Clinical calculator predictive of chemotherapy benefit in stage 1A uterine papillary serous cancers.

OBJECTIVE: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC). PATIENTS AND METHODS: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm. RESULTS: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29). CONCLUSION: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC.

Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study.

BACKGROUND: Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients. PATIENTS AND METHODS: A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life. RESULTS: The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 13.1-33.4); P = 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% CI 32.0-45.3) versus 45.7 weeks (95% CI 35.6-58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity. CONCLUSIONS: Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies.

Incremental risk of obstructive sleep apnea on cardiac surgical outcomes.

AIM: Obstructive sleep apnea (OSA) is not generally acknowledged as a perioperative risk factor. High incidence of Sleep disordered breathing has been noticed in patients with cardiovascular disease. The Sleep Heart Health Research Study Group found Apnea-Hypopnea indices (AHI) as modest as 1-10 to be associated with cardiovascular disease manifestations. Given the lack of data we chose to study the incremental risk of OSA in patients undergoing cardiac surgery. METHODS: We looked at 25 587 patients who underwent cardiac surgery at the Cleveland Clinic. Of these, 37 patients were also identified on the Cleveland Clinic Sleep center database as having OSA. Each of these 37 cases were propensity matched for multiple covariates with 5 controls within a distance of 0.001 units. An assumption was made that if the surgery was performed within two years of the diagnosis of OSA, the patient had OSA at the time of the surgery. RESULTS: Higher incidence of encephalopathy (p=0.008), postoperative infection (0.028) and increased ICU length of stay (p=0.031) were noted in the group with OSA after cardiac surgery. The difference in the rates of infection was mostly accounted for by the presence of mediastinitis (8.1% vs 1.6%). Differences in the rates of reintubation, tube time, and overall postoperative morbidity were not statistically significant. CONCLUSIONS: | Increased risk for postoperative complications is suggested in patients with OSA undergoing cardiac surgery. This risk is underestimated on account of lack of awareness about the incidence of OSA in the general population and the cardiovascular population in particular, difficulties in clinical suspicion and diagnosis and limited use of polysomnography.

Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: results of long-term follow-up.

Data on adjuvant chemotherapy in early-stage uterine sarcomas are conflicting and most often based on small patient groups with relatively short duration of follow-up. Approximately 60% of patients present with stage I disease with an overall 5-year survival of 30-50% when treated with surgery alone. This study examines the efficacy and results of long-term follow-up of a multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma. Between 1982 and 1999, 24 evaluable patients with completely staged uterine sarcomas received adjuvant multiagent chemotherapy with vincristine sulfate (1mg /m(2)) on days 1 and 4, doxorubicin (40 mg /m(2)) and cyclophosphamide (400 mg /m(2)) on day 2, and dacarbazine (200 mg /m(2)) on days 1 through 4 for a total of nine monthly cycles or until recurrence of disease was documented. Survival distributions were calculated by the Kaplan-Meier method, and statistical significance was determined with the log-rank test. Factors significant on univariate analysis were analyzed in a multivariate fashion using Cox proportional hazards model. The histologic distribution of patients was 46% leiomyosarcoma, 33% mixed mullerian tumors, 13% stromal sarcomas, 4% adenosarcomas, and 4% hemangiosarcoma. The patients received 206 of a planned 216 cycles of chemotherapy. The median follow-up of the patient population was 93 months (range 11-213 months). Eight patients (33%) developed recurrent disease. The median time to recurrence was 19 months (range 7-184 months). The estimated survival for the entire group was 88, 75, and 69% at 2, 5, and 15 years, respectively. Factors that did not affect survival included age, histology, and tumor grade. Four patients required dose reductions secondary to grade 2-3 toxicities (hematologic). Grade 1 neurotoxicity was observed in six patients (25%) and grade 2 neurotoxicity in one patient (4%). Adjuvant CYVADIC chemotherapy appears to be safe and well tolerated in patients with stage I uterine sarcomas. Our data provide information on the longest duration of follow-up ever reported and suggests that CYVADIC may have a potential role in the adjuvant treatment of early-stage uterine sarcoma.

Weekly paclitaxel in patients with recurrent or persistent advanced ovarian cancer.

The purpose of the study is to assess the role of palliative chemotherapy with weekly paclitaxel in patients with persistent or recurrent advanced ovarian cancer. Twenty-eight patients with predominantly paclitaxel- and platinum-resistant ovarian cancer disease were treated with weekly paclitaxel at 80 mg/m2 for 6-8 weeks. In 25 patients (89.2%), this combination represented at least a third line of therapy and for 14 patients (50%) it was more than the fifth line. A clinical response rate of 50% (14 partial responses) was obtained in the 28 patients with evaluable disease. Five patients (17.9%) had stable disease and nine patients (32.1%) had progression of disease. In patients with stable disease or a response, the median progression-free interval was 6 months and overall median survival is 8+ months. All the responses in paclitaxel-resistant tumors were seen in patients with a paclitaxel-free interval of more than 12 months. This regimen is well tolerated with acceptable toxicity. These data suggest that weekly paclitaxel has considerable antitumor activity in heavily pretreated patients with platinum- and paclitaxel-resistant advanced ovarian cancer.

Right hemidiaphragmatic elevation with a right-to-left interatrial shunt through a patent foramen ovale: a case report and literature review.

A right-to-left shunt (RLS) is an uncommon complication of a patent foramen ovale (PFO) that may cause hypoxemia from venous admixture and ischemic complications from paradoxic embolization. This report presents the third described patient whose RLS through a PFO and profound hypoxemia developed in association with right hemidiaphragm dysfunction (but without a pressure gradient driving the right-to-left flow). In addition to extending the available experience with this unusual clinical event, we report on the successful closure of the PFO by a catheter-deployed double-umbrella device, after the positioning of which the patient's oxygenation normalized.

Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin.

CD40 is a member of the tumor necrosis factor receptor family and was first identified with a monoclonal antibody raised against bladder carcinoma. Recombinant human CD40L has been shown previously to have a direct antitumor effect on an ovarian cancer cell line and ovarian carcinoma cells isolated from ascites fluid. We show here that rhuCD40L inhibits the growth of several ovarian adenocarcinomas derived from surgical specimens and grown as xenografts in severe combined immunodeficient mice. Two 14-day treatment cycles were more effective than one. This effect is apparently not mediated by natural killer cells, because blocking natural killer cell activity by antiasialo GM-1 did not diminish this effect. In addition to suppression of tumor growth, treatment with rhuCD40L resulted in an increased expression of FasL, an increase in apoptosis, and histological changes including increased fibrosis and areas of tumor destruction. Using this model, we examined the efficacy of rhuCD40L in combination with chemotherapeutic agents. The antitumor effect of rhuCD40L in combination with 4 mg/kg cisplatin (CDDP) was increased over the effect of CDDP alone. Furthermore, rhuCD40L increased the efficacy of a suboptimal dose of CDDP (2mg/kg) such that it matched that of high-dose CDDP alone. These data suggest a role for rhuCD40L therapy in combination with platinum based regimens for primary treatment of epithelial ovarian tumors.

The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer.

OBJECTIVE: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer. METHODS: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed. Information on morbidity, usefulness, and results of surgery and patterns of disease recurrence were obtained. Survival distributions were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: All 51 women were surgically staged by an extra-peritoneal approach. Preoperative CT scans (n=27) when compared with surgical findings showed sensitivity for pelvic and para-aortic lymph node metastasis of 39%, specificity of 88%, positive predictive value of 39% and negative predictive value of 88%. Lymph node metastases were found in 30/51 patients (59%). There were no significant treatment delays or surgical morbidity as a result of extra-peritoneal surgical staging. In 21 patients (41%), the highest level of involved nodes was in the pelvis and they were treated with pelvic radiation. The para-aortic nodes were involved in nine patients (18%) and were treated with extended field radiation. All patients also received concurrent radiosensitization with chemotherapy. The estimated survival for the entire group was 60% at 5 years. For node negative patients, estimated 5-year survival was 67% while it was 54% for all node positive patients (p=0.17). Analysis according to anatomic site of involved nodes showed that the estimated 2-year and 5-year survival for those with pelvic nodal involvement was 81% and 64%, respectively. However, in the group of nine patients with para-aortic nodal disease, the estimated 2-year survival was 44%. Five (56%) were dead of disease with a median time to death of 16.0 months and four patients (44%) were alive with a median duration of follow up of 16.1 months. There was a statistically significant difference in survival for the group of patients with positive pelvic nodes only compared to the group with positive para-aortic nodes (p=0.03). The estimated 5-year survival by FIGO stage was 80%, 70% and 51% for stages Ib, II, III, disease, respectively. Factors that did not significantly affect survival included age, histology and type of chemotherapy. CONCLUSIONS: Pre-therapy extra-peritoneal surgical staging resulted in treatment modification in 18% of patients with locally advanced cervical cancer. The morbidity from surgery and subsequent radiation therapy was acceptable. The procedure is recommended to allow for individualization of treatment in patients with local-regional cervical cancer.

First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cancer of the cervix--a phase II study.

OBJECTIVE: The aim of this study was to assess the role of first-line chemotherapy with paclitaxel and platinum in the treatment of advanced or recurrent cervix cancer. METHODS: Twenty patients with advanced or recurrent cancer of the cervix with no prior chemotherapy and measurable disease were entered in a phase II trial from September 1995 to September 1998. Seventeen patients were treated with paclitaxel at 135 mg/m(2) over 24 h followed by cisplatin at 75 mg/m(2) every 4 weeks. Three patients with impaired renal function were treated with paclitaxel at 135 mg/m(2) over 3 h with carboplatin at 300 mg/m(2). RESULTS: A clinical response rate of 45% was noted (two complete responses and seven partial responses) with a median duration of 6 months (range: 1.5-9). The median progression-free interval and overall survival in patients with a clinical response was 10.5 and 13 months, respectively, compared to 4 (P = 0.015) and 6 months in the nonresponders (P = 0. 14). Seven of nine patients (77.8%) with a clinical response are alive. Patients with recurrences outside the radiation field had twice the response rate (60%) than that of those within the radiated field. The chemotherapy was well tolerated; the most significant toxicity was grade 3/4 neutropenia (55%). No patient had discontinuation of chemotherapy due to toxicity. CONCLUSIONS: First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cervix cancer is promising and deserves consideration for large phase III trials.

Role of salvage chemotherapy with topotecan and cisplatin in patients with paclitaxel- and platinum-resistant recurrent ovarian or primary peritoneal cancer: a phase II pilot study.

BACKGROUND AND OBJECTIVES: We assessed the role of salvage chemotherapy with topotecan and cisplatin in patients with platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer, based on the reported in vivo and in vitro synergism between these two drugs. METHODS: Twenty patients were entered in this phase II trial from November 1997 to November 1998. They received cisplatin at 50 mg/m(2) on day 1 with topotecan at 0.6 mg/m(2) from day 1 to 5 every 28 days. In 70% of patients (14/20), this combination represented at least a third line of therapy. RESULTS: A clinical response rate of 13.3% (two partial responses) was obtained in the 15 patients with evaluable disease. Sixty percent of patients (9/15) had stable disease and 26.7% (4/15) had progression. The median progression-free interval and survival were 4 months and 7 months, respectively. The 20 patients evaluable for toxicity received a mean of four chemotherapy cycles. Dose reductions were required in 45% of patients despite the administration of growth factors. The major dose-limiting toxicity was a 50% occurrence (10/20) of grade 4 thrombocytopenia and 30% (6/20) grade 4 neutropenia. There was one septic death. CONCLUSIONS: These data suggest that combination therapy with topotecan and cisplatin has minimal activity in platinum- and paclitaxel-resistant advanced and recurrent ovarian or primary peritoneal cancer at the doses utilized in this trial.

Effective management of pelvic lymphocysts by laparoscopic marsupialization.

BACKGROUND AND OBJECTIVES: To evaluate laparoscopic transperitoneal marsupialization of pelvic lymphocysts at the time of laparoscopically directed assessment of response to first-line therapy in a population of patients treated for International Federation of Gynecologists and Obstetricians (FIGO) stage IC-IIC epithelial ovarian cancer. METHODS: Between March 1995 and March 1998, eight patients with FIGO stage IC-IIC serous epithelial ovarian tumors who developed pelvic lymphocysts after primary surgical staging underwent transperitoneal laparoscopically directed marsupialization of lymphocysts at the time of second-look laparoscopy. RESULTS: The mean age of the patient population was 50 years (range 23-65 years). The mean length of time required for marsupialization was 30 minutes (range 25-35 minutes). No patient required inpatient postoperative care. No intraoperative complications were observed. Computerized axial tomography (CT) scan of the abdomen and pelvis obtained 12 weeks following surgery failed to demonstrate re-accumulation of lymphocysts among any patient in the study population. With a median follow-up of 20 months (range 3-39 months), no patients have demonstrated pelvic lymphocyst recurrence. CONCLUSIONS AND DISCUSSION: Laparoscopically directed marsupialization of pelvic lymphocysts is technically feasible, safe and effective. Further study of this technique appears to be warranted.

Adenocarcinoma of the ileum with an enterotubal fistula presenting as an adnexal mass.

Small bowel adenocarcinomas account for 3% of gastrointestinal malignancies, and 20 to 25% of these arise in the ileum. Clinical presentation is variable, and early diagnosis is difficult. A 56-year-old postmenopausal woman presented with crampy abdominal pain, anorexia, and weight loss. Pelvic examination and ultrasound revealed a 6 x 8-cm complex right adnexal mass. At laparotomy, en bloc resection of the right adnexa and the densely adherent ileal segment was performed along with a hysterectomy and a left salpingo-oophorectomy. The final pathology showed a moderately differentiated invasive adenocarcinoma of the ileum with a malignant enterotubal fistula. This is the first case reported in the literature of an ileal adenocarcinoma with a tubal fistula masquerading as an adnexal mass.

Acquired inhibitor to factor VIII: report of two unusual cases.

The present report describes two unusual cases of bleeding due to development of inhibitor against factor VIII. One of the patients was known to have severe haemophilia B (factor IX < 1%) and the other, a healthy male of 46 years, spontaneously started to bleed and was found to have developed inhibitors to factor VIII:C along with other autoantibodies. Development of inhibitors to coagulation factors is a serious clinical problem in de-veloped countries and is more so in developing countries where treatment options are often limited.

High levels of CA-125 in a case of a parasitic leiomyoma presenting as an abdominal mass.

A 32-year-old woman presented with increasing abdominal girth and discomfort secondary to a 18-week-size mass and a CA-125 level of 1539. She underwent an exploratory laparotomy and resection of a parasitic fibroid following which the CA-125 levels decreased and normalized within a month. A review of English literature indicates that association of raised CA-125 levels with fibroids is inconsistent and very modest and such high levels have not been previously reported.

Mucinous adenocarcinomas of the vulva.

An 80-year-old nullipara had a 2.0-cm cystic tumor of the right labium majus. Histologic diagnosis was mucinous eccrine carcinoma. Seventy-five percent of these rare skin adnexal tumors arise on the face, eyelid, or scalp; but none has been reported on the vulva. Indolent localized growth is usual with regional nodal spread in 11% and distant metastases in 3%. A 67-year-old multipara had a 1.2-cm polypoidal nodule of the posterior fourchette. Histologically, a colonic type mucinous carcinoma was arising within a villous adenoma. Mucicarmine and CEA stains were positive. Extensive workup failed to reveal other primary cancers in either patient. Both patients are well 19 and 17 months after radical vulvectomies and node-negative groin dissections. These cases illustrate further the diversity in cell type and biologic behavior of vulvar adenocarcinomas.