BRCA-associated hereditary male cancers: can gender affect the prevalence and spectrum of germline pathogenic variants?

Introduction: Although hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations. Patients and methods: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the "Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults" of the University-Hospital Policlinico "P. Giaccone" of Palermo (Italy). Results: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing. Discussion: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.

The "Octopus Head" Dermoglandular Flap: A Novel Technique for Breast Tissue Rearranging after Implant Removal.

Background: Patients with previous breast augmentation may need implant removal for mechanical complications or other causes. After prosthesis removal, the residual parenchyma can be reshaped through a mastopexy with rearrangement of breast tissue. Several techniques have been described in the literature, but none of them can be considered the gold standard. In this study, we present our preliminary experience in breast tissue rearranging after implant removal through a novel technique: the "octopus head" dermoglandular flap. Methods: From January 2019 to October 2022, nine patients (18 breasts) underwent implant removal and simultaneous breast remodeling with the tissue obtained from the dermoglandular excess of the breast and shaped like an octopus head. Patient's demographic and clinical characteristics, postoperative complications, and patient-reported satisfaction were recorded. Results: Mean age was 46.7 years. Body mass index ranged between 22.5 and 27.6 kg per m2. The majority of patients had moderate ptosis (67%). Breast implants were removed due to bilateral capsular contracture (n = 3), unilateral implant rupture with contralateral capsular contracture (n = 2), bilateral implant rupture (n = 3), and unilateral periprosthetic seroma (n = 1). We observed two minor complications: one postoperative hemorrhage with subsequent hematoma that was managed conservatively, and one nipple-areola complex malposition that underwent revision surgery. All patients were satisfied with the aesthetic and functional result. Conclusions: The octopus head dermoglandular flap has proved to be a safe and reliable option for breast tissue rearranging after implant removal, providing a good and stable cosmetic result, a low complication rate, and high patient-reported satisfaction.

The wide base bipedicled (WIBB) flap in nipple-sparing skin-reducing mastectomy.

In this article, we present a modification of the NS/SRM technique in which the mastopexy design for skin reduction is undertaken with a wide-base bipedicled (WIBB) flap. The WIBB flap can be applied in both autologous and implant-based breast reconstruction. Our reconstructive algorithm is also presented. The clinical data of patients operated on from June 2017 to November 2022 were collected: 51 patients for a total of 71 breasts. Personal data, BMI, type and volume of implants used, and major and minor complications were analyzed by descriptive statistics. The mean age was 48.3 years. BMI ranged between 21.5 and 30.9 kg/m2. Thirty-one patients underwent unilateral mastectomy, while twenty patients underwent bilateral surgery. In 25 breasts, immediate reconstruction was performed with implants and ADM. In 40 breasts, reconstruction was performed with a subpectoral tissue expander, and in 6 breasts, reconstruction was performed with a DIEP flap. We observed only one case (1.4%) of periprosthetic infection requiring implant removal under general anesthesia. Minor complications occurred in 14.1% of patients. The use of both the WIBB flap and our algorithm maintained a low complication rate in our series, ensuring oncological radicality and a good aesthetic result at the same time.

Outcomes of Sentinel Lymph Node Biopsy for Patients With Node-positive Breast Cancer Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Clinical trials have shown that the sentinel lymph node biopsy (SLNB) is feasible for patients with cN1 breast carcinoma treated with neoadjuvant chemotherapy (NAC). This study aimed to evaluate the technical outcomes of SLNB by assessing the volume of residual nodal disease. PATIENTS AND METHODS: All patients with cT1-3 cN1 breast cancer undergoing NAC from January 2018 to December 2021 were retrospectively identified from our institutional database. We assessed the outcomes of preoperative clinical examination, ultrasonography, and other imaging to predict the axillary nodal status after NAC for patients converted to cN0 and undergoing SLNB; both adequate mapping and false-negative rate (FNR) at intraoperative evaluation of SLN were assessed. RESULTS: Overall 160 patients were included in the study; 98 were converted to cN0 and underwent SLNB. No difference was found in the adequate mapping rate nor in the mean number of SLNs retrieved compared to the residual LN burden. The intraoperative SLN FNR was 38.2%, with smaller nodal volume being associated with lower FNR (p<0.01). The positive predictive values of physical examination and imaging-based nodal assessment post-NAC were 87.1% and 68.2%, respectively. CONCLUSION: In a significant percentage of patients with cN1 disease converted to cN0 after NAC, it was possible to recover three or more SLNs. The residual volume of LN disease did not impact the SLN mapping rate. However, we found a high FNR for intraoperative SLN evaluation, particularly for patients with small residual nodal disease. It seems that only a small proportion of patients eligible for SLNB after NAC can be spared ALND.

Implant-Based Breast Reconstruction after Risk-Reducing Mastectomy in BRCA Mutation Carriers: A Single-Center Retrospective Study.

Women with BRCA gene mutations have a higher lifetime risk of developing breast cancer. Furthermore, cancer is usually diagnosed at a younger age compared to the wild-type counterpart. Strategies for risk management include intensive surveillance or risk-reducing mastectomy. The latter provides a significant reduction of the risk of developing breast cancer, simultaneously ensuring a natural breast appearance due to the preservation of the skin envelope and the nipple-areola complex. Implant-based breast reconstruction is the most common technique after risk-reducing surgery and can be achieved with either a submuscular or a prepectoral approach, in one or multiple stages. This study analyzes the outcomes of the different reconstructive techniques through a retrospective review on 46 breasts of a consecutive, single-center case series. Data analysis was carried out with EpiInfo version 7.2. Results of this study show no significant differences in postoperative complications between two-stage tissue expander/implant reconstruction and direct-to-implant (DTI) reconstruction, with DTI having superior aesthetic outcomes, especially in the prepectoral subgroup. In our experience, the DTI prepectoral approach has proven to be a safe and less time-consuming alternative to the submuscular two-stage technique, providing a pleasant reconstructed breast and overcoming the drawbacks of subpectoral implant placement.

Low plasma PD-L1 levels, early tumor onset and absence of peritoneal carcinomatosis improve prognosis of women with advanced high-grade serous ovarian cancer.

BACKGROUND: The most common subtype of ovarian cancer (OC) showing immunogenic potential is represented by the high-grade serous ovarian cancer (HGSOC), which is characterized by the presence of tumor-infiltrating immune cells able to modulate immune response. Because several studies showed a close correlation between OC patient's clinical outcome and expression of programmed cell death protein-1 or its ligand (PD-1/PD-L1), the aim of our study was to investigate if plasma levels of immunomodulatory proteins may predict prognosis of advanced HGSOC women. PATIENTS AND METHODS: Through specific ELISA tests, we analyzed plasma concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in one hundred patients affected by advanced HGSOC, before surgery and therapy. The Kaplan-Meier method was used to generate the survival curves, while univariate and multivariate analysis were performed using Cox proportional hazard regression models. RESULTS: For each analyzed circulating biomarker, advanced HGSOC women were discriminated based on long (≥ 30 months) versus short progression-free survival (PFS < 30 months). The concentration cut-offs, obtained by receiver operating characteristic (ROC) analysis, allowed to observe that poor clinical outcome and median PFS ranging between 6 and 16 months were associated with higher baseline levels of PD-L1 (> 0.42 ng/mL), PD-1 (> 2.48 ng/mL), BTN3A1 (> 4.75 ng/mL), pan-BTN3As (> 13.06 ng/mL), BTN2A1 (> 5.59 ng/mL) and BTLA (> 2.78 ng/mL). Furthermore, a lower median PFS was associated with peritoneal carcinomatosis, age at diagnosis > 60 years or Body Mass Index (BMI) > 25. A multivariate analysis also suggested that plasma concentrations of PD-L1 ≤ 0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p = 0.002), age at diagnosis ≤ 60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p = 0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p = 0.003) were significant prognostic marker for a longer PFS in advanced HGSOC patients. CONCLUSIONS: The identification of high-risk HGSOC women could be improved through determination of the plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels.

Helicobacter pylori and Epstein-Barr Virus Co-Infection in Gastric Disease: What Is the Correlation with p53 Mutation, Genes Methylation and Microsatellite Instability in a Cohort of Sicilian Population?

Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with and without gastric diseases. The patients were stratified into four groups. Significant methylation status differences among CDH1, DAPK, COX2, hMLH1 and CDKN2A were observed for coinfected (Hp-EBV group) patients; particularly, a significant presence of COX2 (p = 0.0179) was observed. For microsatellite instability, minor stability was described in the Hp-HBV group (69.23%, p = 0.0456). Finally, for p53 mutation in the EBV group, exon 6 was, significantly, most frequent in comparison to others (p = 0.0124), and in the Hp-EBV group exon 8 was, significantly, most frequent in comparison to others (p < 0.0001). A significant positive relationship was found between patients with infection (Hp, EBV or both) and p53 mutation (rho = 0.383, p = 0.0001), methylation status (rho = 0.432, p < 0.0001) and microsatellite instability (rho = 0.285, p = 0.004). Finally, we observed among infection and methylation status, microsatellite instability, and p53 mutation a significant positive relationship only between infection and methylation status (OR = 3.78, p = 0.0075) and infection and p53 mutation (OR = 6.21, p = 0.0082). According to our analysis, gastric disease in the Sicilian population has different pathways depending on the presence of various factors, including infectious agents such as Hp and EBV and genetic factors of the subject.

Navigating the liquid biopsy Minimal Residual Disease (MRD) in non-small cell lung cancer: Making the invisible visible.

Liquid biopsy has gained increasing interest in the growing era of precision medicine as minimally invasive technique. Recent findings demonstrated that detecting minimal or molecular residual disease (MRD) in NSCLC is a challenging matter of debate that need multidisciplinary competencies, avoiding the overtreatment risk along with achieving a significant survival improvement. This review aims to provide practical consideration for solving data interpretation questions about MRD in NSCLC thanks to the close cooperation between biologists and oncology clinicians. We discussed with a translational approach the critical point of view from benchside, bedside and bunchside to facilitate the future applicability of liquid biopsy in this setting. Herein, we defined the clinical significance of MRD, focusing on relevant practical consideration about advantages and disadvantages, speculating on future clinical trial design and standardization of MRD technology.

The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis.

Background: The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue PIK3CA alterations, encompassing factors that could affect the results. Methods: Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the related area under the curve (AUC) were elaborated for the overall population and each subgroup. Results: The pooled analysis was carried out on 25 cohorts for a total of 1966 patients. The overall ctDNA sensitivity and specificity were 0.73 (95% CI: 0.70-0.77) and 0.87 (95% CI: 0.85-0.89). The AUC was 0.93. Pooled concordance, negative predictive value and positive predictive value values were 0.87 (95% CI: 0.82-0.92), 0.86 (95% CI: 0.81-0.90), and 0.89 (95% CI: 0.81-0.95) with pooled PLR, NLR, and DOR of 7.94 (95% CI: 4.90-12.86), 0.33 (95% CI: 0.25-0.45), and 33.41 (95% CI: 17.23-64.79), respectively. The pooled results consistently favored next-generation sequencing (NGS)- over polymerase chain reaction-based methodologies. The best ctDNA performance in terms of sensitivity, specificity, and AUC (0.85, 0.99, and 0.94, respectively) was observed in the low-time sampling subgroup (⩽18 days between tissue and plasma collection). Meta-regression and subgroup analyses highlighted sampling time as a possible major cause of heterogeneity. Conclusions: These findings reliably estimate the high ctDNA accuracy for the detection of PIK3CA mutations. A ctDNA-first approach for the assessment of PIK3CA mutational status by NGS may accurately replace tissue tumor sampling, representing the preferable strategy at diagnosis of metastatic BC in patients who present with visceral involvement and at least two metastatic lesions, primarily given low clinical compliance or inaccessible metastatic sites.

Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?

The most common subtype of ovarian cancer (OC) is the high-grade serous ovarian carcinoma (HGSOC), accounting for 70%-80% of all OC deaths. Although HGSOC is a potentially immunogenic tumor, clinical studies assessing the effectiveness of inhibitors of programmed death protein and its ligand (PD-1/PD-L1) in OC patients so far showed only response rates <15%. However, recent studies revealed an interesting prognostic role of plasma PD-1/PD-L1 and other circulating immunoregulatory molecules, such as the B- and T-lymphocyte attenuator (BTLA), butyrophilin sub-family 3A/CD277 receptors (BTN3A), and butyrophilin sub-family 2 member A1 (BTN2A1), in several solid tumors. Since evidence showed the prognostic relevance of pretreatment serum CA125 levels in OC, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can enhance prognostic power of CA125 in advanced HGSOC women. Using specific ELISA tests, we examined the circulating PD-1, PD-L1, pan-BTN3As, BTN3A1, BTN2A1, and BTLA levels in 100 advanced HGSOC patients before treatment, correlating them with baseline serum CA125, age at diagnosis, body mass index (BMI), and peritoneal carcinomatosis. A multivariate analysis revealed that plasma BTN3A1 ≤4.75 ng/ml (HR, 1.94; 95% CI, 1.23-3.07; p=0.004), age at diagnosis ≤60 years (HR, 1.65; 95% CI, 1.05-2.59; p=0.03) and absence of peritoneal carcinomatosis (HR, 2.65; 95% CI, 1.66-4.22; p<0.0001) were independent prognostic factors for a longer progression-free survival (PFS) (≥30 months) in advanced HGSOC women. However, further two-factor multivariate analyses highlighted that baseline serum CA125 levels >401 U/ml and each soluble protein above respective concentration cutoff were covariates associated with shorter PFS (<30 months) and unfavorable clinical outcome, suggesting that contemporary measurement of both biomarkers than CA125 only could strengthen prognostic power of serum CA125 in predicting PFS of advanced HGSOC women. Plasma PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1, or BTLA levels could be helpful biomarkers to increase prognostic value of CA125.

Diagnostic performance of 2D-shear wave elastography in the diagnosis of breast cancer: a clinical appraisal of cutoff values.

PURPOSE: To assess the role of 2D-shear wave elastography (2D-SWE) in differentiating benign from malignant focal breast lesions (FBLs), providing new vendor-specific cutoff values. METHODS: 158 FBLs (size: 3.5-50 mm) detected in 151 women (age: 21-87 years) were prospectively evaluated by means 2D-SWE. For each lesion, an expert radiologist assessed US BI-RADS category and calculated the following four 2D-SWE parameters: (1) elasticity maximum (Emax); (2) mean elasticity (Emean); (3) minimum elasticity (Emin); (4) elasticity ratio (Eratio). US-guided core-biopsy was considered as standard of reference for all the FBLs classified as BI-RADS 4 or 5. For each 2D-SWE parameter, the optimal cutoff value for a diagnostic test was calculated using the Youden method. Diagnostic performance of the US BI-RADS and 2D-SWE parameters was calculated accordingly. RESULTS: 83/158 (52.5%) FBLs were benign and 75/158 (47.5%) were malignant. Statistically significant higher stiffness values were observed in malignant FBLs for all 2D-SWE parameters than in benign ones (p < 0.001). 2D-SWE cutoff values were 82.6 kPa, 66.0 kPa and 53.6 kPa, respectively, for Emax, Emean, Emin and 330.8% for Eratio. The 2D-SWE parameter showing the best diagnostic accuracy was Emax (85.44%). Considering US BI-RADS 3 (n = 60) and 4a (n = 32) FBLs, Emax and Emean showed the best diagnostic accuracy (85.87% for both), without a statistically significant decrease in sensitivity (p = 0.7003 and p = 1, respectively). CONCLUSION: Our study provides new vendor-specific cutoff values for 2D-SWE, suggesting its possible clinical use in the adjunctive assessment of category US-BI-RADS 3 and 4a breast masses.

MUTYH-associated tumor syndrome: The other face of MAP.

MUTYH gene is involved in the base excision repair (BER) mechanism and its pathogenic alterations are associated with colorectal polyposis and cancer. MUTYH-associated polyposis (MAP) is a condition which is inherited in an autosomal recessive manner. MAP patients, beyond colorectal cancer (CRC), may develop other types of tumors, including duodenal, breast, ovarian, pancreatic, bladder and skin cancers. Carriers of biallelic MUTYH likely pathogenic/pathogenic variants exhibit a high lifetime risk of CRC, though cancer risk evidence becomes less clear when monoallelic carriers and extraintestinal tumors are considered. However, several studies recently reported an increased genetic susceptibility to cancer also for carriers of germline monoallelic MUTYH mutations. Moreover, experimental evidence highlighted the MUTYH involvement in many other biological functions. In future, MUTYH mutation carriers might benefit from new target therapies involving the use of PD-1 or KRAS inhibitors. Therefore, "MUTYH-associated tumor syndrome" might be the most appropriate term, due to the multiplicity of tumors observed in MAP patients and different biological contexts in which MUTYH acts as a "playmaker". In this Review, we will investigate the impact of germline mono- and biallelic MUTYH mutations on cancer risk, providing a proposal for clinical surveillance of mutation carriers.

BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: Looking for the hidden meaning.

Hereditary breast and ovarian cancer syndrome is caused by germline mutations in BRCA1/2 genes. These genes are very large and their mutations are heterogeneous and scattered throughout the coding sequence. In addition to the above-mentioned mutations, variants of uncertain/unknown significance (VUSs) have been identified in BRCA genes, which make more difficult the clinical management of the patient and risk assessment. In the last decades, several laboratories have developed different databases that contain more than 2000 variants for the two genes and integrated strategies which include multifactorial prediction models based on direct and indirect genetic evidence, to classify the VUSs and attribute them a clinical significance associated with a deleterious, high/low or neutral risk. This review provides a comprehensive overview of literature studies concerning the VUSs, in order to assess their impact on the population and provide new insight useful for the appropriate patient management in clinical practice.

Effectiveness of early administration of a single dose of steroids and escin after loss of signal on electromyographic signal recovery during neuromonitored thyroidectomy.

BACKGROUND: The aim of this study was to evaluate the effect of a single early administration of dexamethasone and escin after loss of signal (LOS) during a neuromonitored total thyroidectomy. METHODS: A retrospective analysis of results concerning consecutive patients undergoing total thyroidectomy was performed. Patients included in the study were divided into two groups: Group 1 for which a "wait and see" strategy was used; Group 2, receiving dexamethasone and escin immediately after LOS detection. RESULTS: Overall 37 patients were included in Group 1 and 35 in Group 2. LOS recovery occurring in 29.7% of cases (n. 11) versus 65.7% (n. 23) respectively (p < 0.001). Postoperative fibrolayngoscopy for patients without LOS recovery showed normal cord function in 4 out of 26 cases (15.4%) in Group 1 and in 7 out of 12 (58.3%) in Group 2 (p < 0.001). CONCLUSIONS: The early administration of dexamethasone and escin after LOS detection may achieve greater EMG signal recovery than a "wait and see" strategy.

Effects of the number of removed lymph nodes on survival outcome in patients with sentinel node-negative breast cancer.

BACKGROUND: Sentinel lymph node biopsy is the gold standard surgical technique for axillary staging in patients with clinically node-negative. However, it is still uncertain what is the optimal number of sentinel lymph nodes (SLNs) to be removed to reduce the false-negative rate. The aim of this study was to investigate whether patients with a single negative SLN have a worse prognosis than those with two or more negative SLNs. METHODS: A retrospective review was conducted on a large series of SLN-negative breast cancer patients. Survival outcomes and regional recurrence rate were evaluated according to the number of removed SLNs. Secondly, the contribution of different adjuvant therapies on disease-free survival was explored. Statistical analysis included the chi-square, Wilcoxon-Mann-Whitney test, and Kaplan-Meier survival analysis. RESULTS: A total of 1080 patients were included in the study. A first group consisted of 328 patients in whom a single SLN was retrieved, and a second group consisted of 752 patients in whom two or more SLNs were retrieved. There was no relevant difference in median DFS (64.9 vs 41.4) for SLN = 1 vs SLN > 1 groups (HR 0.76, CI 95% 0.39-1.46; p = 0.38). A statistically significant difference in mDFS was showed only for HT-treated patients who were SLN = 1 if compared to SLN > 1 (100.6 months versus 35.3 months). CONCLUSIONS: There is likely a relationship between the number of resected SNL and mDFS. Our results, however, showed no relevant difference in median DFS for SLN = 1 vs SLN > 1 group, except for a subset of the patients treated with hormone therapy.

Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery.

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored.Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease.

Value of Neurostimulation Plus Laryngeal Palpation to Predict Postoperative Vocal Fold Motility.

BACKGROUND: The aim of this study was to evaluate the reliability of intraoperative neuromonitoring through recurrent laryngeal nerve stimulation and simultaneous laryngeal palpation (NSLP) in predicting postoperative vocal cord palsy and in providing useful information in the decision to perform a staged surgery in initially planned total thyroidectomy. MATERIALS AND METHODS: A retrospective review was performed involving 552 patients for whom a total thyroidectomy was planned. In all patients, preoperative and postoperative laryngoscopy was performed. The incidence of vocal cord palsy was calculated on 1104 nerves at risk. RESULTS: Sensitivity and specificity of NSLP were 0.9411 and 0.9925 respectively. The positive predictive value was 0.7804, the negative predictive value was 0.9981, the false positive rate was 0.8%. In 41 patients (7.4%) the initial surgical strategy was changed into a staged procedure. Nine patients (21.9%) were false positive, 32 patients (78.1%) were true positive. Finally, a two-stage thyroidectomy was performed in 27 of 41 patients. CONCLUSIONS: High sensitivity and specificity confirm the validity of NSLP in predicting postoperative vocal cord palsy and in driving a possible staged thyroidectomy, both in benign thyroid disease and in differentiated thyroid carcinoma.

Laryngopharyngeal reflux as a potential cause of persistent local neck symptoms after total thyroidectomy.

PURPOSE: Local neck symptoms (LNS) may be related to goiter, but are also reported by patients suffering from laryngeal-pharyngeal reflux (LPR). The aim of this study was to investigate whether LPR could play a role in the persistence of some LNS after total thyroidectomy (TT). METHODS: A consecutive case series of 160 patients with multinodular goiter (MNG) candidate for TT were included in this study. Each patient was closely studied for both the thyroid pathology and reflux disease before and 6 months after surgery to assess the persistence of LNS after surgery. RESULTS: Only throat discomfort showed a significant improvement (p = 0.031) after surgery. On the other hand, swallowing and voice disorders persisted after surgery in 82.3% and 77.3% of patients, respectively (p = 0.250 and p = 0.062), such as the correlated reflux laryngopharyngitis (p = 0.5). CONCLUSIONS: LPR can be considered a predisposing factor or an important concurrent causa to the persistence of LNS after TT, in particular for swallowing disorders and voice disorders. In patients with non-toxic MNG who complain of local neck symptoms, the investigation of a possible coexistence of a reflux disease is appropriate before surgery. Patients should be informed about the possibility that some symptoms can persist even after removal of the goiter.

Impact of BMI on Preoperative Axillary Ultrasound Assessment in Patients With Early Breast Cancer.

BACKGROUND: The accuracy of axillary ultrasound (AUS) with fine-needle aspiration with varying patient body mass index (BMI) is still unclear. The aim of our study was to evaluate whether the US features of axillary lymph nodes changes with BMI of patients. PATIENTS AND METHODS: A retrospective review was performed involving 144 out of 270 patients with early breast cancer who underwent breast surgery with sentinel lymph node biopsy. Diagnostic efficacy of AUS in preoperative axillary nodal staging was assessed in relation to BMI. RESULTS: Negative predictive values of AUS for the overweight and obese groups were statistically significantly lower compared to the normal/underweight group (p=0.02 and p=0.003, respectively). Additionally, Spearman's correlation coefficient R between BMI and positive sentinel lymph node biopsy was 0.257, suggesting a significantly positive linear relationship between the two variables in the cohort overall. CONCLUSION: Our results demonstrate how in our cohort the negative predictive value of AUS was significantly influenced by adipose tissue and that the selection of the most suitable instrumental diagnostic technique might contribute to improving heterogeneous results.

Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells.

Human surfactant protein D (SP-D) belongs to the family of collectins that is composed of a characteristic amino-terminal collagenous region and a carboxy-terminal C-type lectin domain. Being present at the mucosal surfaces, SP-D acts as a potent innate immune molecule and offers protection against non-self and altered self, such as pathogens, allergens, and tumor. Here, we examined the effect of a recombinant fragment of human SP-D (rfhSP-D) on a range of breast cancer lines. Breast cancer has four molecular subtypes characterized by varied expressions of estrogen (ER), progesterone (PR), and epidermal growth factor (EGF) receptors (HER2). The cell viability of HER2-overexpressing (SKBR3) and triple-positive (BT474) breast cancer cell lines [but not of a triple-negative cell line (BT20)] was reduced following rfhSP-D treatment at 24 h. Upregulation of p21/p27 cell cycle inhibitors and p53 phosphorylation (Ser15) in rfhSP-D-treated BT474 and SKBR3 cell lines signified G2/M cell cycle arrest. Cleaved caspases 9 and 3 were detected in rfhSP-D-treated BT474 and SKBR3 cells, suggesting an involvement of the intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid (HA) whose increased level in breast tumor microenvironment is associated with malignant tumor progression and invasion. rfhSP-D bound to solid-phase HA and promoted tumor cell proliferation. rfhSP-D-treated SKBR3 cells in the presence of HA showed decreased transcriptional levels of p53 when compared to cells treated with rfhSP-D only. Thus, HA appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-overexpressing and triple-positive breast cancer cells.