Robotic nipple sparing mastectomy and immediate breast reconstruction: significant attempts with the latissimus dorsi muscle without island flap.

BACKGROUND: This study presents preliminary results of robot-assisted nipple-sparing immediate breast reconstruction (R-NSMIBR) with gel implant combined with latissimus dorsi muscle flap without island flap and validation of the safety and utility of this novel surgical modality. METHODS: Records pertinent to R-NSMIBR with gel implants combined with latissimus dorsi muscle flap surgery for breast reconstruction between September 2022 and May 2023 were examined. A total of 13 patients who underwent R-NSMIBR were analyzed, nine of which were performed without skin island. RESULTS: We divided the patients with and without skin islands into two groups and recorded the operation time and bleeding respectively. The mean total operative time for R-NSMIBR was 436.5±56.88 minutes and 355.75±69.68 minutes. As experience in learning increased, time required to create the operating space and position the robotic arm decreased significantly. Not creating an island of skin also saves a great deal of surgical time. Average total blood loss was 37.5±6.45 mL and 26.25±7.5 mL. No cases of nipple-areolar complex necrosis or perioperative complications or no local recurrences were reported. There were no local recurrences or deaths that occurred during a mean follow-up period of 3±1 months. CONCLUSIONS: All the patients expressed satisfaction with the aesthetic outcome following surgery. There were no significant differences between two groups. This surgical method shows promise for future promotion in the field.

Enhanced protein-metabolite correlation analysis: To investigate the association between Staphylococcus aureus mastitis and metabolic immune pathways.

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.

Breast Cancer-related Lymphedema: Recent Updates on Clinical Efficacy of Therapies and Bioengineering Approaches for a Personalized Therapy.

BACKGROUND: Post-mastectomy lymphedema is a chronic progressive disease characterized by a significant reduction in quality of life and a range of complications. AIM: To this date, no single treatment method provides pathological correction of the mechanisms associated with tissue reorganization observed in later-stage breast cancer-related lymphedema (BCRL). METHODS: To define a personalized approach to the management of patients with iatrogenic lymphedema, we performed a systematic review of literature without a comprehensive meta-analysis to outline existing molecular- genetic patterns, overview current treatment methods and their efficacy, and highlight the specific tissue-associated changes in BCRL conditions and other bio-engineering approaches to develop personalized therapy. RESULTS: Our results show that several tissue-specific and pathological molecular markers may be found, yet current research does not aim to define them. CONCLUSION: As such, currently, a strong foundation for further research into molecular-genetic changes in lymphedema tissue exists, and further research should focus on finding specific targets for personalized treatment through bio-engineering approaches.

Recent Updates on the Efficacy of Mitocans in Photo/Radio-Therapy for Targeting Metabolism in Chemo/Radio-Resistant Cancers: Nanotherapeutics.

Conventional therapeutic modalities against the cancers such as surgery, chemotherapy (CT) and radiotherapy (RT) have limited efficacy due to drug resistance, and adverse effects. Recent developments in nanoscience emphasized novel approaches to overcome the aforementioned limitations and subsequently improve overall clinical outcomes in cancer patients. Photodynamic therapy (PDT), photothermal therapy (PTT), and radiodynamic therapy (RDT) can be used as cancer treatments due to their high selectivity, low drug resistance, and low toxicity. Mitocans are the therapeutic molecules that can produce anti-cancer effects by modulating mitochondria functions and they have significant implications in cancer therapy. Mitochondria- targeted therapy is a promising strategy in cancer treatment as these organelles play a crucial function in the regulation of apoptosis and metabolism in tumor cells and are more vulnerable to hyperthermia and oxidative damage. The aim of this review is used to explore the targeting efficacy of mitocans in the nanotherapeutic formulation when combined with therapies like PDT, PTT, RDT. We searched several databases include Pubmed, relemed, scopus, google scholar, Embase and collected the related information to the efficacy of mitocans in nanotherapeutics when combined with photo-radiotherapy to target chemo/radio-resisant tumor cells. In this review, we vividly described research reports pertinent to the selective delivery of chemotherapy molecules into specific sub-organelles which can significantly improve the efficiency of cancer treatment by targeting tumor cell metabolism. Furthermore, the rational design, functionalization and application of various mitochondrial targeting units, including organic phosphine/sulfur salts, quaternary ammonium salts, transition metal complexes, and mitochondria-targeted cancer therapy such as PDT, PTT, RDT, and others were summarized. Mainly, the efficacy of these modalities against mtDNA and additional nanotherapeutic strategies with photosensitizers, or radiotherapy to target mitochondrial metabolism in tumor cells with chemo/radio-resistance were delineated. This review can benefit nanotechnologists, oncologists, and radiation oncologists to develop rational designs and application of novel mitochondrial targeting drugs mainly to target metabolism in chemo/radio-resistant cancer cells in cancer therapy.

Recent Advances in Therapeutic Modalities Against Breast Cancer-Related Lymphedema: Future Epigenetic Landscape.

Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.

Novel Perspectives on Nanotechnological and Biomedical Implications of Monotherapy or Combination Regimen of Lactoferrin.

Lactoferrin (LF) is a protein molecule with a wide variety of physiological properties. LF has broadspectrum antibacterial, antiviral, antioxidant, and antitumor, and possesses immunomodulatory properties to regulate immunity and gastrointestinal function. The main aim of this review is to explore the recent investigations on the functional role of LF against several human disorders and diseases through monotherapy or combinatorial regimens with other biological/chemotherapeutic agents through novel nanoformulations. We significantly searched public databases such as Pubmed, National Library of Medicine, relemed, Scopus and collected published reports pertaining to these recent reports on lactoferrin as a monotherapy or combination therapy, and its nanoformulations. We have discussed vividly the role of LF as a growth factor with substantial potential that can promote cell growth and regeneration potential for repairing tissues such as bone, skin, mucosa, and tendons. In addition, we have discussed novel perspectives on the role of LF as an inductive factor for the proliferation of stem cells in tissue recovery and discussed its novel modulating effects in ameliorating cancer and microbial growth through several signaling cascades via monotherapy or combinatorial regimens. Furthermore, the regeneration potential of this protein is reviewed to explore the efficacy and prospects of new treatment methods. This review benefits various microbiologists, stem cell therapists, and oncologists to explore the efficacy of LF in several segments of medicine by examining its ability as a stem cell differentiation factor, and anticancer agent or antimicrobial agent through novel formulations in preclinical or clinical study.

Robot-assisted nipple-sparing mastectomy and immediate breast reconstruction with gel implant and latissimus dorsi muscle flap: Our initial experience.

BACKGROUND: This study reports the preliminary results of da Vinci robot XI robot-assisted nipple-sparing mastectomy immediate breast reconstruction (R-NSMIBR) with gel implant and latissimus dorsi muscle flap. METHODS: A total of 15 patients who underwent R-NSMIBR with gel implant and latissimus dorsi muscle flap surgery for breast cancer between September 2022 and November 2022 were evaluated. RESULTS: Mean total operative time for R-NSMIBR was 361.9 ± 77.0 min. As the learning curve increased, the robot arm docking time decreased rapidly from the initial 25-10 min. Average total blood loss was 27.8 ± 10.7 mL and posterior surgical margin positivity rate was 0%. Perioperative complications and local recurrences or deaths were not observed at a mean follow-up of 3 ± 1 month 15 patients were satisfied with postoperative aesthetic results. CONCLUSIONS: R-NSMIBR with a gel implant and latissimus dorsi muscle flap could be a new therapeutic option for breast reconstruction.

Novel Implications of Nanoparticle-Enhanced Radiotherapy and Brachytherapy: Z-Effect and Tumor Hypoxia.

Radiotherapy and internal radioisotope therapy (brachytherapy) induce tumor cell death through different molecular signaling pathways. However, these therapies in cancer patients are constrained by dose-related adverse effects and local discomfort due to the prolonged exposure to the surrounding tissues. Technological advancements in nanotechnology have resulted in synthesis of high atomic elements such as nanomaterials, which can be used as radiosensitizers due to their photoelectric characteristics. The aim of this review is to elucidate the effects of novel nanomaterials in the field of radiation oncology to ameliorate dose-related toxicity through the application of ideal nanoparticle-based radiosensitizers such as Au (gold), Bi (bismuth), and Lu (Lutetium-177) for enhancing cytotoxic effects of radiotherapy via the high-Z effect. In addition, we discuss the role of nanoparticle-enhanced radiotherapy in alleviating tumor hypoxia through the nanodelivery of genes/drugs and other functional anticancer molecules. The implications of engineered nanoparticles in preclinical and clinical studies still need to be studied in order to explore potential mechanisms for radiosensitization by minimizing tumor hypoxia, operational/logistic complications and by overcoming tumor heterogeneity in radiotherapy/brachytherapy.

Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers.

Obesity and associated chronic inflammation were shown to facilitate breast cancer (BC) growth and metastasis. Leptin, adiponectin, estrogen, and several pro-inflammatory cytokines are involved in the development of obesity-driven BC through the activation of multiple oncogenic and pro-inflammatory pathways. The aim of this study was to assess the reported mechanisms of obesity-induced breast carcinogenesis and effectiveness of conventional and complementary BC therapies. We screened published original articles, reviews, and meta-analyses that addressed the involvement of obesity-related signaling mechanisms in BC development, BC treatment/prevention approaches, and posttreatment complications. PubMed, Medline, eMedicine, National Library of Medicine (NLM), and ReleMed databases were used to retrieve relevant studies using a set of keywords, including "obesity," "oncogenic signaling pathways," "inflammation," "surgery," "radiotherapy," "conventional therapies," and "diet." Multiple studies indicated that effective BC treatment requires the involvement of diet- and exercise-based approaches in obese postmenopausal women. Furthermore, active lifestyle and diet-related interventions improved the patients' overall quality of life and minimized adverse side effects after traditional BC treatment, including postsurgical lymphedema, post-chemo nausea, vomiting, and fatigue. Further investigation of beneficial effects of diet and physical activity may help improve obesity-linked cancer therapies.

Retrospective analysis: 5509 cases of "totally implantable venous access port systems implantation (TIVAPS) depth" assisted by digital radiography.

PURPOSE: Modern oncological treatment in breast cancer patients requires the precise delivery of chemotherapy infusion into the central venous systems without toxicity. TIVAPS is the significant method of chemotherapy delivery although certain internal or external complications associated with their placement. However, the long-term use of TIVAPS is still a concern to minimize the complications such as venous thrombosis syndrome (VTS) and cardiac defects. The aim of this study is to investigate the potential disadvantages that may be avoided by digital radiography (DR)-assisted measurement of catheter depth pertinent to TIVAPS implanted system. METHODS: Retrospective analysis related to 5509 TIVAPS recipients of 99% female breast cancer patients and 1% male blood disorder patients registered from April 2013 to November 2017 were included in the study. Patients with TIVAPS catheter tip depth into superior vena cava into upper (group A), middle (group B), and lower (group C) parts were stratified for evaluation during implantation; DR-assisted measurement of TIVAPS was performed to decipher "tip depth of catheter" and determined the relevance of tip depth to complications such as VTS and cardiac defects. RESULTS: Incidence of VTS complications were significantly higher in TIVAPS recipients of group A (82.7%) than group B (16%) and group C (0.12%) in which the "tip depth of TIVAPS was deeper" (P < 0.01). Defects in heart function are higher in group C (59.6%) than group A (15.8%) and group B (24.6%) in which the "tip depth of TIVAPS was deeper" (P < 0.01). CONCLUSION: DR-assisted measurement can more accurately determine the depth of TIVAPS catheter implantation, and avoid the incidence of related complications, and provide a better method for surgeons.

Robot-Assisted Minimally Invasive Breast Surgery: Recent Evidence with Comparative Clinical Outcomes.

In recent times, robot-assisted surgery has been prominently gaining pace to minimize overall postsurgical complications with minimal traumatization, due to technical advancements in telerobotics and ergonomics. The aim of this review is to explore the efficiency of robot-assisted systems for executing breast surgeries, including microsurgeries, direct-to-implant breast reconstruction, deep inferior epigastric perforators-based surgery, latissimus dorsi breast reconstruction, and nipple-sparing mastectomy. Robot-assisted surgery systems are efficient due to 3D-based visualization, dexterity, and range of motion while executing breast surgery. The review describes the comparative efficiency of robot-assisted surgery in relation to conventional or open surgery, in terms of clinical outcomes, morbidity rates, and overall postsurgical complication rates. Potential cost-effective barriers and technical skills were also delineated as the major limitations associated with these systems in the clinical sector. Furthermore, instrument articulation of robot-assisted surgical systems (for example, da Vinci systems) can enable high accuracy and precision surgery due to its promising ability to mitigate tremors at the time of surgery, and shortened learning curve, making it more beneficial than other open surgery procedures.

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To explore the effects of different electron acceptors on soil methane emission and responses of soil microorganisms to different light conditions, a strict anaerobic 20-day incubation experiment was conducted with eight treatments: darkness + Fe3+ (DF); darkness + NO3- (DN); darkness +SO42- (DS); darkness + distilled water (DCK); light + Fe3+ (LF); light + NO3- (LN); light +SO42- (LS); light + distilled water (LCK). The changes of methane concentration in the anaerobic incubation flask and the variation of the abundance of bacteria, archaea, fungi and six soil functional genes were analyzed. Results showed that soil methane emission under NO3-, SO42- addition and control (CK) was significantly lower under light conditions than dark, except the Fe3+ treatment. DN, DCK and LF treatments had the highest abundance of bacteria, fungi and archaea genes, respectively. The gene abundance of methanogenic mcrA, sulfate-reducing bacteria Dsr, and carbon-fixing CbbL were significantly up-regulated in the LF, while that of methanotrophs pmoA, iron-reducing bacteria Geo, and denitrifying bacteria nosZ were significantly up-regulated in the LN, DCK and LCK, respectively. Results of Pearson correlation and RDA analysis showed that CH4 emission was significantly positively correlated with CO2 concentration, pH, ammonium-nitrogen, and total N contents, and negatively correlated with N2O concentration, Eh, nitrate, and total C contents. Under dark condition, methane emission was positively correlated with archaea and pmoA genes abundance, and negatively correlated with other genes abundance. Under light condition, methane emission was negatively correlated with the abundance of soil microbe and functional genes. In general, methane emission under light condition was significantly lower than that under dark condition (except for the Fe3+ treatment). These results showed that it was helpful to reduce methane emission under light condition, but the increase or decrease of methane emission was closely related to the type of electron acceptors and the functional responses of soil micro-organisms.

Patient Management Strategies in Perioperative, Intraoperative, and Postoperative Period in Breast Reconstruction With DIEP-Flap: Clinical Recommendations.

BACKGROUND AND OBJECTIVE: Deep Inferior Epigastric Perforator (DIEP) flap is a tissue isolated from the skin and subcutaneous tissue of the lower abdomen or rectus muscle to foster breast reconstruction. There is limited information about DIEP-flap induced complications associated with breast reconstruction surgery. EVIDENCE: We conducted a systematic review of the published literature in the field of breast cancer reconstruction surgery. Information was gathered through internet resources such as PubMed, Medline, eMedicine, NLM, and ReleMed etc. The following key phrases were used for effective literature collection: "DIEP flap", "Breast reconstruction", "Patient management", "Postoperative DIEP", "Intraoperative anticoagulant therapy", "Clinical recommendations". A total of 106 research papers were retrieved pertaining to this systematic review. CONCLUSION: A successful breast reconstruction with DIEP-flap without complications is the priority achievement for this surgical procedure. This study provides various evidence-based recommendations on patient management in the perioperative, intraoperative, and postoperative periods. The clinical recommendations provided in this review can benefit surgeons to execute breast reconstruction surgery with minimal postoperative complications. These recommendations are beneficial to improve clinical outcomes when performing surgery by minimizing complications in perioperative, intraoperative, and postoperative period.

Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers.

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.

Clinical Analysis of Risk Factors of Postoperative Psychiatric Disorders in Patients With Adult Craniopharyngioma.

Objective: To analyze the risk factors relative to postoperative psychiatric disorders in adult patients with craniopharyngioma. Methods: A retrospective case-control study design was used in this study. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessment tool was used to assess psychiatric disorders in postoperative patients with craniopharyngioma at Beijing Tiantan Hospital from January 2018 to December 2020. The relationship between the psychiatric disorders and basic demographic data as well as several risk factors, such as the tumor characteristics (tumor location, tumor size, pathological finding of the tumor, etc.) and treatment-related factors (the extent of the resection), were analyzed. Results: A total of 173 patients were included in this study. The prevalence of psychiatric disorders was 14.5% among adult craniopharyngioma patients. Irritability represented the most common type of psychological symptom (64%, n = 16), followed by agitation (36%, n = 9), and delusions (28%, n = 7). The risk factors relative to postoperative psychiatric disorders that were identified were a tumor volume larger than 7 cm3 (HR = 3.292, P = 0.042), tumor location (P = 0.003), hypothalamic invasion (HR = 9.766, P = 0.036), and gross-total resection (HR = 0.085, P = 0.042). Conclusion: Neurocognitive assessment and intervention before and after surgery are important in patients with larger tumors, invading the third ventricle, and tumors with hypothalamic invasion. Prediction of these risk factors is essential for the treatment.

Totally Implantable Venous Access Port Systems: Implant Depth-based Complications in Breast Cancer Therapy - A Comparative Study.

BACKGROUND: Totally implantable venous access port system (TIVAPS) is widely used in breast cancer therapy; TIVAPS has several associated complications depending on the depth of implantation in breast cancer (BC) patients during continuous infusional chemotherapy regimens. The purpose of this study is to find out the optimal depth of TIVAPS implantation to reduce the incidence of complications during infusional chemotherapy. METHODS: This study reviewed the depth of TIVAPS implantation in the internal jugular vein in 1282 breast cancer patients over a ten-year period (2009-2019), and associated complications. We segregated the patients as 5 groups: 'Group A (depth < 4 mm), Group B (depth of 4-8 mm), Group C (depth of 8-12 mm), and Group D (depth of 12-16 mm), and Group E (depth of > 16 mm)'. Consequently, the 'internal complications' such as infection, venous thrombotic syndrome, catheter folding & migration, extravasation, whereas the 'external complications' viz., inflammation, local hematoma, local cutaneous reactions, and port exteriorization were significantly analyzed during TIVAPS implantation at different depths in BC patients. RESULTS: Overall incidence of 'internal complications' such as infections (8.6%, 2/23 cases), venous thrombotic syndrome (7.69%, 1/13 cases), catheter folding & migration (8.3%, 1/12 cases), and extravasation (8.3%, 1/12 cases) was comparatively lesser in Group C (8-12 mm) (p<0.01) than the Group A, Group B, Group D, and Group E respectively. Mainly, the external complications such as inflammation in Group C (8-12 mm) (pp< 0.01) was lesser (6.8%, 3/44 cases) than Group A, Group B, Group D, Group E. On the similar note, the local hematoma, and local cutaneous reaction, and port exteriorization were observed as '5% (1/20 cases), 4.2% (2/47 cases), and (3.2%, 1/31 cases)' in Group C patients (p<0.01), which were comparatively lesser than the other groups. CONCLUSION: Subcutaneous implantation of TIVAPS at a depth of 8-12 mm could be preferred due to the lowest incidence of internal and external complications compared to the incidence of these complications in other groups; this depth could be referred to as the safe and convenient implantation depth for the effective delivery of chemotherapy regimen in BC patients without difficulty in transcutaneous access to the port.