Breast cancer patients' postoperative outcomes in nipple-sparing mastectomy and reconstruction with subpectoral implant placement: a single center experience.

Background: The continuous increase in the rate of nipple sparing mastectomy (NSM), the development of several reconstructive techniques and the following introduction of acellular derma matrix (ADM) has revolutionized implant-based breast reconstruction. This study aimed to investigate postoperative complications, health-related quality of life (HRQoL) and patients' satisfaction in patients undergoing NSM and breast reconstruction with or without ADM. Methods: Enrolled patients were divided into three groups: immediate breast reconstruction (IBR) with definitive implant and ADM (Group A), IBR only with definitive prosthesis (Group B), and two-stage breast reconstruction (Group C). The postoperative complications, BREAST-Q outcomes and reoperations were compared. Results: A total of 105 BC patients were enrolled and a total of 139 post-mastectomy breast reconstructions were performed. Seroma was the most prevalent complication observed: 8.3% in Group A, 2.9% in Group B and 5.7% in Group C. Postoperative infection occurred in two patients of Group A (5.6%), one patient of Group B (2.9%) and one of Group C (2.9%). Group A reported larger drain volume (1,125±243.5 cc), longer drain period (13.2±2.8 days), and the lowest incidence of capsular contracture (5.6%). The BREAST-Q patient-reported outcome measures document that all patients aged ≥50 years presented a higher score in "Satisfaction with breast" (P<0.001) and "Satisfaction with outcome" domains (P<0.05). Performing a bilateral breast reconstruction was associated to higher scores in "Physical wellbeing chest domain" (P<0.05). In addition, patients in Group A and Group B reported higher score in "Satisfaction with the breast" domain (P<0.001) but only in Group B we reported a higher score in "Satisfaction with outcome" (P<0.001). Conclusions: Subpectoral IBR results in manageable complications and greater personal satisfaction. The ADM could improve breast reconstruction reducing the rate of capsular contracture. The prepectoral placement of ADM could minimize complications and optimize aesthetic results.

Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: a single-center study.

BACKGROUND: In invasive breast cancer, there are no differences among the mid- and long-term oncological safety results of nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM), and simple mastectomy (SM). There are several reports comparing NSM and SSM with SM in the context of ductal carcinoma in situ (DCIS); however, the eligibility criteria vary among institutions, and there are no reports that compare all three surgical methods simultaneously within the same institution. This study aimed to compare the local recurrence and survival rates of the three techniques (NSM, SSM, and SM) in Japanese patients undergoing mastectomy for DCIS. METHODS: Patients undergoing NSM, SSM, or SM at our institution between 2006 and 2015 were identified, and their outcomes were analyzed. RESULTS: The mean follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). NSM was performed in 152 cases, SSM in 49, and SM in 44. Five of 245 patients developed local recurrences. Four of these patients had invasive cancer. The primary endpoints of 5-year cumulative local recurrence were 2.4% (95% confidence interval [CI]: 0.0-5.0) for NSM, 2.2% (95% CI: 0.0-6.3) for SSM, and 0% (95% CI: 0.0-0.0) for SM. There were no significant differences among the 5-year local recurrence rates. CONCLUSIONS: In this single-center, retrospective study, the oncological safety of SSM and NSM for DCIS was comparable to that of conventional SM.

To acellular dermal matrix or not to acellular dermal matrix?-outcomes of pre-pectoral prosthetic reconstruction after nipple-sparing mastectomy with and without acellular dermal matrix.

Background: Acellular dermal matrix (ADM) has been the go-to biomaterial in post-mastectomy breast reconstruction, particularly in pre-pectoral reconstruction. ADM is thought to decrease capsular contracture, control the pocket, and increase soft tissue, but may yield more complications. This study evaluated whether ADM is even needed. Methods: All patients undergoing immediate breast reconstruction with pre-pectoral tissue expander (TE) or direct-to-implant (DTI) after nipple-sparing mastectomy (NSM) by the senior author between April 2013 and January 2021, were included in this study. Cohorts were stratified into breasts with ADM or no-ADM. Complications within 30 days post-operatively were analyzed. Results: A total of 115 pre-pectoral reconstructions were performed in 66 patients. ADM was applied to 75 breasts. TEs were used in 80 breasts and DTI in 35 breasts. Controlling for implant type, breasts with ADM exhibited more nipple necrosis (28.0% vs. 10.0%, P=0.02). Controlling for ADM status, DTI compared to TE was associated with less necrosis of the nipple (11.4% vs. 26.3%, P=0.04), implant loss (5.7% vs. 38.8%, P=0.004), and surgery for any complication (14.3% vs. 27.5%, P=0.04). Conclusions: Outcomes of prosthetic reconstructions with ADM and no-ADM were similar. DTI reconstruction was associated with less complications, which was likely due to intraoperative bias and placement of TEs more often in breasts with perceived poorer vascularity.

Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots.

Unveiling Intricacies of DIEP Breast Reconstruction Post Early Breast Cancer: A Deep Dive into a Case of Unforeseen Complications.

In the vast expanse of restorative surgical procedures, the Deep Inferior Epigastric Perforator (DIEP) flap, originating from the inferior epigastric artery, has emerged as the preferred method of breast reconstruction, attributable to its myriad advantages. The technique provides reliable vascular supply, robust tissue volume for excision, minimal invasiveness to the donor site, with direct closure and concealment of the said site. This paper embarks on an elaborate elucidation of the DIEP surgical procedure, pivoting on the analytical exploration of a particular instance where necrosis of the skin flap occurred following immediate DIEP breast reconstruction in a patient diagnosed with early-stage breast cancer. This patient had previously undergone Nipple Areola Complex Sparing Mastectomy (NSM). We endeavor to extrapolate insights from this singular case of post-NSM DIEP breast reconstruction failure and correlate our findings with current literature dedicated to similar instances of surgical failure in DIEP breast reconstruction.

Nipple-areolar complex malposition in breast reconstruction after nipple-sparing mastectomy: a multi-institutional retrospective observational study in Japan.

BACKGROUND: Position of the nipple-areolar complex (NAC) is an important factor in the esthetic impression of the breast, and NAC malposition is often an issue in breast reconstruction after nipple-sparing mastectomy (NSM). The purpose of this study was to evaluate the degree of NAC malposition depending on several factors using data quantified with the Mamma Balance application (Medic Engineering K.K., Kyoto, Japan). METHODS: Patients who underwent unilateral breast reconstruction after NSM at eight hospitals in Japan between 2007 and 2020 were retrospectively investigated. Using Mamma Balance, NAC malposition was quantified separately in horizontal and vertical directions using patient photographs from pre-operatively and 6-24 months post-operatively. The degree of malpositioning was then statistically compared using various factors. RESULTS: The NAC deviated more cranially and medially with implants than that with flaps. Cases with latissimus dorsi flap showed lateral malposition more often than cases with deep inferior epigastric artery perforator flap. With flaps, lateral incisions showed more lateral malposition, and peri-areolar incisions tended to show more medial NAC malposition. In cases with severe post-operative infection of the implant, the NAC tended to deviate cranially. In radiation cases, the NAC deviated cranially. No significant difference was observed according to the degree of breast ptosis or use of the pull-down operation. Only a very weak correlation was observed between a larger amount of mastectomy and more cranial NAC malposition with both flaps and implants. CONCLUSIONS: This study provides insights into the tendencies and characteristics of NAC malposition.

The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.

The accumulation of lipid droplets (LDs) and ceramides (Cer) is linked to non-alcoholic fatty liver disease (NAFLD), regularly co-existing with type 2 diabetes and decreased immune function. Chronic inflammation and increased disease severity in viral infections are the hallmarks of the obesity-related immunopathology. The upregulation of neutral sphingomyelinase-2 (NSM2) has shown to be associated with the pathology of obesity in tissues. Nevertheless, the role of sphingolipids and specifically of NSM2 in the regulation of immune cell response to a fatty acid (FA) rich environment is poorly studied. Here, we identified the presence of the LD marker protein perilipin 3 (PLIN3) in the intracellular nano-environment of NSM2 using the ascorbate peroxidase APEX2-catalyzed proximity-dependent biotin labeling method. In line with this, super-resolution structured illumination microscopy (SIM) shows NSM2 and PLIN3 co-localization in LD organelles in the presence of increased extracellular concentrations of oleic acid (OA). Furthermore, the association of enzymatically active NSM2 with isolated LDs correlates with increased Cer levels in these lipid storage organelles. NSM2 enzymatic activity is not required for NSM2 association with LDs, but negatively affects the LD numbers and cellular accumulation of long-chain unsaturated triacylglycerol (TAG) species. Concurrently, NSM2 expression promotes mitochondrial respiration and fatty acid oxidation (FAO) in response to increased OA levels, thereby shifting cells to a high energetic state. Importantly, endogenous NSM2 activity is crucial for primary human CD4+ T cell survival and proliferation in a FA rich environment. To conclude, our study shows a novel NSM2 intracellular localization to LDs and the role of enzymatically active NSM2 in metabolic response to enhanced FA concentrations in T cells.

Reverse-sequence endoscopic nipple-sparing mastectomy with immediate implant-based breast reconstruction: an improvement of conventional minimal access breast surgery.

Background: Our center proposes a new technique that effectively provides space to broaden the surgical field of view and overcomes the limitations of endoscopy-assisted nipple-sparing mastectomy (E-NSM) by changing the dissection sequence and combining it with air inflation. The purpose of this study was to compare the clinical outcomes of the new technique designated "reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) with subpectoral breast reconstruction (SBR)" and the conventional E-NSM (C-E-NSM) with SBR. Method: All patients undergoing E-NSM with SBR at our breast center between April 2017 and December 2022 were included in this study. The cohort was divided into the C-E-NSM group and the R-E-NSM group. The operation time, anesthesia time, medical cost, complications, cosmetic outcomes, and oncological safety were compared. Results: Twenty-six and seventy-nine consecutive patients were included in the C-E-NSM and R-E-NSM groups, with average ages of 36.9 ± 7.0 years and 39.7 ± 8.4 years (P=0.128). Patients in the R-E-NSM group had significantly shorter operation time (204.6 ± 59.2 vs. 318.9 ± 75.5 minutes, p<0.001) and anesthesia time (279.4 ± 83.9 vs. 408.9 ± 87.4 minutes, p<0.001) and decreased medical costs [5063.4 (4439.6-6532.3) vs. 6404.2 (5152.5-7981.5), USD, p=0.001] and increase SCAR-Q scores (77.2 ± 17.1 vs. 68.8 ± 8.7, P=0.002) compared to the C-E-NSM group. Although trends increased in both the excellent rate of Ueda scores (53.8% vs. 42.3%, P = 0.144), excellent rate of Harris scores (44.0% vs. 63.1%, P=0.102), and decreased surgical complications (7.6% vs. 19.2%, P = 0.135) were observed in the R-E-NSM group, the differences were not significant. There were no significant differences in oncological outcomes between the two groups. Conclusion: R-E-NSM improves cosmetic outcomes and efficiency of C-E-NSM, reduces medical costs, and has a trend of lower surgical complications while maintaining the safety of oncology. It is a safe and feasible option for oncological procedures that deserves to be promoted and widely adopted in practice.

A mRNA Vaccine for Crimean-Congo Hemorrhagic Fever Virus Expressing Non-Fusion GnGc Using NSm Linker Elicits Unexpected Immune Responses in Mice.

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo Hemorrhagic virus (CCHFV), is listed in the World Health Organization's list of priority diseases. The high fatality rate in humans, the widespread distribution of CCHFV, and the lack of approved specific vaccines are the primary concerns regarding this disease. We used microfluidic technology to optimize the mRNA vaccine delivery system and demonstrated that vaccination with nucleoside-modified CCHFV mRNA vaccines encoding GnNSmGc (vLMs), Gn (vLMn), or Gc (vLMc) induced different immune responses. We found that both T-cell and B-cell immune responses induced by vLMc were better than those induced by vLMn. Interestingly, immune responses were found to be lower for vLMs, which employed NSm to link Gn and Gc for non-fusion expression, compared to those for vLMc. In conclusion, our results indicated that NSm could be a factor that leads to decreased specific immune responses in the host and should be avoided in the development of CCHFV vaccine antigens.

Clinical Outcomes of Transaxillary Reverse-Sequence Endoscopic Nipple-Sparing Mastectomy and Direct-to-Implant Prepectoral Breast Reconstruction: A Prospective Study of Initial 68 Procedures.

BACKGROUND: Minimal access breast surgery improves cosmetic outcomes over conventional breast surgery but still faces barriers in becoming standard procedure for breast reconstruction. This report introduces a novel technique of transaxillary reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) followed by direct-to-implant prepectoral breast reconstruction (DTI-PBR) and describes its clinical outcomes. METHODS: This prospective study enrolled patients who underwent R-E-NSM and DTI-PBR from March 2021 to December 2021 at a single institution. Perioperative data, surgical complications, oncologic outcomes, and patient- and surgeon-reported cosmetic results were noted. RESULTS: The 60 patients in this study who underwent 68 R-E-NSM and DTI-PBR had a mean age was 40.4 ± 10.3 years. The average durations of uni- and bilateral operations were 156.5 ± 48.3 min and 191.3 ± 36.1 min, respectively. The overall surgical complication rate was 13.3%, including 10.0% of patients with minor complications and 3.3% of patients with major complications. The study had one case (1.7%) of implant loss and one case (1.7%) of skin flap necrosis treated by reoperation. During the median follow-up period of 24 months, one patient (1.7%) who discontinued chemotherapy for myelosuppression experienced liver metastases 5 months postoperatively, and one patient experienced new-onset contralateral ductal carcinoma in situ 24 months postoperatively. The preoperative and 18-month postoperative Breast-Q scores for satisfaction with breasts, psychosocial well-being, sexual well-being, and chest well-being did not differ significantly, and the Scar-Q was 81.2 ± 14.5 points. The good-to-excellent rate in surgeon-reported cosmetic results reached 90%. CONCLUSIONS: Transaxillary R-E-NSM followed by DTI-PBR is a safe and efficient technique with high cosmetic outcomes and reliable medium-term oncologic results.

Is minimal-accessed (endoscopic- or robotic-assisted) nipple-sparing mastectomy contraindicated for large breasts?

BACKGROUND: In the developmental stage of minimal-accessed nipple-sparing mastectomy (MA-NSM), selecting patients with small to medium-sized breasts was common for better cosmetic outcomes and oncological safety. However, the suitability of MA-NSM for large, ptotic breasts remained uncertain. This retrospective study aim to assess MA-NSM outcomes in patients with large breasts. MATERIALS AND METHODS: This retrospective study included patients receiving conventional NSM (C-NSM) and MA-NSM from January 2011 to September 2022, at a single institution. We analyzed perioperative parameters and clinical outcomes based on breast specimen size, classified as small (≤300 g), medium (>300-450 g), large (>450-600 g), and very large (>600 g). RESULTS: A total of 728 patients was enrolled. C-NSM was performed in 51% (371/728) of cases, while MA-NSM was done in 49% (357/728). The overall complication rate of MA-NSM was comparable to C-NSM (p = 0.573), but severe complications (Clavien-Dindo, CD III) was significantly reported more following C-NSM, regardless of breast size. During a median follow-up of 52 months, no significant difference in oncological outcomes was observed. Comparing MA-NSM and C-NSM outcomes in large-very large breasts (>450 g), MA-NSM demonstrated significantly less blood loss (p = 0.036) and lower incidence of severe complications (CD ≥ III) compared to C-NSM (p = 0.002). CONCLUSION: MA-NSM is feasible for large breasts and offers benefits by reducing blood loss and decreasing the incidence of severe complications (CD ≥ III) in this patient group.

Efficacy and safety of intercostal nerve anastomosis in immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy: a randomized, controlled, open-label clinical study.

Purpose: This aims to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Methods: From 2022 to 2023, female patients between the ages of 20 and 60 diagnosed with stage I-IIIA breast cancer, who required and were willing to undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (the nerves with appropriate length and thickness were selected from the 2nd-4th intercostal nerves, which were then dissociated and anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. The patients' breast local sensation was assessed using Semmes-Weinstein monofilaments before the operation as well as at 10 days, 3 months, and 6 months postoperatively. Furthermore, the patients' quality of life was evaluated 6 months postoperatively using the EORTC QLQ-C30 questionnaire. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded. Results: Compared to the pre-operative period, a significant decrease in local sensation was observed 10 days after surgery in both groups. However, the control group showed a significant reduction in sensation at 3 and 6 months postoperatively, while the treatment group showed noticeable recovery. A statistically significant difference (P < 0.001) in local sensation between the pre-operative and post-operative periods was observed at the final follow-up in the two groups. By the time of 3 and 6 months postoperatively, a significant difference was seen in the local sensation between the two groups. Intercostal nerve anastomosis was found to significantly improve the patients' quality of life, including emotional (P = 0.01), physical (P = 0.04), and social functioning (P = 0.02) and pain (P = 0.04). There were no significant differences in general characteristics (such as age, BMI, and subtypes). Although intercostal nerve anastomosis increased the duration of operation by around 20 min (P < 0.001), it did not affect the volume or duration of postoperative drainage tube usage between the two groups. Conclusion: This study indicated that intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=42487, identifier ChiCTR1900026340.

Patient-reported outcomes of mesh in minimally invasive (laparoscopic/robot-assisted) immediate subpectoral prosthesis breast reconstruction: a retrospective study.

BACKGROUND: Although there is increasing interest in minimally invasive prosthesis breast reconstruction (PBR), whether meshes application in minimally invasive PBR can improve complications and cosmetic effects remains controversial. The author retrospectively analyzed postoperative complications and evaluated patient-reported quality-of-life outcomes in minimally invasive PBR with and without mesh. METHODS: This study enrolled patients who underwent minimally invasive nipple-sparing mastectomy (NSM) followed by PBR. We used the TiLOOP bra for the mesh-assisted procedure. Patient demographics and postoperative complications data were compared between the procedures. Patient-reported outcomes were evaluated with the Breast-Q. RESULTS: A total of 158 patients underwent 160 minimally invasive NSM-PBR (with mesh, n = 64; without, n = 94). Postoperative complications were comparable in the mesh-assisted (5 [7.7%]) and non-mesh-assisted (5 [5.3%]) groups (p = 0.533). The most common complication in non-mesh-assisted group was infection, with four (4.2%) cases. In mesh-assisted group, implant exposure occurred in two (3.1%) patients. Removal of prosthesis was uncommon, with two (3.1%) and three (3.2%) cases in the mesh-assisted and non-mesh groups, respectively (p = 0.977). The BREAST-Q questionnaire was completed by 52 (81.3%) patients in the mesh-assisted group and 68 (72.3%) in the non-mesh-assisted group. Comparing the non-mesh group, patients in mesh-assisted group had improved scores on the BREAST-Q Satisfaction with breast (66.0) (p < 0.05), Physical Well-being (80.0), and Sexual Well-being (56.0). CONCLUSIONS: Mesh-assisted minimally invasive NSM-PBR has good aesthetic outcomes and high patient satisfaction. There were no significant differences in complication rates between the mesh-assisted and non-mesh-assisted groups.

Diagnostic Methods in Forensic Pathology: Autoptic Findings and Immunohistochemical Study in Cases of Sudden Death Due to a Colloid Cyst of the Third Ventricle.

The colloid cyst is a non-malignant tumor growth made of a gelatinous material covered by a membrane of epithelial tissue. It is usually located posterior to the foramen of Monro, in the anterior aspect of the third ventricle of the brain. Due to its location, it can cause obstructive hydrocephalus, increased intracranial pressure, and sudden cardiac death, catecholamine-mediated, through hypothalamus compression. All the mechanisms are still controversial, but the role of catecholamine has been confirmed with histological findings that highlighted myocardial injury (coagulative myocytolysis and contraction band necrosis, CBN). This study presents a case of sudden death in a previously healthy 22-year-old male due to a colloid cyst of the third ventricle. A complete autopsy was performed, highlighting in the brain an abundant quantity of cerebrospinal fluid (CSF) and a 2 cm pale grayish-green rounded cyst formation partially filling and distending the third ventricle. The diagnosis was confirmed through immunohistochemical investigation: positivity for Periodic acid-Schiff (PAS) staining and CK7 expression. In cases such as the one reported here, a combined approach of autopsy, histology, and immunohistochemistry is mandatory in order to identify the neoformation's location and morpho-structural characteristics for a correct differential diagnosis, as well as to identify the cause of death.

Do NSm Virulence Factors in the Bunyavirales Viral Order Originate from Gn Gene Duplication?

One-third of the nine WHO shortlisted pathogens prioritized for research and development in public health emergencies belong to the Bunyavirales order. Several Bunyavirales species carry an NSm protein that acts as a virulence factor. We predicted the structures of these NSm proteins and unexpectedly found that in two families, their cytosolic domain was inferred to have a similar fold to that of the cytosolic domain of the viral envelope-forming glycoprotein N (Gncyto) encoded on the same genome fragment. We show that although the sequence identity between the NSmcyto and the Gncyto domains is low, the conservation of the two zinc finger-forming CysCysHisCys motifs explains the predicted structural conservation. Importantly, our predictions provide a first glimpse into the long-unknown structure of NSm. Also, these predictions suggest that NSm is the result of a gene duplication event in the Bunyavirales Nairoviridae and Peribunyaviridae families and that such events may be common in the recent evolutionary history of RNA viruses.

Characteristics of splenic PD-1+ γδT cells in Plasmodium yoelii nigeriensis infection.

Although the functions of programmed death-1 (PD-1) on αß T cells have been extensively reported, a role for PD-1 in regulating γδT cell function is only beginning to emerge. Here, we investigated the phenotypic and functional characteristics of PD-1-expressing γδT cells, and the molecular mechanism was also explored in the Plasmodium yoelii nigeriensis (P. yoelii NSM)-infected mice. Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of RORα, SR3335, was used to investigate the role of RORα in regulating PD-1+ γδT cells. The results indicated that γδT cells continuously upregulated PD-1 expression during the infection period. Higher levels of CD94, IL-10, CX3CR1, and CD107a; and lower levels of CD25, CD69, and CD127 were found in PD-1+ γδT cells from infected mice than in PD-1- γδT cells. Furthermore, GO enrichment analysis revealed that the marker genes in PD-1+ γδT cells were involved in autophagy and processes utilizing autophagic mechanisms. ScRNA-seq results showed that RORα was increased significantly in PD-1+ γδT cells. GSEA identified that RORα was mainly involved in the regulation of I-kappaB kinase/NF-κB signaling and the positive regulation of cytokine production. Consistent with this, PD-1-expressing γδT cells upregulated RORα following Plasmodium yoelii infection. Additionally, in vitro studies revealed that higher levels of p-p65 were found in PD-1+ γδT cells after treatment with a RORα selective synthetic inhibitor. Collectively, these data suggest that RORα-mediated attenuation of NF-κB signaling may be fundamental for PD-1-expressing γδT cells to modulate host immune responses in the spleen of Plasmodium yoelii nigeriensis-infected C57BL/6 mice, and it requires further investigation.

Comparative effectiveness of nipple-sparing mastectomy and breast-conserving surgery on long-term prognosis in breast cancer.

Background: The frequency of nipple-sparing mastectomy (NSM) surgery is presently increasing. Nonetheless, there is a paucity of long-term prognosis data on NSM. This study compared the long-standing prognosis of NSM in relation to breast-conserving surgery (BCS). Methods: Population-level data for 438,588 female breast cancer patients treated with NSM or BCS and postoperative radiation from 2000 to 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database; 321 patients from the Second Xiangya Hospital of Central South University were also included. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables to make valid comparisons. The Kaplan-Meier analysis, log-rank test, and Cox regression were applied to analyze the data. Results: There were no significant differences in long-term survival rates between patients who underwent NSM and those who underwent BCS+radiotherapy (BCS+RT), as indicated by the lack of significant differences in overall survival (OS) (p = 0.566) and breast cancer-specific survival (BCSS) (p = 0.431). Cox regression indicated that NSM and BCS+RT had comparable prognostic values (p = 0.286) after adjusting for other clinicopathological characteristics. For OS and BCSS, subgroup analysis showed that the majority of patients achieved an analogous prognosis whether they underwent NSM or BCS. The groups had comparable recurrence-free survival (RFS), with no significant difference found (p = 0.873). Conclusions: This study offers valuable insights into the long-term safety and comparative effectiveness of NSM and BCS in the treatment of breast cancer. These findings can assist clinicians in making informed decisions on a case-by-case basis.

Single Axillary Incision Reverse Sequence Endoscopic Nipple-Sparing Mastectomy in the Management of Gynecomastia: Short-Term Cosmetic Outcomes, Surgical Safety, and Learning Curve of the Preliminary 156 Consecutive Procedures from a Prospective Cohort Study.

BACKGROUND: Currently, a standard, optimal surgical procedure is still lacking for gynecomastia. Despite the development of a variety of surgical interventions, these techniques were often limited to patients with Simon I and II. The present study aimed to introduce a novel technique for all types and grades of gynecomastia, and reported the preliminary results. METHODS: Patients who received single axillary incision reverse sequence endoscopic nipple-sparing mastectomy (R-E-NSM) from March 2021 to March 2023 were enrolled at a single institution. The data from 3-month follow-up cut-off were collected prospectively and analyzed to determine the short-term esthetic and safety results of this technique, as well as the learning curve. RESULTS: A total of 159 single axillary incision reverse sequence endoscopic nipple-sparing mastectomy procedures were performed in 81 gynecomastia patients. Among these 81 patients, 7 patients (8.6%) were classified as Simon grade I, 29 patients (35.8%) as grade IIa, 24 patients (29.6%) as grade IIb, and 21 patients (25.9%) as grade III. In the patient-reported cosmetic results, the overall satisfaction score was 8.4 ± 1.4. A total of 74.1% of patients were highly satisfied, and 25.9% were satisfied. The overall complication rate was 10.1%, and only 1 patient had a major complication. According to the cumulative sum plot analysis, approximately 12 cases were needed for surgeon B and 11 cases for surgeon C to decrease their operation time significantly. CONCLUSIONS: R-E-NSM is safe and effective for all Simon grade gynecomastia patients, with excellent cosmetic results and a short learning curve. However, a long-term follow-up assessment is still needed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Single-port insufflation endoscopic nipple-sparing mastectomy in early breast cancer: a retrospective cohort study.

Background: Breast cancer is the most common malignancy in female patients. In recent years, more and more studies have focused on how to improve the appearance and the quality of life for patients. This study aimed to compare the oncologic safety, aesthetic results, and upper extremity function between single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) and conventional open mastectomy (C-OM) in early-stage breast cancer treatment. Methods: In our retrospective cohort, 285 patients with stage I and II breast cancer were categorized into the SIE-NSM group (n=71) and the C-OM group (n=214). We assessed local recurrence, distant metastasis, and upper extremity function across the two groups. The BREAST-Q scale was employed to analyze differences in aesthetic results, psychosocial well-being, and sexual health. The risk of local recurrence was evaluated using multivariable binary logistic regression, while a multivariable linear regression model gauged upper extremity function and aesthetic outcomes. Results: Local recurrence rates between the two groups were statistically similar (1/71, 1.4% for SIE-NSM vs. 2/214, 0.9% for C-OM, P=0.735), as confirmed by the multivariable binary logistic regression analysis. Neither group exhibited distant metastases. The SIE-NSM group demonstrated higher scores in satisfaction with breasts, chest wellness, psychosocial health, and sexual well-being (P<0.001). The SIE-NSM group also exhibited superior outcomes regarding chest wall/breast pain, shoulder mobility, and daily arm usage (P<0.001). No subcutaneous effusion was reported in the SIE-NSM group, whereas the C-OM group had a 10.7% incidence rate (P=0.004). Conclusions: SIE-NSM offers comparable oncologic safety to C-OM but provides enhanced satisfaction regarding breast appearance, physical comfort, psychosocial health, sexual health, and improved upper extremity functionality. Consequently, this innovative approach is a suitable surgical alternative for treating early-stage breast cancer.

Single-port three-dimensional (3D) endoscopic-assisted breast surgery-preliminary results and patient-reported satisfaction in 145 breast cancer and gynecomastia cases.

BACKGROUND: Minimal-accessed (robotic and endoscopic) breast cancer surgery is increasingly performed due to better cosmetic results and acceptable oncological outcomes. This study aims to demonstrate the clinical safety and patient-reported cosmetic satisfaction of single-port three-dimensional endoscopic-assisted breast surgery (S-P 3D EABS), which is our new endoscopic surgical innovation, in both malignant and benign breast conditions. METHODS: Patients who underwent S-P 3D EABS from 1 August 2018 to 31 July 2022 in a single institution were enrolled. Clinical outcomes of this procedure were retrospectively reviewed, and the patient-reported cosmetic satisfaction was evaluated by a questionnaire and reported herein. RESULTS: During the study period, 145 patients underwent 164 procedures of S-P 3D EABS. One hundred fifty (91.5%) procedures were endoscopic-assisted nipple-sparing mastectomy (S-P 3D E-NSM; 117 therapeutic procedures for breast cancer, 13 prophylactic mastectomies, 20 procedures for gynecomastia). Fourteen (8.5%) procedures of endoscopic-assisted breast-conserving surgery (S-P 3D E-BCS) were performed (12 S-P 3D E-BCS, 2 S-P 3D E-BCS with 3D videoscope-assisted partial breast reconstruction, which was 1 case of latissimus dorsi flap and 1 case of omental flap). The mean operative time was 245 ± 110 min in S-P 3D E-NSM and 260 ± 142 min in S-P 3D E-BCS. The mean intraoperative blood loss was 49.7 ± 46.9 ml in S-P 3D E-NSM and 32.8 ± 17.5 ml in S-P 3D E-BCS. Subnipple biopsy showed positive malignancy in 3 (2.6%) S-P 3D E-NSM patients. None of the S-P 3D E-BCS patients found margin involvement; however, 3 (2.6%) reported margin involvement in S-P 3D E-NSM patients. Thirty-two complications were found (24.6%): 7 (5.3%) transient nipple-areolar complex (NAC) ischemia, 7 (5.3%) partial NAC necrosis, 1 (0.7%) total NAC necrosis, and 1 (0.7%) implant loss. During the mean follow-up time of 34 months, there were 2 (1.5%) patients with locoregional recurrence, 9 (6.9%) distant metastasis, and 2 (1.5%) mortality. 78.6% (77/98) of patients answering the cosmetic-evaluated questionnaire reported good and excellent overall satisfaction. CONCLUSIONS: S-P 3D EABS is a novel surgical innovation, which is able to perform safely in either malignant or benign breast conditions and offer promising cosmetic results.