Faculty Bibliography

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

OBJECTIVE: To detail the Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center experience with 23 patients treated with radiation therapy for invasive cervical carcinoma who subsequently developed endometrial carcinoma. METHODS: We conducted a retrospective chart and pathology review on patients diagnosed with endometrial cancer between 1976 and 2000 who had previously received definitive radiation treatment for cervical cancer. Abstracted data included patient demographics, type of radiation therapy, histological grade, histological subtype, and stage of endometrial cancer. RESULTS: The mean age at endometrial cancer diagnosis was 64.4 years (range 53-80), and the average latency period from initial therapy to development of endometrial carcinoma was 14 years (range 6-27). Distribution by stage, grade, and histology was as follows: stage I, five (22%); stage II, one (4%); stage III, nine (39%); stage IV, seven (30%); unknown stage, one (4%); grade 1, one (4%); grade 2, three (13%); grade 3, 17 (74%); unknown grade, two (9%); carcinosarcoma, eight (35%); endometrioid, four (17%); papillary serous, six (26%); clear cell, one (4%); mucinous, one (4%); undifferentiated, one (4%); and unknown histology, two (9%). The median survival was 24 months, and the 2- and 5-year survival rates were 50% (95% confidence interval [CI] 31.4%, 78.9%) and 21% (95% CI 8.1%, 56.3%), respectively. CONCLUSION: Patients treated with definitive radiation therapy for invasive cervical cancer may still have viable endometrium at risk for neoplasia. Endometrial cancers that develop after radiation treatment have a preponderance of high-risk histological subtypes and, consequently, a poor prognosis

OBJECTIVE: Intestinal obstruction is a frequent sequela of recurrent ovarian cancer. Previous series report median survivals of 3-6 months in patients undergoing surgery for obstruction due to recurrent disease. We analyze a contemporary series of patients to determine if outcomes have changed in patients undergoing palliative surgery. METHODS: We retrospectively reviewed all patients undergoing surgery for intestinal obstruction due to recurrent ovarian cancer from 1994 to 1999. RESULTS: During the study period, 68 operations were performed on 64 patients. Mean age at the time of obstruction was 57.3 years. Mean time from original diagnosis of ovarian cancer to obstruction was 2.8 years. Surgical correction (intestinal surgery performed for relief of obstruction) was attained in 57 of 68 (84%) cases. Successful palliation (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 pulmonary embolus and one from peritonitis. Two other deaths occurred due to progression of disease, for an overall perioperative mortality rate of 6%. Postoperative chemotherapy was administered in 45 of 57 (79%) 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 <.01). CONCLUSIONS: The majority of our patients undergoing surgery had successful palliation, and were able to receive further chemotherapy. They were discharged home, and could tolerate solid food

BACKGROUND: Although central nervous system (CNS) metastases from epithelial ovarian carcinoma are rare, recent studies indicate that the incidence may be increasing. Numerous series have reported various modalities for treatment with median survivals of 3 to 5 months, but the role of craniotomy has not been specifically addressed. METHODS: We conducted a retrospective review of all patients who underwent craniotomy between 1989 and 2001 for pathologically confirmed recurrent epithelial ovarian cancer metastatic to the CNS. RESULTS: We identified 14 patients who had a mean age at diagnosis of 59.3 years (range, 45 to 70). Distribution by stage and grade was as follows: Stage I, 0; II, 1; III, 12; and IV, 1; and grade 1,0; 2,4; and 3,10. Histologic distribution was as follows: papillary serous, 9; endometrioid, 2; mixed papillary serous and endometrioid, 1; carcinosarcoma, 1; and poorly differentiated adenocarcinoma, 1. Six patients had optimal primary cytoreduction, while 7 had suboptimal primary cytoreduction. All patients received initial platinum-based chemotherapy. Ten of 14 patients underwent second-look evaluation, and in 8 patients the findings were negative. The median time from initial diagnosis of ovarian carcinoma to CNS relapse was 3.5 years (range, 1.3 to 8.2). In 7 patients (50%), the CNS recurrence was the first site of relapse. Eight patients (57%) had extracranial disease at the time of craniotomy. Distribution of CNS lesions were as follows: supratentorial, 12; and cerebellar, 2. The mean operative time for craniotomy was 178 min (range, 70 to 305). The average blood loss was 125 mL (range, 20 to 250). The only major operative complications were deep vein thromboses that developed in two patients. No patient developed a neurologic deficit as a result of craniotomy. One patient died of progressive disease 37 days after surgery. Postoperative treatment included whole-brain radiation in 11 patients, chemotherapy in 4, and hormonal therapy in 4. Four patients (29%) had a CNS relapse after craniotomy. The median survival of patients after craniotomy was 18 months, and the 1- and 2-year survival rates were 66% (95% confidence interval (CI): 43-100) and 39% (95% CI: 17-90), respectively. CONCLUSIONS: Despite optimal cytoreduction, platinum-based chemotherapy, and negative second-look surgical assessment, patients with ovarian cancer can fail distantly with CNS metastases. Craniotomy with adjuvant radiation therapy can provide control of brain metastases in the majority of these patients and may result in improved survival over radiation therapy alone in selected patients

PURPOSE: To determine the accuracy of spiral computed tomography (CT) in the depiction of peritoneal metastases by using surgical findings in patients with ovarian cancer as the standard of reference. MATERIALS AND METHODS: Three independent readers reviewed the preoperative CT scans obtained in 64 patients who underwent primary surgery for ovarian cancer. Readers rated the likelihood of peritoneal metastases on a five-point scale and recorded the presence or absence of ascites, parietal peritoneal thickening or enhancement, and small-bowel wall thickening or distortion. Peritoneal metastases were identified as nodular, plaquelike, or infiltrative soft-tissue lesions in the peritoneal fat or on the peritoneal surface. Area under the receiver operating characteristic curve was calculated for each reader. Interreader agreement was evaluated with the kappa statistic. Descriptive statistical data were determined with dichotomized ratings (1-3 = absent; 4-5 = present). RESULTS: Areas under the receiver operating characteristic curves for the three readers were 0.95, 0.93, and 0.89. Paired kappa values ranged from 0.75 to 0.91. Reader sensitivity for metastases 1 cm or smaller in maximum diameter (25%-50%) was significantly (P <.05) lower than overall sensitivity (85%-93%). Ascites, parietal peritoneal thickening or enhancement, and small-bowel wall thickening or distortion demonstrated positive predictive values of 72%-93%, with kappa values of 0.12-0.80. CONCLUSION: Spiral CT is accurate in the depiction of peritoneal metastases from ovarian cancer, although sensitivity is reduced in patients with tumor implants 1 cm or smaller. Ancillary signs of peritoneal malignancy are limited by low interobserver agreement