Purpose: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. Methods The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Purpose: Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. Methods: A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three nonAsian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy).The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. Results: The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively). Conclusion Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.

Purpose: Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels. Materials and Methods: We identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response. Results: Among 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders. Conclusion Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.

Purpose: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.

Background: Seroprevalence studies of coronavirus disease 2019 (COVID-19) from many countries have shown that the number of undiagnosed missing cases is much larger than that of confirmed cases, irrespective of seroprevalence levels. Considering the strategy of Korea entailing massive testing and contact tracing from the beginning of epidemic, the number of undiagnosed missing cases in Korea may be negligible. This study was conducted to estimate the seroprevalence of COVID-19 among individuals who were never diagnosed with COVID-19 in Daegu, the epicenter of COVID-19 epidemic in Korea. Methods: Serologic testing for immunoglobulin G antibody based on immunochromatographic assay was conducted in 103 patients and 95 guardians aged 18 to 82 years without any history of COVID-19 diagnosis, who visited outpatient clinics of a single university-affiliated hospital from May 25 to June 5, 2020. Results: The estimated seroprevalence was 7.6% (95% confidence interval, 4.3%–12.2%) with 15 positive cases. Among them, only one had a polymerase chain reaction (PCR)-confirmed case among their close contacts and 13 did not experience COVID-19-related symptoms. Seroprevalence was similar between patients and guardians. Based on this figure, the number of undiagnosed missing cases in Daegu was estimated to be a dozen times more than the number of confirmed cases based on PCR testing. Conclusion Despite the limitation of a small and unrepresentative sample, this is the first study on seroprevalence of COVID-19 in Korea. Our study suggested that the number of undiagnosed missing cases was substantial even with the stringent strategy adopted in Korea, similar to that of other countries.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
Classification ; Discrimination (Psychology) ; Disease-Free Survival ; Humans ; Joints ; Neoplasm Staging ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Survival Rate

OBJECTIVE: This study determined whether cognitive behavioral therapy for insomnia (CBT-i) decreased the need for sleep medications and produced better treatment outcomes than pharmacotherapy alone. METHODS: We reviewed data from patients with insomnia in the outpatient clinic of a general hospital between 2009 and 2015. We compared 41 patients who received five sessions of CBT-i with 100 age- and sex-matched patients who received pharmacotherapy only. We evaluated the change in prescription for sleep (i.e., antidepressants, hypnotics, and others) between the first and last visits using repeated measures analysis of variance (ANOVA). Clinical global impressions and completion status at the last visit were assessed using the chisquare test. RESULTS: We found a significant decrease in the prescription rate and the dosage of hypnotics among patients who received CBT-i when compared with control patients. There was no significant change in the dosage of antidepressants between the two groups. Achievement of case closure was better in the CBT-i group at the trend level. Clinical global impression at the last visit was not significantly different. CONCLUSION: These results show that CBT-i reduces the need for hypnotics among insomnia patients. Our results indicate that CBT-i offers additional benefits beyond improving sleep characteristics and thus provides another reason for recommending CBT-i as a first-line treatment for insomnia.
Ambulatory Care Facilities ; Antidepressive Agents ; Cognitive Therapy* ; Drug Therapy ; Hospitals, General ; Humans ; Hypnotics and Sedatives ; Prescriptions* ; Sleep Initiation and Maintenance Disorders*

OBJECTIVE: To determine the possibility of a new measurement tool using electromyography and ultrasonography for quantitative spasticity assessment in post-stroke patients. METHODS: Eight hemiplegic stroke patients with ankle plantarflexor spasticity confirmed by a Modified Ashworth Scale (MAS) were enrolled. Spasticity was evaluated using the MAS and Modified Tardieu Scale (MTS). Each subject underwent surface electromyography (sEMG) using the Brain Motor Control Assessment (BMCA) protocol and was compared with a healthy control group. Using ultrasonography, muscle architecture and elasticity index were measured from the medial gastrocnemius muscle (GCM) on the affected and unaffected sides. RESULTS: MAS and MTS revealed significant correlation with sEMG activity. The fascicle length and pennation angle were significantly decreased in the medial GCM on the hemiplegic side compared with the unaffected side. The elasticity index of the spastic medial GCM was significantly increased compared with the unaffected side. The MTS X and R2–R1 values were significantly correlated with the elasticity index in the hemiplegic GCM. The relationship between clinical evaluation tools and both BMCA and sonoelastography was linear, but not statistically significant in the multiple regression analysis. CONCLUSION: The BMCA protocol and ultrasonographic evaluation provide objective assessment of post-stroke spasticity. Further studies are necessary to conduct accurate assessment and treatment of spasticity.
Ankle ; Brain ; Elasticity ; Elasticity Imaging Techniques ; Electromyography ; Evaluation Studies as Topic* ; Humans ; Muscle Spasticity* ; Muscle, Skeletal ; Muscles ; Pilot Projects* ; Stroke ; Ultrasonography

PURPOSE: The American College of Surgeons Oncology Group Z0011 trial reported that complete dissection of axillary lymph nodes (ALNs) may not be warranted in women with clinical T1-T2 tumors and one or two involved ALNs who were undergoing lumpectomy plus radiation followed by systemic therapy. The present study was conducted to identify preoperative imaging predictors of ≥ 3 ALNs. MATERIALS AND METHODS: The training set consisted of 1,917 patients with clinical T1-T2 and node negative invasive breast cancer. Factors associated with ≥ 3 involved ALNs were evaluated by logistic regression analysis. The validation set consisted of 378 independent patients. The nomogram was applied prospectively to 512 patients who met the Z0011 criteria. RESULTS: Of the 1,917 patients, 204 (10.6%) had ≥ 3 positive nodes. Multivariate analysis showed that involvement of ≥ 3 nodes was significantly associated with ultrasonographic and chest computed tomography findings of suspicious ALNs (p < 0.001 each). These two imaging criteria, plus patient age, were used to develop a nomogram calculating the probability of involvement of ≥ 3 ALNs. The areas under the receiver operating characteristic curve of the nomogram were 0.852 (95% confidence interval [CI], 0.820 to 0.883) for the training set and 0.896 (95% CI, 0.836 to 0.957) for the validation set. Prospective application of the nomogram showed that 60 of 512 patients (11.7%) had scores above the cut-off. Application of the nomogram reduced operation time and cost, with a very low re-operation rate (1.6%). CONCLUSION: Patients likely to have ≥ 3 positive ALNs could be identified by preoperative imaging. The nomogram was helpful in selective intraoperative examination of sentinel lymph nodes.
Breast Neoplasms* ; Breast* ; Female ; Humans ; Logistic Models ; Lymph Nodes* ; Mastectomy, Segmental ; Multivariate Analysis ; Nomograms* ; Prospective Studies ; ROC Curve ; Surgeons ; Thorax

Brachial plexus injuries (BPI) can have devastating effects on upper extremity function, however, treatment in this injuries remains a difficult problem. Several kinds of surgical methods have been used to treat BPI, and nerve repair and nerve grafting have been traditionally used in postganglionic injury of brachial plexus. Because the several studies reported that nerve transfer to restore shoulder and elbow function has yielded superior results to historical reports for nerve grafting in partial BPI, the indication of nerve repair and nerve grafting has been decreased. Nonetheless, nerve repair and nerve grafting is still useful in focal damage in brachial plexus, such as laceration or gunshot wound and postganglionic neuroma in continuity without conduction of nerve action potential. In this paper, we described the basic concept, detailed indication and outcomes of nerve repair or nerve grafting in BPI.
Action Potentials ; Brachial Plexus* ; Elbow ; Lacerations ; Nerve Transfer ; Neuroma ; Shoulder ; Transplants* ; Upper Extremity ; Wounds, Gunshot