Correlation of surgeon radiology assessment with laparoscopic disease site scoring in patients with advanced ovarian cancer.

BACKGROUND: Radiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results. OBJECTIVE: To determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer. METHODS: Fourteen gynecologic oncology surgeons from a single institution performed a blinded review of pre-operative contrast-enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter-class correlation and 95% CI were calculated. RESULTS: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter-rater agreement was -0.017 (95% CI -0.023 to -0.005), indicating low inter-rater agreement between radiology review and actual laparoscopic score. The inter-class correlation in this model was 0.06 (0.02-0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut-off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub-scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub-scale agreement. CONCLUSIONS: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability.

Normal Risk Ovarian Screening Study: 21-Year Update.

PURPOSE: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. METHODS: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. RESULTS: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. CONCLUSION: While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.

Prospective evaluation of insulin resistance among endometrial cancer patients.

OBJECTIVE: Obesity and estrogen are strong risk factors for endometrial cancer (EC). Whereas diabetes also increases the risk, little is known about related insulin resistance (IR). The purpose of this study was to determine the prevalence of IR in newly diagnosed EC patients. STUDY DESIGN: EC patients from a large, metropolitan county were prospectively enrolled from 2005 to 2008. Fasting serum was analyzed for glucose and insulin. IR was defined as a history of diabetes or a quantitative insulin sensitivity check index (QUICKI) (1/[log fasting insulin + log fasting glucose]) value of less than 0.357. RESULTS: Among 99 patients, diabetes was present in 30, and an abnormal QUICKI was found in 36 additional patients. Increased risk of IR was significantly associated with higher body mass index (P < .001), lower socioeconomic status (P = .007), and nulliparity (P = .029). CONCLUSION: IR was highly prevalent in endometrial cancer patients, including nonobese women. Better characterization of metabolic risks in addition to obesity may provide avenues for targeted cancer prevention in the future.

Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer.

OBJECTIVE: To compare intraoperative, pathologic, and postoperative outcomes of total laparoscopic radical hysterectomy with abdominal radical hysterectomy and pelvic lymphadenectomy for women with early-stage cervical cancer. METHODS: We reviewed all patients who underwent total laparoscopic radical hysterectomy or abdominal radical hysterectomy and pelvic lymphadenectomy between 2004 and 2006. RESULTS: Fifty-four patients underwent abdominal radical hysterectomy, and 35 underwent total laparoscopic radical hysterectomy. Mean age was 41.8 years, and mean body mass index 28.1. There was no difference in demographic or tumor factors between the two groups. Mean estimated blood loss was 548 mL with abdominal radical hysterectomy compared with 319 mL with total laparoscopic radical hysterectomy (P=.009), and 15% of patients who underwent abdominal radical hysterectomy required a blood transfusion compared with 11% who underwent total laparoscopic radical hysterectomy (P=.62). Mean operative time was 307 minutes for abdominal radical hysterectomy compared with 344 minutes for total laparoscopic radical hysterectomy (P=.03). On pathologic examination, there was no significant difference in the amount of parametrial tissue, vaginal cuff, or negative margins obtained. A mean 19 pelvic nodes were obtained during abdominal radical hysterectomy compared with 14 during total laparoscopic radical hysterectomy (P=.001). The median duration of hospital stay was significantly shorter for total laparoscopic radical hysterectomy (2.0 compared with 5.0 days, P<.001). For abdominal radical hysterectomy, 53% of patients experienced postoperative infectious morbidity compared with 18% for total laparoscopic radical hysterectomy (P=.001). There was no difference in postoperative noninfectious morbidity. There was no difference in return of urinary function. CONCLUSION: Total laparoscopic radical hysterectomy reduces operative blood loss, postoperative infectious morbidity, and postoperative length of stay without sacrificing the size of radical hysterectomy specimen margins; however, total laparoscopic radical hysterectomy is associated with increased operative time.

Reconstruction of the pelvic floor and perineum with human acellular dermal matrix and thigh flaps following pelvic exenteration.

BACKGROUND: Patients who undergo pelvic floor resection as treatment for recurrent cancer following radiation therapy have increased rates of complications, particularly if permanent prosthetic mesh is used for reconstruction. Human acellular dermal matrix (HADM), commonly used for reconstruction in other torso locations, is associated with lower rates of complications (including infection, adhesions and cutaneous exposure) than synthetic mesh. We describe an effective technique to reconstruct the pelvic floor and perineum with HADM and thigh-based flaps following pelvic exenteration and radical vulvectomy. CASE: A 75-year-old woman underwent radical resection of the pelvic floor and perineum to treat recurrent vulvar squamous cell carcinoma and osteoradionecrosis. The pelvic floor and perineal soft tissue defect were reconstructed with HADM (AlloDerm; LifeCell Corporation, Branchburg, NJ) and bilateral, thigh-based tissue flaps, respectively. Despite a large resection, previous irradiation therapy and bacterial contamination the wounds healed without complications. CONCLUSION: Reconstruction of pelvic floor defects using HADM is an option when wound conditions are unfavorable for the use of permanent prosthetic meshes.

Optimism, distress, health-related quality of life, and change in cancer antigen 125 among patients with ovarian cancer undergoing chemotherapy.

OBJECTIVE: This study investigated whether situational and dispositional optimism were protective against dimensions of distress and aspects of health-related quality of life (HQoL) in patients with ovarian cancer undergoing chemotherapy. This study also evaluated whether optimism predicted a decrease in cancer antigen (CA) 125 levels during treatment. METHODS: Ninety women with epithelial ovarian cancer were assessed at the start and end of chemotherapy. Optimism, distress, and HQoL were measured by self-report; CA 125 levels were gathered from patients' medical charts. RESULTS: Both measures of optimism were inversely associated with baseline anxiety, perceived stress, and depression. In addition, situational optimism was positively associated with baseline social and physical well-being, and dispositional optimism was positively associated with baseline social and functional well-being. However, neither measure of optimism predicted domains of distress or HQoL at the follow-up assessment after controlling for baseline levels. Dispositional optimism predicted CA 125 at the end of treatment after controlling for baseline levels. However, neither situational nor dispositional optimism predicted CA 125 falling to normal levels (< or =35 U/mL). CONCLUSION: Consistent with prior research, optimism was inversely associated with distress and positively associated with HQoL in patients with ovarian cancer undergoing chemotherapy. Higher levels of dispositional optimism at the start of chemotherapy were associated with a greater decline in patients' CA 125 during treatment.

Patchy reaction-diffusion and population abundance: the relative importance of habitat amount and arrangement.

A discrete reaction-diffusion model was used to estimate long-term equilibrium populations of a hypothetical species inhabiting patchy landscapes to examine the relative importance of habitat amount and arrangement in explaining population size. When examined over a broad range of habitat amounts and arrangements, population size was largely determined by a pure amount effect (proportion of habitat in the landscape accounted for >96% of the total variation compared to <1% for the arrangement main effect). However, population response deviated from a pure amount effect as coverage was reduced below 30%-50%. That deviation coincided with a persistence threshold as indicated by a rapid decline in the probability of landscapes supporting viable populations. When we partitioned experimental landscapes into sets of "above" and "below" persistence threshold, habitat arrangement became an important factor in explaining population size below threshold conditions. Regression analysis on below-threshold landscapes using explicit measures of landscape structure (after removing the covariation with habitat amount) indicated that arrangement variables accounted for 33%-39% of the variation in population size, compared to 27%-49% for habitat amount. Thus, habitat arrangement effects became important when species persistence became uncertain due to dispersal mortality.

Frozen section analyses as predictors of lymphatic spread in patients with early-stage uterine cancer.

BACKGROUND: Many gynecologic oncologists use intraoperative frozen section (IFS) assessment of histologic grade and depth of myometrial invasion (DOI) as predictors of final grade and stage in women with endometrial cancer. This clinical decision method has never been critically examined. STUDY DESIGN: We retrospectively reviewed charts of patients with a preoperative diagnosis of uterine endometrioid adenocarcinoma and an intraoperative frozen section assessment of histologic grade and depth of myometrial invasion. Intraoperative predictors combining intraoperative frozen section assessment of histologic grade and depth of myometrial invasion were established and compared with final grade and surgical stage. We then modeled the risks of pelvic and paraaortic lymph node metastases for each predictor. RESULTS: There were 129 patients who met inclusion criteria. Thirty-six patients had the IAG1 predictor; 17 (47%) were stage IAG1 on final pathology. Ten patients had the IAG2 predictor; 3 (30%) were stage IAG2 on final pathology. Thirty-four patients had the IBG1 predictor; 18 (53%) were stage IBG1 on final pathology. Forty-nine patients had the IBG2 predictor; 34 (69%) were stage IBG2 on final pathology. Our decision models predict that the IAG1 predictor has a 1% risk of paraaortic and a 2% risk of pelvic lymph node metastases. The IAG2 and IBG1 predictors have a 2% risk of paraaortic and a 4% risk of pelvic lymph node metastases. The IBG2 predictor has a 2% risk of paraaortic and a 6% risk of pelvic lymph node metastases. CONCLUSIONS: The combination of intraoperative frozen section analysis for histologic grade and depth of myometrial invasion does not correlate well with final pathologic grade and stage. Data from our models suggest a significant risk of lymph node spread even for patients with seemingly low-risk disease. Until better markers of lymphatic spread exist, we recommend complete surgical staging of all patients with endometrial cancer.

Comparison of chemotherapy education and patient preferences in community versus academic gynecology oncology clinics.

PURPOSE: To evaluate and compare patients' preferences in receiving chemotherapy education from health care teams in community versus academic clinics. METHODS: Results from a 13-question questionnaire about the chemotherapy education preferences of patients in three community gynecology oncology clinics were compared to the results from a similar study previously conducted in an academic gynecology oncology clinic. RESULTS: A total of 57% of the 203 community-clinic respondents (116) and 67% of the 282 academic-institution respondents (189) who completed questionnaires had previously received chemotherapy. Of the patients treated in community clinics, almost 60% preferred chemotherapy education to be provided in written form and directly by a health care professional compared to 87% of the patients in academic clinics. Overall, 88% of the patients in the community clinics believed they received adequate information, compared to 63% of the patients in the academic setting. Patients in the community clinics wanted to get more in-depth answers to questions such as 'What is chemotherapy?' (54%) and 'How it is given?' (55%). In addition, community patients also wanted to know more about 'Why chemotherapy stops working?' (72%) and 'What to do and who to call about side effects?' (60%). In the academic setting, patients were less likely to want to know more about these chemotherapy related questions (42, 35, 57, and 49, respectively). CONCLUSIONS: Patients preferred to receive written chemotherapy education that was reviewed with a healthcare professional and that gave more detailed information about the chemotherapeutic drugs themselves and how to prevent and manage side effects. As a result of this questionnaire, the patient education materials used at our institution will be revised to better address patients' preferences in both treatment settings.

Electrothermal bipolar coagulation for pelvic exenterations.

OBJECTIVES: The morbidity associated with pelvic exenteration is high; however, patients undergoing this procedure have no other curative treatment options. Excessive blood loss is a common complication of this procedure. We evaluated whether use of an electrothermal bipolar coagulator (LigaSure Atlas, ValleyLab, Boulder, Colorado, USA) during pelvic exenteration is safe and whether it reduces intraoperative blood loss, intraoperative blood transfusion requirements, and length of hospital stay. METHODS: Between September 2003 and January 2005, 12 patients underwent pelvic exenteration (total, anterior, or posterior) performed using the electrothermal bipolar coagulator. Estimated blood loss, transfusion requirements, length of hospital stay, and complications necessitating reoperation were evaluated. RESULTS: The mean age was 55 years (range, 30-77), the mean estimated blood loss was 1931 ml (range, 1300-1500 ml), the mean number of units of packed red blood cells transfused intraoperatively was 3.4 U (range, 2-12 U), the mean operative time was 609 min (range, 400-940 min), and the mean length of hospital stay was 19.9 days (range, 7-27). There were no intraoperative complications related to the electrothermal bipolar coagulator use. None of the patients had any complications necessitating reoperation. CONCLUSIONS: Use of the electrothermal bipolar coagulator device during pelvic exenteration is safe and may decrease blood loss and the number of units of blood that must be transfused intraoperatively.

Adult granulosa cell tumors of the ovary in two first-degree relatives.

BACKGROUND: Known inherited mutations are responsible for approximately 10% of all epithelial ovarian cancers; however, prior to this report, sex cord-stromal ovarian tumors had not been documented in related females. CASE: We report here on a mother and daughter, each diagnosed with rare, adult-type granulosa cell tumors of the ovary. CONCLUSION: This novel report of granulosa cell tumors occurring in two first-degree relatives must be examined with reserve. No familial tendency has previously been documented, and our finding may be coincidental. However, if additional cases are reported and future research is undertaken, biological markers and inherited mutations for certain sex cord-stromal ovarian tumors may be identified. These advances could lead to targeted therapy and specific surveillance protocols with appropriate surgical interventions for high-risk patients.

Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer.

GOALS OF WORK: Although many patients with ovarian cancer achieve favorable responses to primary chemotherapy, the majority of women will experience recurrence of their cancer. Selection of second- or third-line chemotherapy ultimately depends on patient preferences for different side effects. To better understand this process, we evaluated preferences and symptom distress in patients with ovarian cancer. PATIENTS AND METHODS: A total of 70 women with ovarian cancer who had previously received at least three cycles of platinum-based chemotherapy and currently undergoing chemotherapy for newly diagnosed or recurrent disease were interviewed in an outpatient chemotherapy clinic. The patients were asked to rank order 27 health states using a modified visual analog scale and to complete the Memorial Symptom Assessment Scale (MSAS). MAIN RESULTS: Most favorable health states included perfect health, clinical remission and complete control of chemotherapy-induced nausea and vomiting (CINV). Least favorable health states included more severe CINV health states and death. Patients on first-line chemotherapy had less symptom distress, and rated sexual dysfunction, fatigue and memory loss more favorably than patients on second- or third-line chemotherapy (P<0.05). Married patients generally had less symptom distress compared to patients who were not married, but married patients indicated more distress with sexual dysfunction (P=0.04). Married patients rated alopecia less favorably than unmarried patients (P=0.03), but married patients viewed certain CINV health states more favorably (P=0.02-0.04). CONCLUSIONS: CINV remains one of the most dreaded side effects of chemotherapy. Separate preference profiles exist for patients with newly diagnosed and recurrent disease, as well as for married versus unmarried patients. While MSAS scores and VAS rankings showed consistency across some health states, this was not true for CINV, suggesting that current symptom status may only influence patient preferences for selected side effects.

A phase II trial of cisplatin, ifosfamide, and mesna in patients with advanced or recurrent uterine malignant mixed müllerian tumors with evaluation of potential molecular targets.

OBJECTIVE: The aim of this study was to determine the efficacy of cisplatin, ifosfamide, and mesna in uterine malignant mixed müllerian tumor (MMMT) and to evaluate the expression of clinically relevant molecular markers. METHODS: Women with advanced or recurrent MMMT were treated every 28 days with cisplatin (75 mg/m(2)), ifosfamide (1.2 gm/m(2)), and mesna (240 mg/m(2)). Treatment continued until disease progression or for six courses in the case of nonmeasurable disease. Immunohistochemical analysis for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, C-kit, Abl, and PDGFR-beta expression were performed. RESULTS: Sixteen patients received 1-10 cycles; 2 died of disease progression after 1 cycle; 3 stopped after 1 cycle because of toxicity. Of 6 with measurable disease, 2 had a partial response, 1 had stable disease (SD), and 3 had progression (RR 33%). Partial response durations were 6 and 9 months; SD duration was 6 months. Of 5 patients without measurable disease, 4 received 6 cycles; 1 received 4 cycles. Four died of recurrent disease and 1 was without disease 6.5 years after treatment. Thirty-six percent experienced at least one neutropenic G3 or G4 event. All experienced G1 gastrointestinal toxicity. Four required dose reductions. At 7.5 months, only 1 with measurable disease was still living. Immunohistochemical analyses revealed that 24% expressed ER or PR, 19% expressed HER-2/neu, and none expressed C-kit. However, 45% expressed Abl and 100% expressed PDGFR-beta. CONCLUSION: Although the combination of cisplatin, ifosfamide, and mesna in patients with MMMT had moderate activity, the high toxicity and short response duration in this uncommon, aggressive malignancy suggest that this regiment continues to be a disappointing treatment choice for uterine MMMT. HER-2/Neu, Abl, or PDGFR-beta expression may be of value in order to investigate novel multimodality treatment strategies.

Functional outcomes and complications of continent urinary diversions in patients with gynecologic malignancies.

OBJECTIVE: The purpose of this study was to review our experience with continent urinary diversions in patients with gynecologic malignancies and evaluate the presentation and management of early and late complications. METHODS: A retrospective chart review was performed of all patients who underwent a continent urinary diversion on the Gynecologic Oncology Service at The University of Texas M. D. Anderson Cancer Center during the period January 1988 to March 2001. We analyzed our data to evaluate potential risk factors for complications. Renal status, conduit integrity, and overall patient outcomes were also studied. RESULTS: We identified 40 patients who underwent a continent urinary diversion using an ileocolonic segment (Miami pouch technique). All patients had a history of gynecologic malignancies. The median age at the time of the procedure was 50 years (range 24 to 76 years), and the median weight was 69.6 kg (range 47 to 125 kg). A total of 39 patients (98%) had a history of radiotherapy. Continent urinary diversion was performed as part of an anterior pelvic exenteration in 12 patients (30%), in conjunction with a total pelvic exenteration in 18 patients (45%), and as the main procedure in 10 patients (25%). The median estimated blood loss was 2100 ml (range 200 to 8500 ml). The median length of hospitalization was 19.5 days (range 7 to 56 days). A total of 24 patients (60.0%) had a postoperative complications unrelated to the reservoir. Complications directly related to the continent urinary diversion were seen in 26 (65.0%) of 40 patients. None of the patients in this study group developed chronic renal failure, and there were no perioperative deaths. At last evaluation, 36 (90%) of 40 patients reported normal continent conduit function. CONCLUSIONS: Continent urinary diversion using an ileocolonic segment is a reasonable alternative to the ileal and transverse colon conduit in bladder reconstruction in patients undergoing radical pelvic surgery. The routine use of postoperative total parenteral nutrition, the chronic use of antibiotics after discharge from the hospital, and the routine use of imaging studies remain controversial. In this group of patients, the majority of complications may be successfully managed conservatively.