Faculty Bibliography

BACKGROUND:This study examined whether the volume of isosulfan blue dye used in sentinel lymph node (SLN) mapping in breast cancer is related to the SLN identification rate or to the incidence of allergic reactions. METHODS:From January 2001 to November 2002, 1728 breast cancer patients underwent 1832 SLN mapping procedures with the combined technique of intraparenchymal blue dye and intradermal radioisotope. Details of each procedure and all allergic reactions were prospectively recorded. Bilateral synchronous SLN procedures were considered as one dye exposure but as two distinct procedures for determining mapping success. Dye-only success was defined as the proportion of cases in which the SLN was identified by blue dye alone. Overall dye success was defined as the proportion of cases in which the SLN was identified by blue dye with or without isotope. RESULTS:When stratified by volume of blue dye, there were no significant differences in dye-only successes, overall dye successes, or mapping failures. Allergic reactions were documented in 31 (1.8%) of 1728 patients. Hypotensive reactions occurred in 3 (.2%) of 1728 patients; 2 (.1%) required pressor support. There was a nonsignificant trend toward fewer allergic reactions with smaller volumes of blue dye. CONCLUSIONS:In combined-technique SLN mapping protocols for breast cancer, using smaller volumes of blue dye may represent a means of optimizing the safety of the procedure without compromising its success.

OBJECTIVE:To describe the incidence of clinically detected laparoscopy-related subcutaneous tumor implantation in women with malignant disease who were treated by a gynecologic oncology service. METHODS:We reviewed all cases of primary or metastatic malignancy who underwent a transperitoneal laparoscopy. Open laparoscopy technique was used in all cases with the Hasson trocar, usually placed near the umbilicus. A carbon dioxide pneumoperitoneum was used in all cases, with maximum intraabdominal pressure set at 15 mm Hg. All trocar sites more than 5 mm were closed at the fascia level. Identifying subcutaneous implantation was performed by a detailed review of all available medical records and by review of a prospectively maintained comprehensive complications database. RESULTS:In a 12-year period (July 1991 to July 2003), 2,593 laparoscopic procedures were performed, including 1,335 transperitoneal laparoscopies in 1,288 women with malignant disease. Malignant disease sites included adnexa/peritoneum (584), uterine corpus (355), uterine cervix (100), and other (249). There were no "isolated" trocar-related subcutaneous tumor implantations during the study period. Subcutaneous tumor implantations (n = 13, 0.97%) usually occurred with carcinomatosis, with synchronous metastases to other sites, and in the setting where the preceding laparoscopy was performed in the presence of advanced or recurrent abdominopelvic disease. CONCLUSION/CONCLUSIONS:Laparoscopy-related subcutaneous tumor implantation is rare (0.97%) in women undergoing transperitoneal laparoscopy with malignant disease. Subcutaneous implantation appears to occur in patients with known metastatic disease and is detected in the setting of synchronous advanced intraabdominal or pelvic metastasis and progression of carcinomatosis. The risk of subcutaneous tumor implantation should not be used as an argument against laparoscopy in the majority of women with gynecologic malignancies managed by gynecologic oncologists. LEVEL OF EVIDENCE/METHODS:II-2

OBJECTIVE:To describe the utility of laparoscopic evaluation of adnexal masses in women with stage IV breast cancer. METHODS:A retrospective review of gynecologic and breast surgery databases at our institution was performed to identify patients with stage IV breast cancer who underwent surgical evaluation for an adnexal mass or bilateral salpingo-oophorectomy (BSO) between January 1986 and August 2002. Patient demographics and operative and pathologic findings were reviewed. RESULTS:Thirty-one patients were identified. Median age was 47 years (range, 25-79 years). Pathology of the primary breast tumor was infiltrating ductal carcinoma in 58%, invasive lobular carcinoma in 29%, and unspecified in 13%. Median time from diagnosis of stage IV breast cancer to surgical evaluation of the adnexa was 15 months (range, 0-106 months). Surgery consisted of planned laparotomy in four patients and laparoscopic evaluation in 27 patients. Six patients had laparoscopic BSO for hormonal ablation. The remaining 21 patients had laparoscopic evaluation of an adnexal mass. Conversion to laparotomy occurred in three patients based on intraoperative findings of suspected primary ovarian cancer and for technical reasons in one patient. Overall, metastatic breast cancer was diagnosed in 21 (68%) of 31 patients, including two patients with occult metastases undergoing BSO for hormonal ablation. Primary ovarian cancer was found in 3 (10%) of 31 patients, and 7 (22%) of 31 patients had benign findings. Pathologic intraoperative frozen section was obtained in 21 (84%) of 25 patients undergoing laparoscopic evaluation for an adnexal mass. Intraoperative frozen section was concordant with final pathology in 20 (95%) of 21 patients (18 on laparoscopic evaluation, two on laparotomy). CONCLUSIONS:The majority of patients with stage IV breast cancer who present with an adnexal mass will be diagnosed with metastatic breast cancer. A small subset of patients will be diagnosed with primary ovarian cancer; thus, the evaluation of an adnexal mass even in this stage IV setting is warranted. Accurate diagnosis of metastatic breast cancer versus ovarian cancer can be made laparoscopically, thereby avoiding laparotomy in the metastatic breast cancer setting.

OBJECTIVE: We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5-10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone. METHODS: Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR. RESULTS: With a median follow-up of 31 months (range, 1-75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013). CONCLUSIONS: Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

OBJECTIVE: To determine the percentage of patients with early-stage cervical cancer who may be eligible for fertility preservation with laparoscopic radical vaginal trachelectomy (LRVT). METHODS: We retrospectively reviewed the records of patients who underwent a radical hysterectomy for invasive cervical cancer at our institution from 12/85 to 8/01, before our use of LRVT at Memorial Sloan-Kettering Cancer Center. Institutional eligibility criteria for LRVT were applied. Patients > or =40 years of age were considered ineligible. RESULTS: We identified 435 patients who had undergone radical hysterectomy for cervical cancer; 186 were age < 40 at surgery and constituted our study population. Eighty-nine (48%) patients may have been eligible by our pathologic criteria. In 12 patients, LRVT may have been aborted or altered because of unexpected disease spread. CONCLUSION: A significant number of patients < 40 with early-stage cervical cancer may be pathologically eligible for LRVT and should be counseled on this preoperatively.

OBJECTIVE:The purpose of this study was to describe the characteristics and outcome of women with metastatic breast cancer to the abdomen and pelvis, and to assess the role of surgical resection of abdominal and pelvic metastasis in this disease. METHODS:We retrospectively reviewed the medical records of 59 women with documented metastatic breast cancer to the abdomen or pelvis who had exploratory surgery by the Gynecology Service between 1986 and 2001. RESULTS:Exploratory surgery was performed a median of 5 years (range, 0-25 years) after initial diagnosis of breast cancer. Median survival from diagnosis of abdominal disease was 23 months, and 5-year survival was 24%. Survival was 36 months for optimally debulked patients (<2 cm of residual disease) and 20 months for suboptimally debulked patients (P = 0.07). Patients diagnosed 5 or more years after initial breast cancer diagnosis had a median survival of 36 months versus 17 months if diagnosed earlier (P < 0.01). On multivariate analysis the time to recurrence of breast cancer in the abdomen and optimal debulking were both significant variables. Hazard ratio for dying of disease if recurring before 5 years was 2.7 (CI 1.45-5.03) [P < 0.01]. Hazard ratio for dying of disease if suboptimal debulking was achieved was 2.14 (CI 1.13-4.02) [P = 0.02]. CONCLUSIONS:The disease pattern of metastatic breast carcinoma to the abdomen and pelvis does not appear to effect survival. Survival in patients where optimal debulking is achieved and in those recurring late is improved. Surgical resection of metachronous metastatic breast cancer to the abdomen and pelvis may be an important component of the management of this disease and should be considered in candidate patients.

OBJECTIVES/OBJECTIVE:The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. METHODS:A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons 11 and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma. RESULTS:Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the 11 mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation. CONCLUSIONS:These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Müllerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.

The hereditary breast/ovarian cancer syndrome is responsible for approximately 5% of all breast cancers and 10% of all ovarian cancers. Although this accounts for a small portion of these diseases, much attention has been focused on this syndrome because of the abundance of research in this area. The majority of the hereditary breast/ovarian syndrome can be attributed to germ-line mutations in the BRCA1 and BRCA2 genes. Reliable screening techniques for these mutations have been developed and are readily available in clinical practice. For patients who are thought to have the hereditary breast/ovarian cancer syndrome based on family history or genetic testing, options exist for either intensive screening or prophylactic surgery. This review will discuss the mechanisms by which mutations in the BRCA genes lead to the development of cancer, the limitations of currently available screening techniques, and the efficacy of prophylactic surgery. In general, prophylactic oophorectomy can be performed laparoscopically as an outpatient procedure, carrying as its main drawback the associated consequence of surgical menopause. Prophylactic mastectomy is quite effective in reducing the risk of breast cancer but is a more extensive surgical procedure and results in disfigurement. For any given patient, the best estimates of individual risk of breast or ovarian cancer should be weighed against the benefits of prophylactic surgery and the patient's personal wishes.

OBJECTIVE: The objective was to describe the results, technique, and complications of transperitoneal laparoscopic (LSC) pelvic and aortic lymph node dissection (LND) using the argon-beam coagulator (ABC) and monopolar electrosurgical instruments in women with gynecologic malignancies. METHODS: A retrospective chart review of 114 patients who underwent LSC pelvic and/or aortic LND in addition to other LSC procedures between 1/1994 and 12/2001 was conducted. All intraoperative complications and complications that occurred within the first 30 postoperative days were included. Complications were graded according to an institutional surgical secondary events reference. During the same time period, 89 patients underwent LSC followed immediately by laparotomy that included LND, resulting in a total of 203 cases. These 203 total cases are used as a denominator to determine the etiology of cases converted from LSC to laparotomy. Monopolar electrosurgical instruments or the 10-mm ABC (Conmed) set at 70 W with argon flow of 3-4 L/m min were used for laparoscopic nodal dissection. RESULTS: Sixty-one of 114 (53%) patients underwent pelvic LND, 35 (31%) underwent both pelvic and aortic LND, and 18 (16%) underwent aortic LND only. Mean patient age and body mass index were 53.3 years (range, 16 to 87 years) and 25 (range, 16 to 40), respectively. In addition, the mean number of pelvic and aortic lymph nodes removed was 10.7 (range, 1 to 39) and 5.7 (range, 0 to 21), respectively. The mean estimated blood loss was 151 mL (range, 25 to 600 ml) and the mean hospital stay was 2.8 days (range, 0 to 35 days). Overall, complications occurred in eight (7%) cases. There were no fatal complications, and no patient required conversion to laparotomy due to uncontrollable bleeding from the laparoscopic nodal dissection. Only 17 of 203 (8%) patients required conversion to laparotomy secondary to adhesions and unsatisfactory exposure. CONCLUSION: Laparoscopic pelvic and aortic LND for gynecologic malignancies can be satisfactorily performed in the majority of patients, with only 8% of patients requiring conversion to laparotomy due to adhesions or unsatisfactory exposure. The overall complication rate was 7% and was limited to grade 3 or less.

OBJECTIVES: The aim of this study was to describe the feasibility and outcome of total laparoscopic radical hysterectomy with pelvic lymphadenectomy for stage I cervical cancer using the argon-beam coagulator. METHODS: A retrospective review was performed of patients with FIGO stage IA1-IB1 cervical cancer who underwent a total laparoscopic approach for definitive surgical treatment. Comparison was made to a cohort of 195 patients who were treated with laparotomy. RESULTS: Between 12/2000 and 12/2002, 19 patients were offered the laparoscopic approach. The procedure was completed laparoscopically in 17 patients (89.5%). Two patients, in the beginning of the study, underwent conversion to laparotomy, 1 due to parametrial bleeding and 1 due to pelvic adhesions and cystotomy. Mean age was 42.6 years (range, 30-69 years); mean body mass index was 23.1 (range, 18-30); FIGO stage included IA1 with LVI (2), IA2 (6), IB1 (11). Mean pelvic lymph node count was 25.5 (range, 15-39), and 1 patient (5.3%) had positive nodes. Mean estimated blood loss was 301 cc (range, 75-1500 cc) compared to 693 cc in the laparotomy group (P < 0.01), mean operating time was 371 min (range, 230-600 min) compared to 295 min in the laparotomy group (P < 0.01), and mean hospital stay was 4.5 days (range, 3-11 days) compared to 9.7 days in the laparotomy group (P < 0.01). There were no ureteral injuries or fistula formation. All patients remain clinically disease free at the time of this report. CONCLUSIONS: Total laparoscopic radical hysterectomy with pelvic lymphadenectomy for selected patients with stage I cervical cancer is feasible, safe, and associated with a low morbidity in the pilot phase. Estimated blood loss and postoperative hospitalization appear shorter than historical controls, at the cost of longer operating time. Oncologic outcome requires longer follow-up.