Impact of oophorectomy and hormone suppression in low grade endometrial stromal sarcoma: A multicenter review.

OBJECTIVES: Low grade endometrial stromal sarcoma (LG-ESS) is a rare cancer with an indolent course. We aimed to assess the effectiveness of adjuvant hormonal suppression (HT) with or without oophorectomy (BSO) in prolonging progression free survival (PFS) and overall survival (OS) in patients with LG-ESS. METHODS: We performed a multi-institutional retrospective review of patients treated for low grade LG-ESS from 1985 to 2014. Demographics, treatment and recurrence data were abstracted from medical records. Pathologic diagnosis was confirmed by a gynecologic pathologist. Long-term patient-reported outcomes were obtained via mailed survey. RESULTS: One-hundred-twelve patients underwent surgery for LG-ESS; 59 had postoperative data with a median follow-up of 55months (1-325months). The mean age at diagnosis was 48.5years (22-82years). Forty-nine (61%) had stage I disease. The most common presenting symptoms were abnormal uterine bleeding (38%) and pelvic mass (17%). Seventy-one (63%) patients had BSO at the time of diagnosis. Of the 59 patients with postoperative follow-up information, 49 (73%) underwent BSO, 26 (44%) received HT, 20 (33%) were expectantly managed, and 6 (10%) received chemotherapy, radiation or both. Median PFS for the entire group was 53months and OS was 63months. PFS for those who underwent BSO compared with those who retained their ovaries was 38 vs 11months, p=0.071. PFS for HT vs no HT was 28 vs 23months, p=0.77. CONCLUSIONS: Consistent with prior series, our results support BSO to prolong PFS in LG-ESS but are limited by sample size. Larger studies with more complete follow-up are needed to determine the effect of adjuvant hormonal suppression.

Development of a bench station objective structured assessment of technical skills.

OBJECTIVE: We have previously shown that objective structured assessment of technical skills performed in an animal model was an innovative, reliable, and valid method of assessing surgical skills. Our goal was to develop a less costly bench station objective structured assessment of technical skills and to evaluate the feasibility, reliability, and validity of this exam. METHODS: A seven-station examination was administered to 24 residents. The tests included laparoscopic procedures (salpingostomy, intracorporeal knot tying, closure of port sites) and open abdominal procedures (subcuticular closure, bladder neck suspension, repair of enterotomy, abdominal wall closure). All tasks were performed using life-like surgical models. Residents were timed and assessed at each station using three methods of scoring: a task-specific checklist, a global rating scale, and a pass/fail grade. RESULTS: Assessment of construct validity, the ability of the test to discriminate among residency levels, found significant differences on the checklist, global rating scale, time for procedures, and pass/fail grade by level of training. Reliability indices calculated with Cronbach's alpha were 0.77 for the checklists and 0.94 for the global rating scale. Overall interrater reliability indices were 0.91 for the global rating scale and 0.92 for the checklists. Total cost for replaceable parts and facilities was $1900. CONCLUSION: The less costly and more portable bench station objective structured assessment of technical skills can reliably and validly assess the surgical skills of gynecology residents. This type of examination can be a useful tool to identify residents who need additional surgical instruction, provide remediation, and may become a mechanism to certify surgical skill competence.

Testing surgical skills of obstetric and gynecologic residents in a bench laboratory setting: validity and reliability.

OBJECTIVE: Resident surgical skills are acquired mainly through observing and later performing procedures in the operating room. Evaluation of surgical skills has traditionally been done through subjective faculty evaluation, a technique that has poor reliability and unknown validity. Our goal was to develop specific surgical tasks, both laparoscopic and open abdominal, that could be objectively and reliably evaluated in a bench laboratory setting. STUDY DESIGN: The prospective development of a reliable and valid resident surgical skills test in a bench laboratory setting was our goal. A written test of surgical knowledge and 12 skills tests were administered to 36 residents. Laparoscopic bench tasks were simulated with the use of a box and camera with a video display. Six laparoscopic tasks were assessed, including placing pegs on a board, running the bowel simulation, and other tasks that involve hand-eye coordination and manual dexterity. Open abdominal skills simulated incision closure, suturing a vaginal cuff, knot tying, and using a tie on a passer. Residents were timed at each given station and were given a rating score by 2 examiners. RESULTS: Knowledge scores showed a significant improvement by residency level. Assessment of construct validity (the ability to discriminate among residency levels) demonstrated significant differences on the rating of overall performance and individual tasks by level (determined by 1-way analysis of variance). Interrater reliability (agreement between 2 raters) with the use of intraclass correlation was 0.79 for the total score. The cost to administer the bench laboratory test was less than $50 and required 30 hours of faculty time. CONCLUSION: The results of this study suggest that surgical bench laboratory tasks can assess residents' surgical skills with good reliability and validity on most tasks. Our previous study, which used an animal laboratory, was expensive, and the bench laboratory model may provide an alternative means to assess surgical skills.

Evaluation of chemoresistance markers in women with epithelial ovarian carcinoma.

OBJECTIVE: Preliminary studies have suggested that lung resistance protein (LRP), multidrug resistance protein (MRP), and p27 may be useful markers of chemoresistance. Our goal was to evaluate the expression of LRP, MRP, and p27 in normal ovaries and chemosensitive and chemoresistant ovarian carcinomas. METHODS: Fourteen women with normal ovaries and fifty women with epithelial ovarian carcinoma who underwent cytoreductive surgery from 1996 through 1998 had specimens stained with immunocytochemistry for LRP, MRP, and p27. All women received paclitaxel/platinum-based chemotherapy. Twenty-nine women had a disease-free survival (DFS) of at least 12 months after completion of chemotherapy (sensitive) and 21 women had persistent disease during treatment (resistant). RESULTS: Evaluation of LRP expression revealed significant differences between the normal ovaries and cancers in both the epithelial (57% vs 90%, P = 0.03) and stromal (86% vs 32%, P = 0.001) components. Evaluation of MRP expression revealed significant differences between normal ovaries and cancers in the epithelial component (7% vs 66%, P = 0.001) but not in the stromal component (14% vs 4%, P = 0.1). Evaluation of p27 revealed significant reductions in expression in cancers compared with normal ovaries for both the epithelial (90% vs 55%, P = 0.02) and stromal (88% vs 5%, P = 0.001) components. Comparison between the chemosensitive and chemoresistant groups revealed no significant differences in expression of LRP and MRP, in either the epithelial or stromal component, but significantly lower levels of p27 were expressed in the epithelial component of the chemoresistant group (P = 0.01). CONCLUSIONS: The expression of LRP, MRP, and p27 is significantly different in ovarian cancers compared with normal ovaries. Low levels of p27 expression are associated with chemoresistance; however, LRP and MRP expression are not prognostic for chemosensitivity.

Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis.

OBJECTIVE: BRCA-1 and BRCA-2 germline mutations increase the risk of ovarian and breast cancer. Primary cancer of the fallopian tube is rare; however, recent evidence suggests that patients harboring a germline mutation conferring an increased risk of ovarian cancer may be at risk for fallopian tube cancer as well. We discuss the finding of occult fallopian tube cancer diagnosed at surgical prophylaxis in women harboring BRCA-1 mutations. METHODS/RESULTS: Two patients undergoing surgical prophylaxis to address an increase in ovarian cancer risk were discovered to harbor occult primary fallopian tube carcinoma on final pathology review. Mutational analysis confirmed the presence of a deleterious mutation in BRCA-1 in both patients. CONCLUSION: Currently, consensus opinions regarding ovarian cancer surgical prophylaxis in gene mutation carriers do not include hysterectomy as part of the preventative procedure. This report as well as a growing number of cases of fallopian tube cancer reported in known BRCA-1 and BRCA-2 mutation carriers has important implications for recommendations regarding surgical prophylaxis in these women.

Ovarian carcinoma diagnosis.

BACKGROUND: Ovarian carcinoma often is called the "silent killer" because the disease usually is not detected until an advanced stage. The authors' goal was to evaluate preoperative symptoms and factors that may contribute to delayed diagnosis for women with ovarian carcinoma. METHODS: A two-page survey was distributed to 1500 women who subscribe to CONVERSATIONS!, a newsletter about ovarian carcinoma. Because the survey could be copied and given to other patients, 1725 surveys were returned from women in 46 states and 4 Canadian provinces. RESULTS: The median age of the surveyed women was 52 years, and 70% had Stage III or IV disease (International Federation of Gynecology and Obstetrics). When asked about symptoms before the diagnosis of ovarian carcinoma, 95% reported symptoms, which were categorized as abdominal (77%), gastrointestinal (70%), pain (58%), constitutional (50%), urinary (34%), and pelvic (26%). Only 11% of women with Stage I/II and 3% with Stage III/IV reported no symptoms before their diagnosis. Women who ignored their symptoms were significantly more likely to be diagnosed with advanced disease compared with those who did not (P = 0.002). The time required for a health care provider to make the diagnosis was reported as less than 3 months by 55%, but greater than 6 months by 26% and greater than 1 year by 11%. Factors significantly associated with delay in diagnosis were omission of a pelvic exam at first visit; having a multitude of symptoms; being diagnosed initially with no problem, depression, stress, irritable bowel, or gastritis; not initially receiving an ultrasound, computed tomography, or CA 125 test; and younger age. The type of health care provider seen initially, insurance, and specific symptoms did not correlate with delayed diagnosis. CONCLUSIONS: This large national survey confirms that the majority of women with ovarian carcinoma are symptomatic and frequently have delays in diagnosis.

Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer.

OBJECTIVE: Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis. Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent pattern of deregulation has been characterized. Vascular endothelial growth factor (VEGF) has emerged as an important regulator of tumor neovascularization. Recent work has shown that SPARC modulates the mitogenic activity of VEGF in normal endothelium. While its role in malignant transformation remains elusive, SPARC may contribute to tumor propagation and invasion. This study examines the immunoreactivity of SPARC and VEGF associated with neoplastic transformation of the ovary. METHODS: Immunostaining for VEGF and SPARC protein was performed on 62 archival specimens. RESULTS: Fourteen normal ovaries and 48 ovarian carcinomas were evaluated. SPARC was detected in the stroma of 63% of ovarian carcinomas. In contrast, SPARC was observed in the stroma of only 29% of normal ovaries (P = 0.02). Furthermore, SPARC was limited in normal ovaries to premenopausal patients, juxtaposed either with vesiculated follicles or within the corpus luteum. VEGF was observed in 42% of ovarian carcinomas with immunoreactivity confined to tumor cells. The level of VEGF immunoreactivity was significantly higher in ovarian carcinoma compared to normal ovary epithelium (42 vs 7%, P = 0.02). CONCLUSIONS: Immunoreactivity of SPARC and VEGF is heightened in association with ovarian carcinoma, with a distinct distribution of SPARC in the stroma of neoplastic ovaries and VEGF within tumor cells. No obvious pattern of coincident SPARC and VEGF immunoreactivity was detected. These results indicate the possibility of an aberration in the interaction that has been described in normal endothelium between SPARC and VEGF in association with malignant transformation.

Development of an objective structured assessment of technical skills for obstetric and gynecology residents.

OBJECTIVE: To develop an objective structured assessment for evaluating surgical skills of obstetrics and gynecology residents and to evaluate the reliability and validity of the assessment. METHODS: A seven-station, objective, structured assessment of technical skills was administered to 24 residents. The test included laparoscopic procedures (port placement, salpingostomy, suturing, vessel ligation) and open abdominal procedures (hypogastric ligation, repair of enterotomy, salpingo-oophorectomy.) All surgical tasks were done on pigs. Residents were timed and assessed at each station using three methods of scoring, a task-specific checklist, global rating scale, and pass-fail grade. RESULTS: Assessment of construct validity (the ability of the test to discriminate among residency levels) found significant differences on the checklist and the global rating scale by residency level. Reliability indices calculated with Cronbach's alpha were 0.89 for the global rating scale and 0.89-0.95 for the individual skills checklists. Interrater reliability was 0.87 for the global rating scale and 0.78-0.98 for the checklists. CONCLUSION: Objective, structured assessment of technical skills can assess residents' surgical skills with high reliability and validity. These assessments have possible application for identifying residents who need additional training and might provide a mechanism to ensure competence of surgical skills.

Teaching and evaluating surgical skills.

OBJECTIVE: To examine how surgical skills are taught and evaluated in obstetrics-gynecology residency programs in the United States. METHODS: A questionnaire was mailed to the directors of all 266 residency programs in the United States and to second contact names at 51 sites. Directors were asked to evaluate how surgical skills are taught and evaluated and to rate the importance of specific techniques and procedures for residents at given points in resident training. RESULTS: Two hundred twenty-three surveys were returned (70%), representing 203 of 266 programs (76%). Among responding programs, 99% reported teaching surgical skills in operating rooms, 88% in lectures, 68% with bench procedures, and 54% with animal surgery. Twenty-nine percent indicated they had formal surgical skills curricula. A significantly higher percentage of those programs with formal curricula used animal surgery laboratories (81% versus 42%, P <.001) and were more likely to conduct formal skills assessments (88% versus 69%, P =.005) than programs without formal curricula. Overall, 74% of programs evaluated surgical skills. Of those, 56% reported using subjective faculty evaluations, 12% written evaluations (eg, checklists), 4% written and oral assessments, and 1% a test. Regardless of formal curricula, there was much agreement in respondents' ratings of 60 different skills and procedures as "essential," "important," "nice to know," or "unimportant. CONCLUSION: Most programs teach surgical skills in the operating room and through lectures. Only 29% of reporting programs provide formal surgical curricula. Evaluation of surgical skills is usually done by subjective evaluation, a technique with unknown validity and poor reliability.

The prognostic significance of radiation dose and residual tumor in the treatment of barrel-shaped endophytic cervical carcinoma.

OBJECTIVE: The aim of this study was to evaluate the impact of total radiation dose on residual tumor and the prognostic significance of persistent disease in women with bulky, barrel-shaped cervical carcinoma who received definitive radiation followed by adjuvant hysterectomy. METHODS: The medical records of 57 patients with bulky endophytic cervical carcinoma treated at the University of Washington between 1976 and 1997 were reviewed. All patients received external beam pelvic radiotherapy supplemented by intracavitary brachytherapy, followed by extrafascial hysterectomy 6 to 8 weeks later. RESULTS: The mean pretreatment tumor diameter was 5.9 cm, with a range of 4-9 cm. Total radiation dose to point A ranged from 5040 to 9700 cGy, and the mean for the group was 7966 cGy. Residual disease was present in 35 (61%) of the hysterectomy specimens. The frequency of cervical tumor sterilization correlated significantly with the mean radiation dose to point A (P = 0.016). Patients without histologic residual disease had a significantly improved outcome, with 95% of patients remaining clinically free of disease at last follow-up, versus 31% of those with residual disease (P < 0.001). As expected, the pelvic control rate was excellent (100%) in patients with complete tumor eradication compared to the group with residual tumor (44%). Those with no residual disease enjoyed a significantly improved survival compared to those with residual tumor (P < 0.001). Furthermore, a statistically significant higher survival was realized in patients harboring only microscopic residual compared to those with either macroscopically evident tumor residuum and/or positive surgical margins (P = 0.036). CONCLUSIONS: Higher radiation doses are associated with an improved likelihood of tumor eradication in the treatment of bulky, endophytic cervical cancer and complete tumor sterilization at adjuvant hysterectomy is predictive of significantly enhanced survival and pelvic control. The high rate of histologic tumor persistence in our series emphasizes the need for more efficacious therapies in patients with bulky endophytic cervical cancer and argues for escalation of radiation dose even when adjuvant hysterectomy is planned.

Pretreatment scalene node biopsy in gynecologic malignancy: prudent or passé?

OBJECTIVES: Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. MATERIALS AND METHODS: We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. RESULTS: Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade >/=3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. CONCLUSIONS: Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

Impact of surgical staging in women with locally advanced cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the impact of surgical staging in the treatment and outcome of women with locally advanced cervical cancer. METHODS: Ninety-eight women with locally advanced cervical cancer treated between 1993 and 1997 were retrospectively reviewed. Survival probabilities were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: Of the 98 women treated over the 5-year period, 86 were surgically staged: 61 by a retroperitoneal approach, 18 by laparoscopy, and 7 by laparotomy. Median blood loss was 120 cc and median length of hospitalization was 3 days. Preoperative CT scans (n = 55), when compared with surgical findings, missed macroscopic nodal disease in 20% and microscopic disease in 15% and overcalled disease in 10% of cases. Lymph node metastases were found in 45/86 patients (52%): 12 microscopic and 33 macroscopic. The highest level of nodes found to be involved was pelvic in 23, common iliac nodes in 3, para-aortic nodes in 14, and scalene nodes in 5 cases. Of the 86 patients, 49 received pelvic radiation, 27 received extended field radiation, and 10 were identified for palliative treatment only (5 scalene node metastasis, 5 extensive intraperitoneal disease). For node-negative patients, 5-year survival was 74%; for microscopic nodal involvement it was 58%; and for macroscopic involvement it was 39% (P = 0.007). Five-year survival for women with para-aortic node involvement was 52%. Number of nodes involved was a significant prognostic variable (P = 0.008). Patients who received chemotherapy had a 5-year survival of 68% compared to 35% for those who did not (P = 0.06). Factors which did not affect survival included age, histology, type of surgery, stage, and type of radiation (pelvic vs extended). CONCLUSION: Surgical staging of women with locally advanced cervical cancer can be performed with acceptable morbidity and it provided more accurate information than CT scans and resulted in a modification of the standard pelvic radiation field for 43% of our patients. The information obtained from surgical staging allows better individualization of therapy, which may improve overall clinical outcome.

A new technique for performing Syed template interstitial implants for anterior vaginal tumors using an open retropubic approach.

The Syed template (Alpha-Omega Services, Bellflower, CA) has been established as an advance in interstitial gynecologic brachytherapy. Unfortunately, enthusiasm for the technique is often tempered by certain tumor geometries which require blind insertion of the interstitial needles, potentially risking inaccurate placement of the radioactive sources and viscus perforation. These concerns arise particularly in the management of anterior vaginal tumors where difficulties in negotiating the pubic arch can prevent optimal needle placement. In answer to this problem, a technique utilizing an open retropubic approach for Syed template interstitial implants in anterior vaginal tumors under direct visualization is described. To date, six procedures have been performed. The disease entities include advanced cervical squamous cell carcinoma, clear cell carcinoma of the vagina, recurrent vaginal carcinoma, recurrent endometrial carcinoma, and urethral adenocarcinoma. Complete response was noted in five of six patients but persistent local control of disease was achieved in only one of five complete responses over a relatively short follow-up interval. Complications included paravaginal abscess (n = 1), postoperative deep venous thrombosis (n = 1), abdominal incision cellulitis (n = 1), and radiation enteritis (n = 1). An open retropubic approach allows direct visualization of the bladder and urethra during interstitial implantation of anterior vaginal malignancies and facilitates negotiation of the pubic arch. In our experience, this technique results in improved needle positioning and is thus intuitively likely to aid in avoiding injury to surrounding normal tissues. Additional accrual of a larger cohort will be necessary to arrive at any meaningful objective conclusions regarding the technique's benefit over current modalities.

Port-site recurrence after laparoscopic surgery for endometrial carcinoma.

BACKGROUND: Women with endometrial carcinoma are being treated with laparoscopic surgery, but the risk of port-site recurrences remains undefined. CASE: A 58-year-old woman underwent laparoscopically assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and laparoscopic lymphadenectomy for endometrial cancer. Final surgical stage was IA, with grade 2 histology. Twenty-one months later, she developed a 5-cm recurrent tumor mass at a lateral laparoscopic port site. The mass was resected, and a restaging laparotomy performed, without evidence of other metastases. Radiation therapy was administered to the involved anterior abdominal wall. Two and one half years later, there is no evidence of recurrence. CONCLUSION: An isolated laparoscopic port-site recurrence might be attributable to the initial laparoscopic management of an otherwise good-prognosis endometrial carcinoma.

Formal teaching of surgical skills in an obstetric-gynecologic residency.

OBJECTIVE: To describe a formal teaching program of basic surgical skills in an obstetric-gynecologic residency program and evaluate its effectiveness. METHODS: A surgical skills program was developed for all residents. Using bench and animal laboratory sessions, residents were given instruction and performed both laparoscopic and open abdominal procedures. All were given a pretest and were tested again 6 months later. Residents also evaluated their experiences. RESULTS: To date, the formal teaching sessions have been given to 24 residents, all of whom believed their confidence and technical skills improved as a result of the sessions. On a scale of 1 to 5, the median rating of the bench laboratory experience was 5 (range 4-5), and the pig laboratory was 5 (range 4-5). All residents believed the surgery sessions should be continued and the number of sessions increased. Preliminary evaluation indicated that time to suture a 10-inch incision decreased by 28%, from an average of 225 (standard deviation [SD] 51) seconds to 171 (SD 43) seconds (P < .001), and evaluation of surgical technique significantly improved at the second pretest (P = .013). Laparoscopic placement of pegs on a board in 2 minutes increased from an average of 5 (SD 2.5) to 7.3 (SD 2.6; P = .001). The cost of the bench laboratory sessions was minimal. Each pig was approximately $100, and the facility charge for each 4-hour laboratory session was $1500. CONCLUSION: When formal surgical training was given to obstetric-gynecologic residents, their surgical skills improved subjectively and objectively.

Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure.

OBJECTIVE: This study was undertaken to evaluate whether immunophenotyping of advanced epithelial ovarian cancer could predict response to initial chemotherapy and whether tumor immunophenotype changed after chemotherapy. STUDY DESIGN: Fifty-four patients with stage III and IV ovarian cancer, treated at the University of Washington Medical Center, had pathology specimens evaluated. A subset of 23 patients also had specimens from a secondary surgery evaluated. Using immunocytochemistry, tumors were immunostained for overexpression of c-erb-B-2, epidermal growth factor receptor (EGFR), p53, and expression of the Ki67-defined antigen (a marker of cellular proliferation), tumor necrosis factor alpha (TNFalpha), estrogen receptor (ER), progesterone receptor (PR), and P-glycoprotein (P170, a marker of multidrug resistance). Twenty-four patients had a good response to chemotherapy (defined as a negative, or microscopically positive second look), and 30 had a poor response (defined as grossly positive second look or progressive disease). RESULTS: Comparison of tumor markers from the initial and the secondary surgeries revealed that the only significant change was in the Ki67-defined cell proliferation rate, which showed a marked reduction in those with a good response to chemotherapy (P = 0.002). Comparison of tumor markers at initial surgery between good and poor responders revealed a correlation with p53 expression. Good responders were less likely to have p53 overexpression compared to poor responders, and this result approached significance (P = 0.058). Comparison of tumor markers at secondary surgery revealed a significant reduction in Ki67-defined cell proliferation rate in good responders compared to poor responders (P = 0.01). No significant differences were found between good and poor responders for the other tumor markers evaluated. CONCLUSIONS: The only tumor markers to predict for response to chemotherapy were p53 at initial surgery (P = 0.058) and Ki67 indices at secondary surgery (P = 0.001). Expression of steroid hormone receptors, TNFalpha, and P-glycoprotein and overexpression of c-erb-B-2 or EGFR are not associated with chemoresistance.

Oncogene expression: long-term compared with short-term survival in patients with advanced epithelial ovarian cancer.

OBJECTIVE: To determine if oncogene overexpression in patients with advanced epithelial ovarian cancer correlates with survival. METHODS: Twenty-two women with stage III ovarian cancer, observed for a median of 66 (range 48-204) months were compared with 30 with a median survival of 18 (range 2-28) months. Using immunocytochemistry, tumors were immunostained for overexpression of p53, c-erb-B-2, and epidermal growth factor receptor and were evaluated quantitatively for expression of estrogen receptor, progesterone receptor, and Ki-67 antigen, a marker of cellular proliferation. RESULTS: The median age of long-term survivors was 52 (range 30-76) years compared with 55 (range 36-80) years for short-term survivors. Optimal cytoreduction was achieved in 11 of the 22 long-term survivors compared with seven of the 30 short-term survivors, a significant difference (P=.05). The average level of Ki-67 expression was 43% in long-term survivors and 64% in short-term survivors (P=.007). Overexpression of p53 was seen in 54% of long-term survivors and 80% of short-term survivors (P=.05). A combination of Ki-67 level of 50% or greater plus p53 overexpression was seen in 22% of long-term survivors compared with 68% of short-term survivors (P=.005). Epidermal growth factor receptor, c-erb-B-2, estrogen receptor, and progesterone receptor statuses did not differ significantly between the two groups. CONCLUSION: Markers that did not correlate with survival included the hormone receptors, estrogen receptor and progesterone receptor, and the oncogenes, c-erb-B-2 and epidermal growth factor receptor. Long-term survivors with advanced ovarian cancer were more likely to have had an optimal cytoreduction and lower levels of Ki-67 antigen expression and were less likely to overexpress p53 than were short-term survivors.

Adenocarcinoma of the uterine cervix metastatic to lymph nodes.

OBJECTIVE: We set out to evaluate the prognostic factors in cervical adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a retrospective review of 40 patients with cervical adenocarcinoma and lymph node metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma, and six had adenosquamous carcinoma. Median survival was 50 months. The median survival for patients with stage I disease was 69 months. Stage at diagnosis, treatment with radical hysterectomy, and receiving adjuvant therapy were associated with prolonged survival. A trend toward improved survival was noted with the use of concurrent radiation and chemotherapy as an adjuvant therapy. CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a uniformly poor prognosis, especially with early-stage disease. Improved survival was observed with the use of adjuvant therapy, specifically the use of combined chemotherapy and radiation after radical hysterectomy. The optimal therapy in this setting is yet to be determined.

Uterine papillary serous carcinoma: evaluation of long-term survival in surgically staged patients.

OBJECTIVE: Earlier studies have demonstrated that the uterine papillary serous carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate, even when disease is apparently confined to the uterus. The current study evaluated survival in patients with surgically staged UPSC. METHODS: Patients with UPSC were identified from surgical pathology files and charts were retrospectively reviewed. Only patients who had undergone a TAH-BSO, lymph node dissection, and peritoneal cytology were included. RESULTS: The FIGO stages of the 36 patients were 12 Stage I (4 IA, 4 IB, 4 IC), 2 Stage IIB, 13 Stage III (5 IIIA, 8 IIIC), and 9 Stage IV. Of the 14 Stage I/II patients, 6 did not receive adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole abdominal radiation therapy (WART); after a median follow-up interval of 50 months only 2 (14%) of these Stage I/II patients have developed a recurrence. Both of the recurrences were in Stage IC patients who received radiation; 1 recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients declined therapy and 2 were treated with WART; 3 patients, including the 2 who received radiation therapy, are alive without disease. Of the 8 Stage IIIC patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC patients treated with curative intent are without evidence of disease and 1 died of unrelated causes after a median follow-up interval of 48 months. Both of the Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage IV disease, 8 have died of disease. CONCLUSION: Women with UPSC have a good prognosis when surgical staging confirms that disease is confined to the uterus (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation treatments. Further study is required to define the optimal treatment for women with metastatic UPSC.

Mesothelial pelvic lymph node inclusions mimicking metastatic thyroid carcinoma.

Benign lymph node inclusions are commonly encountered during surgery for gynecologic neoplasms and are potential mimics of metastatic disease. A 52-year-old woman presented with ascites, a complex adnexal mass, and a CA-125 of 1891 units/mL. A staging laparotomy was performed, diagnosing struma ovarii. Pathologic evaluation of pelvic lymph nodes demonstrated mesothelial inclusions in nodal sinuses suspicious for metastatic disease. Immunocytochemical evaluation revealed benign mesothelial inclusions rather than metastatic thyroid carcinoma. Benign mesothelial lymph node inclusions in nodal sinuses are potential mimics of metastatic carcinoma. Their presence in pelvic lymph nodes has not previously been reported. Given the potential difficulty in determining the origin of these inclusions, immunocytochemical evaluation is useful in reaching the correct diagnosis.