Impaired Pre-operative Ambulatory Capacity in Patients Undergoing Elective Endovascular Infrarenal Abdominal Aortic Aneurysm Repair is Associated with Increased Peri-operative Death.

OBJECTIVE: While ambulatory capacity is a readily assessable clinical indicator of functional status, its association with outcomes after endovascular aneurysm repair (EVAR) remains underexplored. This study aimed to investigate the association between pre-operative ambulatory status and outcomes following elective EVAR. METHODS: A retrospective review of the multi-institutional Vascular Quality Initiative database was conducted for all patients who underwent elective infrarenal EVAR from 2009 - 2022. Patients were categorised into independent ambulation and impaired ambulation groups. A propensity score matched analysis was performed to produce two well matched cohorts in a 1:1 ratio without replacement. The primary outcome was 30 day death. Secondary outcomes included one year survival and in hospital major complications. RESULTS: Among 11 474 patients, 10 539 (91.8%) were independently ambulatory pre-operatively. Propensity score matching resulted in 885 matched pairs. The impaired ambulation group, although older (mean 77.6 vs. 76.3 years; p = .001), showed comparable baseline characteristics. Post-operatively, the impaired ambulation group had higher cumulative in hospital complications and death as well as 30 day death. Even after adjustment for age, impaired pre-operative ambulation was associated with increased in hospital and 30 day death (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.26 - 3.95; p = .006). Multivariable analysis demonstrated increasing cumulative risk of 30 day death in the setting of impaired pre-operative ambulatory status with age > 75 years requiring post-operative red blood cell transfusion > 2 units (HR 5.75, 95% CI 2.09 - 15.88; p < .001). Beyond 30 days, impaired pre-operative ambulation was not associated with increased one year death (HR 1.09, 95% CI 0.81 - 1.48; p = .057). CONCLUSION: Among patients who underwent elective infrarenal EVAR in this matched analysis, impaired pre-operative ambulatory capacity was associated with an increased risk of in hospital and 30 day death, further compounded by advanced age and post-operative transfusion. As such, a threshold higher than the traditional size criteria should be considered in shared decision making when determining options for the management of abdominal aortic aneurysm in this high risk cohort.

The development and evanescence of red blood cell antibodies after transfusion: A multi-institutional prospective study in Japan.

BACKGROUND: Despite several reports on red blood cell (RBC) alloimmunization, the actual prevalence and factors contributing to RBC alloimmunization in transfused patients remain poorly investigated. We examined the association between clinical factors and the development and evanescence of RBC antibodies after transfusion. STUDY DESIGN AND METHODS: Each participating institution performed antibody screens before and after RBC transfusion. A survey including patient characteristics, results of antibody screen and identification, antibody screen methods, total amount of RBC transfused, and adverse reactions, was conducted. RESULTS: Between October 2018 and March 2023, 1194 patients were registered at five institutions. Overall, 958 patients underwent at least one follow-up RBC antibody screen after transfusion, revealing new antibody development in 44 (4.6%). Anti-E was identified in 25 patients, anti-Jka in 5, and anti-c in 4. The number of RBC units transfused was significantly associated with antibody development after transfusion (p < .001). Among 55 patients in whom antibodies were identified after transfusion, including historical antibodies, antibodies evanesced in 18 (33%); anti-E in 7, anti-Jka in 4, and anti-Lea in 2. Evanescent antibodies were identified more frequently by saline and/or enzyme methods than persistent antibodies (p = .012). DISCUSSION: The number of RBC units transfused can impact antibody development, and antibodies identified only by saline and/or enzyme methods, deemed clinically insignificant, are likely to have a high evanescence rate. Antibody screen should be carefully performed, especially in those receiving a large number of RBC units. Confirming previous antibody screen results should be performed to prevent omitting evanesced antibodies regardless of clinical relevance.

Prospective external validation of radiomics-based predictive model of distant metastasis after dynamic tumor tracking stereotactic body radiation therapy in patients with non-small-cell lung cancer: A multi-institutional analysis.

BACKGROUND AND PURPOSE: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT). MATERIALS AND METHODS: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test. RESULTS: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116). CONCLUSION: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM.

Optimal Surgical Method and Timing for Low-birth-weight Esophageal Atresia Babies: Multi-institutional Observational Study.

AIM OF THE STUDY: Previous research has shown that low birth weight is one of the risk factors for esophageal atresia. However, there remains a paucity of evidence on the timing and the treatment method. METHOD: Data were collected using a multi-institutional observational study in 11 hospitals that performed surgeries on esophageal atresia babies whose birth weights were ≤1500 g from 2001 to 2020. RESULTS: Of the 46 patients analyzed, median birth weight was 1233 (IQR 1042-1412) g. Within 46 cases, 19 (41%) underwent definitive esophageal anastomosis at the median of age in 8 (IQR 2-101) days. Thirteen out of 19 experienced either closure of tracheoesophageal fistula, gastrostomy, or esophageal banding at the first operation, followed by esophageal anastomosis. Seven infants, including four cases of <1000 g, underwent anastomosis after one month of age to wait for weight gain (variously 2-3000 g). Twenty-one out of 27 infants (78%) who did not receive anastomosis died within one year of age, including 21 (78 %) with major cardiac anomalies and 24 (89%) with severe chromosomal anomalies (trisomy 18). Six survivors in this group, all with trisomy 18, lived with palliative surgical treatments. CONCLUSION: In our study, the definitive esophageal anastomosis was effective either at the first operation or as a later treatment after gaining weight. Although having severe anomalies, some infants receive palliative surgical treatments, and the next surgery was considered depending on their condition. EVIDENCE LEVEL: II.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Thrombus formation at the stump of the pulmonary vein after lobectomy: a prospective multi-institutional study.

PURPOSE: Recent reports suggest that postoperative cerebral infarction following lung cancer surgery is caused by thrombus formation at the stump of the pulmonary vein and that the risk is highest after left upper lobectomy (LUL). Thrombosis at the stump of the pulmonary vein and the incidence of cerebral infarction was investigated prospectively in patients who underwent lobectomy for lung cancer. METHODS: Lung cancer patients undergoing planned pulmonary lobectomy were enrolled. The endpoint was to confirm if there is a higher incidence of thrombus formation (primary) and a higher incidence of cerebral infarction (secondary) in patients undergoing LUL. We planned to accrue 600 patients. An interim analysis was scheduled for just after the data center received the final clinical review form of the 300th patient. RESULTS: The interim analysis revealed a significant difference in the primary endpoint. In the final analysis, thrombus was identified in 16 of 88 LUL patients (20.5%), and in 4 of 247 patients who underwent other types of lobectomy (1.6%) (p < 0.05). Cerebral infarction was identified in 1 of the LUL patients (1.3%) and in 9 of the other patients (3.6%) (p = 0.318). CONCLUSIONS: Thrombus frequently forms at the stump of the left superior pulmonary vein after LUL. However, our study did not identify a relationship between thrombosis and cerebral infarction.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

Positive Predictive Value of ICD-10-CM Codes for Myocarditis in Claims Data: A Multi-Institutional Study in Taiwan.

Purpose: The validity of the diagnosis codes to identify myocarditis cases in healthcare databases research remains unclear, and this study aimed to determine the coding accuracy of myocarditis in Taiwan. Methods: We conducted a cross-sectional study based on Taiwan's largest multi-institutional healthcare system to identify inpatients newly diagnosed with ICD-10-CM myocarditis codes at discharge between January 1st, 2017 and March 31st, 2022. We ascertained the myocarditis diagnosis by a gold standard biopsy or by review of electronic medical records, and the positive predictive values (PPV) with 95% confidence intervals (CI) of the ICD-10-CM codes for myocarditis were determined. Results: We included a total of 498 inpatients (mean age: 33.8 years old; female: 38.8%) with new myocarditis diagnosis at discharge. Codes I409 (30.1%) and I514 (45.4%) constituted the majority of myocarditis diagnostic codes in any coding position, and the overall PPV of the myocarditis codes was 73.5% (95% CI: 69.6-77.4%). However, the highest PPV (96.6%) for myocarditis diagnosis was noted with code I409 as the primary diagnosis. We found 132 inpatients (26.5%) who were false-positive myocarditis cases, identified by the ICD-10-CM codes, and potential reasons for misclassification included other inflammation diseases (n=35, 26.5%), pre-existing heart failure (n= 25, 18.9%) and acute myocardial infarction (n=16, 12.1%). Conclusion: The PPV of ICD-10-CM codes for myocarditis in Taiwan was acceptable, but some other inflammation diseases and pre-existing heart diseases may be falsely coded as myocarditis. Our results may serve future secondary database studies as a fundamental reference on the validity of myocarditis diagnosis codes.

Identification of reproducible radiomic features from on-board volumetric images: A multi-institutional phantom study.

BACKGROUND: Radiomics analysis using on-board volumetric images has attracted research attention as a method for predicting prognosis during treatment; however, the lack of standardization is still one of the main concerns. PURPOSE: This study investigated the factors that influence the reproducibility of radiomic features extracted from on-board volumetric images using an anthropomorphic radiomics phantom. Furthermore, a phantom experiment was conducted with different treatment machines from multiple institutions as external validation to identify reproducible radiomic features. METHODS: The phantom was designed to be 35 × 20 × 20 cm with eight types of heterogeneous spheres (⌀ = 1, 2, and 3 cm). On-board volumetric images were acquired using 15 treatment machines from eight institutions. Of these, kilovoltage cone-beam computed tomography (kV-CBCT) image data acquired from four treatment machines at one institution were used as an internal evaluation dataset to explore the reproducibility of radiomic features. The remaining image data, including kV-CBCT, megavoltage-CBCT (MV-CBCT), and megavoltage computed tomography (MV-CT) provided by seven different institutions (11 treatment machines), were used as an external validation dataset. A total of 1,302 radiomic features, including 18 first-order, 75 texture, 465 (i.e., 93 × 5) Laplacian of Gaussian (LoG) filter-based, and 744 (i.e., 93 × 8) wavelet filter-based features, were extracted within the spheres. The intraclass correlation coefficient (ICC) was calculated to explore feature repeatability and reproducibility using an internal evaluation dataset. Subsequently, the coefficient of variation (COV) was calculated to validate the feature variability of external institutions. An absolute ICC exceeding 0.85 or COV under 5% was considered indicative of a highly reproducible feature. RESULTS: For internal evaluation, ICC analysis showed that the median percentage of radiomic features with high repeatability was 95.2%. The ICC analysis indicated that the median percentages of highly reproducible features for inter-tube current, reconstruction algorithm, and treatment machine were decreased by 20.8%, 29.2%, and 33.3%, respectively. For external validation, the COV analysis showed that the median percentage of reproducible features was 31.5%. A total of 16 features, including nine LoG filter-based and seven wavelet filter-based features, were indicated as highly reproducible features. The gray-level run-length matrix (GLRLM) was classified as containing the most frequent features (N = 8), followed by the gray-level dependence matrix (N = 7) and gray-level co-occurrence matrix (N = 1) features. CONCLUSIONS: We developed the standard phantom for radiomics analysis of kV-CBCT, MV-CBCT, and MV-CT images. With this phantom, we revealed that the differences in the treatment machine and image reconstruction algorithm reduce the reproducibility of radiomic features from on-board volumetric images. Specifically, the most reproducible features for external validation were LoG or wavelet filter-based GLRLM features. However, the acceptability of the identified features should be examined in advance at each institution before applying the findings to prognosis prediction.

Renal transplant recipients undergoing endovascular abdominal aortic aneurysm repair have increased risk of perioperative acute kidney injury but no difference in late mortality.

OBJECTIVE: Renal transplant is associated with substantial survival advantage in patients with end-stage renal disease. However, little is known about the outcomes of renal transplant recipients (RTRs) after endovascular abdominal aortic aneurysm repair (EVAR). This study aimed to study the effect of renal transplant on perioperative outcomes and long-term survival after elective infrarenal EVAR. METHODS: The Vascular Quality Initiative database was queried for all patients undergoing elective EVAR from 2003 to 2021. Functioning RTRs were compared with non-renal transplant recipients without a diagnosis of end-stage renal disease (non-RTRs). The outcomes included 30-day mortality, acute kidney injury (AKI), new renal failure requiring renal replacement therapy (RRT), endoleak, aortic-related reintervention, major adverse cardiac events, and 5-year survival. A logistic regression analysis was used to assess the association between RTRs and perioperative outcomes. RESULTS: Of 60,522 patients undergoing elective EVAR, 180 (0.3%) were RTRs. RTRs were younger (median, 71 years vs 74.5 years; P < .001), with higher incidence of hypertension (92% vs 84%; P = .004) and diabetes (29% vs 21%; P = .005). RTRs had higher median preoperative serum creatinine (1.3 mg/dL vs 1.0 mg/dL; P < .001) and lower estimated glomerular filtration rate (51.6 mL/min vs 69.4 mL/min; P < .001). There was no difference in the abdominal aortic aneurysm diameter and incidence of concurrent iliac aneurysms. Procedurally, RTRs were more likely to undergo general anesthesia with lower amount of contrast used (median, 68.6 mL vs 94.8 ml; P < .001) and higher crystalloid infusion (median, 1700 mL vs 1500 mL; P = .039), but no difference was observed in the incidence of open conversion, endoleak, operative time, and blood loss. Postoperatively, RTRs experienced a higher rate of AKI (9.4% vs 2.7%; P < .001), but the need for new RRT was similar (1.1% vs 0.4%; P = .15). There was no difference in the rates of postoperative mortality, aortic-related reintervention, and major adverse cardiac events. After adjustment for potential confounders, RTRs remained associated with increased odds of postoperative AKI (odds ratio, 3.33; 95% confidence interval, 1.93-5.76; P < .001) but had no association with other postoperative complications. A subgroup analysis identified that diabetes (odds ratio, 4.21; 95% confidence interval, 1.17-15.14; P = .02) is associated with increased odds of postoperative AKI among RTRs. At 5 years, the overall survival rates were similar (83.4% vs 80%; log-rank P = .235). CONCLUSIONS: Among patients undergoing elective infrarenal EVAR, RTRs were independently associated with increased odds of postoperative AKI, without increased postoperative renal failure requiring RRT, mortality, endoleak, aortic-related reintervention, or major adverse cardiac events. Furthermore, 5-year survival was similar. As such, while EVAR may confer comparable benefits and technical success perioperatively, RTRs should have aggressive and maximally optimized renal protection to mitigate the risk of postoperative AKI.

Simultaneous versus staged resection for synchronous colorectal liver metastases: The win ratio approach.

INTRODUCTION: In order to investigate the optimal approach for synchronous colorectal liver metastases (sCRLM), we sought to use the "win ratio" (WR), a novel statistical approach, to assess the relative benefit of simultaneous versus staged surgical treatment. METHODS: Patients who underwent hepatectomy for sCRLM between 2008 and 2020 were identified from a multi-institutional database. The WR approach was utilized to compare composite outcomes of patients undergoing simultaneous versus staged resection. RESULTS: Among 1116 patients, 642 (57.5%) presented with sCRLM; 290 (45.2%) underwent simultaneous resection, while 352 (54.8%) underwent staged resection. In assessing the composite outcome, staged resection yielded a WR of 1.59 (95%CI 1.47-1.71) over the simultaneous approach for sCRLM. The highest WR occurred among patients requiring major hepatectomy (WR = 1.93, 95%CI 1.77-2.10) compared with patients who required minor liver resection (WR = 1.55, 95%CI 1.44-1.70). CONCLUSIONS: Staged resection was superior to simultaneous resection for sCRLM based on a WR assessment.

Clinical Safety and Effectiveness of Robotic-Assisted Surgery in Patients with Rectal Cancer: Real-World Experience over 8 Years of Multiple Institutions with High-Volume Robotic-Assisted Surgery.

The perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) are unclear. This retrospective observational study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions in Taiwan. Of the 605 enrolled patients, 301 (49.75%), 176 (29.09%), and 116 (19.17%) had lower, middle, and upper rectal cancers, respectively. Low anterior resection (377, 62.31%) was the most frequent surgical procedure. Intraoperative blood transfusion was performed in 10 patients (2%). The surgery was converted to an open one for one patient (0.2%), and ten (1.7%) patients underwent reoperation. The overall complication rate was 14.5%, including 3% from anastomosis leakage. No deaths occurred during surgery and within 30 days postoperatively. The positive rates of distal resection margin and circumferential resection margin were observed in 21 (3.5%) and 30 (5.0%) patients, respectively. The 5-year overall and disease-free survival rates for patients with stage I-III rectal cancer were 91.1% and 86.3%, respectively. This is the first multi-institutional study in Taiwan with 605 patients from three high-volume hospitals. The overall surgical and oncological outcomes were equivalent or superior to those estimated in other studies. Hence, RRS is an effective and safe technique for rectal resection in high-volume hospitals.

Clinical Characteristics of Patients with Ossification of the Posterior Longitudinal Ligament and a High OP Index: A Multicenter Cross-Sectional Study (JOSL Study).

BACKGROUND: The purpose of this study was to clarify the clinical features of ossification of the posterior longitudinal ligament (OPLL) and extreme ossification at multiple sites. METHODS: This prospective study involved patients with a diagnosis of cervical OPLL at 16 institutions in Japan. Patient-reported outcome measures, including responses on the Japanese Orthopaedic Association (JOA) Cervical Myelopathy Evaluation Questionnaire (JOA-CMEQ), JOA Back Pain Evaluation Questionnaire (JOA-BPEQ), and visual analog scale pain score, were collected to investigate clinical status. In each patient, the sum of the levels at which OPLL was located (OP index) was evaluated on whole-spine computed tomography, along with ossification of other spinal ligaments including the anterior longitudinal ligament (OALL), ligament flavum (OLF), supra- and intraspinous ligaments (SSL), and diffuse idiopathic skeletal hyperostosis (DISH). The distribution of OP index values in the study population was investigated, and the clinical and radiologic characteristics of patients in the top 10% were assessed. RESULTS: In total, 236 patients (163 male, 73 female; mean age 63.5 years) were enrolled. Twenty-five patients with OP index ≥ 17 were categorized into a high OP index group and the remainder into a moderate/low OP index group. There were significantly more women in the high OP index group. Patients in the high OP index group also had significantly poorer scores for lower extremity function and quality of life on the JOA-CMEQ and in each domain but not for body pain on the JOA-BPEQ compared with those in the moderate/low OP index group. Patients in the high OP index group had more OALL in the cervical spine and more OLF and SSL in the thoracic spine. The prevalence of DISH was also significantly higher in the high OP index group. In the high OP index group, interestingly, OPLL was likely to be present adjacent to DISH in the cervicothoracic and thoracolumbar spine, especially in men, and often coexisted with DISH in the thoracic spine in women. CONCLUSION: This prospective cohort registry study is the first to demonstrate the clinical and radiologic features of patients with OPLL and a high OP index. In this study, patients with a high OP index had poorer physical function in the lumbar spine and lower extremities and were also predisposed to extreme ossification of spinal ligaments other than the OPLL.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Dual block HER2 assessment increased HER2 immunohistochemistry positive rate in resected specimens of gastric cancer: a prospective multicenter clinical trial from China.

BACKGROUND: Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT02843412) was launched to verify its value and generality. METHODS: A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis. RESULTS: In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P < 0.001). Compared with single-block assessment, dual-block assessment increased the positive rate by approximate 20%. Similarly, HER2 equivocal (2+) rate was increased in dual block assessment (25.8%), which was higher than that in single block assessment (block 1: 20.3%, block 2: 20.9%) (P < 0.001). Conversely, dual block assessment demonstrated a lower HER2 negative (0/1+) rate (64.8%) than single block assessment (block1: 71.9%, block 2: 71.3%) (P < 0.001). These findings were also confirmed in individual hospitals. CONCLUSIONS: Dual block HER2 assessment effectively increased HER2 IHC positive rate in resected specimens of GC. We recommended dual block HER2 assessment be promoted in routine clinical practice in GC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02843412 . Registered 1 July 2016 - Retrospectively registered.

Outcomes of Gamma Knife radiosurgery for skull base chondrosarcomas: a multi-institutional retrospective study.

OBJECTIVE: Radiotherapy has an essential role in the management of skull base chondrosarcomas (SBCs) after resection. This multi-institutional study evaluated the outcomes of Gamma Knife radiosurgery (GKRS) for histopathologically proven SBCs. METHODS: Data of patients who underwent GKRS for SBCs at Gamma Knife centers in Japan were retrospectively collected. Patients without a histopathological diagnosis and those who had intracranial metastases from extracranial chondrosarcomas were excluded. Histologically, grade III and some nonconventional variants were identified as aggressive types. The cumulative local control rates (LCRs) and disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method. Factors potentially affecting the LCR were evaluated using the Cox proportional hazards model for bivariate and multivariate analyses. The incidence of radiation-induced adverse effects (RAEs) was calculated as crude rates, and factors associated with RAEs were examined using Fisher's exact test. RESULTS: Fifty-one patients were enrolled, with a median age of 38 years. Thirty patients (59%) were treated with upfront GKRS for residual SBCs after resection (n = 27) or biopsy (n = 3), and 21 (41%) underwent GKRS as a salvage treatment for recurrence. The median tumor volume was 8 cm3. The overall LCRs were 87% at 3 years, 78% at 5 years, and 67% at 10 years after GKRS. A better LCR was associated with a higher prescription dose (p = 0.039) and no history of repeated recurrence before GKRS (p = 0.024). The LCRs among patients with the nonaggressive histological type and treatment with ≥ 16 Gy were 88% at 3 years, 83% at 5 years, and 83% at 10 years. The overall survival rates after GKRS were 96% at 5 years and 83% at 10 years. Although RAEs were observed in 3 patients (6%), no severe RAEs with Common Terminology Criteria for Adverse Events grade 3 or higher were identified. No significant factor was associated with RAEs. CONCLUSIONS: GKRS for SBCs has a favorably low risk of RAEs and could be a reasonable therapeutic option for SBC in multimodality management. A sufficient GKRS prescription dose is necessary for higher LCRs. Histological grading and subtype evaluations are important for excluding exceptional SBCs. Patients with conventional SBCs have a long life expectancy and should be observed for life after treatment.

A multi-institutional study of salivary gland cytopathology: Application of the Milan System for Reporting Salivary Gland Cytopathology in Japan.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan. METHODS: In total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. RESULTS: The cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category. CONCLUSIONS: The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan.

Sites of invasion of cancer of the external auditory canal predicting oncologic outcomes.

BACKGROUND: This study aimed to reveal the influence of the invasion site of external auditory canal (EAC) cancer by analyzing the outcome of patients with advanced tumor. METHODS: A total of 111 patients with T4 EAC cancer were enrolled in this study. Of these patients, 79 underwent chemoradiotherapy and 32 underwent surgery under curative intent. Univariate and multivariate analyses and the Kaplan-Meier method were used to focus on the tumor invasion sites and overall survival of the patients. RESULTS: The 3-year overall survival rate of all patients was 55.0%. In multivariate analysis, the only significant invasion site for overall survival was the facial nerve, with the dura mater being the next most influential site. When Kaplan-Meier survival curve was calculated, facial nerve and dura mater were the significant factors resulting in poor patient outcomes. CONCLUSION: The facial nerve and dura mater are crucial sites of EAC cancer for patient outcomes.

Weight-Based Framework for Predictive Modeling of Multiple Databases With Noniterative Communication Without Data Sharing: Privacy-Protecting Analytic Method for Multi-Institutional Studies.

BACKGROUND: Securing the representativeness of study populations is crucial in biomedical research to ensure high generalizability. In this regard, using multi-institutional data have advantages in medicine. However, combining data physically is difficult as the confidential nature of biomedical data causes privacy issues. Therefore, a methodological approach is necessary when using multi-institution medical data for research to develop a model without sharing data between institutions. OBJECTIVE: This study aims to develop a weight-based integrated predictive model of multi-institutional data, which does not require iterative communication between institutions, to improve average predictive performance by increasing the generalizability of the model under privacy-preserving conditions without sharing patient-level data. METHODS: The weight-based integrated model generates a weight for each institutional model and builds an integrated model for multi-institutional data based on these weights. We performed 3 simulations to show the weight characteristics and to determine the number of repetitions of the weight required to obtain stable values. We also conducted an experiment using real multi-institutional data to verify the developed weight-based integrated model. We selected 10 hospitals (2845 intensive care unit [ICU] stays in total) from the electronic intensive care unit Collaborative Research Database to predict ICU mortality with 11 features. To evaluate the validity of our model, compared with a centralized model, which was developed by combining all the data of 10 hospitals, we used proportional overlap (ie, 0.5 or less indicates a significant difference at a level of .05; and 2 indicates 2 CIs overlapping completely). Standard and firth logistic regression models were applied for the 2 simulations and the experiment. RESULTS: The results of these simulations indicate that the weight of each institution is determined by 2 factors (ie, the data size of each institution and how well each institutional model fits into the overall institutional data) and that repeatedly generating 200 weights is necessary per institution. In the experiment, the estimated area under the receiver operating characteristic curve (AUC) and 95% CIs were 81.36% (79.37%-83.36%) and 81.95% (80.03%-83.87%) in the centralized model and weight-based integrated model, respectively. The proportional overlap of the CIs for AUC in both the weight-based integrated model and the centralized model was approximately 1.70, and that of overlap of the 11 estimated odds ratios was over 1, except for 1 case. CONCLUSIONS: In the experiment where real multi-institutional data were used, our model showed similar results to the centralized model without iterative communication between institutions. In addition, our weight-based integrated model provided a weighted average model by integrating 10 models overfitted or underfitted, compared with the centralized model. The proposed weight-based integrated model is expected to provide an efficient distributed research approach as it increases the generalizability of the model and does not require iterative communication.

Multi-institutional dose-segmented dosiomic analysis for predicting radiation pneumonitis after lung stereotactic body radiation therapy.

PURPOSE: To predict radiation pneumonitis (RP) grade 2 or worse after lung stereotactic body radiation therapy (SBRT) using dose-based radiomic (dosiomic) features. METHODS: This multi-institutional study included 247 early-stage nonsmall cell lung cancer patients who underwent SBRT with a prescribed dose of 48-70 Gy at an isocenter between June 2009 and March 2016. Ten dose-volume indices (DVIs) were used, including the mean lung dose, internal target volume size, and percentage of entire lung excluding the internal target volume receiving greater than x Gy (x = 5, 10, 15, 20, 25, 30, 35, and 40). A total of 6,808 dose-segmented dosiomic features, such as shape, first order, and texture features, were extracted from the dose distribution. Patients were randomly partitioned into two groups: model training (70%) and test datasets (30%) over 100 times. Dosiomic features were converted to z-scores (standardized values) with a mean of zero and a standard deviation (SD) of one to put different variables on the same scale. The feature dimension was reduced using the following methods: interfeature correlation based on Spearman's correlation coefficients and feature importance based on a light gradient boosting machine (LightGBM) feature selection function. Three different models were developed using LightGBM as follows: (a) a model with ten DVIs (DVI model), (b) a model with the selected dosiomic features (dosiomic model), and (c) a model with ten DVIs and selected dosiomic features (hybrid model). Suitable hyperparameters were determined by searching the largest average area under the curve (AUC) value in the receiver operating characteristic curve (ROC-AUC) via stratified fivefold cross-validation. Each of the final three models with the closest the ROC-AUC value to the average ROC-AUC value was applied to the test datasets. The classification performance was evaluated by calculating the ROC-AUC, AUC in the precision-recall curve (PR-AUC), accuracy, precision, recall, and f1-score. The entire process was repeated 100 times with randomization, and 100 individual models were developed for each of the three models. Then the mean value and SD for the 100 random iterations were calculated for each performance metric. RESULTS: Thirty-seven (15.0%) patients developed RP after SBRT. The ROC-AUC and PR-AUC values in the DVI, dosiomic, and hybrid models were 0.660 ± 0.054 and 0.272 ± 0.052, 0.837 ± 0.054 and 0.510 ± 0.115, and 0.846 ± 0.049 and 0.531 ± 0.116, respectively. For each performance metric, the dosiomic and hybrid models outperformed the DVI models (P < 0.05). Texture-based dosiomic feature was confirmed as an effective indicator for predicting RP. CONCLUSIONS: Our dose-segmented dosiomic approach improved the prediction of the incidence of RP after SBRT.