Yukio Sonoda

Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm☆

OBJECTIVE To determine the impact on progression-free survival (PFS) and overall survival (OS) of a programmatic change in surgical approach to advanced epithelial ovarian cancer. METHODS Two groups of patients with stage IIIC and IV ovarian, tubal, and peritoneal carcinoma were compared. Group 1, the control group, consisted of all 168 patients who underwent primary cytoreduction from 1/96 to 12/99. Group 2, the study group, consisted of all 210 patients who underwent primary surgery from 1/01 to 12/04, during which time a more comprehensive debulking of upper abdominal disease was utilized. RESULTS There were no differences between the groups in age, primary site of disease, surgical stage, tumor grade, American Society of Anesthesiologists class, preoperative serum CA-125 and platelet levels, percentage with or amount of ascites, size or location of largest tumor mass, or type of postoperative chemotherapy. Patients in Group 2 vs Group 1 more frequently had extensive upper abdominal procedure(s) (38% vs 0%, respectively; P<0.001) and cytoreduction to residual disease <1 cm (80% vs 46%, respectively; P<0.01). Five-year PFS and OS rates were significantly improved in Group 2. For Group 2 vs Group 1 patients, 5-year PFS rates were 31% vs 14%, respectively (hazard ratio, 0.757; 95% CI, 0.601-0.953; P=0.01]; and 5-year OS rates were 47% vs 35%, respectively (HR, 0.764; 95% CI, 0.592-0.987; P=0.03]. CONCLUSION The incorporation of extensive upper abdominal procedures resulted in increased optimal cytoreduction rates and significantly improved PFS and OS. A paradigm shift toward more complete primary cytoreduction can improve survival for patients with advanced ovarian, tubal, and peritoneal carcinomas.

Total laparoscopic radical hysterectomy with pelvic lymphadenectomy using the argon-beam coagulator: pilot data and comparison to laparotomy

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.

An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT)

OBJECTIVE The recent EORTC-NCIC randomized trial comparing primary debulking surgery (PDS) to neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian carcinoma (EOC) reported a median progression-free survival (PFS) of 12 months and overall survival (OS) of 30 months for both arms. Due to the equivalent survival and decreased morbidity with NACT, many now consider it the preferred approach. We analyzed the outcomes of patients treated with PDS at our institution during the same time period in which the EORTC-NCIC trial was conducted, using identical inclusion criteria. METHODS We identified all patients undergoing primary treatment for advanced EOC at our institution from 9/98-12/06. Study inclusion and exclusion criteria were identical to those of the EORTC-NCIC trial. Standard statistical tests were used. RESULTS Of 316 eligible patients, 285 (90%) underwent PDS and 31 (10%) received NACT due to extra-abdominal disease, medical comorbidities, and/or advanced age (>85 years). Of the 285 patients who underwent PDS, most had carcinoma of ovarian origin (248, 87%); stage IIIC disease (249, 87%); grade 3 tumors (237, 83%); and serous histology (249, 87%). Optimal cytoreduction (≤1 cm residual) was achieved in 203 patients (71%). Postoperative platinum-based chemotherapy was given to 281 of 285 patients (99%). The median PFS and OS were 17 and 50 months, respectively. CONCLUSION PDS should continue to be the preferred initial management for patients with bulky stages IIIC-IV ovarian carcinoma. NACT should be reserved for those who cannot tolerate PDS and/or for whom optimal cytoreduction is not feasible.

The incidence of pelvic lymph node metastasis by FIGO staging for patients with adequately surgically staged endometrial adenocarcinoma of endometrioid histology

The seminal Gynecologic Oncology Group study on surgical pathologic spread patterns of endometrial cancer demonstrated the risk of pelvic lymph node metastasis for clinical stage I endometrial cancer based on tumor grade and thirds of myometrial invasion. However, the FIGO staging system assigns surgical stage by categorizing depth of myometrial invasion in halves. The objective of this study was to determine the incidence of pelvic lymph node metastasis in endometrial cancer based on tumor grade and myometrial invasion as per the current FIGO staging system. We reviewed the records of all patients who underwent primary surgical staging for clinical stage I endometrial cancer at our institution between May 1993 and November 2005. To make the study cohort as homogeneous as possible, we included only cases of endometrioid histology. We also included only patients who had adequate staging, which was defined as a total hysterectomy with removal of at least eight pelvic lymph nodes. During the study period, 1036 patients underwent primary surgery for endometrial cancer. The study cohort was composed of the 349 patients who met study inclusion criteria. Distribution of tumor grade was as follows: grade 1, 80 (23%); grade 2, 182 (52%); and grade 3, 87 (25%). Overall, 30 patients (9%) had pelvic lymph node metastasis. The incidence of pelvic lymph node metastasis in relation to tumor grade and depth of myometrial invasion (none, inner half, and outer half) was as follows: grade 1–0%, 0%, and 0%, respectively; grade 2–4%, 10%, and 17%, respectively; and grade 3–0%, 7%, and 28%, respectively. We determined the incidence of pelvic nodal metastasis in a large cohort of endometrial cancer patients of uniform histologic subtype in relation to tumor grade and a one-half myometrial invasion cutoff. These data are more applicable to current surgical practice than the previously described one-third myometrial invasion cutoff results.

Sentinel lymph node mapping for grade 1 endometrial cancer: Is it the answer to the surgical staging dilemma?

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.

Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease

Patients who have undergone supracervical hysterectomy or uterine morcellation for presumed benign uterine disease and are found to have malignancy on final pathology represent a management dilemma. Our goal was to analyze our experience and make observations regarding staging, treatment, and outcomes. We performed a retrospective case series of patients referred to our institution with uterine malignancy who previously underwent supracervical hysterectomy or uterine morcellation at the time of original surgery for presumed benign uterine disease. Between January 2000 and March 2006, 17 patients with uterine malignancy were identified. Following initial surgery, 15 (88%) patients had presumed stage I disease and 2 (12%) patients had stage III disease. Two (15%) of 13 patients who underwent completion surgery were upstaged; both had leiomyosarcoma (LMS) originally resected with morcellation. Ten of 11 patients whose stage was confirmed with secondary surgery remain disease free. None of the patients who initially underwent supracervical hysterectomy without morcellation were upstaged by secondary surgery. The median follow-up interval was 30 months (range, 2–90 months). Reoperation for completion surgery and staging is important when uterine malignancy is found incidentally after morcellation or supracervical hysterectomy for presumed benign uterine disease. Approximately 15% of patients will be upstaged by reexploration, particularly those with LMS who underwent morcellation. Patients who undergo completion surgery with restaging and are not upstaged appear to have a good prognosis. Surgical staging is valuable for prognosis and may alter postoperative treatments

Oncologic outcome of fertility-sparing radical trachelectomy versus radical hysterectomy for stage IB1 cervical carcinoma.

OBJECTIVE To compare the oncologic outcomes of women who underwent a fertility-sparing radical trachelectomy (RT) to those who underwent a radical hysterectomy (RH) for stage IB1 cervical carcinoma. METHODS We performed a case-control study of all patients with stage IB1 cervical carcinoma who underwent a vaginal or abdominal RT between 11/01 and 6/07. The control group consisted of patients with stage IB1 disease who underwent an RH between 11/91 and 6/07 and who would be considered candidates for fertility-sparing surgery. Information was extracted from a prospectively acquired database. Recurrence-free and disease-specific survival (RFS and DSS) were estimated using Kaplan-Meier estimates and compared with the log-rank test where indicated. Multivariate analysis was performed using the Cox regression method. RESULTS Forty stage IB1 patients underwent an RT and 110 patients underwent an RH. There were no statistical differences between the two groups for the following prognostic variables: histology, median number of lymph nodes removed, node positive rate, lymph-vascular space involvement (LVSI), or deep stromal invasion (DSI). The median follow-up for the entire group was 44 months. The 5-year RFS rate was 96% (for the RT group compared to 86% for the RH group (P=NS). On multivariate analysis in this group of stage IB1 lesions, tumor size <2 cm was not an independent predictor of outcome, but both LVSI and DSI retained independent predictive value (P=0.033 and 0.005, respectively). CONCLUSION For selected patients with stage IB1 cervical cancer, fertility-sparing radical trachelectomy appears to have a similar oncologic outcome to radical hysterectomy. LVSI and DSI appear to be more valuable predictors of outcome than tumor diameter in this subgroup of patients.

Incidence of lymph node and ovarian metastases in leiomyosarcoma of the uterus

OBJECTIVE The purpose of this study was to determine the incidence of lymph node and ovarian metastases in newly diagnosed uterine leiomyosarcoma (LMS), and to describe possible predictive factors. METHODS We used our prospectively acquired databases to identify 275 consecutive patients with uterine LMS treated from 7/82 to 12/01. Patients were included if there was clear documentation of lymph nodes and/or ovarian tissue in the pathologic reports. Clinical data were extracted from electronic medical records. Statistical analysis using the Fisher exact test was used to determine prognostic factors. RESULTS There were 108 patients (39.2%) identified in whom an oophorectomy and 37 patients (13.5%) in whom lymph node sampling was performed as part of the initial surgical management of uterine LMS. Bilateral oophorectomy was performed in 102 (94.4%) of the 108 patients. The median numbers of pelvic, para-aortic, and total lymph nodes acquired were 5 (range, 1-27), 3 (range, 1-9), and 6 (range, 1-34), respectively. Ovarian metastases were found in 4 (3.9%) out of 108 patients. Two (2.8%) of the 71 patients with disease confined to the uterus and/or cervix (stage I/II) and 2 (5.4%) of the 37 patients with gross extrauterine disease had ovarian metastases (P = 0.43). Positive lymph nodes were seen in 3 (8.1%) of 37 patients. No patients with stage I/II disease had positive lymph nodes (P = 0.015). None of the factors analyzed predicted for metastases to the ovary. Only the presence or absence of gross extrauterine disease correlated with lymph node metastasis. In addition, all three of these cases had clinically suspicious (enlarged) lymph nodes. CONCLUSIONS The incidence of ovarian and lymph node metastases in uterine LMS is very low and is most commonly associated with extrauterine disease. Lymph node dissection for uterine LMS should be reserved for patients with clinically suspicious nodes.

Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes

OBJECTIVE To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate. METHODS All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC). RESULTS Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003). CONCLUSION Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread.

The rate of port-site metastases after 2251 laparoscopic procedures in women with underlying malignant disease.

BACKGROUND The aim was to describe the rate of laparoscopic trocar-related subcutaneous tumor implants in women with underlying malignant disease. METHODS An analysis of a prospective database of all patients undergoing transperitoneal laparoscopic procedures for malignant conditions performed by the gynecologic oncology service. RESULTS Between July 1991 and April 2007, laparoscopic procedures were performed in 1694 patients with a malignant intraabdominal condition and in 505 breast cancer patients undergoing risk-reducing, diagnostic or therapeutic laparoscopic procedures without intraabdominal disease. Port-site metastases were documented in 20 of 1694 patients (1.18%) who underwent laparoscopic procedures for a malignant intraabdominal condition. Of these, 15 patients had a diagnosis of epithelial ovarian or fallopian tube carcinoma, 2 had breast cancer, 2 had cervical cancer, and 1 had uterine cancer. Nineteen of 20 patients (95%) had simultaneous carcinomatosis or metastases to other sites at the time of port-site metastasis. Patients who developed port-site metastases within 7 months from the laparoscopic procedure had a median survival of 12 months whereas patients who developed port-site metastasis >7 months had a median survival of 37 months (P=0.004). No port-site recurrence was documented in patients undergoing risk-reducing, diagnostic or therapeutic laparoscopic procedures for breast cancer without intraabdominal disease. CONCLUSION The rate of port-site tumor implantation after laparoscopic procedures in women with malignant disease is low and almost always occurs in the setting of synchronous, advanced intraabdominal or distant metastatic disease. The presence of port-site implantation is a surrogate for advanced disease and should not be used as an argument against laparoscopic surgery in gynecologic malignancies.