Multi-Institutional Collaborative Study Research Articles

Pediatric Myelodysplastic Syndrome.

Myelodysplastic syndromes (MDSs) are rare in children and have unique clinical manifestations and implications. To review the clinical features, pathogenesis, and classification of pediatric MDS. Published literature and personal experience. Pediatric MDS vastly differs from adult MDS. Evaluation for the presence of an underlying germline predisposition syndrome is critical for optimal classification and management. Because of the rarity of cases, resources to aid with the recognition, diagnosis, and management of pediatric MDS are limited, and multi-institutional collaborative studies are needed for the future.

The Inverse Association between the Frequency of Forest Walking (Shinrin-yoku) and the Prevalence of Insomnia Symptoms in the General Japanese Population: A Japan Multi-Institutional Collaborative Cohort Daiko Study.

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29-3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

Study on the Preparation Method of Quality-Assured In-Hospital Drug Formulation for Children-A Multi-Institutional Collaborative Study.

The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification.

MP62-18 NEW FINDINGS REGARDING INDEPENDENT PREDICTORS OF POOR CORPORAL INTEGRITY IN A LARGE SERIES OF PENILE IMPLANT RECIPIENTS: A MULTICENTER INTERNATIONAL INVESTIGATION

You have accessJournal of UrologyCME1 Apr 2023MP62-18 NEW FINDINGS REGARDING INDEPENDENT PREDICTORS OF POOR CORPORAL INTEGRITY IN A LARGE SERIES OF PENILE IMPLANT RECIPIENTS: A MULTICENTER INTERNATIONAL INVESTIGATION Chrystal Chang, Zafardjan Dalimov, David Barham, Daniel Swerdloff, Hossein Sadeghi-Nejad, Robert Andrianne, Mike Hsieh, Martin Gross, Georgios Hatzichristodolou, Maxime Sempels, Daniar Osmonov, Aaron Lentz, Paul Perito, James Hotaling, Koenraad Van Renterghem, Sung Hun Park, Jonathan N. Warner, Faysal A. Yafi, and Jay Simhan Chrystal ChangChrystal Chang More articles by this author , Zafardjan DalimovZafardjan Dalimov More articles by this author , David BarhamDavid Barham More articles by this author , Daniel SwerdloffDaniel Swerdloff More articles by this author , Hossein Sadeghi-NejadHossein Sadeghi-Nejad More articles by this author , Robert AndrianneRobert Andrianne More articles by this author , Mike HsiehMike Hsieh More articles by this author , Martin GrossMartin Gross More articles by this author , Georgios HatzichristodolouGeorgios Hatzichristodolou More articles by this author , Maxime SempelsMaxime Sempels More articles by this author , Daniar OsmonovDaniar Osmonov More articles by this author , Aaron LentzAaron Lentz More articles by this author , Paul PeritoPaul Perito More articles by this author , James HotalingJames Hotaling More articles by this author , Koenraad Van RenterghemKoenraad Van Renterghem More articles by this author , Sung Hun ParkSung Hun Park More articles by this author , Jonathan N. WarnerJonathan N. Warner More articles by this author , Faysal A. YafiFaysal A. Yafi More articles by this author , and Jay SimhanJay Simhan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003320.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Inflatable penile prosthesis (IPP) offers high satisfaction rates for patients, but this procedure is not without complications that can be encountered either intraoperatively or postoperatively. Particularly, predictors of intraoperative corporal perforation and delayed cylinder complications in IPP placement have not been well-delineated. We hypothesize that preoperative and intraoperative variables may impact the integrity of the corporal bodies long-term and thus implant viability. METHODS: We retrospectively reviewed a large, multi-institutional collaborative study of IPP surgeries performed by expert implanters from 2016-2021. All primary and revision cases were included. Salvage cases for infection were excluded. Demographic characteristics, intraoperative variables, and postoperative outcomes were assessed. PCI was defined as intraoperative corporal complications (proximal and/or distal perforation of the corpora, corporal crossover) or postoperative corporal complications (cylinder erosion, extrusion, impending erosion, or deformity). Risk factor analysis and multivariate analysis were performed to identify independent predictors of PCI. RESULTS: After excluding salvage cases for infection, we identified 5,153 patients undergoing IPPs, of which 149 were diagnosed with PCI. The rates of diabetes (p=0.19), immunosuppression (p=0.79), priapism (p=0.06), history of radiation (p=0.29), and prior use of intracavernosal injections (p=0.19) all had no significant effect on corporal integrity. Patients with PCI were more likely to have active coronary artery disease (CAD) or peripheral vascular disease (PVD) (p=0.02), be current smokers (p=0.003), and have a history of IPP infection (p<0.001). On multivariate analysis, predictors of PCI included older age (OR 1.02 (1.00-1.04), p=0.03), CAD/PVD (OR 1.58 (1.06-2.35), p=0.025) and history of IPP infection (OR 5.82 (3.27-10.34), p<0.001). Obesity (OR 0.582 (0.40-0.86), p=.006) and non-Caucasian race (OR 0.60 (0.41-0.88), p=0.01) were found to be protective. CONCLUSIONS: Our multicenter analysis found that CAD/PVD, current smoking, and history of IPP infection were risk factors for complications associated with poor corporal integrity. Recognizing these risk factors preoperatively can allow for improved patient-specific counseling and changes in surgical strategy to potentially promote longer term device viability. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e869 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chrystal Chang More articles by this author Zafardjan Dalimov More articles by this author David Barham More articles by this author Daniel Swerdloff More articles by this author Hossein Sadeghi-Nejad More articles by this author Robert Andrianne More articles by this author Mike Hsieh More articles by this author Martin Gross More articles by this author Georgios Hatzichristodolou More articles by this author Maxime Sempels More articles by this author Daniar Osmonov More articles by this author Aaron Lentz More articles by this author Paul Perito More articles by this author James Hotaling More articles by this author Koenraad Van Renterghem More articles by this author Sung Hun Park More articles by this author Jonathan N. Warner More articles by this author Faysal A. Yafi More articles by this author Jay Simhan More articles by this author Expand All Advertisement PDF downloadLoading ...

Validation of the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non-muscle invasive bladder cancer: A multi-institutional collaborative study.

To validate the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non-muscle invasive bladder cancer and provide a more accurate stratification model for a heterogeneous intermediate-risk group. A total of 1610 patients, who underwent transurethral resection, diagnosed with non-muscle invasive bladder cancer in nine collaborating hospitals were retrospectively reviewed. They were classified into low-risk, intermediate-risk, high-risk, and highest-risk groups, and recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival were compared among the groups. The intermediate-risk group was subdivided into two groups based on the multivariable Cox regression model of recurrence and progression risk factors, and a revised risk model was created. The progression-free survival, cancer-specific survival, and overall survival were well stratified, while the recurrence-free survival of the intermediate-risk group was the shortest among the four groups (p < 0.001). The independent risk factors for recurrence and progression-free survival in the intermediate-risk group were as follows: age ≥ 70 years, sex, multiple tumors, tumor size ≥3 cm, and recurrent cases. The intermediate-risk group was subdivided into two groups: favorable intermediate-risk group and unfavorable intermediate-risk group. The revised risk model showed significant differences. We validated the Japanese Urological Association guidelines 2019 stratification model. The revised risk model provided a more accurate treatment selection for this disease subset.

Variability of Low-Z Inhomogeneity Correction in IMRT/SBRT: A Multi-Institutional Collaborative Study.

Dose-calculation algorithms are critical for radiation treatment outcomes that vary among treatment planning systems (TPS). Modern algorithms use sophisticated radiation transport calculation with detailed three-dimensional beam modeling to provide accurate doses, especially in heterogeneous medium and small fields used in IMRT/SBRT. While the dosimetric accuracy in heterogeneous mediums (lung) is qualitatively known, the accuracy is unknown. The aim of this work is to analyze the calculated dose in lung patients and compare the validity of dose-calculation algorithms by measurements in a low-Z phantom for two main classes of algorithms: type A (pencil beam) and type B (collapse cone). The CT scans with volumes (target and organs at risk, OARs) of a lung patient and a phantom build to replicate the human lung data were sent to nine institutions for planning. Doses at different depths and field sizes were measured in the phantom with and without inhomogeneity correction across multiple institutions to understand the impact of clinically used dose algorithms. Wide dosimetric variations were observed in target and OAR coverage in patient plans. The correction factor for collapsed cone algorithms was less than pencil beam algorithms in the small fields used in SBRT. The pencil beam showed ≈70% variations between measured and calculated correction factors for various field sizes and depths. For large field sizes the trends of both types of algorithms were similar. The differences in measured versus calculated dose for type-B algorithms were within ±10%. Significant variations in the target and OARs were observed among various TPS. The results suggest that the pencil beam algorithm does not provide an accurate dose and should not be considered with small fields (IMRT/SBRT). Type-B collapsed-cone algorithms provide better agreement with measurements, but still vary among various systems.

Olfactory Neuroblastoma: Morphological Reappraisal and Molecular Insights with Quantum Leap in Clinical Perspectives.

The purpose of review is to provide a comprehensive review of the literature focusing on the recent advances in the diagnosis, molecular underpinning, and targeted therapy of olfactory neuroblastoma (ONB). Studies focused on the molecular fingerprinting of ONB are critical to engage new promising treatment strategies. Molecular-based subtype classifications have been proposed (basal-like ONB and neural-like ONB) but are not widely used. The rationale for implementation of DNA methylation analysis and IDH2 sequencing in routine work-up for ONB is gaining recognition. Expression of somatostatin receptors (SSTR) in ONB open new avenues for both, diagnostic (especially metastatic disease) and new treatment protocols with somatostatin analogs. Olfactory carcinoma is proposed as a unifying diagnostic terminology pertinent to epithelial divergent differentiation in olfactory neuroblastoma. Molecular (genetic and epigenetic) efforts on olfactory neuroblastoma are promising; however further refinement is needed for employment of these biomarkers as clinical standard of care. Ongoing and future multi-institutional collaborative studies will contribute to further understanding of ONB biology and aid the development of targeted treatments for this disease.

Patterns of recurrences in sinonasal cancers undergoing an endoscopic surgery-based treatment: Results of the MUSES* on 940 patients: *MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers

ObjectivesThe improvements in survival with expansion of the survivors’ population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence. Materials and MethodsAll patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence. ResultsThe 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes. ConclusionThis study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers

BackgroundOver the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. MethodologyAll patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. ResultsThe training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5–76.0%) and 66.4% (63.1–69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. ConclusionsOutcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Outcomes Following Norwood Procedures: Analysis of a "Small Volume" Program.

Institutional survival following Norwood procedures is traditionally correlated with a center's surgical volume. Multiple single and multi-institutional studies conducted at large-volume centers have recently demonstrated improved survival following Norwood procedures. We report both short- and long-term outcomes at a single, small-volume institution and comment on factors potentially influencing outcomes at this institution. All patients undergoing Norwood procedures from January 1, 2005, to January 1, 2020, at our institution were included in this study. Kaplan-Meier survival and Cox regression risk factor analyses were performed in addition to first interstage risk factor scoring to compare observed versus expected survival. The cohort included 113 patients. Kaplan-Meier freedom from death or transplant was 88%, 80%, and 76% at 1, 5, and 10 years, respectively. Freedom from death following hospital discharge after Norwood procedures was 94%, 87%, and 83% at 1, 5, and 10 years, respectively. The presence of genetic syndromes was a significant risk factor for mortality. First interstage observed-to-expected mortality following discharge was 0.57 (P = .04). Postoperative length of stay was comparable to that reported for the period 2015 to 2018 in the Society of Thoracic Surgeons Database. Survival outcomes at this single, small-volume institution were similar to those reported by large-volume centers and multi-institutional collaborative studies. These results may be related to structural and functional features that have been demonstrated to influence outcomes in other studies. These factors are achievable by small-volume programs with sufficient resource allocation.

Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA

AimOsteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Circulating free (cfDNA) and circulating tumour DNA (ctDNA) are promising biomarkers for disease surveillance and prognostication in several cancer types; however, few such studies are reported for OS. The purpose of this study was to discover and validate methylation-based biomarkers to detect plasma ctDNA in patients with OS and explore their utility as prognostic markers. MethodsCandidate CpG markers were selected through analysis of methylation array data for OS, non-OS tumours and germline samples. Candidates were validated in two independent OS datasets (n = 162, n = 107) and the four top-performing markers were selected. Methylation-specific digital droplet PCR (ddPCR) assays were designed and experimentally validated in OS tumour samples (n = 20) and control plasma samples. Finally, ddPCR assays were applied to pre-operative plasma and where available post-operative plasma from 72 patients with OS, and findings correlated with outcome. ResultsCustom ddPCR assays detected ctDNA in 69% and 40% of pre-operative plasma samples (n = 72), based on thresholds of one or two positive markers respectively. ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients, which in four cases were associated with or preceded disease relapse. Both pre-operative cfDNA levels and ctDNA detection independently correlated with overall survival (p = 0.0015 and p = 0.0096, respectively). ConclusionOur findings illustrate the potential of mutation-independent methylation-based ctDNA assays for OS. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers in the management of OS.

Myelodysplastic/myeloproliferative neoplasms-unclassifiable with isolated isochromosome 17q represents a distinct clinico-biologic subset: a multi-institutional collaborative study from the Bone Marrow Pathology Group

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated megakaryocytes (62% vs. 20%; P = 0.06), and a higher frequency of SETBP1 (69% vs. 5%; P = 0.002) and SRSF2 (63% vs. 5%; P = 0.006) mutations that were frequently co-existent (44% vs. 0%; P = 0.01). TP53 mutations were rare. The mutation profile of MDS/MPN-U-i(17q) was similar to other myeloid neoplasms with i(17q) including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, myelodysplastic syndrome and acute myeloid leukemia, with frequent concomitant SETBP1/SRSF2 mutations observed across all the diagnostic entities. Over a median follow-up of 52 months, patients with MDS/MPN-i(17q) showed a shorter median overall survival (11 vs. 28 months; P < 0.001). The presence of i(17q) retained independent poor prognostic value in multivariable Cox-regression analysis [HR 3.686 (1.17–11.6); P = 0.026] along with splenomegaly. We suggest that MDS/MPN-i(17q) warrants recognition as a distinct subtype within the MDS/MPN-U category based on its unique clinico-biologic features and uniformly poor prognosis.

Influence of Treatment Package Time on outcomes in High-Risk Oral Cavity Carcinoma in patients receiving Adjuvant Radiation and Concurrent Systemic Therapy: A Multi-Institutional Oral Cavity Collaborative study

ObjectivesTo explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT). Materials and MethodsWe queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival. ResultsWe identified 187 cases: median age 58 (range, 24–87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63–162 days). OS was worse for TPT > 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT > 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1–1.28]; P = 0.043), perineural invasion, age and positive LN (p < 0.05 for all). ConclusionIn one of the largest multi-institutional cohorts, TPT > 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes.

Dosimetric evaluation of high-Z inhomogeneity used for hip prosthesis: A multi-institutional collaborative study

PurposeA multi-institutional investigation for dosimetric evaluation of high-Z hip prosthetic device in photon beam. MethodsA bilateral hip prosthetic case was chosen. An in-house phantom was built to replicate the human pelvis with two different prostheses. Dosimetric parameters: dose to the target and organs at risk (OARs) were compared for the clinical case generated by various treatment planning system (TPS) with varied algorithms. Single beam plans with different TPS for phantom using 6 MV and 15 MV photon beams with and without density correction were compared with measurement. ResultsWide variations in target and OAR dosimetry were recorded for different TPS. For clinical case ideal PTV coverage was noted for plans generated with Corvus and Prowess TPS only. However, none of the TPS were able to meet plan objective for the bladder. Good correlation was noticed for the measured and the Pinnacle TPS for corrected dose calculation at the interfaces as well as the dose ratio in elsewhere. On comparing measured and calculated dose, the difference across the TPS varied from −20% to 60% for 6 MV and 3% to 50% for the 15 MV, respectively. ConclusionMost TPS do not provide accurate dosimetry with high-Z prosthesis. It is important to check the TPS under extreme conditions of beams passing through the high-Z region. Metal artifact reduction algorithms may reduce the difference between the measured and calculated dose but still significant differences exist. Further studies are required to validate the calculational accuracy.

A Multi-Institutional Collaboration to Understand Neoplasia, Treatment and Survival of Snakes.

Simple SummaryMultiple studies have focused on types of neoplasia found in snakes, but an overall estimation of prevalence including total populations of animals at multiple facilities has not been conducted. Additionally, an in-depth evaluation of methods of therapy and survival of snakes with neoplasia has not been carried out. This study calculated the prevalence of tumors in 133 snakes, representing 65 different species, housed in six zoos and aquariums. Survival times were evaluated to determine whether these snakes were more likely to die from their tumors versus another cause. Treatment outcomes were evaluated to determine if the used treatment types lengthened the snakes’ life spans. Common or northern watersnakes (Nerodia sipedon), eastern diamond-backed rattlesnakes (Crotalus adamanteus), and timber rattlesnakes (Crotalus horridus) had the highest prevalence of tumors. Malignant (cancerous) tumors predominated, and the snakes with these tumors were significantly more likely to die of their cancer than those with benign tumors. Thirty-six of the 133 snakes received treatment for their tumors. There was no significant difference in survival times for those treated and not treated. This population is a subset of the overall snake population under managed human care, and a larger collection of snake tumor and population data could yield different results. Therefore, additional snake cases, along with other non-domestic species, are continuing to be curated in a database (Exotic Species Cancer Research Alliance tumor database). The goal of this data collection is to provide data on a select population of snakes to help veterinarians gain greater understanding of cancer types and to treat cancer in these animals.This multi-institutional collaborative study of neoplasia in snakes reviewed medical records of snakes at each facility to determine species prevalence, survival, and methods of treatment. Complete species numbers of snakes were also collected at each facility. In total, 65 species, 133 snakes, and 149 unique neoplasias were included in this study. Affected species, age, sex, and their tumor prevalence, tumor type and location, metastasis, treatment, and survival data are reported. The highest species-specific tumor prevalence was in Common or Northern Watersnakes (Nerodia sipedon) (30.8%, n = 4 of 13), Eastern Diamond-Backed Rattlesnakes (Crotalus adamanteus) (26.3%, n = 5 of 19), and Timber rattlesnakes (Crotalus horridus) (22.7%, n = 5 of 22). Malignant tumors predominated (86.6%, n = 129 of 149) with soft tissue sarcomas being the most common (30.2%, n = 45 of 149). Snakes with malignant neoplasia, metastases, or indeterminate presence of metastases were statistically more likely to die from their neoplasms than snakes having either benign neoplasia or no diagnosed metastases (p < 0.05). Gender, taxonomic family, and species of those evaluated did not significantly affect the outcome of snakes with neoplasia. Only 27.1% (n = 36 of 133) of snakes received a reported form of treatment and, for those treated, surgical excision was the most common treatment modality. There was not a significant difference in outcome based on treatment; however, surgery and chemotherapy were associated with death from a cause other than their tumor.

Management and outcomes of atrial fibrillation in 241 healthy children and young adults: Revisiting "lone" atrial fibrillation-A multi-institutional PACES collaborative study.

Atrial fibrillation (AF) in healthy children and young adults is rare. Risk of recurrence and treatment efficacy are not well defined. The purpose of this study was to assess recurrence patterns and treatment efficacy in AF. A retrospective multicenter cohort study including 13 congenital heart centers was facilitated by the Pediatric & Congenital Electrophysiology Society (PACES). Patients ≤21 years of age with documented AF from January 2004 to December 2018 were included. Demographics, family and clinical history, medications, electrophysiological study parameters, and outcomes related to the treatment of AF were recorded and analyzed. Patients with contributory diseases were excluded. In 241 subjects (83% male; mean age at onset 16 years), AF recurred in 94 patients (39%) during 2.1 ± 2.6 years of follow-up. In multivariable analysis, predictors of AF recurrence were family history in a first-degree relative <50 years of age (odds ratio [OR] 1.9; P= .047) and longer PR interval in sinus rhythm (OR 1.1 per 10 ms; P= .037). AF recurrence was similar whether patients began no treatment (39/125 [31%]), began daily antiarrhythmic therapy (24/63 [38%]), or had an ablation at any time (14/53 [26%]; P = .39). Ablating non-AF substrate with supraventricular tachycardia improved freedom from AF recurrence (P = .013). Recurrence of AF in the pediatric population is common, and the incidence of recurrence was not impacted by "no treatment," "medication only," or "ablation" treatment strategy. Ablation of pathways and other reentrant targets was the only intervention that decreased AF recurrence in children and young adults.

Is synoptic operative reporting necessary for Crohn's disease surgery? Variability in surgical reports across inflammatory bowel disease referral centres.

Ileocolic resection (ICR) is the most commonly performed operation in Crohn's disease (CD) patients. The surgical report is a vital tool for accessing information to gauge a patient's long-term prognosis and guide treatment decisions. Dictated narrative reports are the traditional method for surgical documentation but often lack essential information. The objective was to assess the quality of operation note in CD patients undergoing ICR. This was a multi-institutional retrospective cohort collaborative study involving four tertiary inflammatory bowel disease referral centres in the USA and Canada. The patients were consecutive CD patients undergoing ICR between 2014 and 2020. There were no interventions. The main outcome measures were the variability and frequency of 28 critical items in the operation note. An analysis of 400 consecutive operation reports in four institutions (n=100/institution) revealed significant variability in almost all variables. The initial surgical approach and wound protector use were the most consistently or frequently reported across all inflammatory bowel disease centres. The limitation was that this was a retrospective cohort study with inevitable selection bias. This study highlights the need for synoptic reporting in CD patients undergoing ICR.

Plasmacytoma and plasma cell myeloma affecting the jaws: A multi-institutional collaborative study.

Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed and follow-up status were retrieved from the pathology reports. Fifty-two cases were retrieved (mean age: 59.4years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumours usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5years of follow-up was 26.6%. Plasma cell neoplasms are aggressive tumours with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.

Abstract PS1-04: Utility of rapid- immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer

Abstract Axillary lymph node status and pathological diagnosis of sentinel lymph nodes (SLNs) is an important factor that influences management of postoperative therapy. Recent reports indicate that one-step nucleic acid amplification (OSNA) and hematoxylin and eosin (HE)-stained frozen sections are effective for intraoperative diagnosis of SLNs. In the present study, we report a rapid-immunohistochemical staining (R-IHC) method that enables intraoperative detection of SLN metastases within 16 min using an anti-cytokeratin antibody. With this R-IHC system, we apply a high-voltage, low-frequency AC electric field to lymph node sections while they are incubating with the antibodies. The antibodies are mixed within microdroplets and the opportunity for contact between the antibody and antigen is increased. This greatly reduces the time required for the antigen-antibody reaction. This is the report on SLN diagnosis using R-IHC in patients with breast cancer. We prospectively examined 632 dissected SLNs from 260 breast cancer patients who underwent surgery at our institute between July 2014 and March 2020. The dissected SLNs were sectioned and conventionally stained with HE or immunohistochemically labeled with anti-cytokeratin antibody using R-IHC procedures. Intraoperative R-IHC analyses were completed within 16 min, after which diagnoses were made by two pathologists. The total time required for intraoperative diagnosis was about 20 min. In this study, R-IHC detected four metastatic SLNs that were undetected using conventional HE staining (10/52, 19.2%). Compared with subsequent permanent diagnosis, R-IHC offered 98.0% sensitivity, 100% specificity and 99.8% accuracy while those values for intraoperative HE were 80.4%, 100%, 98.4%, respectively (isolated tumor cells were counted as negative). These findings indicate R-IHC is a clinically applicable technique that enables precise, and quick intraoperative detection of micro- and macrometastases in breast cancer. Moreover, R-IHC is cost-effective method: it’s cost is less than a quarter of OSNA and previous report showed that the concentration of primary antibody could be reduced by more than 90% by using R-IHC because AC mixing activated antigen-antibody reaction. Another benefit is its ability to shorten the time needed for microscopic diagnosis itself. When using R-IHC, pathologists are able to readily find metastatic lesions, even within low-power fields (e.g. 40x). This reduces not only the time needed for intraoperative diagnosis, but also the effort necessary to find unclear lesions like small cancer cells (even though it is macrometastasis), micrometastasis, and artifacts of frozen section. This study was conducted at a single institute. Further investigation in a multi-institutional collaborative prospective study will be needed to confirm the utility of this method. But for now, R-IHC appears to be a cost-effective and clinically applicable method for diagnosis of breast cancer and SLN metastasis. Citation Format: Kaori Terata, Hiroshi Nanjo, Eriko Takahashi, Ryuta Nakamura, Yoichi Akagami, Ayuko Yamaguchi, Misako Yatsuyanagi, Chiaki Kudo, Yoshihiro Minamiya. Utility of rapid- immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-04.

Failure rate in the untreated contralateral node negative neck of small lateralized oral cavity cancers: A multi-institutional collaborative study

ObjectivesThe importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment. Materials and methodsWe performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS). Results176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2–7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4–32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2–95.0%) and 80.6% (95% CI 74.5–86.8%), respectively. ConclusionObservation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging.