Siobhan M. Kehoe

Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma

OBJECTIVE To compare the accuracy of D&C vs office endometrial biopsy in predicting final post-hysterectomy FIGO grade in patients diagnosed with a preoperative FIGO grade 1 endometrial adenocarcinoma. METHODS We reviewed 1423 consecutive cases of endometrial cancer treated at our institution between 1/1/93 and 5/31/06 and identified cases with an unequivocal preoperative endometrial biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were pathologically confirmed and underwent surgical therapy at our institution. FIGO grade and histology diagnosed in the hysterectomy specimen were noted. The findings in the hysterectomy specimen were then compared between those patients who had a preoperative D&C vs an office endometrial sampling. Chi-square and Fisher-exact test were used as appropriate. RESULTS We identified 490 cases with a preoperative FIGO grade 1 endometrial adenocarcinoma. In 482 cases, FIGO grade was determined to be greater in 71 (14.7%) cases; in the final hysterectomy specimen, 66 (13.7%) were found to be grade 2 and 5 (1%) were found to be grades 2-3/3. Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases. D&C was performed in 187 (38.6%) cases and office endometrial sampling in 298 (61.4%); in 5 cases the method used was not discernible. The final post-hysterectomy FIGO grade was higher in 16/187 (8.7%) cases diagnosed by D&C compared to 52/298 (17.4%) diagnosed by office endometrial sampling (P=0.007). CONCLUSIONS Preoperative FIGO grade 1 diagnosis correlates with final grade diagnosis in 85% of cases. While D&C more accurately reflects final FIGO grade, a higher grade will be found in 8.7% of the cases at the time of hysterectomy.

Accuracy of preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma

OBJECTIVE To evaluate the ability of a preoperative diagnosis of FIGO grade 1 endometrial adenocarcinoma and intraoperative depth of myoinvasion (DOI) to predict low-risk (LR) and high-risk (HR) final uterine pathology. METHODS We reviewed 1423 consecutive cases of endometrial cancer treated at our institution between 1/1/93 and 5/31/06 to identify cases with a preoperative endometrial biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were pathologically reviewed at our institution and underwent surgical therapy at our institution. We excluded equivocal preoperative biopsies as well as those with serous or clear cell histology. Final uterine pathologic findings were grouped into low- and high-risk. Chi-square and Fisher-exact tests were used as appropriate. RESULTS We identified 490 cases with a median age of 60 years (range 29-90 years). In 482 cases in which final pathologic grade was assessable, FIGO grade was greater in 71 (14.7%) cases; (66 [13.7%] were grade 2, and 5 [1%] were grades 2-3/3). Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases. HR final uterine pathology was seen in 86 (18.5%) cases. Frozen section assessment of DOI, when performed, was associated with HR pathology (p<0.001). HR pathology was present in 3 (3.6%) of 84 cases with either no tumor or myoinvasion identified on frozen section. Lymph node metastasis was identified in 9 (4.4%) of 205 patients that underwent nodal evaluation. CONCLUSIONS Preoperative FIGO grade 1 diagnosis correlates with final post-hysterectomy grade in 85% of cases. The rate of HR uterine pathology based on preoperative grade 1 alone is 18.5%. Frozen section may help further stratify for the risk of final HR uterine pathology but is not entirely accurate. The rate of HR uterine pathology is 4% if no cancer or myoinvasion is identified on frozen section and 18% if myoinvasion up to 50% is identified.

Upper abdominal surgical procedures: Liver mobilization and diaphragm peritonectomy/resection, splenectomy, and distal pancreatectomy

Patients with advanced-stage ovarian cancer often have metastatic disease in the upper abdominal region. In particular, metastases to the diaphragm are exceedingly common in these patients. A comprehensive approach to surgical cytoreduction, which has been associated with improved survival in patients with advanced ovarian cancer, should incorporate upper abdominal resection.

Incidence and management of pancreatic leaks after splenectomy with distal pancreatectomy performed during primary cytoreductive surgery for advanced ovarian, peritoneal and fallopian tube cancer☆

OBJECTIVE To determine the incidence, management, and outcome of patients diagnosed with a pancreatic leak after a distal pancreatectomy during primary surgical cytoreduction for ovarian, peritoneal, or tubal cancer. METHODS We performed a retrospective chart review of all patients who had a distal pancreatectomy at the time of primary surgery. Charts were reviewed to identify those patients who developed a persistent left upper quadrant abdominal fluid collection with elevated amylase levels. RESULTS A total of 17 patients had a distal pancreatectomy; of these, 4 patients (24%) developed a postoperative pancreatic leak. In these patients, persistent leukocytosis prompted evaluation with a computed tomography scan, which subsequently revealed a fluid collection. The median time from surgery to drainage of this collection was 9 days (range, 8-66). The drain remained in situ for a median of 29 days (range, 22-82). The median amylase level of the fluid was 22,945 U/L (range, 763-47,250). The median length of hospital stay for those patients with a leak was 33 days (range, 25-44), which was longer than those without a leak. However, the median time from surgery to treatment with systemic chemotherapy was 31 days (range, 16-43), which was equivalent to those without a pancreatic leak. CONCLUSION Twenty-four percent of patients who had undergone a distal pancreatectomy developed a pancreatic leak. This complication, which usually presents early in the postoperative period, can be managed conservatively with percutaneous drainage. Oral intake may be resumed, and total parenteral nutrition is not needed in the majority of cases. Systemic chemotherapy can be administered without significant delay.

The role of lymphadenectomy in endometrial cancer.

The role of lymphadenectomy in the management of endometrial cancer is rapidly evolving. Although retrospective reports have suggested that lymphadenectomy is associated with a therapeutic benefit, recent prospective trials have questioned the therapeutic effect of lymphadenectomy. Lymphadenectomy remains the gold standard for detecting metastatic disease to the regional nodes. In this review, we discuss the controversies surrounding lymphadenectomy for endometrial cancer.

Clinicopathologic features of bone metastases and outcomes in patients with primary endometrial cancer

OBJECTIVE Patients with advanced or recurrent endometrial cancer often have distant metastases found within the lymph nodes, liver, and/or lung. However, there have been reported cases of primary endometrial cancer with metastasis to the bone. The objective of this study was to describe the clinical and pathologic features of endometrial cancer metastatic to bone. METHODS A retrospective chart review of our clinical and pathology database was performed to identify women diagnosed with endometrial cancer metastatic to the bone between 1990 and 2007. Clinical data and outcomes were obtained from medical records. Slides were re-reviewed to confirm the diagnosis. RESULTS Twenty-one patients with endometrial cancer metastatic to the bone were identified; in 12 patients (57%), the diagnosis was confirmed by a bone biopsy. The median age of diagnosis of primary endometrial cancer was 60 years (range, 32-84). Fourteen patients (67%) had FIGO stage III/IV disease. Six patients (29%) had a bone metastasis at the time of diagnosis while 15 patients (71%) had a bone lesion as a recurrence. The median time to a diagnosis of bone metastasis recurrence was 10 months (range, 3-148). The overall survival of those patients with bone metastases at primary diagnosis was 17 months (95% CI: 2-32) compared to 32 months (95% CI: 14-49) for those with a recurrent bone metastasis. CONCLUSION Although a rare event, endometrial cancer can metastasize to the bone. If a bone lesion is identified, treatment using a multimodality approach is reasonable, especially if found as an isolated recurrence.

Incidence of intestinal obstruction following intraperitoneal chemotherapy for ovarian tubal and peritoneal malignancies

OBJECTIVES To report the incidence of intestinal obstruction after intraperitoneal chemotherapy (IP) in women with ovarian, tubal, or peritoneal malignancies, and determine the frequency of malignant versus adhesion-related obstruction. METHODS Patients who were treated with at least one dose of IP chemotherapy between 1986 and 1997, and who had at least 3 month follow-up, were included. Data regarding admissions for gastrointestinal obstruction complaints, radiologic diagnosis of intestinal obstruction and medical or surgical management of obstruction were recorded. RESULTS We identified 334 patients; 307 met our inclusion criteria. A total of 104 (34%) patients developed symptomatic intestinal obstruction after IP therapy commenced. The overall incidence of adhesion-related or mechanical bowel obstruction was only 4%. In the group of patients with a mechanical bowel obstruction, the median time to diagnosis of obstruction was 21 months (range, 2-51) after initiation of IP treatment. Surgical intervention to relieve the obstruction was performed in 6 (50%) patients diagnosed with adhesion-related bowel obstruction. Similarly, in those diagnosed with a malignant bowel obstruction, 42 (48%) were taken to the operating room in an attempt to relieve the obstruction. CONCLUSION Intestinal obstructions developed in a third of patients who received IP therapy as part of their treatment for advanced ovarian, tubal, or peritoneal cancer. However, the majority of the obstructions are related to progression of malignant intra-abdominal disease. Only 4% of the patients develop intestinal obstruction due to intestinal adhesions after IP treatment.

Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: A multi-institution study

OBJECTIVE There is paucity of data in regard to prognostic factors and outcome of women with 2009 FIGO stage II disease. The objective of this study was to investigate prognostic factors, recurrence patterns and survival endpoints in this group of patients. METHODS Data from four academic institutions were analyzed. 130 women were identified with 2009 FIGO stage II. All patients underwent hysterectomy, oophorectomy and lymph node evaluation with or without pelvic and paraaortic lymph node dissections and peritoneal cytology. The Kaplan-Meier approach and Cox regression analysis were used to estimate recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). RESULTS Median follow-up was 44months. 120 patients (92%) underwent simple hysterectomy, 78% had lymph node dissection and 95% had peritoneal cytology examination. 99 patients (76%) received adjuvant radiation treatment (RT). 5-year RFS, DSS and OS were 77%, 90%, and 72%, respectively. On multivariate analysis of RFS, adjuvant RT, the presence of lymphovascular space invasion (LVSI) and high tumor grades were significant predictors. For DSS, LVSI and high tumor grades were significant predictors while older age and high tumor grade were the only predictors of OS. CONCLUSIONS In this multi-institutional study, disease-specific survival for women with FIGO stage II uterine endometrioid carcinoma is excellent. High tumor grade, lymphovascular space invasion, adjuvant radiation treatment and old age are important prognostic factors. There was no significant difference in the outcome between patients who received vaginal cuff brachytherapy compared to those who received pelvic external beam radiation treatment.

Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer.

OBJECTIVE Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy. METHODS Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests. RESULTS Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P=0.018). CONCLUSIONS Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.

Malignant ovarian germ cell tumor — Role of surgical staging and gonadal dysgenesis ☆

OBJECTIVE To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor. METHODS We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012. RESULTS Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p=0.048) and endodermal sinus tumor (p=0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p=0.029) and endodermal sinus tumor (p=0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype. CONCLUSIONS Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype.