Faculty Bibliography

Percutaneous gastrostomy tube placement is a technically feasible and safe procedure for palliation in patients with small bowel obstruction (SBO) caused by advanced gynecologic malignancies. It is used commonly in patients who are poor surgical candidates, those who elect to not undergo surgery, and in patients with a limited lifespan because of end-stage cancer. Percutaneous gastrostomy tube placement is even technically possible in patients with tumor encasing the stomach, diffuse carcinomatosis, and ascites. Percutaneous endoscopic gastrostomy (PEG) tubes provide symptomatic relief of nausea and vomiting in most patients with advanced gynecologic cancer and SBO. PEG tube placement allows most patients to have end- of-life care at home or in an inpatient hospice. It is a cost effective procedure and is associated with low morbidity and mortality. Placement of PEG tubes should be highly considered in patients who present with recurrent bowel obstruction and who have undergone a prior operation for SBO in the setting of advanced gynecologic malignancy

INTRODUCTION.: Previous reports have suggested that patients who have undergone pelvic radiation for cervical cancer are at risk for developing poorly differentiated endometrial cancers with poor prognoses. MATERIALS AND METHODS.: We conducted a retrospective chart and histologic review of patients from Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center diagnosed with endometrial cancer after radiation therapy (RT) for cervical cancer from 1976 to 2000. The comparison group comprised MSKCC endometrial cancer patients whose tumors were not radiation associated ('sporadic cancers'). RESULTS.: We identified 23 patients who developed endometrial carcinoma or carcinomasarcoma after RT for cervical carcinoma and 527 sporadic endometrial cancer patients. When radiation-associated endometrial cancers (RAECs) were compared with sporadic cancers, significant differences were noted with regard to stage, grade and histologic subtype distribution. In the RAEC group, there were 16 (70%) stages III and IV cancers compared with 101 (19%) in the sporadic group (P < 0.001). There were 20 (87%) grade 3 cancers in the RAEC group versus 161 (31%) in the sporadic group (P < 0.001). There were 16 (70%) high-risk histologic subtypes (serous, clear cell, carcinosarcoma, undifferentiated) in the RAEC group versus 79 (15%) in the sporadic group (P < 0.001). Median survival in the RAEC group was 24 months versus not reached in the sporadic group (P < 0.001). Radiation remained a significant factor for poor prognosis in a stratified analysis, in which we compared sporadic and RAEC cancers controlled for age, histology, grade and stage. However, radiation lost significance in a multivariate analysis, in which stage- and grade-matched cancers from both groups were compared. DISCUSSION.: The clinicopathologic characteristics of RAECs, which include a preponderance of high-stage, high-grade and high-risk histologic subtypes, indicate that these tumors differ from sporadic endometrial carcinomas. However, patients with RAECs do not appear to have a significantly worse prognosis when compared with patients with high-stage and high-grade sporadic cancers

Surgery and chemotherapy form the cornerstone of the treatment for ovarian cancer. Currently, the standard of care for primary ovarian cancer is platinum and taxane-based therapy. Even among women with advanced and suboptimal disease (i.e. tumors greater than 1 cm) following surgery, the clinical efficacy of chemotherapy is noteworthy. Despite the favorable response characteristics, however, most women with advanced-stage ovarian cancer will relapse, including about 50% of women who have no evidence of disease after primary therapy. A multitude of treatment options are available at the time of recurrence, but there is no clear consensus about how these patients should be managed. Options include surgery, chemotherapy, hormones, and sometimes, radiation therapy. The sequence, combinations of treatment, and manner in which any or all of these options should be employed in an individual patient, which heretofore have not been standardized, are the subjects of ongoing clinical investigations

INTRODUCTION: Fertility sparing therapy for epithelial ovarian cancer has been suggested for well-selected patients with early stage disease. The overall recurrence rate of 10% and 5-year disease free survival greater than 90% is similar in conservative and traditional surgical management of epithelial ovarian cancer. Thus, conservative approaches may be considered in young women diagnosed with FIGO stage I cancer who wish to preserve reproductive function. Subsequent use of assisted reproductive technologies (ART) may facilitate production of biologic offspring in these cancer survivors. However, each candidate requires unique consideration by subspecialists to avoid potentially fatal management errors. CASE REPORT: We present two cases in which fertility sparing therapy for early stage epithelial ovarian cancer was considered. The first case delineates the comprehensive work-up required to identify candidates for this therapy, while the second case illustrates the successful application of a fertility sparing approach. DISCUSSION: The conservative management of early epithelial ovarian cancer and use of ART to obtain offspring are reviewed

OBJECTIVES: To analyze the feasibility of using percutaneous endoscopic gastrostomy (PEG) tube placement in ovarian cancer patients with malignant bowel obstruction and to analyze the outcome of these patients. METHODS: We performed a retrospective review of all patients with ovarian carcinoma who underwent PEG tube placement between 1995 and 2002 at our institution. Abstracted data included patient demographics, procedure information, symptom resolution, diet tolerated, complications, further treatment, and survival. RESULTS: Ninety-four patients with ovarian carcinoma requiring PEG tube placement for malignant bowel obstruction were identified. The mean age at the time of PEG tube placement was 56 years. The mean interval from the initial cancer diagnosis to the placement of the PEG tube was 3.1 years. Twenty-two of 77 patients who had a computed tomography (CT) scan prior to PEG tube placement had tumor encasing the stomach. Fifty-nine (63%) of 94 patients had ascites, 25 of whom underwent a pre-PEG paracentesis (mean, 2845 ml). Ninety-four patients had a successful PEG tube placement under conscious sedation by the gastroenterology service (92) and/or by interventional radiology (2). Symptomatic relief, defined as no nausea or vomiting within 7 days of PEG tube placement, was noted in 86 (91%) of 94 patients undergoing PEG tube placement. Diets tolerated with and without the PEG tube being clamped were as follows: none, 3; sips, 9; liquids, 40; soft/regular, 40; and unknown, 2. The mean hospital stay after the procedure was 6 days. Eighteen patients had one or more of the following complications: leakage, 8; peristomal infection, 3; obstruction, 3; PEG tube migration, 2; catheter malfunction, 2; hemorrhage, 2; and peritonitis, 1. Nine patients required PEG tube revision due to complications. Chemotherapy after PEG tube placement was administered in 29 (31%) of the 94 patients, with resolution of obstruction and removal of the PEG tube in 4. In addition, 14 (15%) received limited total parental nutrition (TPN) after PEG tube insertion. Seventy-five (85%) of 88 patients died at home or under hospice care. The median overall survival for the 94 patients undergoing PEG tube placement was 8 weeks (95% CI, 6-10). Multivariate survival analysis revealed the presence of liver metastases (P < 0.001) and older age (P = 0.01) to be statistically significant predictors of shorter survival. The use of TPN after PEG tube placement was not a statistically significant prognostic factor in this model (P = 0.09). CONCLUSIONS: PEG tube placement in ovarian carcinoma is technically feasible and safe in the palliative setting. In addition, PEG tube placement allowed the majority of patients to have end-of-life care either at home or in an inpatient hospice. For the total population, no benefit was seen regarding survival with the use of TPN in this setting. Selected patients (younger age and without liver metastasis) may benefit from chemotherapy after PEG tube placement

OBJECTIVE: Acute large-bowel obstruction (LBO) is considered a surgical emergency. In gynecologic oncology patients with LBO due to recurrent tumor, surgery has been the standard treatment. However, operative intervention has significant associated morbidity and mortality. Recent reports have addressed the use of colorectal stents for the treatment of colonic malignancies. We are reporting our experience with colorectal stents in gynecologic oncology patients. METHODS: We reviewed the records of all patients who underwent colorectal stent placement for palliation of LBO due to recurrent gynecologic malignancy from August 2001 to January 2003. RESULTS: Six patients were identified; five patients had recurrent ovarian cancer and one had recurrent endometrial cancer. The mean age of the six patients at the time of stent placement was 51.5 years (range, 22-83 years).The length of LBO ranged from 2 to 10 cm. Two patients had a lumen of 1 to 2 mm before stent placement, while the other four had a complete obstruction and needed balloon dilatation before the deployment of the stent. Four (67%) of six patients had immediate relief, with passage of stool and flatus noted at the time of the colorectal stent placement. Stent placement failed to relieve the LBO in two patients (33%); these patients went on to receive colostomies. Of the four patients who had successful stent placement, the mean survival after stent placement was 120 days. One patient had a contained sigmoid bowel perforation noted 12 days after stent placement, which resolved with conservative measures. CONCLUSION: Colonic stents appear to be a useful option in the management of patients with LBO due to recurrent gynecologic malignancy

OBJECTIVE: While initial surgical treatment for palliation of malignant bowel obstruction is well described, data on reoperation for palliation of recurrent obstruction in ovarian carcinoma are limited. The purpose of this study was to analyze the outcome of patients undergoing reoperation for repeat bowel obstruction. METHODS: We reviewed the records of all patients with ovarian cancer who underwent repeat surgery for recurrent, malignant bowel obstruction at our institution between 1994 and 2002. RESULTS: Ten patients were identified. All patients had bowel obstruction caused by recurrent ovarian carcinoma and had a previous corrective surgical procedure for malignant bowel obstruction. The mean age at diagnosis of repeat obstruction was 54.1 years (range, 34-74 years). All patients had initial stage III or IV disease with moderately to poorly differentiated cancers. No patient received prior radiation therapy. The sites of obstruction in patients were as follows: small bowel, 3; large bowel, 3; both small and large bowel, 4. The mean number of prior laparotomies was 2.7 (range, 2-5). The mean interval from previous surgery for bowel obstruction to recurrent bowel obstruction was 8.3 months (range, 1-22 months). Surgical correction was possible in 5 (50%) of 10 patients, with 3 (60%) of these 5 patients obtaining successful palliation. Successful palliation is defined as the ability to tolerate a regular or low-residue diet at least 60 days postoperatively. Complications included enterocutaneous fistulas in three patients (two had enterotomies at time of surgery) and wound infection in one patient. There were no postoperative mortalities. The mean postoperative stay was 15.8 days (range, 8-29 days). Two of the three patients successfully palliated presented with a subsequent obstruction at 3 and 5 months postoperatively and were treated with gastrostomy tubes. The median length of survival for the entire cohort from the date of surgery for repeat obstruction was 4.5 months (range, 3-17 months). CONCLUSIONS: Patients undergoing repeat surgery for recurrent bowel obstruction have a low likelihood of successful palliation (30%). The surgery is associated with significant complications after surgery, rapid development of subsequent bowel obstructions, and limited survival rates. Alternative management approaches such as percutaneous endoscopic gastrostomy (PEG) tube placement should be considered in this group of patients

Patients with advanced stage invasive cervical cancer (CC) exhibit highly complex genomic alterations and respond poorly to conventional treatment protocols. In our efforts to understand the molecular genetic basis of CC, we examined the role of Fanconi Anemia (FA)-BRCA pathway. Here, we show that FANCF gene is disrupted by either promoter hypermethylation and/or deregulated gene expression in a majority of CC. Inhibition of DNA methylation and histone deacetylases induces FANCF gene re-expression in CC cell lines. FANCF-deregulated CC cell lines also exhibit a chromosomal hypersensitivity phenotype after exposure to an alkylating agent, a characteristic of FA patients. We also show the involvement of BRCA1 gene by promoter hypermethylation or down-regulated expression in a small subset of CC patients. Thus, we have found inactivation of genes in the FA-BRCA pathway by epigenetic alterations in a high proportion of CC patients, suggesting a major role for this pathway in the development of cervical cancer. Thus, these results have important implications in understanding the molecular basis of CC tumorigenesis and clinical management in designing targeted experimental therapeutic protocols