Clinical characteristics and prognosis of postpartum breast cancer.

PURPOSE: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, previous studies show that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). We aimed to analyze the clinical characteristics and prognosis of PPBC based on the diagnosis period of PPBC. METHODS: We retrospectively reviewed 208,780 patients with breast cancer from the Korean Breast Cancer Society registry (KBCSR) database between January 2000 and December 2014. We included premenopausal women aged 20-50 years who underwent breast cancer surgery. The patients were classified by 5-year intervals according to the diagnosis period of breast cancer, from the first birth to the breast cancer diagnosis. RESULTS: Compared with patients in the other groups, patients diagnosed within postpartum 5 years (PPBC < 5 years) group were younger, had a more advanced stage, had lower estrogen receptor (ER) and progesterone receptor (PR) expression, and had a higher human epidermal growth factor receptor 2 (HER2) positive rate. Further, PPBC < 5 years group had a worse survival rate than the nulliparous and other groups (5-year cumulative survival: PPBC < 5 years group, 89%; nulliparous group, 97.3%; 5 ≤ PPBC < 10 years group, 93%). In the multivariate analysis, the PPBC < 5 years group was associated with a worse survival rate (hazard ratio 1.55, 95% confidence interval [CI] 1.148-2.094, p 0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. CONCLUSION: Our findings indicated that patients diagnosed with breast cancer within the first 5 years after delivery had aggressive characteristics and a poor survival rate. It is important to elucidate the pathophysiology of PPBC and establish novel therapeutic strategies to improve the survival rate.

A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. METHODS: This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. DISCUSSION: This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

Clinicopathologic and Molecular Characteristics of and Diagnostic Dilemmas in Invasive Breast Carcinoma with Choriocarcinomatous Pattern apropos a New Case: A Literature Review with New Findings.

BACKGROUND: Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with ß-human chorionic gonadotropin (ß-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. METHODS: Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. RESULTS: Compared to the MC-B patients, the IBC-CP patients were older (p < 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed ß-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. CONCLUSION: The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.

Clinical significance of HER2 status in T1bN0 breast cancer: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: The prognosis of patients with node-negative T1b tumors according to human epidermal growth factor receptor 2 (HER2) status is not known. This group of patients has not been studied in the available randomized trials. The objective of this study was to evaluate the survival of patients in a monoethnic group diagnosed with T1b lymph node-negative breast cancer depending on HER2 status. METHODS: We analyzed 3110 patients with T1bN0M0 breast cancer whose data were deposited into the Korean Breast Cancer Society Registry database between 2000 and 2009. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared according to HER2 status. RESULTS: Among all patients, 494 (15.9%) had HER2-positive breast cancer. At a mean follow-up of 93 months, 108 deaths and 86 breast cancer-specific deaths were noted among all patients. There was no significant difference in OS between the HER2-negative and HER2-positive groups (p = 0.103). The same result was observed for BCSS. However, in the subgroup of estrogen receptor (ER)-positive women, HER2-negative patients had a better BCSS prognosis than HER2-positive patients (p = 0.025). Multivariate analysis also indicated a significant difference in BCSS in the ER-positive subgroup (HR 2.60; 95% CI 1.15-5.87; p = 0.021). CONCLUSION: This study analyzed a large nationwide and monoethnic cohort and found a significant difference only in BCSS in the ER-positive subgroup according to HER2 status. Anti-HER2 therapy may be considered in HER2-positive and ER-positive patients with small, node-negative breast cancer.

Differences in Perspectives of Medical Device Adverse Events: Observational Results in Training Program Using Virtual Cases.

BACKGROUND: Medical device adverse event reporting is an essential activity for mitigating device-related risks. Reporting of adverse events can be done by anyone like healthcare workers, patients, and others. However, for an individual to determine the reporting, he or she should recognize the current situation as an adverse event. The objective of this report is to share observed individual differences in the perception of a medical device adverse event, which may affect the judgment and the reporting of adverse events. METHODS: We trained twenty-three participants from twelve Asia-Pacific Economic Cooperation (APEC) member economies about international guidelines for medical device vigilance. We developed and used six virtual cases and six questions. We divided participants into six groups and compared their opinions. We also surveyed the country's opinion to investigate the beginning point of 'patient use'. The phases of 'patient use' are divided into: 1) inspecting, 2) preparing, and 3) applying medical device. RESULTS: As for the question on the beginning point of 'patient use,' 28.6%, 35.7%, and 35.7% of participants provided answers regarding the first, second, and third phases, respectively. In training for applying international guidelines to virtual cases, only one of the six questions reached a consensus between the two groups in all six virtual cases. For the other five questions, different judgments were given in at least two groups. CONCLUSION: From training courses using virtual cases, we found that there was no consensus on 'patient use' point of view of medical devices. There was a significant difference in applying definitions of adverse events written in guidelines regarding the medical device associated incidents. Our results point out that international harmonization effort is needed not only to harmonize differences in regulations between countries but also to overcome diversity in perspectives existing at the site of medical device use.

Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.

PURPOSE: Many breast cancer patients with positive axillary lymph nodes achieve complete node remission after neoadjuvant chemotherapy. The usefulness of sentinel lymph node biopsy in this situation is uncertain. This study evaluated the outcomes of sentinel biopsy-guided decisions in patients who had conversion of axillary nodes from clinically positive to negative following neoadjuvant chemotherapy. METHODS: We reviewed the records of 1247 patients from five hospitals in Korea who had breast cancer with clinically axillary lymph node-positive status and negative conversion after neoadjuvant chemotherapy, between 2005 and 2012. Patients who underwent axillary operations with sentinel biopsy-guided decisions (Group A) were compared with patients who underwent complete axillary lymph node dissection without sentinel lymph node biopsy (Group B). Axillary node recurrence and distant recurrence-free survival were compared. RESULTS: There were 428 cases in Group A and 819 in Group B. Kaplan-Meier analysis showed that recurrence-free survivals were not significantly different between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%; p = 0.148). Multivariate analysis also indicated the two groups had no significant difference in axillary and distant recurrence-free survival. CONCLUSIONS: For breast cancer patients who had clinical conversion of axillary lymph nodes from positive to negative following neoadjuvant chemotherapy, sentinel biopsy-guided axillary surgery, and axillary lymph node dissection without sentinel lymph node biopsy had similar rates of recurrence. Thus, sentinel biopsy-guided axillary operation in breast cancer patients who have clinically axillary lymph node positive to negative conversion following neoadjuvant chemotherapy is a useful strategy.

Clinical characteristics and outcomes of injuries in agricultural and nonagricultural workers visiting the emergency department: a propensity-matched analysis.

OBJECTIVE: Agriculture is a hazardous industry. However, previous studies have focused on injuries to agricultural workers without comparison with injuries to nonagricultural workers. Therefore, we compared the clinical characteristics and outcomes of injuries reported at an emergency department (ED) between agricultural workers and nonagricultural workers. METHODS: We established a prospective ED-based agricultural injury surveillance system at a tertiary university hospital. Adult patients visiting the ED for an injury were divided into farmer and non-farmer groups depending on their engagement with agriculture. Using an adjusted multivariate analysis and propensity score matching (age, sex, inhabitant, and insurance type), we compared the clinical characteristics and outcomes of injuries between the farmer and non-farmer groups. RESULTS: In total, 38,556 injured adult patients (37,746 in the non-farmer group and 810 in the farmer group) were available for the unmatched sample analysis. The 1,620 matched subjects were equally classified after one-to-one nearest-neighbor propensity score matching. A multivariate logistic regression analysis of the unmatched sample revealed higher adjusted odds ratios (ORs) for intensive care unit admission (adjusted OR, 1.752; P=0.003) and overall surgery (adjusted OR, 1.870; P<0.001) in the farmer group. In contrast, univariate logistic regression analyses of the propensity score-matched sample found a higher OR in the farmer group only for overall surgery (OR, 1.786; P<0.001). CONCLUSION: Injuries of agricultural workers had higher odds only of requiring surgery; differences in injury-related mortality between groups were not statistically significant in either the matched or unmatched sample analyses.

Minimal Access vs Conventional Nipple-Sparing Mastectomy.

Importance: While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM). Objective: To examine the differences in postoperative complications between C-NSM and M-NSM. Design, Setting, Participants: This was a retrospective multicenter cohort study enrolling 1583 female patients aged 19 years and older with breast cancer who underwent NSM at 21 university hospitals in Korea between January 2018 and December 2020. Those with mastectomy without preserving the nipple-areolar complex (NAC), clinical or pathological malignancy in the NAC, inflammatory breast cancer, breast cancer infiltrating the chest wall or skin, metastatic breast cancer, or insufficient medical records were excluded. Data were analyzed from November 2021 to March 2024. Exposures: M-NSM or C-NSM. Main Outcomes and Measures: Clinicopathological factors and postoperative complications within 3 months of surgery were assessed. Statistical analyses, including logistic regression, were used to identify the factors associated with complications. Results: There were 1356 individuals (mean [SD] age, 45.47 [8.56] years) undergoing C-NSM and 227 (mean [SD] age, 45.41 [7.99] years) undergoing M-NSM (35 endoscopy assisted and 192 robot assisted). There was no significant difference between the 2 groups regarding short- and long-term postoperative complications (<30 days: C-NSM, 465 of 1356 [34.29%] vs M-NSM, 73 of 227 [32.16%]; P = .53; <90 days: C-NSM, 525 of 1356 [38.72%] vs M-NSM, 73 of 227 [32.16%]; P = .06). Nipple-areolar complex necrosis was more common in the long term after C-NSM than M-NSM (C-NSM, 91 of 1356 [6.71%] vs M-NSM, 5 of 227 [2.20%]; P = .04). Wound infection occurred more frequently after M-NSM (C-NSM, 58 of 1356 [4.28%] vs M-NSM, 18 of 227 [7.93%]; P = .03). Postoperative seroma occurred more frequently after C-NSM (C-NSM, 193 of 1356 [14.23%] vs M-NSM, 21 of 227 [9.25%]; P = .04). Mild or severe breast ptosis was a significant risk factor for nipple or areolar necrosis (odds ratio [OR], 4.75; 95% CI, 1.66-13.60; P = .004 and OR, 8.78; 95% CI, 1.88-41.02; P = .006, respectively). Conversely, use of a midaxillary, anterior axillary, or axillary incision was associated with a lower risk of necrosis (OR for other incisions, 32.72; 95% CI, 2.11-508.36; P = .01). Necrosis occurred significantly less often in direct-to-implant breast reconstruction compared to other breast reconstructions (OR, 2.85; 95% CI, 1.11-7.34; P = .03). Conclusions and Relevance: The similar complication rates between C-NSM and M-NSM demonstrates that both methods were equally safe, allowing the choice to be guided by patient preferences and specific needs.

Current practices for paediatric procedural sedation and analgesia in emergency departments: results of a nationwide survey in Korea.

OBJECTIVE: Procedural sedation and analgesia (PSA) in children has become a standard tool in emergency settings, but no national PSA guidelines have been developed for the emergency department (ED) in Korea. Therefore, we investigated the practice of PSA and the level of adherence to institutional PSA guidelines in EDs of teaching hospitals. METHODS: This study was a cross-sectional, web-based survey. The study subjects were the faculty of EDs from 96 teaching hospitals. The questionnaire was posted on an internet site, and the participants were requested that the questionnaire be answered by email and telephone in May 2009. RESULTS: The questionnaires were completed by 67.7% of the participants. Only 20% of EDs had institutional PSA guidelines, 21.5% of those had discharge criteria and 13.8% of EDs had a discharge instruction form. Residents were administered PSA at 76.9% of EDs. The airway rescue equipment was near the area where PSA was performed in 76.9% of EDs. The most commonly used medication for both diagnostic imaging and painful procedure was oral chloral hydrate (87.7%, 61.5%). In 64.6% of EDs, patients were monitored. In only 21 cases, EDs (50.0%) monitored the patients to recovery after PSA or discharge. CONCLUSIONS: Current PSA for paediatric patients have not been appropriately applied in Korea. Unified PSA guidelines were rare in the hospitals surveyed, and many patients were not monitored over an appropriate duration, nor did they receive adequate medications for sedation by the best trained personnel. Therefore, the national PSA guidelines must be developed and implemented as early as possible.

Faculty perceptions and use of e-learning resources for medical education and future predictions.

PURPOSE: This study aims to investigate medical faculties' perceptions and current practice of using e-learning resources, needs and suggestions for more effective use of such resources, and future directions of e-learning in medical education. METHODS: This descriptive study was conducted on full-time faculty members who were registered users of the e-learning portal of the consortium of Korean medical schools. Participants were invited to an online survey containing 45 items that addressed their perceptions and use of e-learning resources, and their predictions of future use. Descriptive analysis and reliability analysis were conducted as well as a thematic analysis of qualitative data. RESULTS: Ninety faculty members from 31 medical schools returned the questionnaires. Participants positively perceived e-learning resources and that they predicted their use would become increasingly popular. Still, only half of the respondents were using e-learning resources for teaching and agreed that they were willing to share their e-learning resources. Our study illustrates several barriers inhibit faculty use and sharing of e-learning resources, and a need for a more comprehensive, better-organized resource repository. Participants also pointed out the needs for more resources on multimedia assessment items, clinical videos, and virtual patients. CONCLUSION: Our study sheds light on medical faculty needs for institutional support and faculty development programs on e-learning, and institutional policies that address faculty concerns regarding ownership, intellectual property rights, and so forth on creating and sharing such resources. Collaborations among medical schools are suggested for creating a better organized around learning outcomes and more comprehensive repository of resources.

Robot-assisted Nipple Sparing Mastectomy: Recent Advancements and Ongoing Controversies.

Purpose of review: The purpose of this review is to summarize the recent technical advancements in RNSM, describe the ongoing teaching programs, and discuss the ongoing controversies. Recent findings: Robot-assisted nipple sparing mastectomy (RNSM) is the newest addition to the armamentarium of surgical techniques for patients who require a mastectomy. The potential benefits of using the da Vinci® Robotic Surgical System (Intuitive Surgical, Sunnyvale, CA) are the small 3D camera and lighting offering superior visualization, the Endowrist robotic instruments offering greater range of motion, and surgeon being at a seated position at the console rendering a more ergonomic operating position. Summary: RNSM can potentially help overcome the technical difficulties of performing a conventional NSM. Further studies are needed to elucidate the oncologic safety and cost-effectiveness of RNSM.

Predictive biological factors for late survival in patients with HER2-positive breast cancer.

The human epidermal growth factor receptor-2 (HER2) enriched subtype of breast cancer is associated with early recurrence, mostly within 5 years. However, anti-HER2 therapies have improved outcomes and their benefits persist in the long term. This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. We analyzed 20,672 patients with HER2-positive stage I-III breast cancer. The patients were divided into two groups based on a follow-up period of 60 months. The multivariate analysis of factors associated with poor overall survival included old age, advanced pathologic tumor size stage (pT), advanced pathologic regional lymph node stage (pN), high histological grade, presence of lymphatic and vascular invasion, and HR-negative status within 60 months. In the breast cancer-specific survival (BCSS) of the > 60 months follow-up group, the hazard ratios (HRa) based on pN-negative were 3.038, 3.722, and 4.877 in pN1 (p = 0.001), pN2 (p < 0.001), and pN3 (p < 0.001), respectively. Only pT4 level was statistically significant in the pT group (HRa, 4.528; p = 0.007). Age (HRa, 1.045, p < 0.001) and hormone receptor-positive status (HRa, 1.705, p = 0.022) were also associated to worse BCSS. Although lymphatic invasion was not significantly associated with BCSS, there was a tendency toward a relationship (p = 0.079) with worse BCSS. In HER2-positive breast cancer patients, node status had a more significant relationship with long-term prognosis than T stage. Patients with HER2-positive breast cancer who have T4 or node-positive should be considered for clinical observation and education beyond 5 years.

A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery.

Based on the American College of Surgeons Oncology Group (ACOSOG)-Z0011, a useful nomogram has been constructed to identify patients who do not require intraoperative frozen sections to evaluate sentinel lymph nodes in the previous study. This study investigated the developed nomogram by ultrasonography (US) and positron emission tomography (PET)/computed tomography (CT) as a modality. In the training set, 89/1030 (8.6%) patients had three or more positive nodes. Larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT were associated in multivariate analysis. The areas under the receiver operating characteristic curve (AUC) of the nomogram were 0.856 [95% CI 0.815-0.897] in the training set. The AUC in the validation set was 0.866 [95% CI 0.799-0.934]. Application of the nomogram to 1067 patients who met the inclusion criteria of ACOSOG-Z0011 showed that 90 (8.4%) patients had scores above the cut-off and a false-negative result was 37 (3.8%) patients. And the specificity was 93.8%, and the negative predictive value was 96.4%. The upgraded nomogram improved the predictive accuracy, using only US and PET/CT. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes and considering candidates for identifying neoadjuvant chemotherapy. The patients consisted of clinical T1-2 and node-negative invasive breast cancer. The training and validation set consisted of 1030 and 781 patients, respectively. A nomogram was constructed by analyzing factors related to three or more axillary lymph node metastases. The patients who matched the ACOSOG-Z0011 criteria were selected and applied to the new nomogram.

Traumatic brain injury in patients aged ≥65 years versus patients aged ≥80 years: a multicenter prospective study of mortality and medical resource utilization.

OBJECTIVE: This study aimed to determine whether there is a difference in mortality and medical resource utilization between geriatric (aged ≥65 years) and super-geriatric patients (aged ≥80 years) with traumatic brain injury (TBI). METHODS: We obtained comprehensive data (demographics, injury characteristics, injury severities, and outcomes) of geriatric and super-geriatric TBI patients from an emergency department-based injury surveillance system database from 2011 to 2016. Multivariate logistic regression analysis was performed to compare the mortality and nonroutine discharge (NRDC) status between both groups. RESULTS: Among 442,533 TBI patients, 48,624 were older than 65 years. A total of 48,446 patients (37,140 geriatric and 11,306 super-geriatric) without exclusion criteria were included in the final analysis. Both overall in-hospital mortality (adjusted odds ratio, 1.88; 95% confidence interval [CI], 1.28 to 2.74; P=0.001) and NRDC (adjusted odds ratio, 1.35; 95% CI, 1.07 to 1.71; P=0.011) were significantly higher in the super-geriatric group. In the stratified analysis, there were no significant differences in NRDC rate for all stratifications of treatment timing (emergency department vs. ward admission), but mortality remained to be significant for all stratifications. CONCLUSION: Super-geriatric TBI patients showed a significantly higher risk-adjusted overall mortality and more inadequate medical resource utilization than did geriatric TBI patients. However, super-geriatric patients were more likely to undergo NRDC after admission; thus, further research about age-related health inequalities is needed in the treatment of super-geriatric patients.

Impact of the COVID-19 Pandemic on the Diagnosis and Surgery of Breast Cancer: A Multi-Institutional Study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the rates of screening, case identification, and referral for cancer diagnosis. We investigated the diagnosis and surgery status of breast cancer before and after the COVID-19 pandemic at a multi-institutional level. METHODS: We collected breast cancer data from the clinical data warehouse which contained the medical records of patients from six academic institutions in South Korea. Patients were divided into two groups: February to April (period A) and May to July (period B). The data from the two groups were then compared against the same periods in 2019 and 2020. The primary objective was to investigate the differences in breast cancer stages before and after the COVID-19 pandemic. RESULTS: Among 3,038 patients, there was a 9.9% reduction in the number of diagnoses in 2020. This decrease was more significant during period A than period B. The breast cancer stage was not statistically different in period A (p = 0.115), but it was in period B (p = 0.001). In the subset analysis according to age, there was a statistical difference between 2019 and 2020 in period B for patients under the age of 65 years (p = 0.002), but no difference was observed in the other groups. CONCLUSION: The number of breast cancer cases declined during the pandemic, and the staging distribution has changed after the pandemic peak.

A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial).

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03975179; Clinical Research Information Service Identifier: KCT0004606.

Peripheral Pain Modulation of Chrysaora pacifica Jellyfish Venom Requires Both Ca2+ Influx and TRPA1 Channel Activation in Rats.

The venom of jellyfish triggers severe dermal pain along with inflammation and tissue necrosis, and occasionally, induces internal organ dysfunction. However, the basic mechanisms underlying its cytotoxic effects are still unknown. Here, we report one of the mechanisms involved in peripheral pain modulation associated with inflammatory and neurotoxic oxidative signaling in rats using the venom of jellyfish, Chrysaora pacifica (CpV). This jellyfish is identified by brown tentacles carrying nematocysts filled with cytotoxic venom that induces severe pain, pruritus, tentacle marks, and blisters. The subcutaneous injection of CpV into rat forepaws in behavioral tests triggered nociceptive response with a decreased threshold for mechanical pain perception. These responses lasted up to 48 h and were completely blocked by verapamil and TTA-P2, T-type Ca2+ channel blockers, or HC030031, a transient receptor potential cation ankyrin 1 (TRPA1) channel blocker, while another Ca2+ channel blocker, nimodipine, was ineffective. Also, treatment with Ca2+ chelators (EGTA and BaptaAM) significantly alleviated the CpV-induced pain response. These results indicate that CpV-induced pain modulation may require both Ca2+ influx through the T-type Ca2+ channels and activation of TRPA1 channels. Furthermore, CpV induced Ca2+-mediated oxidative neurotoxicity in the dorsal root ganglion (DRG) and cortical neurons dissociated from rats, resulting in decreased neuronal viability and increased intracellular levels of ROS. Taken together, CpV may activate Ca2+-mediated oxidative signaling to produce excessive ROS acting as an endogenous agonist of TRPA1 channels in the peripheral terminals of the primary afferent neurons, resulting in persistent inflammatory pain. These findings provide strong evidence supporting the therapeutic effectiveness of blocking oxidative signaling against pain and cytotoxicity induced by jellyfish venom.