The Effect of Neoadjuvant vs Adjuvant Chemotherapy on Final Outcome of Patients with Triple Negative Breast Cancer.

Background: Triple negative breast cancer (TNBC) accounts for about 10% to 20% of breast cancers, does not respond to endocrine treatment, and is more aggressive. Two chemotherapy methods suggested include neoadjuvant chemotherapy (NAC), performed before surgery, and adjuvant chemotherapy (AC), performed after surgery. In order to determine whether the choice of chemotherapy method has any impact on patients' outcome, the present study aimed to compare the overall survival (OS) and disease-free survival (DFS) of TNBC patients with a 10-year follow-up. Methods: The present study aimed to investigate the effect of neoadjuvant versus adjuvant chemotherapy on the final outcome of patients with TNBC. Women with TNBC stages II and III who referred to the Cancer Research Center of Shahid Beheshti University of Medical Sciences during 2000 and 2020 were included (N = 237) and visited or called by phone to obtain their consent and complete their information. The participants were categorized into 2 groups according to the treatment protocol they received; one group received NAC (N = 85) and the other group received AC (N = 188); patients' age, tumor's grade and stage, lymphovascular invasion (LVI), DFS, and OS were compared between the 2 treatment types. For the statistical analysis, the statistical software IBM SPSS Statistics for Windows, Version 24.0. (IBM Corp) was used. All tests were 2-sided and P values < 0.050 were considered statistically significant. Results: The frequency of pathologies, LVI, and type of surgery was not different between the groups (p = 0.543, p = 0.352, p = 0.935), while the frequency of age categories and tumor grade was significantly different between the groups (p = 0.003, p = 0.001). Ten-year OS and DFS were not different between the groups (p = 0.771, p = 0.506). The Multivariate Cox analysis results showed clinical stage, pathologic grade, age >70, and LVI as significant predictors of death. Conclusion: These results showed that the choice of chemotherapy method, performed before or after surgery, does not influence the 10-year OS and DFS of TNBC patients.

Accuracy of cancer diagnostic probe for intra-surgical checking of cavity side margins in neoadjuvant breast cancer cases: A human model study.

BACKGROUND: Background Recently, a real-time system, named cancer diagnostic probe (CDP), has been developed to diagnose the presence of pre-neoplastic/neoplastic cells in breast cavity side margins. Detecting mechanism is real-time determination of the ROS/H2 O2 released from cancer or atypical cells, through reverse Warburg effect and hypoxia glycolysis pathways. AIMS: Here, we designed a human model study based on real-time checking of 387 internal margins (IM) from 39 neoadjuvant breast cancer cases by CDP. MATERIALS & METHODS: Each lesion was checked by entered needle sensor and electrical scores were recorded. The permanent pathology result of each tested lesion was our gold standard to evaluate CDP scoring. CDP results were compared with permanent pathology of tumour side margins (as a conventional margin evaluation procedure). RESULTS: Results showed that the sensitivity of CDP in scoring the cavity side margins of those cases is 91%. A total of 18 involved IM which had been detected by CDP were declared as free margins in pathology section of tumour side samples. Just five involved IM were missed by CDP. DISCUSSIONS: Such sensitivity revealed that metabolism based (here: hypoxia glycolysis) tracing of cancer cells show distinct electrochemical responses between clear and involved cavity side margin evaluation. CONCLUSION: This human study showed the promising role of CDP to achieve clear margins after BCS of neoadjuvant cases.

RNA interfering molecule delivery from in situ forming biodegradable hydrogels for enhancement of bone formation in rat calvarial bone defects.

RNA interference (RNAi) may be an effective and valuable tool for promoting the growth of functional tissue, as short interfering RNA (siRNA) and microRNA (miRNA) can block the expression of genes that have negative effects on tissue regeneration. Our group has recently reported that the localized and sustained presentation of siRNA against noggin (siNoggin) and miRNA-20a from in situ forming poly(ethylene glycol) (PEG) hydrogels enhanced osteogenic differentiation of encapsulated human bone marrow-derived mesenchymal stem cells (hMSCs). Here, the capacity of the hydrogel system to accelerate bone formation in a rat calvarial bone defect model is presented. After 12 weeks post-implantation, the hydrogels containing encapsulated hMSCs and miRNA-20a resulted in more bone formation in the defects than the hydrogels containing hMSCs without siRNA or with negative control siRNA. This localized and sustained RNA interfering molecule delivery system may provide an excellent platform for healing bony defects and other tissues. STATEMENT OF SIGNIFICANCE: Delivery of RNAi molecules may be a valuable strategy to guide cell behavior for tissue engineering applications, but to date there have been no reports of a biomaterial system capable of both encapsulation of cells and controlled delivery of incorporated RNA. Here, we present PEG hydrogels that form in situ via Michael type reaction, and that permit encapsulation of hMSCs and the concomitant controlled delivery of siNoggin and/or miRNA-20a. These RNAs were chosen to suppress noggin, a BMP-2 antagonist, and/or PPAR-γ, a negative regulator of BMP-2-mediated osteogenesis, and therefore promote osteogenic differentiation of hMSCs and subsequent bone repair in critical-sized rat calvarial defects. Simultaneous delivery of hMSCs and miRNA-20a enhanced repair of these defects compared to hydrogels containing hMSCs without siRNA or with negative control siRNA. This in situ forming PEG hydrogel system offers an exciting platform for healing critical-sized bone defects by localized, controlled delivery of RNAi molecules to encapsulated hMSCs and surrounding cells.

The Incidence of Psychiatric Medication Use and Its Effect on Intraoperative Bleeding in Facial Cosmetic Patients.

PURPOSE: Psychiatric medications, particularly the selective serotonin reuptake inhibitors, have been associated with increased surgical bleeding. This study aims to compare intraoperative surgical bleeding between cosmetic surgery patients who are and are not taking psychiatric medications. METHODS: The charts of 392 consecutive patients who underwent cosmetic facial surgery at the senior author's practice were reviewed. Independent variables included self-reported psychiatric history, psychiatric diagnoses, and psychiatric medications as documented in the preoperative history and physical examination. The primary endpoint was administration of desmopressin (DDAVP), our proxy for increased surgical bleeding. Significant predictors of these endpoints were determined via Chi-squared testing. RESULTS: One hundred and seventeen patients had a psychiatric diagnosis (30%), and 129 patients were taking some class of psychiatric medication (33%). Seventy-two patients received DDAVP (18%). A psychiatric diagnosis did not predict DDAVP administration (14.3% for patients with a psychiatric diagnosis vs. 20.88% for those without, p = 0.14). The use of a psychiatric medication was not associated with DDAVP administration (14.7 vs. 21%, p = 0.14). Male gender significantly predicted DDAVP administration (27.8 vs. 16.9% for females, p = 0.04). CONCLUSION: The use of psychiatric medications does not predict increased intraoperative surgical bleeding. This is useful given the prevalence of psychiatric medication use among this patient population and obviates the need for discontinuation of these medications, which otherwise could be consequential. 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 .

Endochondral Ossification in Critical-Sized Bone Defects via Readily Implantable Scaffold-Free Stem Cell Constructs.

The growing socioeconomic burden of musculoskeletal injuries and limitations of current therapies have motivated tissue engineering approaches to generate functional tissues to aid in defect healing. A readily implantable scaffold-free system comprised of human bone marrow-derived mesenchymal stem cells embedded with bioactive microparticles capable of controlled delivery of transforming growth factor-beta 1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) was engineered to guide endochondral bone formation. The microparticles were formulated to release TGF-ß1 early to induce cartilage formation and BMP-2 in a more sustained manner to promote remodeling into bone. Cell constructs containing microparticles, empty or loaded with one or both growth factors, were implanted into rat critical-sized calvarial defects. Micro-computed tomography and histological analyses after 4 weeks showed that microparticle-incorporated constructs with or without growth factor promoted greater bone formation compared to sham controls, with the greatest degree of healing with bony bridging resulting from constructs loaded with BMP-2 and TGF-ß1. Importantly, bone volume fraction increased significantly from 4 to 8 weeks in defects treated with both growth factors. Immunohistochemistry revealed the presence of types I, II, and X collagen, suggesting defect healing via endochondral ossification in all experimental groups. The presence of vascularized red bone marrow provided strong evidence for the ability of these constructs to stimulate angiogenesis. This system has great translational potential as a readily implantable combination therapy that can initiate and accelerate endochondral ossification in vivo. Importantly, construct implantation does not require prior lengthy in vitro culture for chondrogenic cell priming with growth factors that is necessary for current scaffold-free combination therapies. Stem Cells Translational Medicine 2017;6:1644-1659.

Massive Nasal Arterio-Venous Malformation (AVM) Excision and Reconstruction with Expanded Forehead Flap: A Case Report.

Nasal arterio-venous malformations (AVM) are uncommon lesions. We present a rare case of huge, long standing AVM in the nasal area which was treated by angioembolization, followed by surgical excision and forehead flap reconstruction.

Contact Cooling of Random-Pattern Cutaneous Flaps: Does it Increase Necrosis?

BACKGROUND: Cooling after surgery reduces pain, swelling and ecchymosis. However, the fear of adverse effects of vasoconstriction caused by cooling may prevent its use when the skin is undermined extensively, for example, after rhytidectomy. The purpose of this study is to determine whether the contact cooling of random-pattern skin flaps increases the area of necrosis observed. METHODS: Twenty-eight random-pattern skin flaps (4 × 10 cm) were raised on four pigs. Flaps were divided into three groups: control, intermittently cooled and continuously cooled. Pads connected to a ThermaZone cooling device delivered local hypothermia in the range of 4-6 °C for 24 h postoperatively. ImageJ software was used to calculate the area of necrosis on each flap on postoperative day 7, confirmed with histological analysis. RESULTS: The average areas of necrosis observed were as follows: control (17.61 cm2; SD 5.23), intermittent cooling (15.65 cm2; SD 3.76) and continuous cooling (14.16 cm2; SD 3.91). An ANOVA revealed no statistically significant differences between the three interventions (p = 0.35). CONCLUSIONS: Postoperative continuous or intermittent cooling does not increase the area of necrosis in random-pattern flaps. In fact, a trend was observed, demonstrating decreasing area of necrosis with increased periods of hypothermia. NO LEVEL ASSIGNED: 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 .

Syndromic lipomatosis of the head and neck: a review of the literature.

INTRODUCTION: Patients with syndromic causes of lipomatosis of the head and neck, although rare, often present late in the course of the disease in a myriad of ways, including concomitant airway obstruction, severe functional limitations, and/or significant cosmetic defects. The goal of this report was to review the literature and present a concise overview of the major syndromes causing lipomatosis of the head and neck. METHODS: A literature search was performed to gather information on syndromic lipomatosis of the head and neck region. PubMed was searched for the following conditions: Familial multiple lipomatosis (FML), multiple symmetrical lipomatosis (MSL), congenital infiltrating lipomatosis of the face (CIL-F), and Nasopalpebral lipoma-coloboma syndrome (NLCS). Data gathered included results of surgical cases of the head and neck region. RESULTS: A total of 48 reports comprising 172 cases of syndromic lipomatosis of the head and neck region were deemed eligible for review. Eighty-five percent of patients were male with an average age of 35 years. Seventy-four percent of cases appeared in the neck region, whereas 23 % presented in the face and scalp. 89 % of cases were treated with surgical excision, with 11 % of cases treated with liposuction. The most common complications were hematoma and seroma in MSL, recurrence in FML, neuropraxia in CIL-F, and mild telecanthus in NLCS. CONCLUSIONS: Syndromic causes of lipomatosis are generally benign in nature but difficult to control long term. Because these conditions include frequent recurrence and subsequent difficulty in clearing the disease, the authors advocate early and aggressive surgical excision of syndromic lipomatosis. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Use of a Doppler signal to confirm migraine headache trigger sites.

BACKGROUND: The senior author (B.G.) has been able to use the Doppler as a tool for identifying the site of irritation of a nerve by an adjacent artery in different migraine trigger sites. The purpose of this study was to assess the correlation between the most intense pain site identified by the patients, presence of Doppler signal, and the intraoperative finding of an artery in the target site. METHODS: This was a retrospective review of the charts of patients who underwent surgical treatment of migraine headaches involving the auriculotemporal nerve. The target area was identified by asking patients to point to the most intense headache site and most tender area at the time of examination using the index finger tip. This site was marked and Doppler was used to identify the vascular signal. Doppler examination results, intraoperative presence of the superficial temporal artery or its branches, and the involved nerve were recorded and tabulated. RESULTS: A positive Doppler signal over the area of most intense temporal pain, identified by the patient preoperatively, correlated with intraoperative presence of the artery in 100 percent of the patients. Doppler signal was noted on 34 sites and arterectomy was carried out in all 34 sites. CONCLUSION: Doppler signal in the site of most intense pain can predictably document the presence of an artery in the most painful site and lead to precise location of the nerve irritation by a vessel and successful removal of the offending artery.

Repeated transsphenoidal surgery or gamma knife radiosurgery in recurrent cushing disease after transsphenoidal surgery.

BACKGROUND: This study compared Gamma knife radiosurgery (GKRS) and repeated transsphenoidal adenomectomy (TSA) to find the best approach for recurrence of Cushing disease (CD) after unsuccessful first TSA. MATERIAL AND METHODS: Fifty-two patients with relapse of CD after TSA were enrolled and randomly underwent a second surgery or GKRS as the next therapeutic approach. They were followed for a mean period of 3.05 ± 0.8 years by physical examination and hormone measurement as well as magnetic resonance imaging. RESULTS: No significant difference was observed in sex ratio, mean age, adenoma type, follow-up duration, and initial hormone level between the two groups. No significant relationship was found between preoperative 24-hour free urine cortisol and disease-free months or tumor volume among both groups. Our statistical analysis showed higher recurrence-free interval in the GKRS group compared with TSA group. CONCLUSION: With longer recurrence-free interval, GKRS could be considered a good treatment alternative to repeated TSA in recurrent CD.