Breast Cancer is Common in Women With Ovarian Malignant Mixed Mullerian Tumors.

BACKGROUND: Ovarian malignant mixed Mullerian tumors (MMMTs) are uncommon cancers. The purpose of the study was to determine the rate of metachronous or synchronous breast cancer as well as the rate of truncating germline BRCA1 and/or BRCA2 mutations in a series of women with these uncommon tumors. MATERIALS AND METHODS: Records were reviewed to identify all women with MMMTs treated by the gynecologic oncology service. The stage, grade, histology, survival, and rate of coexistent breast cancer were determined. Tumor and/or peripheral blood was tested for BRCA1 and BRCA2 truncating mutations. RESULTS: Twenty-four patients with MMMTs were found. Tumor and paired peripheral blood was available on 20 patients and 4 more patients had only peripheral blood available. Family pedigrees were available on all 24 patients. Fifteen of 24 (62.5%) patients were found to have metachronous or synchronous breast cancers with 9 of 15 (60%) having bilateral breast cancer. No BRCA1 or BRCA2 mutations were found (somatic or germline) in this cohort. CONCLUSIONS: Although an uncommon tumor, MMMTs are often found in women with breast cancer. Despite this finding, BRCA1 or BRCA2 germline mutations are not common in this population. PRECIS: Ovarian MMMTs are frequently found in women with cancer but are not frequently associated with defects in BRCA1 or BRCA2.

Assessment of False-negative Ascites Cytology in Epithelial Ovarian Carcinoma: A Study of 313 Patients.

OBJECTIVE: The objective was to determine how often peritoneal cytology is positive for malignancy in women with known ovarian cancer. Knowing this fact would help determine the usefulness of diagnostic paracentesis. METHODS: Records of all women diagnosed with invasive epithelial ovarian cancer from 2004 to 2012 were examined to correlate presence of ascites, cytologic, and pathologic findings. RESULTS: A total of 313 patients were included in analysis. A total of 210 of 313 patients (67.1%) with ascites had cytology positive for malignancy. This left 103 patients with ascites and cancer without malignant cells found in the ascites removed at the time of surgery. CONCLUSIONS: Except in a few cases, paracentesis is not recommended for the diagnosis of ovarian cancer because of the potential spreading of cancer. Furthermore, with only just over two thirds of cases of known cancer and ascites having cytology positive for malignancy, the value of paracentesis for diagnosis of ovarian cancer is minimal.

Is the routine use of bevacizumab in the treatment of women with advanced or recurrent cancer of the cervix sustainable?

BACKGROUND: New chemotherapy combinations are being tested for the treatment of women with advanced, persistent or recurrent cervical cancer. We sought to evaluate the cost effectiveness of some newer combination therapies in cervical cancer. PATIENTS AND METHODS: A cost effectiveness decision model was used to analyze Gynecologic Oncology Group 240. All regimens were modeled for seven cycles. The regimens studied are as follows: regimen 1, cisplatin/paclitaxel (CP); regimen 2, CP with bevacizumab (CP+B); regimen 3, paclitaxel/topotecan (PT); and regimen 4, PT with bevacizumab (PT+B). Overall survival, cost, and complications were studied. Sensitivity analyses were performed. RESULTS: Mean chemotherapy costs over mean total costs for seven cycles of each follows: CP $571/$32,966; CP+B $61,671/$96,842; PT $9,211/$71,620; and PT+B $70,312/$109,211. Incremental cost-effectiveness ratio (ICER) for CP+B was $133,559/quality adjusted life year (QALY). ICER for PT+B was $124,576/QALY. To achieve an incremental ICER for CP+B:CP of <$50,000/QALY gained, the mean overall survival has to increase from 1.1 years with CP to 3.5 years with CP+B. An ICER <$50,000/QALY for the other regimens would take a survival of >10 years for PT and 4.1 years for PT+B. Treating 1,000 women with cervical cancer with CP+B would cost almost double the cost of treating >18,000 women with ovarian cancer annually (carboplatin/paclitaxel). CONCLUSION: CP is the most cost effective regimen. A 12-month increase in overall survival will not even make the newer combinations cost effective. Currently, the use of bevacizumab is not sustainable at today's costs.

Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy.

Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient's diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

Electrosurgical Settings and Vaginal Cuff Complications.

BACKGROUND AND OBJECTIVES: After being encouraged to change the technique for opening the vaginal cuff during robotic surgery, this study was performed to determine the correlation between vaginal cuff complications and electrosurgical techniques. METHODS: The study group consisted of patients who had their vaginal cuffs opened with a cutting current compared to the group of patients having their vaginal cuff opened with a coagulation current. Data were collected on 150 women who underwent robotic surgery for endometrial cancer. All patients received preoperative antibiotics. Data, including operative time, type of electrosurgery used, estimated blood loss, transfusion rate, and complications, were collected from the patients' records. RESULTS: Surgeries in 150 women and the associated complications were studied. The mean age of the patients was not significantly different between the groups (P = .63). The mean body mass index was 38 kg/m(2) in the coagulation arm and 36 kg/m(2) in the cutting arm (P = .03). Transfusion was not required. Estimated blood loss and operative time were not significantly different in the coagulation versus the cutting arms (P = .29 and .5; respectively). No patients in the cutting arm and 4 patients (with 5 complications) in the coagulation arm had cuff complications (P = .02). CONCLUSIONS: Complications involving the vaginal cuff appear to occur more frequently when the vagina is entered by using electrosurgery with coagulation versus cutting in this cohort of patients undergoing robot-assisted surgery for endometrial cancer..

The interaction of ifosfamide and aprepitant in gynecologic malignancies.

•Aprepitant combined with ifosfamide may lead to encephalopathy.•Aprepitant-ifosfamide induced encephalopathy was of short duration in these cases.

Treatment of advanced or recurrent cervical cancer with Cisplatin or Cisplatin containing regimens: a cost effective analysis.

BACKGROUND: Trials have demonstrated improvements in survival with adding paclitaxel (P) or topotecan (T) to cisplatin (C) for the treatment of advanced cervical cancer. We sought to evaluate the cost effectiveness of these regimens. METHODS: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 169 and 179. Arm 1 is 6 cycles of cisplatin. Arm 2 is 6 cycles of CP while arm 3 is 6 cycles of CT. Parameters include overall survival (OS), cost and complications. Sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) for C versus CP is $13,654/quality-adjusted life-year (QALY) gained. For CT compared to C, the ICER is $152,327/QALY. When compared simultaneously, CT is dominated. At a willingness to pay (WTP) threshold of $50,000/QALY, C is the preferred option but CP is acceptable. Sensitivity analyses suggest that CT would become the preferred option if it was to improve OS to 24 months (compared to 9.4 months). CONCLUSIONS: In this model, CP is an acceptable alternative to cisplatin for the treatment of these patients with an increase in cost of only $13,654/QALY. The addition of topotecan did not increase survival enough to justify the increased cost.

Ovarian cancer risk assessment: a tool for preoperative assessment.

OBJECTIVES: The objective of this pilot study was to determine if the combination of CA 125, menopausal status and prealbumin can be used to accurately predict ovarian cancer in women with pelvic masses. STUDY DESIGN: Preoperative serum CA 125, prealbumin and menopausal status were prospectively determined. Results were formulated into an ovarian cancer risk assessment (OCRA) score and compared with final surgical pathology. RESULTS: OCRA was studied in 130 women. No cancers were found in women with a score less than 200. For all cancers, an OCRA score ≥ 200 had a sensitivity of 96%, specificity of 95% and positive predictive value of 95%. When the OCRA score of ≥ 200 was evaluated for its ability to predict ovarian cancer, the sensitivity, specificity, and positive predictive value were 100%, 83%, and 78%, respectively. CONCLUSIONS: In this pilot study, OCRA was able to predict which women with pelvic masses were more likely to have ovarian cancer. The scoring system easily applied clinically and may help facilitate appropriate referral of women to gynecologic oncologists for optimal care.

Robotically assisted laparoscopic radical hysterectomy compared with open radical hysterectomy.

BACKGROUND: Radical hysterectomy is a common and effective treatment of early cervical cancer. Modern advances include the use of robotic assistance to perform equivalent minimally invasive procedures. The purpose was to compare surgical and short-term outcomes, as well as margins, between robotic-assisted laparoscopic radical hysterectomy and open radical hysterectomy. METHODS: The first 30 cases of robotically assisted type III radical hysterectomy for cervical cancer were compared with the 30 previous cases of open type III radical hysterectomy. Body mass index, length of operation, nodal yield, margins, estimated blood loss, hospital stay, and complications were all documented and compared. RESULTS: The 30 patients undergoing robotically assisted laparoscopic radical hysterectomy were similar in body mass index to the women undergoing open radical hysterectomy (34 kg/m robotic, 32 kg/m open, P = 0.22). The mean operating time was 154 minutes compared with 166 minutes in the open arm (P = 0.36). The mean blood loss was 165 mL compared with 323 mL in the open arm (P = 0.001). The mean pelvic nodal yield was 25 nodes compared with 26 nodes in the open group (P = 0.45). The mean parametrial margin size was not significantly different between groups. The mean postoperative length of stay was 1.4 days compared with 2.8 days for the open cases (P < 0.001). Urinary retention was significantly more common in the robotic arm. CONCLUSIONS: Radical surgery for cervical cancer can be accomplished using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, Calif) with acceptable blood loss, operating time, parametrial margins, and nodal yield. Future studies need to address long-term outcomes.

Imiquimod in vulvar Paget's disease: a case report.

BACKGROUND: Vulvar Paget's disease is a relatively rare gynecologic neoplasm that is problematic because of its propensity to recur. CASE: An 80-year-old woman was found to have recurrent Paget's disease of the vulva. She was initially diagnosed 12 years previously and had had multiple resections for the disease. She was found to have histologically proven Paget's disease and underwent a course of topical immune modulator therapy with imiquimod. Biopsy proved histologic regression of the disease progress. The patient remained without recurrence 12 months after therapy. CONCLUSION: In select patients imiquimod may be used to treat or facilitate treatment of vulvar Paget's disease.

Primary carcinoma of the fallopian tube and epithelial ovarian carcinoma: a case-control analysis.

OBJECTIVE: To determine whether differences exist in clinicopathologic variables or survival between women with primary carcinoma of the fallopian tube (PCFT) and with epithelial ovarian carcinoma (EOC). STUDY DESIGN: University of Iowa Hospitals and Clinics (UIHC) tumor board records were analyzed from January 1, 1991, to April 30, 2001. No cases were knowingly excluded. Each case of PCFT was matched with 2 cases of EOC. Controls were the next 2 cases of EOC diagnosed at UIHC after each case of PFTC, with priority given to stage of disease, then histologic grade, followed by histology, with 1 year the limit for obtaining the closest match. RESULTS: Twenty-eight cases of PCFT were found. These were matched with 56 cases of EOC. The mean age at diagnosis was significantly older for women with PCFT (67 years) vs. women with EOC (60 years) (p = 0.005). The was no difference in prediagnosis hormonal contraceptive use (p=0.38), body mass index (p = 0.5) or rate of positive nodes (p = 0.19). Kaplan-Meier analysis revealed no difference in survival between PCFT and EOC (p = 0.5). CONCLUSION: There is no significant difference in clinical parameters or survival between patients with PCFT or EOC when matched for stage, grade and histology.

Robotically assisted total laparoscopic radical trachelectomy for fertility sparing in stage IB1 adenosarcoma of the cervix.

Adenosarcomas are rare cervical tumors with unknown optimal treatment, which often affects young women. A 23-year-old woman was found to have a stage IB1 adenosarcoma of the cervix. She underwent a robotically assisted total laparoscopic radical trachelectomy with the placement of abdominal cerclage for the sparing of fertility.

Recombinant factor VIIa to treat late radiation-induced hemorrhagic cystitis: a case report.

BACKGROUND: Late radiation cystitis is one of the most difficult complications of radiation therapy for pelvic malignancies. CASE: A 29-year-old woman with a history of cervical cancer presented with radiation-induced hemorrhagic cystitis. The patient received multiple units of packed red blood cells while undergoing several intravesical treatments, including continuous bladder irrigation, 4% formalin, 0.15% AgNO3 and Mg(OH)2 with Al(OH)3. The bleeding finally was stopped by the use of intravenous recombinant factor VIIa. CONCLUSION: When hemorrhagic cystitis related to late radiation complications is refractory to conventional management, intravenous recombinant factor VIIa may be of benefit.

Vascular endothelial growth factor staining and elevated INR in advanced epithelial ovarian carcinoma.

BACKGROUND: The purpose of this study was to determine whether vascular endothelial growth factor (VEGF) expression in tumors correlates with the incidence of an elevated prothrombin time (PT), specifically an international normalized ratio (INR) > or = 1.4, in patients undergoing primary surgical cytoreduction for ovarian cancer. METHODS: INRs were obtained on all patients perioperatively. VEGF expression was determined by immunostaining of tumor specimens using published protocols. RESULTS: One hundred patients underwent surgical cytoreduction. Sixty-seven percent of patients had postoperative INR of 1.4 or greater. INRs of greater than or equal to 1.8 were found in 5% of patients. INR elevation was independent of mean estimated blood loss (EBL) with the EBL in the patients with INRs > or = 1.4 not significantly different than the EBL in the patients with INRs < 1.4 (660 ml vs. 530 ml, P = 0.09). There was a significant correlation between elevated INR and tumor VEGF immunostaining (P < 0.005). All but one patient with an elevated INR had positive VEGF staining. CONCLUSIONS: In conclusion, development of an elevated INR (INR > or = 1.4) is common in patients undergoing primary surgical cytoreduction. Positive tumor VEGF staining is very common in patients having a postoperative coagulopathy.

Extreme drug resistance is common after prior exposure to paclitaxel.

OBJECTIVE: The platinum-free interval (PFI) is an important entity in the treatment of women with epithelial ovarian cancer. The purpose of this study was to determine on clinical samples whether a taxane-free interval (TFI), as defined by in vitro extreme drug resistance assay, existed in women previously exposed to platinum and taxane chemotherapy. METHODS: Records were examined from 2003 to 2006 to find all patients with epithelial ovarian cancer who had previous exposure to platinum and taxane therapy. Further examination was done to find all patients who underwent secondary cytoreduction and had their tumor submitted for extreme drug resistance assay. RESULTS: Thirty-four women meeting the above criteria were found. The mean PFI was 25 months (median 18). The mean TFI was 27 months (median 20). Over 44% of the patients have been exposed to more than just a course of platinum and a course of a taxane. In patients having a PFI of >or=12 months, 38.8% had extreme drug resistance (EDR) to carboplatin and 41.9% EDR to cisplatin. Conversely, in patients having a TFI of >or=12 months, 89.7% had EDR to paclitaxel and 82.8% EDR to docetaxel. CONCLUSIONS: While only a small percentage have EDR to carboplatin and cisplatin after a PFI of >or=12 months, almost 90% of patients with a TFI>or=12 months showed EDR to paclitaxel in vitro.

Nutritional assessment using prealbumin as an objective criterion to determine whom should not undergo primary radical cytoreductive surgery for ovarian cancer.

BACKGROUND: The purpose of this study was to determine if serum prealbumin could be used to objectively determine which patients could not safely undergo cytoreductive surgery. METHODS: Patients with suspected ovarian cancer in a 24-month period underwent nutritional assessment during their preoperative workup and were followed for development of postoperative complications. RESULTS: One hundred and eight of 114 patients underwent surgical cytoreduction. Of the 108 surgical patients, 88 patients had prealbumin levels <18 mg/dl and 24 patients had prealbumin levels <10 mg/dl. Postoperative complications increased with lower prealbumin levels. All complications occurred in group of patients with prealbumin <18 mg/dl (P=0.013). A significantly increased number of complications occurred in patients with prealbumin <10 mg/dl (61.5% vs. 6.4%, P<0.001, RR 9.6). All postoperative mortality in this series occurred in patients with prealbumin <10 mg/dl (23.1% vs. 0%, P<0.001). Patients whose prealbumin started low but was able to be raised to >10 mg/dl by TPN did not have significantly increased complications or EBL compared to patients whose initial prealbumin was >10 mg/dl (18.2% vs. 4.8%, P=0.95 and 570 vs. 600 ml, P=0.87). CONCLUSIONS: Significantly more blood loss, morbidity, and mortality occurred in patients with abnormal preoperative prealbumin. This was especially true in patients with a prealbumin <10 mg/dl. With these significantly increased risks, patients with extremely poor nutritional status (prealbumin <10 mg/dl) may be better served by neoadjuvant chemotherapy with interval cytoreductive surgery if nutrition improves.

Neoadjuvant chemotherapy in vulvar cancer: avoiding primary exenteration.

OBJECTIVE: To determine whether neoadjuvant cisplatin and 5-fluorouracil chemotherapy can be used to preserve the anal sphincter and/or urethra in patients with advanced vulvar cancer involving these sites. METHODS: Fourteen patients with advanced vulvar cancer (1997-2003) involving the anal sphincter and/or urethra were given 3-4 cycles of neoadjuvant chemotherapy to attempt preservation of these pelvic structures rather than undergoing a primary pelvic exenteration. Following 3 cycles, a radical vulvectomy and groin lymph node dissection were planned. All patients had lesion size documented by measurement and photograph prior to and following chemotherapy. RESULTS: The median age was 63 years (range 39-88). Thirteen patients received a median of 3 cycles (range 2-4) of neoadjuvant chemotherapy. Ten patients received cisplatin and 5-fluorouracil, while three received cisplatin alone. The median time from diagnosis to surgery was 77 days (range 54-143). All patients with cisplatin and 5-fluorouracil chemotherapy underwent surgery except one patient who had a synchronous renal cell carcinoma and died prior to surgery. Patients receiving cisplatin alone showed no measurable response, while all patients receiving cisplatin and 5-fluorouracil demonstrated at least a partial response. Two patients had no residual invasive carcinoma on final pathology. All patients receiving cisplatin and 5-fluorouracil followed by surgery are disease-free, while two of three receiving cisplatin have progressive disease. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. CONCLUSION: Neoadjuvant cisplatin and 5-fluorouracil in advanced vulvar cancer demonstrated a response rate of 100%. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Responders are disease-free at this time. This response rate demonstrates superior activity of 5-fluorouracil in vulvar cancer and spares these patients the morbidity of exenteration or radiation.

Gemcitabine associated vasculitis leading to necrotizing enterocolitis and death in women undergoing primary treatment for epithelial ovarian/peritoneal cancer.

We present two patients who developed necrotizing enterocolitis following their first cycle of chemotherapy for epithelial ovarian/peritoneal cancer. After optimal cytoreductive surgery, both women received gemcitabine as part of a chemotherapy protocol. One patient developed necrotizing enterocolitis, 1 day after chemotherapy and the other 8 days after chemotherapy. The first patient succumbed to the enterocolitis despite aggressive supportive care. The second patient succumbed despite both aggressive supportive care and surgical intervention. Pathologic review for both patients revealed a drug induced vasculitis causing necrotizing enterocolitis.