mapping in uterine cancer requires a dedicated effort to achieve high detection rates. Surgeons should determine their individual detection rates and false negative rates. Our data demonstrate that high SLN detection rates can be achieved in women with uterine cancer and increasing surgical volume (30 cases) is associated with significantly increased detection rates.

BACKGROUND:The therapeutic significance of intramammary lymph nodes is uncertain. The purpose of this study was to identify the appropriate surgical management of the axilla in intramammary node-positive patients undergoing sentinel lymph node (SLN) biopsy. METHODS:A retrospective review of consecutive patients staged between September 1996 and December 2004 was performed. Intramammary node identification and pathologic findings were compared with the status of axilla. RESULTS:Among 7,140 patients, intramammary nodes were identified in 151 (2%). Positive intramammary nodes were identified in 36 patients (24%). Axillary disease was identified in 61% of intramammary node-positive patients. No additional axillary disease was identified when axillary lymph node dissection was performed in intramammary node-positive patients with negative axillary SLN biopsy results. CONCLUSIONS:The results suggest that completion axillary lymph node dissection may be based on the status of axillary SLN biopsies in clinically node negative patients when intramammary lymph node metastases are identified in the breast specimens.

The treatment of gynecologic malignancies can include surgery, systemic therapy, and radiation. Depending on the primary site of disease and the extent of the disease, these treatment strategies are applied alone or in combination. Trends over the past few decades have concentrated on performing more comprehensive staging procedures for a large percentage of patients with gynecologic malignancies. The surgical techniques available for comprehensive staging have facilitated a greater understanding of stage and prognosis overall, and better tailoring of postsurgical treatment. One such technique is regional lymphadenectomy. Although the role of regional lymphadenectomy as a therapeutic procedure in some gynecologic cancers is debated and challenged (regional lymphadenectomy and multimodality therapy increases adverse side effects and long-term sequelae without proven survival benefit), there is no controversy regarding the staging and prognostic benefit of the evaluation of regional lymph nodes. The sentinel lymph node (SLN) concept was successfully introduced in melanoma. It has since become the standard of care in breast cancer and has had a significant impact on postoperative morbidity for a large percentage of breast cancer patients. Interest in using SLN techniques in gynecologic cancers was thus a natural progression. In light of the growing body of evidence in the literature opposing the therapeutic benefit of systematic lymphadenectomy, the SLN concept will continue to play an important role in the treatment of gynecologic malignancies. This technique can provide accurate staging information in some gynecologic cancers. Increased use of this technique could potentially impact the quality of life of gynecologic cancer survivors while still providing important staging information without compromising oncologic safety. In this review, we examine the body of literature related to gynecologic cancer malignancies and SLN biopsy.

BACKGROUND:Completion axillary lymph node dissection (CALND) is routinely performed in breast cancer patients with positive sentinel lymph nodes (SLN). We sought to determine the sociodemographic, pathologic, and therapeutic variables that were associated with CALND. METHODS:From 7/1997 to 7/2003, 1,470 patients with invasive breast cancer were SLN positive by intraoperative frozen section or final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Fisher's exact, Wilcoxon tests, and multivariate logistic regression analysis were used. RESULTS:CALND was performed less often in patients with age >or= 70 years compared with age < 70 years, moderate or severe comorbidities compared with no or mild, IHC-only positive SLN and breast conservation therapy (BCT compared with mastectomy. Patients who did not undergo CALND were less likely than CALND patients to have grade III disease, lymphovascular invasion multifocal disease, tumor size > 2 cm or to receive adjuvant chemotherapy. However, they were more likely to undergo axillary radiotherapy (RT). On multivariate analysis, age >or= 70 years [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.26-0.63], IHC-only positive SLN (OR 0.13, 95%CI 0.09-0.19), presence of moderate to severe comorbidities (OR 0.64, 95%CI 0.41-0.99), tumor size <or= 2 cm (OR 0.44, 95%CI 0.29-0.66), axillary RT (OR 0.39, 95%CI 0.20-0.78), and BCT (OR 0.54, 95%CI 0.37-0.79) were all independently associated with lower odds of CALND. CONCLUSIONS:The decision to perform CALND following positive SLN biopsy was multifactorial. Patient factors were a primary determinant for the use of CALND in our study. The decreased use of CALND in the BCT patients probably reflects reliance on the radiotherapy tangents to maintain local control in the axilla.

OBJECTIVE: To describe the accuracy of SLN mapping in patients with a preoperative diagnosis of grade 1 endometrial cancer. METHODS: A prospective, non-randomized study of women with a preoperative diagnosis of endometrial cancer and clinical stage I disease was conducted. A subset analysis of patients with a preoperative diagnosis of grade 1 endometrial endometrioid cancer was performed. All patients had preoperative lymphoscintigraphy with Tc99m on the day of or day before surgery followed by an intraoperative injection of 2 cm(3) of isosulfan or methylene blue dye deep into the cervix or both cervix and fundus. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and regional nodal dissection. Hot and/or blue nodes were labeled as SLNs and sent for histopathological analysis. RESULTS: Forty-two patients with a preoperative diagnosis of grade 1 endometrial carcinoma treated from 3/06 to 8/08 were identified. Twenty-five (60%) had laparoscopic surgery; 17 (40%) were treated by laparotomy. Preoperative lymphoscintigraphy visualized SLNs in 30 patients (71%); intraoperative localization of the SLN was possible in 36 patients (86%). A median of 3 SLNs (range, 1-14) and 14.5 non-SLNs (range, 4-55) were examined. In all, 4/36 (11%) had positive SLNs-3 seen on H&E and 1 as cytokeratin-positive cells on IHC. All node-positive cases were picked up by the SLN; there were no false-negative cases. The sensitivity of the SLN procedure in the 36 patients who had an SLN identified was 100%. CONCLUSION: Sentinel lymph node mapping using a cervical injection with combined Tc and blue dye is feasible and accurate in patients with grade 1 endometrial cancer and may be a reasonable option for this select group of patients. Regional lymphadenectomy remains the gold standard in many practices, particularly for the approximately 15% of cases with failed SLN mapping.

OBJECTIVE:A breast and/or axillary mass in a patient with epithelial ovarian cancer (EOC) may be due to an EOC breast metastasis or a second primary breast cancer. We sought to review our experience with patients with a history of EOC presenting with a breast and/or axillary mass to determine if clinical features differed between these entities. METHODS:Between 1/90 and 10/07, 29 women with epithelial EOC presented with a breast or axillary mass, including 10 patients with EOC metastatic to the breast and/or axilla and 19 patients with a second primary breast cancer following their original EOC diagnosis. Clinicopathologic factors/survival were retrospectively abstracted from medical records. RESULTS:The mean EOC disease-free survival (DFS) was 14.9 mo versus 77.4 mo (P<0.001) for patients with recurrent epithelial ovarian cancer metastatic to the breast and/or axilla and patients with a second primary breast cancer, respectively. Similarly, the mean interval between diagnosis of EOC and the breast and/or axillary event was 31.2 mo versus 70.7 mo for those patients who had metastatic recurrent EOC and those patients with breast cancer (P=0.02). Patients with a second primary breast cancer were more likely to be diagnosed on mammogram and have a family history of breast and ovarian carcinoma than patients with metastatic EOC to the breast and/or axilla (14/19 [73.7%] versus 2/9 [22.8%], P=0.02; and 12/18 [66.7%] versus 2/10 [20%], P=0.05, respectively). Median overall survival for patients with EOC metastasis was 26 mo but was not yet reached for those patients with a second primary breast cancer. On univariate analysis, an ovarian cancer DFS of 12 mo or more and the performance of breast/axillary surgery were associated with a significantly longer overall survival (P=0.01 and 0.02, respectively), whereas an elevated CA125 level at the time of the breast/axilla event and the presence of EOC metastases to the breast and axilla were significant negative predictors of survival (P=0.01 and 0.05, respectively). CONCLUSION/CONCLUSIONS:The interval between EOC diagnosis and the breast and/or axilla event, an elevated CA125 level, and a family history of breast and/or ovarian cancer may help differentiate patients with metastatic EOC to the breast and/or axilla from those patients with a second primary breast cancer. The presence of a metastatic EOC portends a poor prognosis.

Techniques for sentinel lymph node injections have varied over the years in both cervical and uterine malignancy lymph node mapping. There remains considerable variation in techniques, particularly for uterine malignancies. This review summarizes some of the techniques that have been published and are currently utilized in sentinel lymph node mapping for cervical and uterine malignancies.

OBJECTIVES/OBJECTIVE:To describe the surgical and pathologic findings of fertility-sparing radical abdominal trachelectomy using a standardized surgical technique, and report the rate of post-trachelectomy adjuvant therapy that results in permanent sterility. METHODS:A prospectively maintained database of all patients with FIGO stage IB1 cervical cancer admitted to the operating room for planned fertility-sparing radical abdominal trachelectomy was analyzed. Sentinel node mapping was performed via cervical injection of Technetium and blue dye. RESULTS:Between 6/2005 and 5/2008, 22 consecutive patients with FIGO stage IB1 cervical cancer underwent laparotomy for planned fertility-sparing radical abdominal trachelectomy. Median age was 33 years (range, 23-43). Histology included 13 (59%) with adenocarcinoma and 9 (41%) with squamous carcinoma. Lymph-vascular invasion was seen in 9 (41%) cases. Only 3 (14%) needed immediate completion radical hysterectomy due to intraoperative findings (2 for positive nodes, 1 for positive endocervical margin). Median number of nodes evaluated was 23 (range, 11-44); and 6 (27%) patients had positive pelvic nodes on final pathology - all received postoperative chemoradiation. Sixteen (73%) patients agreed to participate in sentinel node mapping which yielded a detection rate of 100%, sensitivity of 83%, specificity of 100% and false-negative rate of 17%. Eighteen of 19 (95%) patients who completed trachelectomy had a cerclage placed, and 9/22 (41%) patients had no residual cervical carcinoma on final pathology. Median time in the operating room was 298 min (range, 180-425). Median estimated blood loss was 250 ml (range, 50-700), and median hospital stay was 4 days (range, 3-6). No recurrences were noted at the time of this report. CONCLUSIONS:Cervical adenocarcinoma and lymph-vascular invasion are common features of patients selected for radical abdominal trachelectomy. The majority of patients can undergo the operation successfully; however, nearly 32% of all selected cases will require hysterectomy or postoperative chemoradiation for oncologic reasons. Sentinel node mapping is useful but until lower false-negative rates are achieved total lymphadenectomy remains the gold standard. Investigating alternative fertility-sparing adjuvant therapy in node positive patients is needed.

OBJECTIVE: The objective of the study was to compare chemotherapy response and survival of patients with advanced primary peritoneal carcinoma (PPC) vs those with epithelial ovarian carcinoma (EOC). STUDY DESIGN: From 1998 to 2004, 43 PPC patients were identified and matched to 129 patients with International Federation of Gynecology and Obstetrics stage IIIC-IV EOC by criteria abstracted from medical records. Primary endpoints were chemotherapy response, platinum resistance, progression-free survival (PFS), and overall survival (OS). RESULTS: All patients received primary platinum-taxane chemotherapy. There was no significant difference in achieving a clinical complete response. PPC patients were more likely to be platinum resistant at 6 months and had significantly impaired PFS and OS. After multivariate analysis, PPC was independently associated with a worse prognosis for both survival endpoints. CONCLUSION: PPC was associated with a similar initial response but a higher rate of platinum resistance and shorter PFS and OS. Consideration of these results may be useful for patient counseling, trial stratification, and molecular comparisons.

BACKGROUND: For individuals genetically predisposed to breast and ovarian cancer through inheritance of a mutant BRCA allele, somatic loss of heterozygosity affecting the wild-type allele is considered obligatory for cancer initiation and/or progression. However, several lines of evidence suggest that phenotypic effects may result from BRCA haploinsufficiency. METHODS: Archival fixed and embedded tissue specimens from women with germ line deleterious mutations in BRCA1 or BRCA2 were identified. After pathologic review, focal areas of normal breast epithelium, atypical ductal hyperplasia, ductal carcinoma-in-situ, and invasive ductal carcinoma were identified from 14 BRCA1-linked and 9 BRCA2-linked breast cancers. Ten BRCA-linked prophylactic mastectomy specimens and 12 BRCA-linked invasive ovarian carcinomas were also studied. Laser catapult microdissection was used to isolate cells from the various pathologic lesions and corresponding normal tissues. After DNA isolation, real-time polymerase chain reaction assays were used to quantitate the proportion of wild-type to mutant BRCA alleles in each tissue sample. RESULTS: Quantitative allelotyping of microdissected cells revealed a high level of heterogeneity in loss of heterozygosity within and between preinvasive lesions and invasive cancers from BRCA1 and BRCA2 heterozygotes with breast cancer. In contrast, all BRCA-associated ovarian cancers displayed complete loss of the wild-type BRCA allele. CONCLUSIONS: These data suggest that loss of the wild-type BRCA allele is not required for BRCA-linked breast tumorigenesis, which would have important implications for the genetic mechanism of BRCA tumor suppression and for the clinical management of this patient population.