International Multicenter Database Research Articles

The ISSPP PIPAC database: design, process, access, and first interim analysis.

ObjectivesSeveral trials have documented the favorable safety profile, and promising clinical results of pressurized intraperitoneal aerosol chemotherapy (PIPAC) directed treatment in different types of peritoneal malignancies. However, until the results of randomized trials are available, the quality of documentation and acceptance by the users may be improved through a worldwide registry. The International Society for the Study of Pleura and Peritoneum (www.ISSPP.org) facilitated this process by creating a dedicated focus group and providing the funding needed for the creation and implementation of an international database. This article describes the design and the journey of establishing this international database and the first, preliminary results from the ISSPP PIPAC online database.MethodsIn 2019 the ISSPP PIPAC Registry Group started to create a database with a minimal dataset relevant to many diseases and applicable in different framework conditions. The task was divided into three phases including design, testing, implementation, protocol, handbook, legal requirements, as well as registry rules and bylaws for the registry group.ResultsThe ISSPP PIPAC online database has six key elements (patient, consent, treatment, complications, response evaluation and follow-up). Following design, testing and implementation the database was successfully launched in June 2020. Ten institutions reported on 459 PIPAC procedures in 181 patients during the first 6 months, and the recorded data were comparable to the present literature.ConclusionsA new international multicenter PIPAC database has been developed, tested and implemented under the auspices of ISSPP. The database is accessible through the ISSPP website (www.ISSPP.org), and PIPAC institutions worldwide are highly encouraged to participate.

Development and validation of an individualized prediction calculator of postoperative mortality within 6 months after surgical resection for hepatocellular carcinoma: an international multicenter study.

Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6months following resection. Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves. Independent factors associated with death within 6months of surgery included age, Child-Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542-0.748). An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.

Nomogram to Predict the Risk of Recurrence after Curative Liver Resection for Neuroendocrine Liver Metastasis

Introduction: We sought to develop and externally validate a novel nomogram to predict recurrence and long-term prognosisof patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM). Methods: Patients who underwent curative liver resection for NELM were identified from an international multicenter database between 1980-2015. A nomogram to predict recurrence was developed and validated externally. Results: Among 279 patients with NELM who underwent resection, multivariable analysis identified primary tumor location(pancreatic vs. others, HR 2.1, 95% CI 1.3-3.4), tumor grade(moderate vs. well, HR 1.9, 95% CI 1.1-3.1; poor vs. well, HR 1.6, 95% CI 0.7-3.3), lymphatic metastasis (HR 2.6, 95% CI 1.4-4.6) and the type of hepatectomy(major resection vs. parenchymal-sparingresection, HR 0.3, 95% CI 0.1-0.6) to be independently associated with recurrence-free survival (RFS). A weighted nomogram was constructed based on the beta-coefficients of the final multivariable model. The nomogram demonstrated a good ability to predict risk of recurrence in both test and external validation cohorts (c-index; test cohort: 0.754; validation cohort: 0.748).Specifically, the calibrated nomogram predicted survival that closely corresponded to actual survival with a good net benefit for most threshold probabilities especially between 20% to 60% in both the development and validation cohorts. Conclusions: A novel nomogram predicted recurrence-free survival rates for patients with NELM with excellent discrimination and calibration. The proposed nomogram may be helpful to discuss with patients their anticipated prognosis following resection of NELM.

Bile Leakage after Laparoscopic and Open Liver Resection; Incidence and Clinical Impact: An International Multicenter Propensity Score-matched Study of 13,379 Patients

Purpose: Despite many developments, postoperative bile leakage (POBL) remains a relatively common postoperative complication after laparoscopic liver resection (LLR) and open liver resection (OLR). Previous studies regarding the incidence and clinical impact of POBL have mainly focused on patients undergoing OLR. The aim of this study is to compare the incidence and clinical impact of POBL between patients undergoing LLR and OLR in a large international multicenter cohort using a propensity score matched analysis. Methods: Patients undergoing LLR or OLR for all indications between January 2000 and October 2019 were analyzed using a large, international multicenter liver database including data from 15 tertiary referral centers. Primary outcome was clinically relevant POBL (CR-POBL), defined as Grade B/C POBL. Patients were matched based on propensity scores in a 1 : 1 ratio. The incidence and clinical impact of POBL were compared between LLR and OLR after propensity score matching (PSM). Results: Overall, 13,379 patients met the inclusion criteria and were included in the analysis (6,369 LLR and 7,010 OLR), with 6.0% POBL. After PSM, a total of 3,563 LLR patients were matched to 3,563 OLR patients. POBL occurred in 405 patients (5.6%), including 121 patients after LLR (3.4%) and 284 patients after OLR (8.8%) (P<0.001). The incidence of CR-POBL was significantly lower in patients after LLR as compared to patients after OLR (2.6% vs. 6.4%; P<0.001). Among the subgroup of patients with CR-POBL, patients after LLR experienced less severe (non-POBL) postoperative complications (10.1% vs. 20.9%; P=0.028), less surgical site infections (4.4% vs. 17.9%; P=0.002), a shorter hospital stay (12.5 vs. 17 days; P=0.001), and a lower 90-day/in-hospital mortality (0% vs. 5.4%; P=0.027) as compared to patients after OLR with CR-POBL. Conclusions: This international multicenter study shows that LLR is associated with a lower rate of CR-POBL as compared to the open approach. Our findings demonstrate that in patients with CR-POBL, those after LLR experience a less impactful postoperative course as compared to patients after OLR. A further stepwise implementation of LLR into daily clinical practice may be encouraged to improve outcomes of liver surgery.

Immediate Versus Delayed Cord Clamping in Management of Placenta Accreta Spectrum: Secondary Analysis of Multicenter International Study

Objective: To compare maternal and neonatal outcomes of immediate versus delayed cord clamping in women with placenta accreta spectrum (PAS). Study Design: PAS-ID is an international retrospective multicenter database originating from 11 centers (9 countries), which included women with confirmed PAS between January 1st, 2010 and December 31st, 2019. Women were considered eligible to this study if diagnosis of PAS was confirmed, women were adequately followed ante- and postpartum. Women with intrauterine fetal death were excluded. Primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥ 2500 ml, bleeding associated massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Secondary outcomes include 1-minute, 5-minute APGAR scores, and admission to neonatal intensive care unit (NICU). Multivariable logistic regression was used for analysis and results were presented as adjusted odds ratios (aOR) and 95% confidence interval (CI). Results: Out of 797 women, 716 met our inclusion criteria. Of these women, 120 underwent delayed cord clamping (16.76%). After adjustment for potential confounders, delayed cord clamping was associated with lower risk of massive blood loss (aOR 0.26, 95% CI 0.11 – 0.63) and admission to NICU (aOR 0.45, 95% CI 0.29 - 0.87). It was not associated with lower risk of 1 minute APGAR < 7 (aOR 1.88, 95% CI 0.92 - 3.85) or 5-minute APGAR < 7 (aOR 0.67, 95% CI 0.21 - 2.10). Conclusion: Delayed cord clamping does not seem to increase risk of PAS-associated massive blood loss. However, maternal, and neonatal stability should be considered before a decision can be made. Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: The authors have no conflicts of interest. Ethics Approval Statement: Ethical approval was obtained in each contributing center from their receptive institutional review board before the study was conducted. This includes Aswan University, Egypt (Ethics Committee on Feb 11th, 2020, reference N; Aswu/439/2/20), Inonu University (reference number: 2020/476, dated 3/3/2020), Yuzuncu yil University (reference number: 55163642-100-E.36909, dated 09/06/2020), and Ege University (reference number: 20-4.1 T/3, dated 14/4/2020) in Turkey, Fatima memorial hospital/College of Medicine, and Dentistry, Pakistan (reference number: FMH-03-2020-IRB747-M, dated 5/12/2020), Kazan State University, Russia (reference number: 1765, dated 30/6/2020), Centro Hospitalar Sao Joao, Portugal (reference number: 76/2020, dated 21/5/2020), National Taiwan University College of Medicine, Taiwan (reference number: 202003007RINC, dated 30/3/2020), Faculty of Medicine of University of Yaounde I, Cameroon (reference numbers: 1019/CIERSH/DM/2020, dated 25/2/2020). Both Peking University Shenzhen Hospital and Universitas Padjadjaran Bandung were waived for the minimal risk per their local hospital policies. All data were anonymized and authorized for use before submission for analysis.

Robot-assisted partial nephrectomy: 7-year outcomes.

BACKGROUND The role of robot-assisted partial nephrectomy (RAPN) in the management of renal masses has exponentially grown over the past 10 years. Nevertheless, data on long term outcomes of the procedure remains limited. Herein we report oncological and functional outcomes of patients who underwent RAPN for a malignant mass with a median follow-up of 7 years, the longest follow-up to date. METHODS A retrospective analysis of an international multicenter database was performed. All consecutive patients undergoing surgery between 2009 and 2013 with a minimum of 3-year follow-up and complete data on renal function were included. Demographics, surgical and perioperative outcomes were analyzed. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analysis. RESULTS Overall, our study cohort was composed of eighty-five patients with a median follow-up of 88 months. Median clinical tumor size was 3 cm, with mostly (74.1%) clinical stage T1a, and median RENAL score 6. Final histopathologic analysis revealed clear cell RCC in 76.5% of cases. PSM was present in seven patients (8.2%). Eleven overall deaths (12.9%) occurred in the cohort during the follow-up period. Two of these (2.33%) were attributed to metastatic RCC. The OS, CSS, and DFS rates were 91.7%, 97.7%, and 91.7% at 84 months, respectively. Regarding the renal functional outcomes, seventeen patients (20.1%) presented a CKD upstaging in our cohort. CONCLUSIONS Our findings show excellent 7-year oncologic and functional outcomes of the procedure, which duplicate those achieved in historical series of open and laparoscopic surgery.

Association Between Human Papillomavirus Infection and Outcome of Perioperative Nodal Radiotherapy for Penile Carcinoma

BackgroundData on the impact of human papillomavirus (HPV) infection status and outcomes for perioperative treatments for patients with lymph node–involved penile squamous-cell carcinoma (PSCC) are lacking. ObjectiveTo analyze the benefit from perioperative radiotherapy (RT) for PSCC according to HPV infection status. Design, setting, and participantsIn an international multicenter database of 1254 patients with PSCC who received inguinal lymph node dissection (ILND), 507 had suitable clinical information. InterventionILND, with or without chemotherapy or RT for involved lymph nodes. Outcome measurements and statistical analysisKaplan-Meier and restricted mean survival time (RMST) analyses for overall survival (OS) were performed for all patients and after propensity score-matching (PSM; n = 136), for which patient age, histology, type of penile surgical procedure, pathological tumor and nodal stage, ILND laterality, pelvic LND, and perioperative treatment were taken into account when assessing differences between HPV+ and HPV– patients. Finally, we looked at genomic alterations in PSCC using data from the Foundation Medicine database (n = 199) to characterize HPV+ PSCC. Results and limitationsPatients with HPV+ PSCC (n = 86; 17%) had lower clinical N stage (p < 0.001) and inguinal lymph node metastasis density (p < 0.001). Perioperative RT was delivered in 49 patients (9.7%), with the vast majority receiving adjuvant RT (n = 40). HPV+ patients had similar median OS (p = 0.1) but longer RMST than HPV– patients at different time points. Nevertheless, HPV+ patients treated with perioperative RT exhibited longer median OS (p = 0.015) and longer RMST compared to HPV– patients. In the PSM cohorts, HPV+ status remained significantly associated with longer OS after RT. The HPV– PSCC group had a higher frequency of TP53 mutations compared to HPV+ PSCC (75% vs 15%; p < 0.001). The results are limited by the retrospective nature of the data. ConclusionsPerioperative RT was more effective in the HPV+ PSCC subgroup. Reasons for the enhanced radiosensitivity may be related to the lack of TP53 mutations. Patient summaryWe analyzed data from a large multicenter database for patients with penile cancer who had received inguinal lymph node dissection, with or without chemotherapy or radiotherapy. We found that for tumors positive for human papillomavirus (HPV), use of radiotherapy resulted in prolonged survival compared to HPV-negative tumors. On the basis of these results we are inspired to design studies on the use of radiotherapy in HPV-selected patients.

Does thoracoplasty adversely affect lung function in complex pediatric spine deformity? A 2-year follow-up review.

Retrospective review of prospective multi-center cohort. To investigate the impact of thoracoplasty on pulmonary function at 2-year follow-up among complex pediatric spine deformity patients. Complex pediatric spine deformities may be associated with significant rib prominence causing body image concerns. Surgical correction of spine deformity may include thoracoplasty to correct the rotational prominence. Some surgeons refrain from performing thoracoplasty due to its purported negative effect on pulmonary function. There is paucity of literature on the effect of thoracoplasty on pulmonary function at 2-year follow-up in pediatric patients with complex spine deformity. We reviewed data of 312 patients (> 100°, with or without vertebral column resection (VCR)) or (< 100° with VCR)) from an international multicenter database. Data of 106 patients with complete radiographic and pulmonary function test (PFT) assessment with a minimum of 2-year follow-up was analyzed. Paired t test was performed to compare pre-op and 2-year PFT results. PFT comparison was stratified based on thoracoplasty status (thoracoplasty: Group 1 vs. no thoracoplasty: Group 2). 106 patients (61 patients Group 1 vs. 45 in Group 2). The average age and gender ratio were similar in both groups (p > 0.05). Group 1 had significantly lower body mass index (BMI) compared to Group 2 (18.4kgm-2 ± 2.8 vs. 19.9kgm-2 ± 4.8, p = 0.0351). The average baseline coronal and sagittal Cobbs were larger for Group 1 relative to Group 2 (p <0.05). The distribution of deformity etiology and curve types, and apices were similar between the two groups (p > 0.05). The rate of pre-op utilization of halo gravity traction (HGT) was 52.5% vs. 26.7% (p = 0.008), at an average duration of 103days vs. 47days, p = 0.0001. The rate of surgical osteotomies was similar in both groups. Estimated blood volume (EBV) loss was greater in Group 1 (63.1% vs. 43.1%, p = 0.0012). Post-op coronal and sagittal Cobb correction was similar in both groups. The incidence of post-op pulmonary complication was similar in both groups (8.2% vs. 8.9%, p = 0.899). Baseline and 2-year follow-up PFT did not differ significantly between and within the groups. Vertebral column resection (VCR) did not negatively affect PFT in both groups. Despite higher curve magnitudes in patients undergoing surgical correction and thoracoplasty for complex pediatric spine deformity, our findings revealed that thoracoplasty does not negatively affect pulmonary function at 2-year follow-up.

Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy

BackgroundMelanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT).MethodsThis retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS.ResultsOne hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0–40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03).ConclusionThe molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.

Multi-institutional Development and External Validation of a Nomogram Predicting Recurrence After Curative Liver Resection for Neuroendocrine Liver Metastasis.

To establish and externally validate a novel nomogram to predict recurrence of patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM). A total of 279 patients who underwent curative liver resection for NELM identified from an international multicenter database were utilized to develop a nomogram to predict recurrence; 98 cases from two different institutions were used to externally validate the nomogram. Among 279 patients in the development cohort, median age was 57years, and 50.5% were male. On multivariate analysis, primary tumor location (pancreatic vs nonpancreatic, HR 2.1, p = 0.004), tumor grade (Ref. well, moderate HR 1.9, p = 0.022; poor HR 1.6, p = 0.238), lymph node metastasis (positive vs negative, HR 2.6, p = 0.002), and extent of resection (major vs parenchymal-sparing resection, HR 0.3, p = 0.001) were independently associated with recurrence-free survival. The beta coefficients from the final multivariable model were utilized to develop a nomogram. The nomogram demonstrated good ability to predict risk of recurrence (training cohort, C-index 0.754; validation cohort, C-index 0.748). The calibrated nomogram predicted recurrence-free survival that closely corresponded to actual recurrence. Decision curve analysis demonstrated that the nomogram had a good net benefit for most of the threshold probabilities, especially between 20 and 60%, in both development and validation cohorts. The externally validated novel nomogram predicted 3- and 5-year recurrence-free survival among patients with NELM. Prediction of individual recurrence risk may help guide personalized estimates of prognosis, as well as surveillance protocols and consideration of adjuvant therapies.

Clinical outcomes of abiraterone acetate + prednisone (AA) + bone resorption inhibitors (BRI) versus AA alone as first-line therapy for castration-resistant prostate cancer (CRPC) with bone metastases (BM) in an international multicenter database.

30 Background: BM in patients (pts) with CRPC are associated with shorter overall survival (OS) and higher costs. BRI zoledronic acid and denosumab are frequently used to prevent skeletal-related events (SRE) in pts with CRPC and BM. AA is the most common 1st line therapy for men with metastatic CRPC. We aimed to assess the impact of BRI on OS and time to first SRE (ttSRE) of pts receiving 1st line treatment AA for CRPC with BM. Methods: A retrospective cohort of pts starting AA as 1st line therapy for CRPC with BM between 2013-2016 was identified through 8 hospitals’ IRB approved registries. Pts were classified by use of concomitant BRI and subgrouped by volume of disease (per E3805 definition) at AA start. Kaplan-Meier method and Cox models were used to assess OS and ttSRE with hazard ratio (HR) estimates (95% CI). Results: Of the 745 pts included (543 deaths), 529 (71.0%) had AA alone and 216 (29.0%) AA+BRI. Median follow-up was 23.5 months. Pts receiving concomitant BRI showed a significantly longer OS and a 35% reduced risk of death compared to AA alone (HR=0.65; 95% CI, 0.54-0.79; P&lt;.0001). The OS benefit with BRI was greater for the subgroup with high volume disease (HV) (HR=0.51; 95% CI, 0.38-0.68; P&lt;.0001). The cohort with AA+BRI had a significantly shorter ttSRE (HR=1.27; 95% CI; 1.0-1.60; P=.0439) and, notably, the risk of first SRE was more than doubled for the subgroup with LV (HR=2.29; 95% CI, 1.57-3.35; P&lt;.0001). On MVA, BRI vs. no BRI, prior local therapy (PLT) vs. no PLT, LV vs. HV, baseline VAS pain ≤3 vs. &gt;5, PS 0 vs. ≥1, and PSA are independently associated with longer OS. Conclusions: The addition of BRI to 1st line AA for CRPC men with BM was associated with improved OS, particularly in HV, and worsened ttSRE, more evident in LV. These data suggest a potentially different impact of concomitant BRI on HV vs. LV, which could affect clinical decision making.[Table: see text]

Which staging system better predicts 10-year survival for gastric cancer? A study using an international multicenter database

PurposeOur aim was to evaluate the prognostic performance of the 8th edition AJCC staging system for gastric cancer survival after 10 years or more. Patients and methodsAn international multicenter database was constructed (total n = 4537) by combining gastric cancer cases from the SEER database (n = 3066) and the database (n = 1471) of the Department of Gastric Surgery, Fujian Medical University Union Hospital. The relative discriminatory abilities were assessed using the likelihood ratio chi-square test, Akaike's Information Criterion (AIC) and Harrell's concordance index (c-statistic). ResultsThe 10-year overall survival rate for all the patients was 32.2%. A 2-step multivariate analysis showed that the 8th edition staging system was an independent factor for long-term overall survival. It also had higher likelihood ratio chi-square score, c-statistic and smaller AIC values compared with the 7th edition. However, stages IB and IIA of the TNM staging system showed a similar prognosis (both P > 0.05). Based on the survival data, we revised the 8th edition by merging stages IB and IIA into 1 category in the training set. The modified staging system demonstrated superior prognostic stratification with a higher c-statistic, likelihood ratio chi-square score and smaller AIC values compared to the 8th edition. Similar results were observed in the external validation set. ConclusionThe 8th edition AJCC TNM classification predicts the 10-year survival of gastric cancer patients more accurately than the 7th edition. However, by merging stages IB and IIA into 1 category, we propose a revised TNM stage system that provides an optimal prognosis.

Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort

AbstractAlthough hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment–refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

Peritoneal Carcinomatosis of Urachus Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An International Registry of 36 Patients.

Peritoneal carcinomatosis or pseudomyxoma peritonei from urachus is a rare form of presentation, often diagnosed at an advanced state of tumor burden. Because of its rarity, little is known about its natural history, prognosis, or optimal treatment. We searched a large international multicenter database of peritoneal surface disease to identify cases of peritoneal carcinomatosis of urachus that were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at expert centers. The aim is to improve knowledge and understanding of the disease and standardize its treatment. A prospective multicenter international database was retrospectively searched to identify all patients with urachus tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). Postoperative complications, long-term results, and principal prognostic factors were analyzed. The analysis included 36 patients. After median follow-up of 48months, median overall survival (OS) was 58.5months. Three- and 5-year OS was 55.4 and 46.2%, respectively. Patients who underwent complete macroscopic CRS had significantly better survival than those treated with incomplete CRS, with median OS not achieved and of 20.1months, respectively [95% confidence interval (CI) 4.4-30.5, p<0.001]. There were no postoperative deaths, and 37.9% of patients had major complications. CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of urachus origin, especially when complete CRS is achieved.

Treatment Strategies for Congenital Diaphragmatic Hernia: Change Sometimes Comes Bearing Gifts.

To report treatment strategies' evolution and its impact on congenital diaphragmatic hernia (CDH) outcome. Registry-based cohort study using the CDH Study Group database, 1995-2013. International multicenter database. CDH patients entered into the registry. Late presenters or patients with very incomplete data were excluded. Patients were divided into three Eras (1995-2000; 2001-2006; 2007-2013). Treatment strategies and outcomes. One-way ANOVA, X2 test, and X2 test for trend were used. A Sydak-adjusted p < 0.0027 was considered significant. Prevalence or mean (SE) are reported. Patients: 8,603; included: 7,716; Era I: 2,146; Era II: 2,572; Era III: 2,998. From Era I to Era III, significant changes happened. Some severity indicators such as gestational age, prevalence of prenatal diagnosis, and inborn patients significantly worsened. Also, treatment strategies such as the use of prenatal steroids and inhaled nitric oxide, age at operation, prevalence of minimal access surgery, and the use of surfactant significantly changed. Finally, length of hospital stay became significantly longer and survival to discharge slightly but significantly improved, from 67.7 to 71.4% (p for trend 0.0019). Treatment strategies for patients registered since 1995 in the CDH Study Group significantly changed. Survival to discharge slightly but significantly improved.

Organ Preservation Is Less Frequently Performed in Women Surgically Treated for Papillary Renal Cell Carcinoma—Results of a Comprehensive Multicenter Study

To analyze the impact of gender on the clinicopathologic features and survival of patients with surgically treated papillary renal cell carcinoma (papRCC) using a comprehensive international multicenter database. Data of 2325 patients undergoing surgery for unilateral papRCC between 1984 and 2015 in 17 European and North American centers were retrospectively collated. The impact of clinicopathologic features on the likelihood of nephron-sparing surgery (NSS) was evaluated using a multivariable logistic regression model. The influence on cancer-specific mortality (CSM) and other-cause mortality was analyzed by multivariable competing-risk regression models. Finally, subgroup analyses were conducted for organ-confined (n = 2075) and non-organ-confined tumors (n = 250). The median follow-up was 47 months. The study cohort included 1782 (77%) male patients (male-to-female ratio 3.3:1.0). Considering age, symptoms at presentation, performance status, pathologic tumor size, stage, and grade, we observed that there were no significant gender-specific differences. In contrast, female patients underwent NSS significantly less frequently (P <.001). On multivariable analysis, the likelihood of NSS was 72% higher in male patients after adjusting for all relevant cofactors (P <.001). No significant gender-specific differences in terms of CSM and other-cause mortality were demonstrated, but CSM was 59% lower in female patients in the subgroup of organ-confined tumors (P = .001). No impact of gender on survival was found analyzing this large cohort of patients undergoing surgery for papRCC. However, CSM appears to be lower in female patients with organ-confined disease. In this context, it is interesting that the likelihood of NSS seems to be significantly higher in male patients.

Moyamoya Disease in Children: Results From the International Pediatric Stroke Study.

This study aimed to describe children with moyamoya disease from an international multicenter stroke database, and explore risk factors for stroke recurrence. We reviewed data of children >28-days old with moyamoya disease enrolled in the International Pediatric Stroke Study from January 2003 to March 2013. A total of 174 children from 32 sites and 14 countries had moyamoya disease; median age 7.4 years, 49% male. Of these, 90% presented with ischemic stroke, 7.5% with transient ischemic attack, and 2.5% with hemorrhagic stroke. One-third of patients had moyamoya syndrome. Stroke recurrence was 20% over median follow-up of 13 months; 9% had multiple recurrences. Children treated with surgical revascularization were less likely to have stroke recurrence ( P = .046). Moyamoya disease accounted for 8% of arterial strokes in this international pediatric stroke registry. One-third of pediatric patients with moyamoya disease have an underlying syndromic condition. Surgical revascularization is effective at reducing the incidence of stroke recurrence.

Imaging response during therapy with radium-223 for castration-resistant prostate cancer with bone metastases-analysis of an international multicenter database.

The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate cancer (CRPC) patients treated with radium-223, in eight centers in three countries. A total of 130 patients were included, the majority (n=84, 65%) received radium-223 post docetaxel. Thirty-four of 99 patients with available data (34%) received concomitant abiraterone or enzalutamide. A total of 54% (n=70) patients completed the planned six injections of radium-223. In patients with available data, a transient increase in bone metastases-related pain was observed in 27% (n=33/124) and an improvement of bone metastases-related pain on treatment with radium-223 was noted in 49% of patients (n=61/124). At 3 and 6 months of treatment with radium-223, bone imaging showed stable disease in 74% (n=84/113) and 94% of patients (n=93/99) with available data, respectively. An increase in the number of bone lesions was documented at 3 months compared with baseline in 26% (n=29/113) and at 6 months compared with 3 months in 6% of patients (n=6/99), respectively. Radiological extraskeletal disease progression occurred in 46% of patients (n=57/124) with available CT data at 3 and/or 6 months. Progression of bone metastases during radium-223 therapy is uncommon. A bone flare (pain and/or radiological) may be noted during the first 3 months, and should not be confused with progression. Imaging by CT scan should be considered after three and six doses of radium-223 to rule out extraskeletal disease progression.

Seasonality at the clinical onset of type 1 diabetes-Lessons from the SWEET database.

Seasonality at the clinical onset of type 1 diabetes (T1D) has been suggested by different studies, however, the results are conflicting. This study aimed to evaluate the presence of seasonality at clinical onset of T1D based on the SWEET database comprising data from 32 different countries. The study cohort included 23 603 patients (52% males) recorded in the international multicenter SWEET database (48 centers), with T1D onset ≤20 years, year of onset between 1980 and 2015, gender, year and month of birth and T1D-diagnosis documented. Data were stratified according to four age groups (<5, 5-<10, 10-<15, 15-20 years) at T1D onset, the latitude of European center (Northern ≥50°N and Southern Europe <50°N) and the year of onset ≤ or >2009. Analysis by month revealed significant seasonality with January being the month with the highest and June with the lowest percentage of incident cases (P < .001). Winter, early spring and late autumn months had higher percentage of incident cases compared with late spring and summer months. Stratification by age showed similar seasonality patterns in all four age groups (P ≤ .003 each), but not in children <24 months of age. There was no gender or latitude effect on seasonality pattern, however, the pattern differed by the year of onset (P < .001). Seasonality of diagnosis conformed to a sinusoidal model for all cases, females and males, age groups, northern and southern European countries. Seasonality at T1D clinical onset is documented by the large SWEET database with no gender or latitude (Europe only) effect except from the year of manifestation.

Analgesia in Neurocritical Care: An International Survey and Practice Audit.

To characterize analgesic administration in neurocritical care. ICU pharmacy database analgesic delivery audits from five countries. A 31-question analgesic agent survey was constructed, validated, and e-distributed in four countries. International multicenter neuro-ICU database audit and electronic survey. Six ICUs provided individual, anonymized analgesic delivery data in primary neurological diagnosis patients. Prescriber surveys were disseminated by neurocritical care societies. None. Analgesic delivery data from 173 patients in French, Canadian, American, and Australian and New Zealand ICUs suggest that acetaminophen/paracetamol is the most common first-line analgesic (49.1% of patients); opiates are the "second line" in 31.5% of patients; however, 33% patients received no second agent. In the 2.3% with demyelinating disease, gabapentin was the most likely second analgesic (50.0%). Third-line analgesics were scarce across sites and neuropathologies. Few national or regional differences were found. The analgesic preference rankings noted by the 95 international physicians who completed the survey matched the audits. However, self-reported analgesic prescription rates were much higher than pharmacy records indicate, with self-reported prescribing of both acetaminophen/paracetamol and opiates in 97% of patients and gabapentin in 45% of patients. Third-line analgesic variability appeared to be driven by neuropathology; ibuprofen was preferred for traumatic brain injury, postcraniotomy, and thromboembolic stroke patients, whereas gabapentin/pregabalin were favored in subarachnoid hemorrhage, intracranial hemorrhage, spine, demyelinating disease, and epileptic patients. Opiates and acetaminophen are preferred analgesic agents, and gabapentin is a contextual third choice, in neurocritically ill patients. Other agents are rarely prescribed. The discordance in physician self-reports and objective audits suggest that pain management optimization studies are warranted.