Trends in specific procedures performed at the time of cytoreduction for ovarian cancer: Is interval debulking surgery truly less radical? A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: To evaluate procedures performed during primary debulking surgery (PDS) and interval debulking surgery (IDS) for ovarian cancer. METHODS: Patients surgically treated at our institution for newly diagnosed stage IIIC/IV epithelial ovarian cancer between 6/1/2015-12/31/2021 were identified using a prospectively collected database. Patients were triaged to PDS or neoadjuvant chemotherapy (NACT) followed by IDS using an institutional algorithm. Data on specific procedures performed, including consultants called, were collected from operative and pathology reports. Appropriate statistical analyses were applied. RESULTS: Overall, 467 patients underwent PDS and 434 underwent IDS; 76% (PDS) and 71% (IDS) of cases achieved complete gross resection. Comparing PDS vs IDS cohorts, median age was 63 years (range, 23-86) vs 67 years (range, 35-95), 79% vs 86% of patients had high-grade serous histology, and 38% vs 70% had stage IV disease. Most procedures (except ostomy, distal pancreatectomy) were more common during PDS (P < .05). Bowel surgery was performed during 65% of PDS and 33% of IDS, and upper abdominal surgery during 72% of PDS and 52% of IDS; both were more common during PDS (P < .001). Estimated blood loss (median, 500 mL [PDS] vs 300 mL [IDS]) and operative time (median, 362 min [PDS] vs 267 min [IDS]) were higher for PDS (P < .001). A consulting surgeon was utilized during 31% of PDS and 18% of IDS, with hepatopancreaticobiliary as the most commonly called service (61% and 65%, respectively). CONCLUSIONS: In our study of patients with advanced-stage ovarian cancer, while most procedures were more often performed during PDS, NACT did not obviate the need for radical surgical resection. Thus, advanced surgical skills remain essential.

Isolated vaginal recurrence in women with stage I endometrial cancer.

OBJECTIVE: To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence. METHODS: Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests. RESULTS: Of 2815 women identified, 278 (10%) experienced a recurrence. Sixty-one patients (2%) had an isolated vaginal recurrence, including 42 (69%) at the vaginal apex; 217 (8%) had an extravaginal recurrence, including 18 with a vaginal component. Median time to recurrence was 11 months (range, 1-68) for isolated vaginal recurrence and 20 months (range, 1-98) for extravaginal recurrence (P < .004). Of 960 patients (34%) treated with adjuvant vaginal brachytherapy (VBT), 156 (16%) recurred; 19 (2%) had an isolated vaginal recurrence, including 16 (84%) at the vaginal apex. Three-year PFS rates for isolated vaginal recurrence were 97.6% (SE ± 0.4%) with minimally invasive surgery (MIS) versus 96.9% (SE ± 1.1%) with open (P = .8), and for extravaginal recurrence were 91.8% (SE ± 0.7%) with MIS versus 90.8% (SE ± 1.8%) with open (P = .8). CONCLUSIONS: Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences. Surgical approach does not appear to impact recurrence. Adjuvant VBT after primary surgery carries a 1%-2% risk of isolated vaginal apex recurrence.

Ten-year conditional probability of survival for patients with ovarian cancer: A new metric tailored to Long-term survivors.

OBJECTIVES: We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years. METHODS: We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001-12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S(x + y)/S(x). Confidence intervals were estimated using a variation of Greenwood's formula. RESULTS: Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25-95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%-32%)-75% (95% CI: 68%-82%) for stage I/II disease, 22% (95% CI: 19%-26%) for stage III, and 6.9% (95% CI: 3.9%-12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%-70%); for those ≥65 years, it was 48% (95% CI: 38%-57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%-94%); stage III, 58% (95% CI: 50%-66%); and stage IV, 26% (95% CI: 12%-42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%-91%), 42% (95% CI: 30%-53%), and 29% (95% CI: 7%-56%), respectively. CONCLUSIONS: For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods.

Tear nanoDSF Denaturation Profile Is Predictive of Glaucoma.

Primary open-angle glaucoma (POAG) is a frequent blindness-causing neurodegenerative disorder characterized by optic nerve and retinal ganglion cell damage most commonly due to a chronic increase in intraocular pressure. The preservation of visual function in patients critically depends on the timeliness of detection and treatment of the disease, which is challenging due to its asymptomatic course at early stages and lack of objective diagnostic approaches. Recent studies revealed that the pathophysiology of glaucoma includes complex metabolomic and proteomic alterations in the eye liquids, including tear fluid (TF). Although TF can be collected by a non-invasive procedure and may serve as a source of the appropriate biomarkers, its multi-omics analysis is technically sophisticated and unsuitable for clinical practice. In this study, we tested a novel concept of glaucoma diagnostics based on the rapid high-performance analysis of the TF proteome by differential scanning fluorimetry (nanoDSF). An examination of the thermal denaturation of TF proteins in a cohort of 311 ophthalmic patients revealed typical profiles, with two peaks exhibiting characteristic shifts in POAG. Clustering of the profiles according to peaks maxima allowed us to identify glaucoma in 70% of cases, while the employment of artificial intelligence (machine learning) algorithms reduced the amount of false-positive diagnoses to 13.5%. The POAG-associated alterations in the core TF proteins included an increase in the concentration of serum albumin, accompanied by a decrease in lysozyme C, lipocalin-1, and lactotransferrin contents. Unexpectedly, these changes were not the only factor affecting the observed denaturation profile shifts, which considerably depended on the presence of low-molecular-weight ligands of tear proteins, such as fatty acids and iron. Overall, we recognized the TF denaturation profile as a novel biomarker of glaucoma, which integrates proteomic, lipidomic, and metallomic alterations in tears, and monitoring of which could be adapted for rapid non-invasive screening of the disease in a clinical setting.

A modern-day experience with Brunschwig's operation: Outcomes associated with pelvic exenteration.

OBJECTIVE: To evaluate postoperative and oncologic outcomes associated with pelvic exenteration for non-ovarian gynecologic malignancies. METHODS: This was a retrospective review of patients who underwent pelvic exenteration for non-ovarian gynecologic malignancies at our institution from 1/1/2010-12/31/2019. Palliative exenteration cases were excluded from survival analysis. Postoperative complications were early (≤30 days) or late (31-180 days). Complications were graded using a validated institutional scale. Major complications were considered grade ≥ 3. Categorical variables were compared using the chi-square test, and the Kaplan-Meier method was used for survival analysis. RESULTS: Of 100 patients identified, 89 underwent pelvic exenteration for recurrent disease, 5 for palliation, 5 for primary disease, and 1 for persistent disease. Thirty percent had cervical, 27% vulvar, 24% uterine, and 19% vaginal cancer. Sixty-two percent underwent total, 30% anterior, and 8% posterior exenteration. No deaths occurred intraoperatively or within 30 days of surgery. Six patients died after 30 days. Ninety-seven experienced a perioperative complication-49 early, 1 late, and 47 both. Fifty experienced a major complication-22 (44%) early, 19 (38%) late, and 9 (18%) both. No variables were statistically associated with complication development. The 3-year progression-free survival rate was 61.0%; the 3-year overall survival rate was 61.6%. Of 58 surviving patients, 16 (28%) and 4 (7%) were alive after 5 and 10 years, respectively. CONCLUSION: The overall complication rate for pelvic exenteration remains high. No variables demonstrated association with complication development as the rate was nearly 100%. The low rate of perioperative mortality is likely due to improved perioperative care.

Safety and efficacy of an outpatient 12-step desensitization protocol for antineoplastic agents.

OBJECTIVE: Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to re-introduce agents after the development of a hypersensitivity reaction, these protocols vary across institutions. Our study evaluated the safety and efficacy of our desensitization protocol. METHODS: All patients who underwent desensitization to platinum, taxane, liposomal doxorubicin, or trastuzumab between November 2016 and May 2021 after a prior hypersensitivity reaction to the specific agent were included in a retrospective review. The 12-step, outpatient desensitization protocol included pretreatment with a leukotriene receptor antagonist, antihistamines, and corticosteroids, as well as extended infusion times. Successful desensitization was defined as the completion of ≥3 cycles without discontinuation of the agent due to a hypersensitivity reaction. RESULTS: A total of 186 eligible patients were included. Median age was 59.5 years (range 26-87). 155 (83%) patients were treated with platinum. 55 (30%) patients were treated for colorectal cancer and 52 (28%) for ovarian cancer. 104 (56%) patients completed ≥3 cycles of therapy during desensitization. The median infusion time was 380 min (range 325-360 min). The median number of desensitization cycles was 3, with 694 cycles completed among all patients. A total of 79 (42%) patients had a breakthrough hypersensitivity reaction during desensitization, 4 of whom required epinephrine, and 84 (45%) patients discontinued the agent undergoing desensitization due to progression of disease. CONCLUSIONS: Our outpatient 12-step, institutional desensitization protocol for antineoplastic therapy proved safe and efficacious, with 56% of patients successfully completing ≥3 cycles and not requiring an inpatient admission.

Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer.

OBJECTIVES: To determine whether the Memorial Sloan Kettering Frailty Index (MSK-FI) is associated with decision-making in older women surgically treated for advanced-stage ovarian cancer. METHODS: We retrospectively applied the MSK-FI to women ≥70 years with newly diagnosed advanced-stage ovarian cancer surgically treated at our institution from 01/2001-05/2017. MSK-FI components, including 10 comorbidities and functional assessment, were extracted from medical records. The MSK-FI ranges from 0 to 11, with higher scores indicating greater frailty. The primary outcome was the association between frailty and rate of primary debulking surgery (PDS), for which a multivariable logistic regression was used, adjusted for stage and histology. RESULTS: We identified 430 women treated with PDS (n = 231, 54%) or neoadjuvant chemotherapy/interval debulking (n = 199, 46%) with complete data. MSK-FI score distribution was: "0", 95 patients (22%); "1", 172 (40%); "2", 89 (21%); and "3+", 74 (17%). More-frail patients were less likely to have undergone PDS (OR for a unit increase of MSK-FI: 0.64; 95%CI, 0.53-0.77; p < 0.0001). Grade 3+ complications and unintended intensive care admission occurred in 40 (9%) and 38 (9%) women, respectively, but were not associated with frailty (OR 1.21; 95%CI, 0.96-1.52; p = 0.11). More-frail patients were more likely to delay postoperative chemotherapy (non-linear association p = 0.009) and less likely to enroll in research (OR 0.84; 95%CI, 0.70-1.00; p = 0.049). Greater frailty was associated with poorer overall survival (HR 1.16; 95%CI, 1.05-1.30; p = 0.005). CONCLUSIONS: Frailty, as calculated by the MSK-FI, is strongly associated with treatment approach in older women with advanced ovarian cancer, suggesting objective or subjective correlates of the MSK-FI influence decision-making.

Pelvic exenteration for recurrent or persistent gynecologic malignancies: Clinical and histopathologic factors predicting recurrence and survival in a modern cohort.

OBJECTIVES: To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. METHODS: A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. RESULTS: Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28-86 years). Vulvar cancer was the most common primary diagnosis (32%); 30% had cervical cancer; 23%, uterine cancer; 15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1-116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27-5.79), American Society of Anesthesia (ASA) 3-4 (HR: 3.41 (95% CI 1.03-11.29), and vulvar cancer (HR 4.19 (95% CI 1.17-14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. CONCLUSIONS: PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration.

Molecular characterization of high-grade serous ovarian cancers occurring in younger and older women.

OBJECTIVES: To determine if the mutational landscapes and genomic features of homologous recombination DNA repair defects (HRD) vary between younger and older patients with high-grade serous ovarian cancer (HGSOC). METHODS: Younger and older women were defined as bottom and top age quartiles, respectively. HGSOCs from 15 younger (median 49 years, range 35-53) and 15 older women (median 72 years, range 70-87) were subjected to whole-exome sequencing (WES). For validation, HGSOC WES data were obtained from The Cancer Genome Atlas (TCGA), including 38 younger (median 45 years, range 34-50) and 30 older women (median 74 years, range 68-84). Mutational profiles, BRCA1/2 status, genomic HRD features, and for TCGA cases RNA-sequencing-based HRD transcriptomic signatures were assessed. RESULTS: In the institutional cohort, pathogenic germline BRCA1/2 mutations were more frequent in younger (5/15) than older women (0/15, p = 0.042). No somatic BRCA1/2 mutations were identified. HGSOCs from older patients preferentially displayed aging-related mutational signatures and, in contrast to younger patients, harbored CCNE1 amplifications (3/15, 20%). In the TCGA cohort, pathogenic germline BRCA1 (younger 8/38, older 0/30, p = 0.007) but not BRCA2 mutations (young 3/38, older 4/30, p = 0.691) were more frequent in younger patients. Again, no somatic BRCA1/2 mutations were identified. HGSOCs from younger women more frequently displayed genomic features of HRD (all, p < 0.05), a significant HRD gene-signature enrichment, but less frequently CCNE1 amplification (p = 0.05). Immunoreactive CLOVAR subtypes were more common in HGSOCs from younger women, and proliferative subtypes in HGSOCs from older women (p = 0.041). CONCLUSIONS: HGSOC patients diagnosed at an older age less frequently harbor pathogenic BRCA1 germline mutations and genomic features of HRD than younger women. Individualized treatment options, particularly pertaining to use of PARP inhibitors, in older women may be warranted.

Survival outcomes of acute normovolemic hemodilution in patients undergoing primary debulking surgery for advanced ovarian cancer: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVE: To describe oncologic outcomes after using acute normovolemic hemodilution (ANH) to reduce requirement for allogenic red blood cell transfusions (ABT) in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer. METHODS: We performed a post-hoc analysis of a recent prospective trial investigating the safety and feasibility of ANH during PDS for advanced ovarian cancer. We report long-term survival outcomes. We compared demographics, clinicopathological characteristics, survival outcomes in this cohort of Stage IIIB-IVB high-grade serous ovarian cancer patients undergoing ANH (ANH group), with a retrospective cohort of all other patients (standard group) undergoing PDS during the same time period (01/2012-04/2017). Standard statistical tests were used. RESULTS: There were no demographic or clinicopathological differences between ANH (n = 33) and standard groups (n = 360), except for higher median age at diagnosis (57 vs. 62 years, respectively; p = 0.044) and shorter operative time (357 vs. 446 min, respectively; p < 0.001) in the standard group. Cytoreductive outcomes (ANH vs. standard): 0 mm, 69.7 vs. 63.9%; gross residual disease (RD) ≤1 cm, 21.2 vs. 26.9%; >1 cm, 9.1 vs. 9.2% (p = 0.78). RD after PDS was the only independent factor associated with worse progression-free survival (PFS) on multivariable analysis (p < 0.001). Patients with BRCA mutations trended towards improved PFS (p = 0.057). Significant factors for overall survival (OS) on multivariable analysis: preoperative CA125 (p = 0.004), ascites (p = 0.018), RD after PDS (p = 0.04), BRCA mutation status (p < 0.001). After adjustment for potential confounders, ANH was not independently associated with PFS or OS [PFS: HR 0.928 (0.618-1.395); p = 0.721; OS: HR 0.588 (95%CI: 0.317-1.092); p = 0.093]. CONCLUSIONS: ANH is an innovative approach in intraoperative management. It was previously proven to decrease need for ABT while maintaining the ability to achieve complete gross resection and associated benefits.

Prioritising earthquake retrofitting in Wellington, New Zealand.

This study describes the application of multi-criteria decision analysis (MCDA) to prioritise the seismic risk mitigation of existing buildings in earthquake-prone Wellington, New Zealand. Through retrofitting or demolition, this is an important requirement in many cities around the Pacific Rim and in other high-level seismic hazard locations. The prioritisation strategy proposed here, based on MCDA methods, can provide decision-makers with a fast and reliable support tool for identifying the optimal sequencing of their retrofitting programmes. The premise of the MCDA analysis presented in this paper is that there are multiple criteria that determine societal prioritisation preferences; these are limited not just to life safety (often the explicit/exclusive priority of governments) and commercial value (the main concern of many building owners). The study demonstrates how different measures, within four general criteria-life safety and geo-spatial, economic, and socio-cultural roles-can be operationalised as a viable framework for establishing intervention policy priorities.

Video-assisted thoracic surgery in the primary management of advanced ovarian carcinoma with moderate to large pleural effusions: A Memorial Sloan Kettering Cancer Center Team Ovary Study.

OBJECTIVES: We assessed the utility of video-assisted thoracic surgery (VATS) in defining extent of intrathoracic disease in advanced ovarian carcinoma with moderate-to-large pleural effusions. METHODS: Beginning in 2001, VATS was performed on all patients with suspected advanced ovarian carcinoma and moderate-to-large pleural effusions, evaluating for macroscopic intrathoracic disease. The algorithm recommended primary debulking surgery (PDS) for ≤1 cm, neoadjuvant chemotherapy (NACT)/interval debulking surgery (IDS) for >1 cm intrathoracic disease. We reviewed records of patients undergoing VATS from 10/01-01/19. Differences between treatment groups were tested using standard statistical techniques. RESULTS: One-hundred patients met eligibility criteria (median age, 60; median CA-125 level, 1158 U/mL; medium serum albumin, 3.8 g/dL). Macroscopic pleural disease was found in 70 (70%). After VATS, 50 (50%) underwent attempted PDS (PDS group), 50 (50%) received NACT (NACT/IDS group). Forty-seven (94%) underwent IDS. Median overall survival (OS) for the entire cohort (n = 100) was 44.5 months (95% CI: 37.8-51.7). The PDS group had significantly longer survival than the NACT/IDS group [45.8 (95% CI: 40.5-87.8) vs. 37.4 months (95% CI: 33.3-45.2); p = .016]. On multivariable analysis, macroscopic intrathoracic disease (HR 2.18, 95% CI: 1.14-4.18; p = .019) and age ≥ 65 (HR 1.98, 95% CI: 1.16-3.40; p = .013) were independently associated with elevated death risk. Patients with the best outcome had no macroscopic disease at VATS and underwent PDS (median OS, 87.8 months). CONCLUSIONS: VATS is useful in therapeutic decision-making for PDS vs. NACT/IDS in advanced ovarian cancer with moderate-to-large pleural effusions.

Role of delayed interval debulking for persistent residual disease after more than 5 cycles of chemotherapy for primary advanced ovarian cancer. An international multicenter study.

BACKGROUND: Standard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3-4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a "delayed" interval debulking surgery (DID) is poorly defined. METHODS: We analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. RESULTS: 308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5-9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34-561), the median surgical complexity score was 4 (range 1-16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0-5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1-10 mm) compared to residual disease >1 cm. CONCLUSION: Our data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

A multimodality triage algorithm to improve cytoreductive outcomes in patients undergoing primary debulking surgery for advanced ovarian cancer: A Memorial Sloan Kettering Cancer Center team ovary initiative.

OBJECTIVE: To describe outcomes using a multimodal algorithm to triage patients with advanced epithelial ovarian cancer (EOC) to primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT). METHODS: All patients with EOC treated at our institution from 04/2015-08/2018 were identified. We included patients without contraindication to PDS who underwent prospective calculation of a Resectability (R)-score. A low risk score for suboptimal cytoreduction was defined as ≤6, and a high risk score ≥7. Patients were triaged to laparotomy/PDS, laparoscopic evaluation of resectability (LSC), or NACT depending on R-score. RESULTS: Among 299 participants, 226 (76%) had a low risk score and 73 (24%) a high risk score. For patients with a low risk score, management included laparotomy/PDS, 181 (80%); LSC, 43 (19%) (with subsequent triage: PDS, 31; NACT, 12); and NACT, 2 (1%). For patients with a high risk score, management included laparotomy/PDS, 9 (12%); LSC, 51 (70%) (with subsequent triage: PDS, 28; NACT, 23); and NACT, 13 (18%). Overall, 83% underwent PDS, with a 75% CGR rate and 94% optimal cytoreduction rate. Use of the algorithm resulted in a 31% LSC rate and a 6% rate of suboptimal PDS. CONCLUSIONS: The multimodal algorithm led to excellent surgical results; 94% of patients achieved an optimal resection, with a very low rate of suboptimal cytoreduction.

Hematologic changes after splenectomy for ovarian cancer debulking surgery, and association with infection and venous thromboembolism.

INTRODUCTION: The spleen plays a role in the immune and coagulative responses, yet a splenectomy may be required during ovarian cancer surgery to achieve complete cytoreduction. The aim of the study was to correlate hematologic changes with the development of infection and venous thromboembolism in patients undergoing splenectomy. METHODS: This single-institution retrospective review includes all patients undergoing splenectomy during cytoreductive surgery for advanced ovarian cancer, March 2001 to December 2016. We compared postoperative hematologic changes (evaluated daily before discharge) in patients developing infection within 30 days' post-surgery (Infection group) with those who did not (No-Infection group). We also compared patients developing venous thromboembolism with those without. RESULTS: A total of 265 patients underwent splenectomy. Median age was 64 years (range 22-88): 146 (55%) patients had stage IIIC and 114 (43%) patients had stage IV. The majority, 201 (76%) patients underwent splenectomy during primary debulking. A total of 132 (50%) patients comprised the Infection group (most common: urinary tract infection, 54%). Median time from surgery to infection was 8 days (range, 0-29). After initial rise in white blood cell count in both groups, the Infection group had a second peak on postoperative day 10 (median 16.6K/mcL, IQR 12.5-21.2) not seen in the No-Infection group (median 12K/mcL, IQR 9.3-16.3). A total of 40 (15%) patients developed venous thromboembolism, median time of 6.5 days (range, 1-43). All patients demonstrated a continuous rise in platelets during postoperative days 0-15. Thrombocytosis was present in 38/40 (95%) patients with venous thromboembolism vs 183/225 (81%) patients without (P=0.036). Median days with thrombocytosis was higher in venous thromboembolism (8 days, range 1-15) vs non groups (6 days, range 1-16, P=0.049). CONCLUSION: We identified initial leukocytosis after splenectomy in all patients. The Infection group had a second peak in white blood cell count on postoperative day 10, not present in the No-Infection group. Among patients with venous thromboembolism, thrombocytosis was more frequent and of longer duration.

Delays from neoadjuvant chemotherapy to interval debulking surgery and survival in ovarian cancer.

INTRODUCTION: Delays from primary surgery to chemotherapy are associated with worse survival in ovarian cancer, however the impact of delays from neoadjuvant chemotherapy to interval debulking surgery is unknown. We sought to evaluate the association of delays from neoadjuvant chemotherapy to interval debulking with survival. METHODS: Patients with a diagnosis of stage III/IV ovarian cancer receiving neoadjuvant chemotherapy from July 2015 to December 2017 were included in our analysis. Delays from neoadjuvant chemotherapy to interval debulking were defined as time from last preoperative carboplatin to interval debulking >6 weeks. Fisher's exact/Wilcoxon rank sum tests were used to compare clinical characteristics. The Kaplan-Meier method, log-rank test, and multivariate Cox Proportional-Hazards models were used to estimate progression-free and overall survival and examine differences by delay groups, adjusting for covariates. RESULTS: Of the 224 women, 159 (71%) underwent interval debulking and 34 (21%) of these experienced delays from neoadjuvant chemotherapy to interval debulking. These women were older (median 68 vs 65 years, P=0.05) and received more preoperative chemotherapy cycles (median 6 vs 4, P=0.003). Delays from neoadjuvant chemotherapy to interval debulking were associated with worse overall survival (HR 2.4 95% CI 1.2 to 4.8, P=0.01), however survival was not significantly shortened after adjusting for age, stage, and complete gross resection, HR 1.66 95% CI 0.8 to 3.4, P=0.17. Delays from neoadjuvant chemotherapy to interval debulking were not associated with worse progression-free survival (HR 1.55 95% CI 0.97 to 2.5, P=0.062). Increase in number of preoperative cycles (P=0.005) and lack of complete gross resection (P<0.001) were the only variables predictive of worse progression-free survival. DISCUSSION: Delays from neoadjuvant chemotherapy to interval debulking were not associated with worse overall survival after adjustment for age, stage, and complete gross resection.

Earthquake-strengthening policy for commercial buildings in small-town New Zealand.

New Zealand introduced a seismic retrofitting policy in the wake of the catastrophic Canterbury earthquakes of 2010-11. The aim was to enforce seismic strengthening of earthquake-prone commercial buildings throughout the country. This study focuses on regional urban centres and the economic obstacles to strengthening their aging building stock. In investigating one town, Whanganui, we describe conditions, analyse cases, and identify incentives that apply equally to many other towns in New Zealand. We argue that incentives that suit high-growth, high-value major urban centres are a poor fit for the periphery. Around the world, many places need to upgrade their privately-owned building stock to protect it from disasters, while governments face similar challenges as they struggle to initiate the strengthening of commercial buildings. We analyse the current incentive schemes that aim to support the achievement of policy goals and suggest alternative incentive schemes that can be implemented to improve strengthening outcomes.

Geriatric co-management leads to safely performed cytoreductive surgery in older women with advanced stage ovarian cancer treated at a tertiary care cancer center.

OBJECTIVE: To assess fitness and outcomes in older women undergoing cytoreductive surgery for advanced ovarian cancer (OC). METHODS: A prospective study of OC patients referred to Geriatrics Clinic for preoperative evaluation. All completed the electronic Rapid Fitness Assessment (eRFA) and were followed by Geriatrics Service during inpatient postoperative course, co-managed by Surgical Service. Outcomes were 30-day Intensive Care Unit (ICU) admission, emergency room (ER) visit, readmission, mortality, adverse surgical events. Descriptive statistics were used. RESULTS: Forty-two women (median age 79, range 74-88), 38 with newly diagnosed advanced OC, 4 with recurrent OC, underwent cytoreductive surgery between 5/2015 and 1/2018. Preoperative age-related impairments per eRFA: high level of distress (71%), functional dependency (59%), limited social activity (59%), depression (57%), slow Time Up and Go (54%), Karnofsky Performance Score (KPS) ≤ 80 (41%), poor social support (43%), polypharmacy (35%), weight loss>10 lbs. (25%), fall history (244%), cognitive impairment (13%). Median number of comorbid conditions = 3. Among 38 newly diagnosed women, 26 (68%) had stage IIIC, 11 (29%) stage IV. Sixteen (42%) underwent primary debulking surgery, 22 (58%) neoadjuvant chemotherapy followed by interval debulking surgery. Median duration of surgery = 245.5 min (range 95-621); median hospital length of stay = 6 days (range 0-22). Optimal debulking rate = 97%, complete gross resection rate = 63%. One patient was admitted to ICU, 26% had 30-day ER visit, 10% were readmitted. Any complication, minor complication, major complication occurred in 58%, 55%, 8%, respectively. Median time from surgery to postoperative chemotherapy = 34.5 days (range 19-66). Median follow-up = 15.7 months (range 3.7-38.0), 12-month survival = 93.3%. There was no 180-day mortality. CONCLUSION: Cytoreductive surgery among older women with advanced OC and frailty can be performed safely in a tertiary care center with preoperative/postoperative geriatric and surgical co-management.

Prognostic significance of supraclavicular lymphadenopathy in patients with high-grade serous ovarian cancer.

OBJECTIVES: To assess outcomes and patterns of recurrence in patients with high-grade serous ovarian/tubal/primary peritoneal cancers with radiographic supraclavicular lymphadenopathy at diagnosis. METHODS: We evaluated all patients with newly diagnosed high-grade serous ovarian cancers treated at our center between January 1, 2008 and May 1, 2013 who had supraclavicular lymphadenopathy (defined as ≥1 cm in short axis) on radiographic imaging (either computed tomography or positron emission tomography) at the time of diagnosis. RESULTS: Of 586 patients with high-grade serous ovarian cancer receiving primary treatment during the study period, we identified 13 (2.2%) with supraclavicular lymphadenopathy diagnosed on pre-treatment imaging. The median age at diagnosis was 52.0 years (range 38.2-72.3). Five (31%) had clinically palpable nodes on physical examination. Four (31%) had a known BRCA mutation. All 13 patients underwent neoadjuvant chemotherapy, followed by interval debulking surgery. Each patient received a median of four cycles of neoadjuvant intravenous chemotherapy (range 3-7). At interval debulking surgery, complete gross resection was achieved in nine (70%) patients, and optimal resection (0.1-1 cm residual disease) in four (30%). Eleven patients (85%) recurred; however, only one (8%) recurred in the supraclavicular lymph nodes. Median follow-up time was 44.3 months (range 22.4-95.0). Median progression-free survival for the cohort was 11.7 months (95% CI 9.2 to 14.1). Median overall survival was 44.3 months (95% CI 41.5 to 47.1). In patients obtaining complete gross resection at interval debulking surgery, median progression-free survival and overall survival were 13.9 months (95% CI 8.9 to 18.9) and 78.1 months (95% CI 11.1 to 145.1), respectively. CONCLUSIONS: In our study, approximately 2% of patients with high-grade serous ovarian cancer presented with radiographic evidence of supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy at diagnosis did not portend an unfavorable outcome when complete gross resection was achieved at interval debulking surgery.

It's time to warm up to hyperthermic intraperitoneal chemotherapy for patients with ovarian cancer.

The peritoneal spread of ovarian cancer makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Intraperitoneal delivery exposes the tumor to concentrations of cytotoxic drugs much greater than with intravenous delivery, and in vitro studies have also shown that combining hyperthermia and platinum leads to an additive cytotoxic effect. Pharmacokinetic analyses have confirmed very high concentrations of cytotoxic drugs in the peritoneal cavity, with minimal systemic exposure and toxicity. The majority of historical data evaluating HIPEC in ovarian cancer are based on retrospective research, which included heterogeneous groups of patients and drugs used for HIPEC. Recent publications on the findings of prospective studies, including the first randomized trial in which the only difference in intervention was the addition of HIPEC with cisplatin to interval debulking surgery in stage III patients, have shown a benefit in favor of HIPEC. Yet, a recent prospective study from Korea did not find a benefit. Opponents of HIPEC have cited higher rates of complications with this approach, yet most of the serious adverse events observed are likely related to the surgery itself, and are comparable to the rates reported in studies evaluating cytoreductive surgery without HIPEC. Findings from a recent randomized controlled trial showed no delays in initiation or completion of postoperative chemotherapy in patients treated with HIPEC. A growing body of evidence is indicating that it might be time to seriously consider HIPEC as a complementary treatment at the time of cytoreductive surgery for patients with advanced-stage ovarian cancer in the setting of an experienced center. Yet, more research is needed to identify the population of patients who gain the most benefit from this therapy.