Comparison of peritoneal adhesion formation in bowel retraction by cotton towels versus the silicone lap pak device in a rabbit model.

OBJECTIVE: Manipulation of cotton operating room towels within the abdominal cavity in open abdominal surgery has been associated with the formation of peritoneal adhesions. In a rabbit model, the use of standard cotton operating room towels is compared to the Lap Pak, a silicone bowel-packing device, to determine the potential for reducing the risk of adhesions. METHODS: Thirty rabbits were randomly assigned to 3 groups. The rabbits underwent a sham surgery with incision only (n = 10), placement of operating room towels (n = 10), or placement of a Lap Pak (n = 10). After 14 days, the rabbits were sacrificed and the peritoneal cavity explored for adhesions. The number, tenacity, ease of dissection, and density of adhesions were recorded, and the adhesions quantitatively graded using a Modified Hopkins Adhesion scoring system. RESULTS: The operating room towel group had an average adhesion score of 2.5, and 8 (80%) rabbits developed adhesions. The sham group had an average adhesion score of 0.3 and one rabbit (10%) developed adhesions. The Lap Pak group had an average adhesion score of 0.2 and 1 rabbit (10%) developed adhesions. The frequency and severity of adhesions in the operating room towel group were significantly greater from that of the baseline sham group. There was no significant difference between the Lap Pak and sham groups. CONCLUSIONS: In this rabbit laparotomy model, the use of the Lap Pak to retract the bowels resulted in significantly fewer adhesions compared to cotton operating room towels. Lap Pak may be beneficial for bowel packing in general abdominal surgeries.

Small bowel obstruction after FloSeal use.

OBJECTIVE: FloSeal is a thrombin-gelatin hemostatic matrix that is used to obtain hemostasis. There have been isolated case reports of FloSeal causing bowel obstructions, requiring surgical intervention. We report 3 cases of what we believe were FloSeal-induced small bowel obstructions (SBO). METHODS: We present a series of small bowel obstructions after FloSeal use. Our series includes urology, gynecologic oncology, and general surgery cases at the same institution where the product was appropriately used and resulted in the same complication. RESULTS: FloSeal was used for hemostasis in all patients. In each instance, a small bowel obstruction developed in 7 days to 9 days. All patients were reexplored laparoscopically and found to have an intense inflammatory reaction at the site of the FloSeal. The adhesions were lysed and the obstructions resolved. CONCLUSIONS: Although further study is needed, the common factor in all these SBOs was a hemostatic agent. In our and others' series, the time to SBO was 7 days to 9 days. If an early postoperative SBO occurs after FloSeal is used, prompt reexploration should be considered.

Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment.

OBJECTIVE: Define subgroups of patients at highest risk for major morbidity and mortality after a traditional approach of maximal surgical efforts followed by chemotherapy for advanced ovarian cancer (AOC). METHODS: Preoperative health, intra-operative findings and outcomes were assessed in consecutive patients with primary AOC from 4 centers. Initial tumor dissemination was stratified into 3 groups based on volume of disease. Surgery was categorized using a previously described surgical complexity score (SCS). Statistical analysis was directed toward validating a multivariable risk-adjusted model. RESULTS: 576 patients with stage IIIC (N=447, 77.6%) or IV AOC (N=129, 22.4%) were analyzed. Age (HR (per year): 1.02; 95%CI: 1.01-1.03), high tumor dissemination (HTD) (HR: 1.73; 95%CI: 1.19-2.56), residual disease (RD) >1 cm (HR: 2.46; 95%CI: 1.74-3.53), and stage IV (HR: 1.93; 95% CI: 1.51-2.45), independently correlated with OS. We identified a small subgroup of patients who comprised a high-risk group (N=38, 6.6%) characterized by all of the following characteristics: high initial tumor dissemination (HTD) or stage IV plus poor performance or nutritional status plus age ≥ 75. In this group, high SCS to achieve low RD was associated with morbidity of 63.6% and limited survival benefit. CONCLUSIONS: Optimal management of AOC requires accurate, risk-adjusted predictors of outcomes allowing a tailored approach starting with primary therapy. Complex surgical procedures to render low RD improve survival, and in the majority of cases, the benefits of such surgery appear to outweigh the morbidity. However careful analysis identifies a subgroup of patients in whom an alternative approach may be the better strategy.

Surveillance for the detection of recurrent ovarian cancer: survival impact or lead-time bias?

OBJECTIVE: To compare the survival impact of diagnosing recurrent disease by routine surveillance testing versus clinical symptomatology in patients with recurrent epithelial ovarian cancer (EOC) who have achieved a complete response following primary therapy. METHODS: We identified all patients who underwent primary surgery for EOC at two institutions between 1/1997 and 12/2004 and were diagnosed with recurrent disease following a complete clinical response to primary chemotherapy. Survival and post-recurrence management were compared between asymptomatic patients in which recurrent disease was diagnosed at a scheduled visit by routine surveillance testing and symptomatic patients in which recurrent disease was diagnosed based on clinical symptomatology at an unscheduled office visit or hospitalization. RESULTS: Of the 121 patients that met inclusion criteria, 22 (18.2%) were diagnosed with a symptomatic recurrence. Median primary PFS was similar for asymptomatic and symptomatic patients (24.8 versus 22.6 months, P = 0.36); however, post-recurrence survival was significantly greater in asymptomatic patients (45.0 versus 29.4 months, P = 0.006). Secondary cytoreductive surgery (SCRS) was attempted equally in both groups (41% versus 32%, P = NS); however, optimal residual disease (

Radical surgical cytoreduction of progressive leiomyomatosis peritonealis disseminata: a case report.

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is an uncommon, benign smooth muscle condition of the peritoneal cavity that appears clinically as a metastatic malignant neoplasm. Generally, radical surgery is not recommended. This unique case involves curative radical surgery after disease progression during depo-medroxyprogesterone acetate therapy. In vitro assays and future implications are discussed. CASE: A 31-year-old woman presented with abdominal pain and uterine leiomyomas. During exploratory laparotomy, she had gross evidence of LPD. Despite initial surgery and hormonal therapy, she had progression of disease. She then underwent optimal cytoreductive surgery. Tumor response to megestrol acetate in vitro was evaluated and noted to be heterogeneous; therefore it was not given as adjuvant therapy. Five years after radical surgery, she was without evidence of disease, CONCLUSION: Radical secondary cytoreductive surgery can achieve a durable remission for LPD refractory to primary surgical castration and depomedroxyprogesterone acetate therapy.

p53 autoantibodies, cytokine levels and ovarian carcinogenesis.

OBJECTIVE: To address the hypothesis that type II ovarian carcinoma, mutation of p53 and plasma levels of particular cytokines are associated with the generation of p53-specific serum autoantibody (AAb) responses in patients. METHODS: Levels of CA125, 17 cytokines and AAbs to tumor-associated antigens including p53 were measured in plasma of 130 gynecologic tumor patients and 84 healthy controls. TP53 exons 4-9 were sequenced in tumor specimens. RESULTS: p53 AAbs are associated with high grade, but not low grade ovarian carcinoma. Seropositivity for p53 AAb occurred only in those ovarian carcinoma patients whose tumors contained mutated TP53, regardless of the exon targeted. Higher p53 AAb levels were detected in ovarian carcinoma patients who had higher stage disease, but p53 AAb levels were not correlated with CA125 levels. Among high-grade carcinoma patients, there was no relationship between p53 AAb seropositivity and seropositivity to other tumor-associated antigens tested, CA125 level or survival outcome. Both high and low grade ovarian carcinoma patients exhibited elevated levels of IL6, IL8 and IL10 as compared to healthy volunteers, although increased levels of IL5, MCP1, MIP1 and TNFalpha were associated only with high grade and advanced disease. Higher levels of p53AAb responses were correlated with elevated circulating IL4 and IL12, but reduced IL8 levels. CONCLUSION: Type II, but not type I, ovarian carcinoma patients had elevated serum levels of p53 AAb. P53 AAb is associated with mutation of TP53, higher plasma IL4 and IL12 but lower plasma IL8 levels and no survival advantage.

Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor.

PURPOSE: Elevated metabolic activity of ovarian cancer cells causes increased ubiquitin-proteasome-system (UPS) stress, resulting in their greater sensitivity to the toxic effects of proteasomal inhibition. The proteasomes and a potentially compensatory histone deacetylase 6 (HDAC6)-dependent lysosomal pathway mediate eukaryotic protein turnover. We hypothesized that up-regulation of the HDAC6-dependent lysosomal pathway occurs in response to UPS stress and proteasomal inhibition, and thus, ovarian cancer cell death can be triggered most effectively by coinhibition of both the proteasome- and HDAC6-dependent protein degradation pathways. EXPERIMENTAL DESIGN: To address this hypothesis, we examined HDAC6 expression patterns in normal and cancerous ovarian tissues and used a novel HDAC6-specific inhibitor, NK84, to address HDAC6 function in ovarian cancer. RESULTS: Abnormally high levels of HDAC6 are expressed by ovarian cancer cells in situ and in culture relative to benign epithelium and immortalized ovarian surface epithelium, respectively. Specific HDAC6 inhibition acts in synergy with the proteasome inhibitor Bortezomib (PS-341) to cause selective apoptotic cell death of ovarian cancer cells at doses that do not cause significant toxicity when used individually. Levels of UPS stress regulate the sensitivity of ovarian cancer cells to proteasome/HDAC6 inhibition. Pharmacologic inhibition of HDAC6 also reduces ovarian cancer cell spreading and migration consistent with its known function in regulating microtubule polymerization via deacetylation of alpha-tubulin. CONCLUSION: Our results suggest the elevation of both the proteasomal and alternate HDAC6-dependent proteolytic pathways in ovarian cancer and the potential of combined inhibition of proteasome and HDAC6 as a therapy for ovarian cancer.

Feasibility and economic impact of a clinical pathway for pap test utilization in Gynecologic Oncology practice.

OBJECTIVE: To evaluate the feasibility and impact on cost to the U.S. healthcare system of implementing a clinical pathway for Pap test utilization in screening and surveillance of gynecologic cancers in a university-based gynecologic oncology practice. METHODS: Baseline data were collected for Pap test utilization between 1/1/04 and 6/30/05 and prospectively compared to Pap test utilization following the implementation of a clinical pathway (7/1/05 to 5/30/06). The clinical pathway: 1) employed ACOG guidelines for asymptomatic screening of non-cancer patients, 2) allowed testing at 4 months intervals for cervical/vaginal cancer surveillance, 3) limited testing for endometrial cancer surveillance to 2 tests/60 months, and 4) eliminated testing as part of ovarian cancer surveillance. Relevant costs were calculated using Medicare charge-to-cost ratios and adjusted to 2006 USD. For statistical analysis, differences in Pap test utilization and cost were evaluated using student's t-test. RESULTS: During the baseline period, 1725 Pap tests were collected from 5605 ambulatory encounters, for a Pap test rate of 30.8% and an annualized cost of $93,759. After implementation of the clinical pathway, 4209 ambulatory encounters yielded an annual Pap test rate of 11% and an annual cost of $35,728 (p<0.0001), a savings of $58,031. In addition, clinical pathway implementation also registered an opportunity cost savings of 180.3 nursing personnel work hours ($4,162). CONCLUSIONS: Reduction in the unnecessary use of Pap testing for asymptomatic screening and surveillance for gynecologic cancers through a straightforward clinical pathway is feasible and offers an opportunity for significant cost savings in gynecologic oncology healthcare expenditure.

A clinical pathway for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian and primary peritoneal cancers.

OBJECTIVES: To evaluate the safety, feasibility, and economic impact of a clinical pathway, including rapid diet advancement, for patients undergoing rectosigmoid colectomy as part of cytoreductive surgery for advanced ovarian and primary peritoneal cancers. METHODS: Between 8/1/98 and 6/30/06, 64 consecutive patients met study inclusion criteria. Using case-control methodology, post-operative management was dictated by a prescribed clinical pathway in 19 patients (Group A) and directed by individual surgeon preference in 45 patients (Group B). Critical elements of the clinical pathway included: rapid diet advancement, early discontinuance of nasogastric suction, criteria-based utilization of parenteral nutrition, selective laboratory testing, and deferring initiation of chemotherapy until after discharge. RESULTS: Stage IIIC/IV disease was present in 94% of all patients. The median time to flatus was 6 days for both groups (p=0.95); however, the median time to tolerance of diet was 3 days for Group A and 6 days for Group B (p=0.013). Compared to Group B, patients in Group A had a significantly shorter median length of hospital stay (7 days vs 10 days, p=0.014) and lower median 30-day post-operative hospital cost ($19,700 vs $25,110, p=0.028), with no significant difference in 30-day readmission rate (21% vs 33%, p=0.379). Clinical pathway-directed management was associated with a median reduction in hospital cost of $5410 per patient. CONCLUSIONS: A critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for ovarian and primary peritoneal cancers is feasible, safe, and associated with a significant reduction in length of hospital stay and hospital-related costs.

Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility.

Both tumor cell proliferation and metastasis are dependent on myosin II. Because UNC-45 is required to chaperone the assembly of a functional myosin II motor, we examined the expression of the general cell (GC) UNC-45 isoform in ovarian tumors. Serous carcinoma expressed elevated levels of GC UNC-45 compared with normal ovarian surface epithelium and benign cystadenoma. High-stage exhibited greater GC UNC-45 expression than low-stage serous carcinoma. Similarly, GC UNC-45 transcripts and protein levels were higher in ovarian cell lines than in immortalized ovarian surface epithelial cells. Elevation of GC UNC-45 levels by ectopic expression enhanced the rate of ovarian cancer cell proliferation, whereas siRNA knockdown of GC UNC-45 suppressed proliferation without altering myosin II levels. GC UNC-45 and myosin II were diffuse within the cytoplasm of confluent interphase cells, but both accumulated together at the cleavage furrow during cytokinesis. GC UNC-45 and myosin II also trafficked to the leading edges of ovarian cancer cells induced to move in a scratch assay. Knockdown of GC UNC-45 reduced the spreading ability of ovarian cancer cells whereas it was enhanced by GC UNC-45 overexpression. In sum, these findings implicate elevated GC UNC-45 protein expression in ovarian carcinoma proliferation and metastasis.

Survival impact of multiple bowel resections in patients undergoing primary cytoreductive surgery for advanced ovarian cancer: a case-control study.

OBJECTIVE: To evaluate clinicopathological factors and survival outcome of patients with advanced epithelial ovarian carcinoma undergoing multiple bowel resections to achieve optimal (< or = 1 cm) cytoreduction. METHODS: A case-control study was performed identifying patients undergoing optimal primary cytoreductive surgery with > or = 2 bowel resections between 10/1997 and 2/2006. The two control groups consisted of (1) patients undergoing optimal cytoreduction with < or = 1 bowel resections matched [1:2] for age and stage and (2) patients left with suboptimal disease. Cox proportional hazards model were used to evaluate the effects of demographic and surgico-pathologic factors on survival outcome. RESULTS: A total of 34 patients underwent > or = 2 bowel resections. Sixty-eight patients underwent < or = 1 bowel resections. All patients had optimal cytoreduction and 40/102 patients (39.2%) underwent complete cytoreduction. Patients undergoing multiple bowel resections experienced a higher EBL (700 v 500 mL, p=0.01) and longer LOS (10 v 7 days, p=0.01) compared to patients with < or = 1 bowel resections. Multivariate analysis revealed the amount of residual disease to be a statistically significant and radiation therapy to the right pelvic sidewall and cul-de-sac independent predictor of overall survival. The median overall survival time for patients undergoing > or = 2 bowel resections was 28.3 months, which was comparable to patients undergoing < or = 1 bowel resections, (37.8 months, p=0.09) but statistically significantly superior to patients left with suboptimal residual disease (12 months, p=0.02). CONCLUSIONS: Although primary surgery that includes > or = 2 bowel resections is associated with longer LOS and a higher EBL, such extensive procedures are warranted if they will contribute to an overall optimal residual disease state.

Intraperitoneal cisplatin and paclitaxel versus intravenous carboplatin and paclitaxel chemotherapy for Stage III ovarian cancer: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of intraperitoneal cisplatin and paclitaxel chemotherapy as front-line treatment for patients with Stage III epithelial ovarian cancer following optimal primary cytoreductive surgery. METHODS: Based on Gynecologic Oncology Group protocols #172 and #158, a decision analysis model was created to compare two treatment strategies for patients with optimal residual disease Stage III ovarian cancer: (1) inpatient intravenous paclitaxel (24 h) and intraperitoneal cisplatin plus outpatient intraperitoneal paclitaxel chemotherapy (IP/IV), and (2) outpatient intravenous paclitaxel (3 h) and carboplatin chemotherapy (IV/IV). The cost-effectiveness of each strategy was evaluated from the perspective of society. RESULTS: Cost-effectiveness analysis revealed that the strategy of IP/IV chemotherapy had an overall cost per patient of $39,861 and effectiveness of 5.16 QALYs compared to $18,822 and 4.59 QALYs for IV/IV chemotherapy. The IP/IV chemotherapy strategy was associated with an additional 0.56 QALYs at an incremental cost of $21,039. The incremental C/E ratio for IP/IV chemotherapy was $37,454/QALY. Inpatient treatment accounted for 43.2% of the cost of IP/IV chemotherapy. Sensitivity analysis testing confirmed the robustness of the model. CONCLUSIONS: In this model, IP/IV chemotherapy was associated with a modest extension in quality-adjusted survival time but was also more costly than IV/IV chemotherapy. On balance, the IP/IV strategy can be considered a good healthcare value. However, these data also suggest that efforts to reduce the cost of IP/IV chemotherapy, such as through development of an ambulatory regimen with equivalent therapeutic efficacy but an improved toxicity profile, would improve the overall value of this adjuvant treatment program.

A new frontier for quality of care in gynecologic oncology surgery: multi-institutional assessment of short-term outcomes for ovarian cancer using a risk-adjusted model.

OBJECTIVE: To test the feasibility and utility of a risk-adjusted, multicenter outcomes model for ovarian cancer surgery as a tool for quality improvement. METHODS: Patient characteristics, intra-operative findings, procedures, and outcomes were assessed in primary advanced stage ovarian cancer cases from 3 independent centers. A surgical complexity score (SCS) was developed to adjust for extent of surgery. Outcomes measures were: 30-day morbidity (sepsis, thrombo-embolic, cardiac, readmission or re-operation), 3-month mortality, length of stay (LOS), and ability to receive chemotherapy. A multivariable risk-adjusted model was developed for all the outcomes. Observed-to-expected (O/E) outcome ratios were calculated from all data. RESULTS: 564 consecutive patients from 3 centers were analyzed. The strongest predictors of 30-day morbidity were endogenous [albumin (p<0.001) and ASA (p=0.008)] and complexity of surgery [SCS (p<0.001)]. Age (p=0.002) and ASA (p=0.001) independently predicted mortality. LOS independently correlated with age (p=0.007), albumin (p=0.004), SCS (p=0.002), and stage (p=0.024). ASA (p<0.001) and SCS (p=0.003) both impacted ability to receive chemotherapy. Observed to expected (O/E) ratios for dependent outcome variables were similar for all 3 institutions. CONCLUSIONS: We demonstrate the benefits of a national system for studying outcomes in gynecologic surgery using a risk-adjusted model. We specifically find that endogenous patient factors and complexity of surgery are primary drivers of morbidity in ovarian cancer surgery. These data can successfully be used to formulate expected, risk-adjusted rates of complications thus providing a meaningful mechanism to identify areas ripe for quality improvement.

Centralization of care for patients with advanced-stage ovarian cancer: a cost-effectiveness analysis.

BACKGROUND: The objective of this study was to evaluate the cost-effectiveness of centralized referral of patients with advanced-stage epithelial ovarian cancer who underwent primary cytoreductive surgery and adjuvant chemotherapy. METHODS: A decision-analysis model was used to compare 2 referral strategies for patients with advanced-stage ovarian cancer: 1) referral to an expert center, with a rate of optimal primary cytoreduction of 75% and utilization of combined intraperitoneal and intravenous adjuvant chemotherapy, and 2) referral to a less experienced center, with a rate of optimal primary cytoreduction of 25% and adjuvant treatment that consisted predominantly of intravenous chemotherapy alone. The cost-effectiveness of each strategy was evaluated from the perspective of society. RESULTS: A cost-effectiveness analysis revealed that the strategy of expert center referral had an overall cost per patient of $50,652 and had an effectiveness of 5.12 quality-adjusted life years (QALYs). The strategy of referral to a less experienced center carried an overall cost of $39,957 and had an effectiveness of 2.33 QALYs. The expert center strategy was associated with an additional 2.78 QALYs at an incremental cost of $10,695 but was more cost-effective, with a cost-effective ratio of $9893 per QALY compared with $17,149 per QALY for the less experienced center referral strategy. Sensitivity analyses and a Monte Carlo simulation confirmed the robustness of the model. CONCLUSIONS: According to results from the decision-analysis model, centralized referral of patients with ovarian cancer to an expert center was a cost-effective healthcare strategy and represents a paradigm for quality cancer care, delivering superior patient outcomes at an economically affordable cost. Increased efforts to align current patterns of care with a universal strategy of centralized expert referral are warranted.

Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome.

BACKGROUND: The objective of this study was to evaluate the role of secondary cytoreductive surgery in the outcome of patients who had recurrent epithelial ovarian carcinoma that was limited to or=12 months between initial diagnosis and recurrence, and or=18 months (median survival, 49 months vs 3 months; P < .01), the number of radiographic recurrence sites (median survival, 50 months for patients with 1 or 2 sites vs 12 months for patients with 3 to 5 sites; P < .03), and residual disease (median survival, 50 months for patients with no macroscopic residual disease vs 7.2 months for patients with macroscopic residual disease; P < .01). Age, tumor grade, histology, CA-125 level, ascites, and tumor size were not associated significantly with survival. CONCLUSIONS: : The current data supported the definition of localized recurrent ovarian cancer as patients with 1 or 2 radiographic recurrence sites. In this select population, a diagnosis-to-recurrence interval >or=18 months and complete secondary surgical cytoreduction, which was achievable in the majority of patients, were associated with a median postrecurrence survival of approximately 50 months.

Tertiary cytoreductive surgery in recurrent ovarian cancer: selection criteria and survival outcome.

OBJECTIVES: Studies of tertiary cytoreductive surgery (TCS) in recurrent epithelial ovarian cancer are limited, and appropriate patient selection remains a clinical challenge. We sought to evaluate the impact of TCS on survival and to determine predictors of optimal tertiary resection. METHODS: Between January 1997 and July 2004, 47 women with recurrent epithelial ovarian cancer underwent TCS at two institutions. All patients received initial platinum and taxane-based chemotherapy following primary cytoreductive surgery. Clinico-pathologic factors and survival were retrospectively abstracted from medical records. Optimal TCS was defined as microscopic residual disease. RESULTS: Thirty of 47 (64%) patients underwent optimal TCS. Size of tumor implants<5 cm on preoperative imaging was the only significant predictor of achieving optimal TCS. Overall survival after TCS was statistically longer in patients with microscopic versus macroscopic residual disease (24 versus 16 months, p=0.03). After controlling for age, time to progression and optimal TCS, only the presence of diffuse disease at tertiary exploration remained a significant poor predictor of survival. However, in a cohort of patients with limited disease implants, multivariate analysis indicated that optimal TCS retained prognostic significance as a positive predictor of survival. Twelve patients (26%) experienced severe postoperative complications, including six with pulmonary embolism, four with fistulae and two with postoperative myocardial infarctions. CONCLUSIONS: Size of disease implants on preoperative imaging may guide the selection of candidates for TCS. In those patients with limited disease implants at laparotomy, optimal TCS is associated with improved survival.

Secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer.

OBJECTIVES: To evaluate the feasibility and associated survival outcome of secondary cytoreductive surgery in patients with isolated lymph node recurrence of epithelial ovarian cancer. METHODS: Twenty-five patients with epithelial ovarian cancer who underwent secondary cytoreductive surgery for isolated lymph node recurrence were identified from tumor registry databases. Demographic, diagnostic, operative, pathologic, and follow-up data were abstracted retrospectively. Overall survival was calculated using the Kaplan-Meier method. RESULTS: The median age at time of primary surgery for ovarian cancer was 55 years; 72% of patients had FIGO III/IV disease, and all had high-grade tumors. All patients received platinum-based chemotherapy following primary surgery. The median time from completion of primary chemotherapy to nodal recurrence surgery was 16 months (range=6 to 40 months). The distribution of nodal involvement was pelvic=12% (n=3), para-aortic=60% (n=15), inguinal=20% (n=5), peri-cardiac=4% (n=1), and pelvic plus para-aortic=4% (n=1). The maximal nodal tumor diameter ranged from 1.5 cm to 14 cm, with a median of 3.0 cm. Optimal secondary cytoreductive surgery (residual disease

Prevention of adhesion formation after radical hysterectomy using a sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of an adhesion prevention strategy compared to routine care, in which no adhesion prevention measures are taken, through a decision analysis model in the clinical setting of patients undergoing radical hysterectomy and pelvic lymphadenectomy for Stage IB cervical cancer. METHODS: A decision analysis model compared two strategies to manage the risk of adhesion-related morbidity following radical hysterectomy for Stage IB cervical cancer: (1) routine care with no adhesion prevention measures, and (2) the intervention strategy with a HA-CMC anti-adhesion barrier. The cost-effectiveness of each strategy was evaluated from the perspective of society and that of a third party payer. RESULTS: From the perspective of society, the HA-CMC strategy had an overall cost per patient of $1932 and effectiveness of 7.901 QALYs and dominated the routine care strategy, which had a cost per patient of $3043 and effectiveness of 7.805 QALYs. From the perspective of a third party payer, the HA-CMC strategy had an overall cost per patient of $1247 and effectiveness of 7.987 QALYs and dominated the routine care strategy, which had a cost per patient of $1629 and effectiveness of 7.970 QALYs. A series of one-way sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: Under a conservative set of clinical and economic assumptions, an adhesion prevention strategy utilizing a HA-CMC barrier in patients undergoing radical hysterectomy for Stage IB cervical cancer is cost-effective from both the perspective of society as a whole and that of a third party payer.

Delaying the primary surgical effort for advanced ovarian cancer: a systematic review of neoadjuvant chemotherapy and interval cytoreduction.

OBJECTIVE: To summarize the existing data on interval cytoreductive surgery and neoadjuvant chemotherapy as alternative treatment strategies for patients with advanced-stage ovarian cancer. METHODS: All investigational studies with evaluable survival data on interval cytoreductive surgery and neoadjuvant chemotherapy for ovarian cancer reported in the English language literature between 1989 and 2006 were systematically reviewed. RESULTS: Three randomized trials and six non-randomized studies of interval cytoreduction following suboptimal initial surgery were identified. Twenty-six studies, including a total of 1336 patients, reporting on neoadjuvant chemotherapy administered in lieu of primary cytoreductive surgery were analyzed according to the survival outcome achieved, the degree of surgical effort or success, and the particular selection criteria employed to justify deferring an attempt at primary cytoreductive surgery. CONCLUSIONS: Interval surgery following a concerted but suboptimal attempt at up-front cytoreduction does not appear to have an appreciable impact on survival outcome. Maximal primary cytoreductive surgery remains the standard of care for the majority of women with suspected advanced ovarian cancer. Neoadjuvant chemotherapy represents a viable alternative management strategy for the limited number of patients felt to be optimally unresectable by an experienced ovarian cancer surgical team; however, currently available data suggest that the survival outcome achievable with initial chemotherapy is inferior to successful up-front cytoreductive surgery. Additional research is needed to devise universal selection criteria for neoadjuvant chemotherapy, determine the most efficacious treatment program, and characterize the appropriate proportion of patients in which an attempt at primary surgery should be abandoned in favor of initial chemotherapy.

A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival.

Recent studies have suggested an oncogenic role of the BTB/POZ-domain genes in hematopoietic malignancy. The aim of this study is to identify and characterize BTB/POZ-domain genes in the development of human epithelial cancers, i.e., carcinomas. In this study, we focused on ovarian carcinoma and analyzed gene expression levels using the serial analysis of gene expression (SAGE) data in all 130 deduced BTB/POZ genes. Our analysis reveals that NAC-1 is significantly overexpressed in ovarian serous carcinomas and several other types of carcinomas. Immunohistochemistry studies in ovarian serous carcinomas demonstrate that NAC-1 is localized in discrete nuclear bodies (tentatively named NAC-1 bodies), and the levels of NAC-1 expression correlate with tumor recurrence. Furthermore, intense NAC-1 immunoreactivity in primary tumors predicts early recurrence in ovarian cancer. Both coimmunoprecipitation and double immunofluorescence staining demonstrate that NAC-1 molecules homooligomerize through the BTB/POZ domain. Induced expression of the NAC-1 mutant containing only the BTB/POZ domain disrupts NAC-1 bodies, prevents tumor formation, and promotes tumor cell apoptosis in established tumors in a mouse xenograft model. Overexpression of full-length NAC-1 enhanced tumorigenicity of ovarian surface epithelial cells and NIH 3T3 cells in athymic nu/nu mice. In summary, NAC-1 is a tumor recurrence-associated gene with oncogenic potential, and the interaction between BTB/POZ domains of NAC-1 proteins is critical to form the discrete NAC-1 nuclear bodies and essential for tumor cell proliferation and survival.