To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation.
We conducted a population-based cohort study. ...All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting.
There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval CI 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation.
Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.
Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal ...timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions.
Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000–9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records.
26 Non-BRCA (9 BRIP1, 9 RAD51C, and 8 RAD51D) and 75 Lynch (36 MLH1, 18 MSH2, 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively.
No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated.
•Median age of RRSO was 47 yo with no occult ovarian/fallopian tube cancer supporting current RRSO guidelines.•Surgical complications in this population were largely seen with concomitant hysterectomy and colectomy.•There was very low uptake in post-surgery hormone replacement therapy in these patients undergoing RRSO.
•Adjuvant gemcitabine-docetaxel chemotherapy increased significantly from 2006 to 2013•White women were more likely to receive adjuvant chemotherapy than other ethnicities.•Adjuvant ...gemcitabine-docetaxel was not associated with improved survival.
To assess recent trends of administering adjuvant gemcitabine-docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare disease-free and overall survival between women who received and did not receive adjuvant GD chemotherapy.
All patients diagnosed with Stage I uterine leiomyosarcoma in a California-Colorado population-based health plan inclusive of 2006–2013 were included in a retrospective cohort. Adjuvant GD chemotherapy rates, clinico-pathologic characteristics and survival estimates were assessed.
Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non-GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index, and Charlson comorbidity score. Non-Hispanic white women were twice as likely to receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%, P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased from 6.5% in 2006–2008 to 46.9% in 2009–2013 (P<0.001). There was no significance difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts. Corresponding adjusted Cox proportional hazard ratios for adjuvant GD chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval CI 0.57–1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69–2.36, P-0.48) for mortality.
Use of adjuvant GD chemotherapy for Stage I uterine leiomyosarcoma has increased significantly in the last decade, despite unclear benefit. Compared to no chemotherapy, 4–6cycles of adjuvant GD chemotherapy does not appear to alter survival outcomes.
Recent literature reports highlight the importance of the renal outer medullary potassium (ROMK) channel in renal sodium and potassium homeostasis and emphasize the potential impact that ROMK ...inhibitors could have as a novel mechanism diuretic in heart failure patients. A series of piperazine-based ROMK inhibitors were designed and optimized to achieve excellent ROMK potency, hERG selectivity, and ADME properties, which led to the identification of compound 28 (BMS-986308). BMS-986308 demonstrated efficacy in the volume-loaded rat diuresis model as well as promising in vitro and in vivo profiles and was therefore advanced to clinical development.
Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies.
A retrospective study of endometrial cancer (EC) cases from 2 ...regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified.
During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04–0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18–0.80).
Universal IHC screening did not result in increased LS detection in EC.
•Significant factors associated with an abnormal IHC screen included endometrioid histology and tumor grade >1.•Significant factors associated with Lynch Syndrome were younger age and lower BMI.•Universal IHC screening did not lead to increased detection of Lynch Syndrome compared to risk-based IHC screening.•Uptake of IHC screening was inconsistent when a physician order was required.
To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations.
Women with BRCA mutations and intact ovaries were ...invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy.
A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%).
A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.
•Using a pure BRCA population, we have developed a novel Risk of Ovarian Cancer (ROCA) algorithm for HE4.•A combined CA-125 and HE4 two-marker ROCA reduces the number of false positive patient tests.•The two-marker ROCA surveillance option deserves further study to define test positive predictive value and test sensitivity
We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 ...and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months.
Women were recruited 6/13/16–9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale.
There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034).
This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.
•Compliance with biomarker blood tests performed every 4 months was high (83.2%).•Compliance with standard surveillance ultrasounds and CA 125 was significantly lower (51.9%).•Women who did biomarker testing every 4 months had lower stress scores at 12 months than at baseline.
The prevalence of obesity (BMI ≥30) in US women approximates 40%. Severely obese women (BMI ≥40) have increased rates of perioperative morbidity and mortality. Minimally invasive surgical (MIS) ...options have improved perioperative outcomes but become limited for patients with severely elevated BMI, particularly ≥60. Contrary to previously published conclusions, utilizing panniculectomy at the time of surgical staging can make laparoscopic surgery feasible in this patient population.
Retrospective review of patients undergoing concurrent panniculectomy and total laparoscopic hysterectomy (TLH). Twenty-one patients between 2009–2022 were identified through surgical logs. Data was collected regarding successful completion of laparoscopy as well as intraoperative and postoperative complications within 30 days of surgery.
Average preoperative BMI was 53.3 (range 41–79). A laparoscopic procedure was scheduled in all 21 patients. Laparoscopy was successfully completed in 20/21 cases (95%). One case required conversion from laparoscopic hysterectomy to laparotomy. Mean blood loss was 238ml (range 100–500 ml). The median weight of pannus resection was 6.6 kg (range 4.2–38.5 kg). One patient required intraoperative blood transfusion due to operative losses as the pannus removed was >38 kg. Median operative time was minutes 214 (range 169–322 mins). 90% of patients were discharged by post operative day 2 (range day 1–5). Two-thirds of patients were discharged without need for home health services. No patients required readmission within 30 days following surgery and no patients required ICU admission. There were no events of venous thromboembolism, bowel obstruction or surgical site complications occurred.
Our pilot data demonstrates utilizing panniculectomy at the time of hysterectomy is successful in facilitating laparoscopic surgery for severely obese patients. No major complications were seen during admission or in the 30-day postoperative period, and the additional inpatient stay is minimal. The current data is the basis of ongoing research regarding long-term effects of combined panniculectomy and laparoscopic hysterectomy, with specific attention to hypertension, diabetes, weight management and patient quality of life.
Risk factors and infection rates of radical robotic procedures have yet to be described in gynecology. A practice improvement strategy using a solitary dose of vaginal metronidazole the night before ...surgery was initiated to determine if it decreased the risk of pelvic infection.
A retrospective chart review of robotic radical hysterectomies for gynecologic malignancy at our institution from April 2010 through April 2016 was performed. Demographic data, operative data, and data on use of metronidazole before surgery were collected. χ Statistical analysis, Student t test, and multivariate analysis were performed to analyze the data.
Ninety-four patients met the inclusion criteria, and 46 patients received vaginal metronidazole. Demographic and clinical factors were similar between the 2 groups. The pelvic infection rate was significantly higher in nonusers at 13% (6/46) compared with users at 0% (0/42) (P ≤ 0.05). The genitourinary infection rate was also significantly higher in nonusers at 20% as compared with users at 2.2% (P = 0.02). Operative risk factors found to be associated with pelvic infection included hospital length of stay, blood loss, and metronidazole use. Multivariate regression analysis determined that only vaginal metronidazole had a clinically significant reduction of pelvic and genitourinary infection.
A single dose of preoperative vaginal metronidazole reduces the risk of pelvic and genitourinary infection after robotic radical hysterectomy.
Cervical cancer guidelines discontinue screening for women over 65 with adequate prior data, however, more than 20% of cervical cancer cases are diagnosed in women of this age group, often at a ...higher stage. We sought to leverage our large, closed healthcare system to more clearly characterize the cases in this age group.
The Kaiser Permanente Southern California Region (KPSCR) was queried from 2012–2021 for patients >65 using ICD-10 and respective ICD-9 codes. Demographic, medical, screening, pathologic, follow-up and treatment data was extracted. Patients were considered to be adequately screened if they met ASCCP guidelines. Statistical analyses, including Chi-squared test and logistic regression, were used. Cancer-specific survival was estimated using the Kaplan-Meier method.
Of 2175 patients screened, 231 met study criteria; 22 were excluded for atypical histology. Annual incidence rate remained stable around 6.3 per 100,000 (range 4.7–7.7). Median age was 72 (65–103), the majority were non-white (62.5%), English-speaking (78.6%), and never-smokers (61.7%). Most were diagnosed at stage II or higher (62.7%) and had squamous histology (75.7%). HPV status was unknown in 43.5% and 31.6% were positive for HPV high-risk strains. Only 23.9% of patients met ASCCP exit criteria and 41% of patients died of their disease. A membership duration >5 years was positively correlated with proper exit screening (p<0.001), however, 64% still did not meet criteria to end screening at age 65, with 42.6% of these patients having >25 physician visit opportunities to be screened. Increased number of physician visits negatively correlated with tumor stage (p=0.01). Median cancer-specific survival was significantly better in properly screened patients, 68 vs. 30 months respectively (p=0.03).
Most patients diagnosed with cervical cancer after age 65 within KPSCR did not meet criteria for exit screening, including patients who were members >5 years. There were many missed opportunities for screening, despite multiple provider touch-points; most patients had advanced disease and a large proportion died of cervical cancer. Our data suggests that adequate screening confers a survival benefit secondary to earlier stage at diagnosis. Further study in this age group is needed to redefine the criteria to end cervix cancer screening.
