2002 Abstracts Presented
Low Complication Rate of Laparoscopic Pelvic and Paraaortic Lymph Node Dissection: An 8-Year Study
NR Abu-Rustum, D Chi, Y Sonoda, MJ DiClemente, G Bekker, M Gemignani, E Poynor, CL Brown, RR Barakat. Memorial Sloan-Kettering Cancer Center Gynecology Service, Department of Surgery, New York, New York.
Objective: To describe the complications and outcome of laparoscopic (LSC) pelvic and aortic lymph node dissection using the argon-beam coagulator (ABC) and monopolar electrosurgical instruments in women with gynecologic malignancies.
Methods: Retrospective chart review of 121 consecutive patients who underwent LSC pelvic and/or aortic nodal dissection in addition to other LSC procedures between 1/94 and 12/01. Patient characteristics and outcome were compared to 89 consecutive patients who during the same time period underwent LSC followed immediately by laparotomy (LAP) that included a lymph node dissection. All intraoperative and perioperative complications were included in the analysis. Surgical complications were presented at a weekly gynecology service disease management team conference and maintained in a prospective database. The 10 mm ABC (Conmed) was set at 70W with argon flow of 3-4 L/m min; monopolar electrosurgical instruments were also used in the initial phase of the study. Statistical analysis was performed using chi-square, t-test, and Fischer’s exact test.
Results: The 121 LSC procedures included: LAVH (57), second-look/EOD (22), LSC staging (19), LSC radical hysterectomy (11), LSC node dissection only (10), and LSC trachelectomy (2). Sixty-one of 121 (50%) patients underwent pelvic node dissection, 42 (35%) underwent both pelvic and aortic dissections, and 18 (15%) underwent aortic node dissection only. Of the 210 patients who started with LSC, 20 (9.5%) were converted to LAP to resect malignancy, 17 (8.1%) due to adhesions or unsatisfactory exposure, 14 (6.7%) after a LSC excluded diffuse metastasis as part of a planned open resection, 13 (6.2%) due to adnexal malignancy on frozen section, 7 (3.3%) following negative second-look LSC, 7 (3.3%) due to a suspicious pelvic mass, 4 (1.9%) due to a bulky uterus for LAVH, 2 (0.9%) for staging after LAVH revealed corpus cancer by frozen section, 2 (0.9%) due to bleeding (1 IP ligament during BSO, 1 parametrial during RH), and one of each cystotomy, enterotomy, and uterine perforation with cancer.
Mean patient age and Quetelet index were similar in the LSC and LAP groups: 53.9 years (16-87) vs. 55.8 (18-83), and BMI 25.6 (16-40) vs. BMI 26.7 (18-44). In addition, the mean number of pelvic and aortic lymph nodes removed were similar: 10.7 (1-39) vs. 9.2 (1-38) pelvic, and 5.7 (0-21) vs. 4.8 (1-12) aortic. Estimated blood loss and hospital stay were significantly less for the LSC group 151ml (25-600) vs. 337 (50-2000) [p<0.001], and 2.8 days (0-35) vs. 6.8 days (3-68) [p<0.001], respectively. Although the duration of the nodal dissection was not timed separately, the overall operating times were similar: 255 minutes (60-535) vs. 250 minutes (120-900). Positive pelvic lymph nodes were noted in 4 (4.5%) LSC patients, with a mean of 3.3 positive nodes, compared to 13 (21%, p=0.007) in LAP patients, with a mean of 2.6 positive nodes; in addition, positive paraaortic nodes were noted in 4 (7.1%) LSC patients, with a mean of 1.3 positive nodes, compared to 21 (36.8%, p<0.001) LAP patients, with a mean of 2.4 positive nodes.
Overall complications were significantly less in the LSC group compared to LAP (p=0.006) and are summarized in the following table:
|
Complication |
LSC (n=121) |
LAP (n=89) |
|
GI |
3 (2.5%) |
4 (4.5%) |
|
Infectious |
4 (3.3%) |
10 (11.2%) |
|
Bleeding/Hematoma |
2 (1.6%) |
4 (4.5%) |
|
DVT/PE |
1 (0.8%) |
1 (1.1%) |
|
Overall |
10 (8.3%) |
19 (21.3%) |
|
None |
111 (91.7%) |
70 (78.6%) |
There were no fatal complications, and no patient required conversion to laparotomy due to uncontrollable bleeding from the LSC nodal dissection.
Conclusions: Laparoscopic pelvic and aortic lymph node dissection for gynecologic malignancies using the argon-beam coagulator or monopolar electrosurgical instruments can be satisfactorily performed in the majority of patients, with only 8% of patients requiring conversion to laparotomy due to adhesions or unsatisfactory exposure. There were no conversions required due to uncontrollable bleeding secondary to the nodal dissection, and the overall complication rate (including other procedures performed laparoscopically) was approximately 8%.
RB1 and p53 Nuclear Staining and Survival in Patients with Stage III and IV Epithelial Ovarian Carcinoma
JP Geisler, HE Geisler, GA Miller, MC Wiemann, Z Zhou, W Crabtree. Division Of Gynecologic Oncology, St. Vincent Hospitals and Health Services, Indianapolis, Indiana.
Objective: The retinoblastoma gene and its protein RB1 are closely involved in the transition of cells from G1 to S phase. The authors wanted to analyze whether the percent-positive nuclear area staining of the RB1 protein correlated with DNA index, p53 staining survival in patients with Stage III or IV epithelial ovarian carcinoma.
Methods: One hundred and thirty-five patients with epithelial ovarian carcinoma were studied. Slides were prepared from snap-frozen tissue. Quantification of RB1 nuclear staining, p53 nuclear staining, and DNA index was performed using image analysis. In addition to RB1, p53, and DNA index, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors.
Results: Of the 98 patients with Stage III disease and the 37 with Stage IV disease, optimal cytoreduction was accomplished in 78.5%. There was not a significant correlation between RB1 staining and grade (p = 0.15), stage (p = 0.07) or DNA index (P = 0.56). RB1 staining and p53 staining were inversely related (p = 0.001). Kaplan-Meier analysis, using the median RB1 staining as a cut-off, demonstrated that those with low RB1 tumor staining (mean, 41 months; median, 27 months) had a significantly decreased survival as compared to those with high RB1 tumor staining (mean, 67 months; median, not yet reached) [p < 0.0001]. Cox-regression analysis revealed that optimal cytoreduction (p = 0.0078) and an RB1 staining greater than the cohort’s median (55.6%) were the two most important prognostic factors in these patients with advanced disease.
Conclusion: The RB1 protein can be readily quantified by immunohistochemical methods and image analysis. Patients whose tumors had high RB1 staining had significantly increased survival over patients whose tumors had low RB1 staining.
TP53 Mutation in Early-Stage Sporadic Epithelial Ovarian Carcinoma
M Leitao, R Soslow, N Olvera, C Arroyo, R Baergen, J Boyd. Departments of Surgery, Pathology, and Human Genetics, Memorial Sloan-Kettering Cancer Center and Department of Pathology, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, New York
Objective: To determine the incidence of TP53 mutation in early stage sporadic epithelial ovarian carcinoma and to compare this to p53 immunohistochemical (IHC) staining.
Methods: All cases of FIGO Stage I and II invasive epithelial ovarian carcinoma that underwent primary surgical staging at our institution over a 20-year period were identified. Ashkenazi Jewish cases identified since December 1986 have been genotyped for the presence of the three germ-line founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2) and were excluded as well as cases whose family history was significant for breast/ovarian cancer. Tissue was available for 73 of the 140 cases that underwent pathologic review. IHC analysis of p53 using mouse monoclonal antibody (clone DO-7, DAKO) was performed on all cases. Nested amplification (PCR) was carried out on manually microdissected tissue using intron-based primers for the entire coding region of TP53 (exons 2-11) and automated sequencing was performed on all cases. Statistical analyses were performed using χ2 analysis and Fischer’s exact test.
Results: The histologic subtypes included 21 serous (Stage I, 6; Stage II, 15), 17 clear-cell (Stage I, 16; Stage II, 1), 20 endometrioid (Stage I, 15; Stage II, 5), 7 mixed (Stage I, 2; Stage II, 5), 2 malignant Brenner (both Stage I), 5 mucinous tumors (all Stage I) and 1 adenocarcinoma, NOS (Stage II). Overall, 25 (34%) cases demonstrated a mutation in TP53 on direct sequencing with more Stage II tumors containing a mutation (p=0.0006). However, 14 (67%) of the 21 serous tumors contained a mutation as compared to 10 (23%) of the 44 non-serous tumors (p=0.0002). The association of TP53 mutation with stage was maintained for non-serous tumors (p=0.047) but was lost for serous tumors (p=0.9). Of the 26 mutations identified, 20 (76.9%) were single-base substitutions leading to 13 (50%) missense mutations. Five (19.2%) mutations were outside exons 5-8. The sensitivity, specificity, positive predictive value, and negative predictive value of IHC in predicting for mutation was 58.3%, 70.8%, 63.6%, and 82.9%, respectively.
Conclusions: TP53 is frequently mutated in early-stage sporadic serous ovarian carcinomas. This may have implications in early detection and therapeutic targets. IHC analysis of p53 is a poor predictor of TP53 mutation. Accurate assessment of TP53 mutations requires direct sequencing of the entire genomic coding region.
Analysis of in vitro chemosensitivity assays from second-look laparotomy in ovarian cancer
JN McAlpine, SC Ballon. Women’s Cancer Center, Palo Alto, California.
Objectives: No single chemotherapeutic regimen has proven superior for recurrent ovarian cancer in terms of long-term survival, quality of life, or response rate. Several practitioners utilize in vitro chemosensitivity assays (IVCAs) for primary surgery or second look in hopes of guiding treatment. Initial therapy for epithelial ovarian cancer is somewhat standardized with staging laparotomy followed by platinum- and Taxol®-based regimens. We sought to analyze specific results of chemosensitivity assays obtained during second-look laparotomy following this standardized regimen.
Methods: Retrospective chart review identified 50 patients who had undergone surgical staging for ovarian cancer, by a single individual, followed by six cycles of carboplatinum and Taxol® chemotherapy administered at standard doses (AUC 5, 135mg/m2 respectively). Patients then underwent second-look laparotomy with ONCOTECH in vitro chemosensitivity assays performed. The assays were then analyzed and the sensitivities (sensitive, intermediate, resistant) of each single agent and multiple agents recorded to see if specific trends could be identified. Parameters such as patient age, BMI, performance status, tumor stage, grade, and time schedule from surgery, chemotherapy, and second look were recorded with select comparisons made.
Results: Preliminary results suggest a combination of cisplatin or gemcitabine with other agents yielded the greatest sensitivity, even when intermediate or resistant assays were shown with the single agent alone. In the patients who had their second-look laparotomy less than 6 months from initial therapy, platinum resistance was increased. Final analysis is pending.
Conclusions: Consistent with prior literature, the time between chemotherapeutic regimens affects sensitivity significantly. We were unable to elicit any specific patterns of predictability of chemosensitivity in second-look patients; however, further accumulation and analysis of our own data is in progress.
ASSESSMENT OF MAXIMUM DOSE AND RESPONSE OF WEEKLY TOPOTECAN COMBINED WITH WEEKLY PACLITAXEL IN EPITHELIAL OVARIAN CARCINOMA
H Homesley, B Benigno, J Williams Jr, L Vaccarello. Brookview Research Inc.
Toxicity, maximum tolerated dose (MTD), and estimate of response were assessed in this prospective trial of the combination of weekly topotecan and weekly paclitaxel. For second- or third-line therapy, 26 patients, both platinum- sensitive and platinum-resistant, with measurable disease and/or increasing CA-125 values were entered. Initially, patients were dosed with 60 mg/m2 paclitaxel along with 2 mg/m2 weekly bolus topotecan. Every 21 days, intrapatient escalation of both agents as tolerated produced six patient cohorts. The initial dose was increased when indicated in successive patients.
Weekly Topotecan ( mg/m2 ) Weekly Paclitaxel (mg/m2)
Cohort 1 2 60
Cohort 2 2.5 80
Cohort 3 3 80
Cohort 4 3.5 90
Cohort 5 4 100
Cohort 6 4.5 110
Twenty-one patients were evaluable. The MTD of topotecan was 4 mg/m2 and 110 mg/m2 of paclitaxel. Fatigue, anemia, and neutropenia were dose limiting. Ten of 21 patients received epoetin alpha and one was transfused. Seven of 21 patients received colony-stimulating growth factor. There were six complete responses (CR) (29%) with five based on CA-125 and the remaining CR on measurable disease. There was one partial response (5%) for a total response rate of 33%. Fifty percent of the eight patients with only CA-125 elevations had complete responses. Of the 13 patients with measurable disease, there were two complete responses (15%). One patient had a partial response with a decreased CA-125, while her measurable disease remained stable. Thus, anemia, fatigue, and neutropenia, along with the weekly grind of this chemotherapy regimen limited escalation of the weekly dose of topotecan and paclitaxel. The maximum dose would be estimated to be 4 mg/m2 of topotecan combined with 100 mg/m2 of paclitaxel with six of seven responses occurring with a minimum topotecan dose of 3 mg/m2. Further evaluations of this regimen of topotecan and paclitaxel are required to confirm the efficacy and tolerability demonstrated in this study. A comparative trial of paclitaxel vs this combination would better assess response.
Palliative surgery for bowel obstruction in recurrent ovarian cancer: an updated series
Bhavana Pothuri, Ami Vaidya, Carol Aghajanian, Ennapadam Venkatraman, Richard R. Barakat, and Dennis S. Chi, Memorial Sloan-Kettering Cancer Center, New York, NY.
Objective: Intestinal obstruction is one of the most frequent sequelae of recurrent ovarian cancer. Previous series have reported median survivals of 3 to 6 months in patients who have undergone surgery for bowel obstruction due to recurrent disease. The purpose of this study is to analyze a contemporary series of patients to determine if outcomes have changed in patients undergoing palliative surgery.
Methods: We performed a retrospective review of all patients undergoing surgery for intestinal obstruction due to recurrent ovarian cancer from 1994 to 1999.
Results: During the study period, 69 operations were performed on 64 patients. The mean age at the time of obstruction was 57.3 years (range, 28.6 to 79.3 years). The mean time from original diagnosis of ovarian cancer to obstruction was 2.8 years (range, 0.3 to 8.6 years). Surgical correction, defined as intestinal surgery performed for relief of obstruction, was attained in 57/69 (83%) cases. Successful palliation, defined as the ability to tolerate a regular or low-residue diet at least 60 days postoperatively, was achieved in 71% of cases where surgical correction was possible. The rate of major surgical morbidity was 22%. There was one death from a pulmonary embolus and one from peritonitis. Two other deaths occurred due to progression of disease for an overall peri-operative mortality rate of 6%. Postoperative chemotherapy was administered in 45/57 (79%) of cases where surgical correction was possible. The median survival of the entire cohort was 8 months. If surgery resulted in successful palliation, median survival was 11.6 months versus 3.9 months for all other patients (p<0.01).
Conclusions: Our current series reveals that the majority of patients undergoing surgery have successful palliation, and are able to receive further chemotherapy. These successfully palliated patients were discharged home and able to tolerate solid food with a median survival of 11.6 months.
Pattern of retroperitoneal disease distribution in patients with persistent epithelial ovarian cancer at second-look laparotomy
Christopher S. Awtrey, Nadeem Abu-Rustum, Dennis Chi, Carol Brown, Elizabeth Poynor, Mary Gemignani, Richard R. Barakat, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
Objectives: To evaluate the pattern of retroperitoneal disease distribution in patients found to have persistent disease at second-look laparotomy.
Methods: A retrospective review of the medical records of all epithelial ovarian cancer patients admitted to our institution who were found to have a positive second-look laparotomy and had undergone retroperitoneal lymph node sampling at time of second- look procedure between 1991 and 2001 was undertaken. The medical records were reviewed for clinical, surgical, and pathologic findings.
Results: A total of 49 patients were identified. Nodal metastases were found in 25 of 49 (51%) patients, and in five of these patients (10.2%) was the only evidence of persistent disease at second-look procedure. Of the five patients with isolated positive lymph nodes, all had undergone a lymph node sampling at their initial staging procedure and 4/5 (80%) had had positive lymph nodes resected at that time. All 49 patients in this group underwent a para-aortic lymph node dissection at the time of second-look laparotomy and in 11/49 (22.4%) a pelvic lymph node dissection was also preformed. Of the 49 patients with para-aortic lymph nodes dissected, 23/49 (47%) had disease noted in this area. Of the 11 patients that had both pelvic and para-aortic lymph node dissections, 2/11 (18%) had isolated positive pelvic lymph nodes with negative para-aortics. In 6 of these 11 (55%) patients, isolated positive para-aortic lymph nodes with negative pelvic nodes were noted.
Conclusions: The majority of patients undergoing second-look laparotomy and retroperitoneal lymph node dissection had disease detected in retroperitoneal nodes with the majority involving para-aortic lymph nodes. The incidence of isolated retroperitoneal disease was 10%, underscoring the need for retroperitoneal nodal sampling at the time of second-look surgery.
PROGNOSTIC SIGNIFICANCE OF CYTOKERATIN STAINING OF PELVIC LYMPH NODES REMOVED AT THE TIME OF RADICAL HYSTERECTOMY
A Turmero, P DiSilvestro, C Tornos, R McDonell. Long Island Gynecologic Oncologists, PC, Stony Brook University Hospital, Long Island, New York.
Objective: To find out whether immunohistochemical methods (cytokeratin staining) can be used to detect occult node metastases reliably and to identify patients with pelvic lymph node micrometastases in early-stage cervical cancer.
Methods: This was a retrospective case-control study. A total of 20 women, ages 37-51, who underwent radical hysterectomy with pelvic lymph node dissection for stages IB-IIA cervical cancer were selected from Stony Brook University Hospital between 1995 and 2000. Cases were patients who had negative nodes upon routine hematoxylin eosin examination and had documented clinical recurrence. Controls were those patients with negative pelvic lymph nodes without recurrence. Cytokeratin staining using an antibody mixture (prediluted CK 22) were performed in a total of 169 slides that were reviewed by the same pathologist. Cases and controls were matched based on age, tumor size, parametrial invasion, and presence or absence of lymphovascular space invasion. A Fisher's exact test was performed to compare proportions.
Results: Of the 20 patients who were analyzed in this study, mean age was 43.2 years, 20% had parametrial invasion, 15% lymphovascular space invasion, and mean recurrence for cases was 20 months. One case out of nine had cytokeratin positive lymph nodes. This patient developed a recurrence in the distal small bowel within 10 months after surgery. Cytokeratin positive cells were found in the subcapsular region of the lymph node. There was no significance difference between the two groups (p = 0.95).
Conclusion: Future studies with greater samples and specific antibody mixtures can be done to determine if cytokeratin can be used in clinical pathology to detect occult node metastases and suggest patterns of invasion that could affect prognosis in patients with early-stage cervical cancer.
A CLUSTER OF THREE UNUSUAL CASES
G Fort. Baton Rouge, Louisiana.
In a recent brief period of time a case of adenosarcoma of the cervix, a case of metastatic placental site trophoblastic tumor, and a case of ectopic production of bHCG were seen and treated. These case reports will be presented along with relevant literature review.
WHO DUNNIT? : ENDOMETRIAL CANCER SURVIVAL. IS IT DEPENDENT ON THE SPECIALTY OF THE MANAGING PHYSICIAN?
EG George, WA Nahhas. Miami Valley Hospital, Wright State University School of Medicine, Dayton, Ohio.
Objective: To determine whether the survival of patients with endometrial cancer is dependent on the specialty of the primary managing physician.
Methods: This is a retrospective review conducted at Miami Valley Hospital, Wright State University School of Medicine; comparing the 5-year survival of patients with endometrial cancer treated by Academic Board Certified Gynecologic Oncologist to the survival of patients treated by community-based Obstetrician Gynecologists.
Using the hospital cancer registry, two groups of patients were identified. From January 1990 to December 1995, 175 patients (group I) were treated by Gynecologic Oncologists while 129 patients (group II) were treated by community-based Obstetrician Gynecologists. The 5-year survival rate of both groups was then compared by AJCC Stage, age, race, and histology.
Results: 5-year survival in both groups was related to AJCC Stage, age, race, and histology. Grade distribution was similar between the groups. The survival rate was not related to the specialty of the treating physician. Survival rate in both groups was comparable to that in the SEER database.
A CASE-CONTROL RETROSPECTIVE COMPARATIVE ANALYSIS OF PRIMARY CARCINOMA OF THE FALLOPIAN TUBE AND EPITHELIAL OVARIAN CARCINOMA
JP Geisler, MS Dunn, JI Sorosky, B Anderson, RE Buller, KJ Manahan, AK Sood
Division of Gynecologic Oncology, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Objective: To determine whether or not differences exist in clinicopathologic variables or in survival between women with primary carcinoma of the fallopian tube (PCFT) and women with epithelial ovarian carcinoma (EOC).
Methods: University of Iowa tumor board records were analyzed from January 1, 1991, to April 30, 2001. No cases were knowingly excluded. Each case of PCFT was matched with two cases of EOC. Controls were the next two cases of EOC diagnosed at UIHC after each case of PFTC, with priority given to stage of disease, then histological grade, followed by histology, with 1 year being the limit for obtaining the closest match.
Results: Twenty-eight cases of PCFT were found. These were matched with 56 cases of EOC. The mean age of diagnosis was significantly older for women with PCFT (67 years) versus women with EOC (60 years) [p = 0.005]. There was no difference in pre-diagnosis hormonal contraceptive use (p = 0.06), body mass index (p = 0.6), or rate of positive nodes (p = 0.7). Kaplan-Meier analysis revealed no difference in survival between PCFT and EOC (p = 0.32).
Conclusions: There is no significant difference in clinical parameters or survival between patients with PCFT and EOC when matched for stage, grade, and histology.
PRIMARY CANCER OF THE FALLOPIAN TUBE
W Kim, AR Gaba. Department of Gynecology and Obstetrics and Pathology, Henry Ford Hospital, Detroit, Michigan.
Objective: To assess the incidence, biologic behavior, clinical characteristics, pathology, and response to surgery and chemotherapy of primary fallopian tube cancers.
Methods: From the tumor registry and pathology data file, 12 patients with primary cancer of the fallopian tube have been identified from 1991 to 2000. Retrospective analysis was done for demographic data, stage and other clinical characteristics, treatment modalities and their responses to treatment, and survival. Pathology materials were reviewed for histology, grade of tumor, and presence of in situ cancer.
Results: The median age of the patients was 63.3 years (range, 42 to 79 years). All but one patient were postmenopausal. Symptoms and signs of these patients were very similar to ovarian cancer patients. Of the 12 patients, three patients were Stage I, two were Stage II, six were Stage III, and one was Stage IV. One patient had mixed mullerian tumor, one had mixed cell type, endometrioid and papillary serous, and the remaining 10 patients all had papillary serous carcinoma. All but one patient had platinum-based combination chemotherapy after surgery, and response and survival of each patient will be presented.
Conclusions: Clinical characteristics and response to chemotherapy were similar to ovarian cancer, but certain clinical and pathologic behaviors were slightly different. Primary fallopian tube cancer seems to be diagnosed in earlier stage; extra pelvic spread was less prominent, yet higher incidence of retroperitoneal lymph node metastasis was noted.
INCIDENCE OF LYMPH NODE METASTASES IN LEIOMYOSARCOMA OF THE UTERUS
MM Leitao, MF Brennan, RR Barakat, DS Chi. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
Objective: To determine the incidence of lymph node metastases in newly diagnosed uterine leiomyosarcoma (LMS) and to describe possible predictive factors.
Patients/Methods: We used our prospectively acquired databases containing all patients treated at our institution for sarcomas to identify 227 patients with uterine LMS treated from 1/1/84 to 12/31/01. Pathology reports were reviewed and patients were included if there was clear documentation of the presence of lymph nodes in the pathologic specimens. Data abstracted from the medical records included patient age, size of largest tumor, tumor grade, presence of lymph-vascular space invasion (LVSI), presence of serosal involvement, presence of cervical involvement, presence of extrauterine disease, number of lymph nodes removed, use of adjuvant or postoperative therapy, and sites of future recurrences. Stage was determined based on a modified staging system for endometrial adenocarcinomas (Berchuck, et al. Obstet Gynecol 71:845-850, 1988). Statistical analysis using Fischer’s exact test was used to determine prognostic factors.
Results: Thirty-five patients were identified who underwent lymph node sampling as part of the surgical management of uterine LMS. The median age of our patient cohort was 51 years (range, 31 to 74 years). The median number of pelvic, para-aortic, and total lymph nodes acquired was 5 (range, 1 to 27), 3 (range, 1 to 9), and 6 (range, 1 to 34), respectively. Extrauterine disease was present in 10 (28.6%) patients with 4 (11.4%) patients having Stage III disease and 6 (17.1%) having Stage IV disease. Seventeen (48.6%) patients did not receive postoperative therapy and 17 (48.6%) received either postoperative chemotherapy and/or radiation therapy. Positive lymph nodes were seen in 3/35 (8.3%) patients. All three of these patients had gross extrauterine disease at the time of surgery. No patients with disease grossly confined to the uterus and/or cervix (Stage I/II) had positive lymph nodes. (p=0.018) Only one of the 25 patients (4%) with Stage I/II disease developed a recurrence in the retroperitoneum. Other than the presence or absence of grosss extrauterine disease, no other analyzed factors were identified that correlated with lymph node metastasis.
Conclusion: The incidence of lymph node metastasis in uterine LMS is low, with no positive lymph nodes seen in patients with disease grossly confined to the uterus. The routine sampling of lymph nodes in these patients remains questionable.
Frequency of BRCA Founder Mutations among Ashkenazi Jewish (AJ) Patients with Primary Peritoneal (PPC) and Fallopian Tube (FTC) Adenocarcinoma
DA Levine, C Yee, DS Marshall, N Olvera, F Bogomolniy, RR Barakat, RA Soslow, J Boyd, Memorial Sloan-Kettering Cancer Center, New York, NY.
Objective: Inherited mutations in the BRCA1 or BRCA2 genes are present in approximately 40% of Ashkenazi Jewish (AJ) patients with epithelial ovarian cancer (EOC). The incidence of BRCA mutations among all patients with fallopian tube cancer (FTC) is reported to be 16%. The purpose of this study was to test the hypothesis that the incidence of founder mutations among AJ patients with primary peritoneal carcinoma (PPC) and FTC is similar to the incidence among AJ patients with ovarian cancer.
Methods: A retrospective review conducted over a 13-year period identified 39 AJ patients at this institution with PPC or FTC. All patients were genotyped according to standard laboratory methods for the three BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2) that exist in this population. Demographics, family history, tumor characteristics and survival data were obtained from hospital records. Thirty (77%) cases were available for pathology review.
Results: The mean age of the study population was 67, ± 9 years (range, 44 to 87 years). The stages at diagnosis were: I, 3 (8%); II, 3 (8%); III, 32 (82%); and IV, 1 (3%). All tumors had serous histology. Nine (23%) patients had at least one first-degree relative with breast or ovarian cancer. There were nine (41%) BRCA founder mutations among 22 patients with PPC and three (18%) mutations among 17 patients with FTC. There were seven mutations in BRCA1 (five at 185delAG and two at 5382insC) and seven mutations in BRCA2. One patient with PPC and one with FTC had mutations at both 185delAG and 6174delT. Patients with founder mutations had a lower mean age (61 vs. 70 years, p<0.01) and had a nonsignificant increase of first-degree relatives with breast or ovarian cancer (46% vs. 20%, p=0.22). With a median follow-up of 23 months, the overall median survival was 57 months; 40 months for patients without mutations and not reached for mutation carriers (p=0.22).
Conclusions: The data suggest that for AJ patients with PPC, the incidence of BRCA founder mutations is similar to the incidence of mutations in AJ patients with EOC. The incidence of mutations in AJ patients with FTC is lower than found in AJ patients with EOC, yet similar to the reported incidence among all patients with FTC. Patients with founder mutations in the BRCA genes are almost 10 years younger at the time of diagnosis than those patients without such mutations.
LAPAROSCOPIC PROPHYLACTIC OOPHORECTOMY IN PATIENTS AT RISK FOR HEREDITARY OVARIAN CARCINOMA
Richard R. Barakat M.D.1, Lois Almadrones1 R.N., Mark E. Robson M.D.2, Kenneth Offit M.D.2, and Jeff Boyd Ph.D1. Gynecology Service, Department of Surgery1, and Human Genetics2, Memorial Sloan-Kettering Cancer Center, New York, New York.
Background: Women who are known carriers of germline mutations in BRCA 1 /2 are estimated to have a 16-63% lifetime risk of developing ovarian cancer. The purpose of this study was to review our experience with laparoscopic prophylactic oophorectomy in women with known or suspected hereditary breast/ovarian cancer syndrome. In addition, we wanted to determine the incidence of occult primary ovarian carcinoma and the subsequent development of primary peritoneal cancer.
Methods: Between 2/95 and 6/99 we performed 95 prophylactic oophorectomies in 31(33%) patients with documented BRCA mutations and 64 (67%) with family pedigrees suspicious for the hereditary breast/ovarian cancer syndrome. This report focuses on 92 of these patients in whom the procedures were performed utilizing video-laparoscopy. Four of these patients underwent prophylactic hysterectomy as well.
Results: The mean patient age was 50 (range 30-65). The mean operative time for patients undergoing laparoscopic oophorectomy alone was 71 minutes, with no major intraoperative complications and an estimated blood loss of less than 100 cc in every case. Fourteen patients (15%) required admission for persistent nausea, urinary retention, and anxiety. Pathologic evaluation of the ovaries revealed no cases of occult ovarian cancer. With a mean follow-up of 14 months (range 1-27), no patient has developed primary peritoneal cancer.
Conclusions: Prophylactic oophorectomy utilizing video-laparoscopy is a safe and effective outpatient method for primary prevention of ovarian cancer in women with known or suspected HBOC. Longer follow-up in a greater number of patients will be required to determine the incidence of subsequent primary peritoneal cancer.
STAGE IB2 CERVIX CANCER. INFORMATION, MISINFORMATION, AND MALEFICENCE: FIGO, GOG, THE NCI AND OTHER CONTEMPORARY CONTRIBUTIONS
Richard C. Boronow, M.D. University of Mississippi Medical Center, Jackson, Mississippi.
Recently, the essayist surveyed clinical management preferences regarding cancer of the cervix from two groups of clinicians: program directors of approved gynecologic oncology training programs and a geographic sampling of gynecologic oncologists working in the private sector. Divergent opinions were observed in Stage IB2 management as well as almost all other aspects of clinical care. The lack of an adequate definition of Stage IB2 will be stressed. Current information, opinion, and investigation from FIGO, GOG, and the NCI as well as several other contemporary sources will be surveyed.