Surgery for elastofibroma dorsi: optimizing the management of a benign tumor – an analysis of 70 cases

Background: Elastofibroma dorsi (ED) is a benign soft-tissue tumor of the chest wall located near the tip of the scapula. Clinical presentation includes swelling, pain and impairment of shoulder movements. The present literature relies only on few small case series. The aim of this study was to analyze the surgical management of ED, focusing on the debated topics regarding preoperative evaluation, operative technique, post-operative outcome and follow-up. Methods: We conducted a single-center retrospective cohort analysis of patients operated for ED between 2003 and 2018. Diagnostic techniques were ultrasonography (US), computed tomography (CT-scan) and magnetic resonance imaging (MRI). CT-scan represented our preferred imaging study for preoperative assessment. Surgery was proposed for symptomatic and/or large lesions. Marginal excision through a musclesparing approach was performed. An open-door follow-up policy was adopted. All clinical, radiological, perioperative and pathological variables were matched in a univariate analysis. A multivariate analysis was performed to investigate risk factors for postoperative complications. Correlations analysis between radiological and pathological measurements of elastofibroma was conducted. Results: Seventy elastofibromas were excised in 59 patients. Mean age was 59 years and female prevalence was 59%. All elastofibromas were completely resected with no recurrence. Postoperative complications rate was 17%. Complications were mild in most cases. At the univariate analysis, patients with body mass index (BMI) >25 had a longer operative time (P=0.048), patients on antiplatelet medications experienced a prolonged drainage time (P=0.006) and a higher rate of complications (P=0.038); the occurrence of complications resulted in prolonged drainage time (P=0.047) and length of stay (P=0.023). A BMI ≤25 was the only independent risk factor for postoperative morbidity (OR 8.71, P=0.024). CT-scan showed the highest correlation with pathological size (r=0.819), US the lowest (r=0.421). Conclusions: Marginal resection through a muscle-sparing approach is safe and effective for the treatment of ED. CT-scan can be adequate for preoperative assessment. Giving the benign nature of the lesion and the absence of recurrence after complete resection, an open-door follow-up may be appropriate

On some notions of good reduction for endomorphisms of the projective line

Let $\Phi$ be an endomorphism of \SR(\bar{\Q}), the projective line over the algebraic closure of \Q, of degree $\geq2$ defined over a number field $K$. Let $v$ be a non-archimedean valuation of $K$. We say that $\Phi$ has critically good reduction at $v$ if any pair of distinct ramification points of $\Phi$ do not collide under reduction modulo $v$ and the same holds for any pair of branch points. We say that $\Phi$ has simple good reduction at $v$ if the map $\Phi_v$, the reduction of $\Phi$ modulo $v$, has the same degree of $\Phi$. We prove that if $\Phi$ has critically good reduction at $v$ and the reduction map $\Phi_v$ is separable, then $\Phi$ has simple good reduction at $v$.Comment: 15 page

A case of cervico-mediastinal paraganglioma mimicking an ectopic goiter

Introduction and importance: Mediastinal paragangliomas are rare neuroendocrine tumors that originate from extra-adrenal paraganglia, occasionally secreting catecholamines. Nonfunctional mediastinal paragangliomas present nonspecific clinical and radiological features and represent a diagnostic challenge. Case presentation: A 53-year old woman presented with cough and dyspnea increasing over time. CT-scan and ultrasonography showed a large vascularized cervico-mediastinal mass, consistent with an intrathoracic ectopic goiter. Preoperative angiography showed a blood supply from neck vessels. The lesion was completely removed through a cervical approach. The diagnosis of paraganglioma was a histological surprise. The patient is alive without recurrence 30 months after surgery. Clinical discussion: When preoperatively diagnosed, the treatment of choice of a mediastinal paraganglioma is surgical excision. However, a preoperative diagnosis of mediastinal paraganglioma is difficult to obtain, especially in cases of nonfunctional lesions. Distinction between an intrathoracic goiter and a nonfunctional paraganglioma can be extremely difficult and, given the rarity of the latter, an ectopic goiter is suspected in first instance. CT-scan and ultrasonography are of little use in the differential diagnosis. However, scintigraphy with 123I-metaiodobenzylguanidine can be an useful diagnostic tool when a paraganglioma is suspected. In case of vascularized cervico-mediastinal mass, such as paragangliomas or intrathoracic goiter, preoperative angiography should be performed to study the blood supply and orient the surgical approach. Conclusion: Although uncommon, paragangliomas should be considered in the differential diagnosis of mediastinal masses, especially when an ectopic goiter is suspected

Secondary spontaneous pneumothorax and bullous lung disease in cannabis and tobacco smokers. A case-control study.

Background The notion that smoking cannabis may damage the respiratory tract has been introduced in recent years but there is still a paucity of studies on this subject. The aim of this study was to investigate the relationship between cannabis smoking, pneumothorax and bullous lung disease in a population of operated patients. Methods and findings We performed a retrospective study on patients operated on for spontaneous pneumothorax. Patients were divided into three groups according to their smoking habit: cannabis smokers, only-tobacco smokers and nonsmokers. Cannabis lifetime exposure was expressed in dose-years (1d/y = 1 gram of cannabis/week for one year). Clinical, radiological and perioperative variables were collected. The variables were analyzed to find associations with smoking habit. The impact of the amount of cannabis consumption was also investigated by ROC curves analysis. Of 112 patients, 39 smoked cannabis, 23 smoked only tobacco and 50 were nonsmokers. Median cannabis consumption was 28 dose/years, median tobacco consumption was 6 pack/years. Cannabis smokers presented with more severe chronic respiratory symptoms and bullous lung disease and with a higher incidence of tension pneumothorax than both tobacco smokers and nonsmokers. Cannabis smokers also developed a larger pneumothorax, experienced prolonged postoperative stay and demonstrated a higher incidence of pneumothorax recurrence after the operation than nonsmokers did. The risk of occurrence of chronic respiratory symptoms and bullous lung disease in cannabis smokers was dose-related. Conclusions Cannabis smoking seems to increase the risk of suffering from respiratory complaints and can have detrimental effects on lung parenchyma, in a dose-dependent manner. Cannabis smoking also negatively affected the outcome of patients operated for spontaneous pneumothorax. A history of cannabis abuse should always be taken in patients with pneumothorax. There may be need for a specific treatment for pneumothorax in cannabis smokers

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study.

Purpose Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL). Experimental design This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis. Results Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25). Conclusion No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages

Prediction of Distant Recurrence-Free Survival in Resectable Lung Adenocarcinoma.

OBJECTIVES: Optimal procedures for adjuvant treatment and post-surgical surveillance of resected non-small-cell lung cancer remain under discussion. Pathological features are the main determinant of follow-up therapy but have limited ability to identify patients at risk of recurrence. Increasingly, molecular markers are incorporated into clinical decision-making, including measures of tumor growth. The CCP score is a quantitative, molecular measure of proliferation derived from the RNA expression of 31 cell cycle genes and a component of the molecular prognostic score (mPS). The mPS score is a linear combination of CCP score and pathological stage. CCP score and mPS are independent predictors of survival in resected lung adenocarcinoma. MATERIALS AND METHODS: CCP scores were determined by RT-qPCR for 318 patients diagnosed with stage I-II lung adenocarcinoma. Association of mPS and CCP score with distant recurrence and lung-cancer specific survival was assessed in Cox proportional hazards regression models adjusted for age, gender, tumor size, pathological stage and pleural invasion. Distant recurrence-free survival and lung-cancer specific survival by mPS risk group were calculated by Kaplan-Meier survival analysis. RESULTS: CCP scores were obtained for 205 stage I and 84 stage II patients. CCP score and mPS were independent markers of distant recurrence (CCP: HR 1.62, 95%CI 1.15-2.29, p=0.0055; mPS: HR 2.22, 95%CI 1.11-4.44, p=0.023). Patients with low mPS tumors were at significantly reduced risk of distant recurrence (log-rank p=4.2×10-5). Among stage I patients, stratification by mPS identified a patient group with increased risk of distant recurrence (36%, 95%CI 28-46%, log-rank p=0.0011) CONCLUSIONS: The molecular prognostic score stratifies early-stage, resected lung cancer patients for risk of distant recurrence and could be useful to inform treatment and surveillance decisions

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process

Endometrioid Cancer Associated With Endometriosis: From the Seed and Soil Theory to Clinical Practice

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. It is still debated whether endometriosis is a disease that can predispose to the pathogenesis of endometrial cancer outside the uterus. Deficiencies in mismatch repair (MMR) genes are a known risk factor for developing endometrioid cancer. Starting from two cases of patients with abnormal MMR endometrioid carcinoma of the uterus and synchronous endometrioid carcinoma in non-ovarian and ovarian endometriosis, we performed a somatic mutation profile and phylogenetic analysis of the lesions in order to identify if they were metastasis or primary de novo tumors. In the first case, we identified de novo activating mutations in PIK3CA and KRAS in endometrioid cancer lesions but not in endometriosis. Although the acquisition of a de novo mutation in ESR1 and a decrease in mutant allele fraction (MAF) from the endometrial tumor to the localizations in the endometriosis lesions, the clonal relationship was confirmed by the limited number of heteroplasmic mutations in D-loop mitochondrial DNA region. In the other case, the clonal behavior was demonstrated by the overlap of MAF at each site. Our data support the hypothesis of a retrograde dissemination of tumor cells, moving from the primary carcinoma in the endometrium to ectopic sites of endometriosis where localizations of tumor arise

Maternal sensitivity buffers the association between SLC6A4 methylation and socio-emotional stress response in 3-month-old full term, but not very preterm infants

Background: Very preterm (VPT) infants are hospitalized in Neonatal Intensive Care Units (NICUs) and are exposed to life-saving procedures eliciting pain-related stress. Recent research documented that pain-related stress might result in birth-to-discharge increased methylation of serotonin transporter gene (SLC6A4) in VPT infants, leading to poorer stress regulation at 3 months of age in VPT infants compared to their full-term (FT) counterparts. Maternal sensitivity is thought to support infants' stress response, but its role in moderating the effects of altered SLC6A4 methylation is unknown. Main aim: To assess the role of maternal sensitivity in moderating the association between altered SLC6A4 methylation and stress response in 3-month-old VPT and FT infants. Methods: 53 infants (27 VPTs, 26 FTs) and their mothers were enrolled. SLC6A4 methylation was obtained from peripheral blood samples at NICU discharge for VPT infants and from cord blood at birth for FT infants. At 3 months (age corrected for prematurity), both groups participated to the face-to-face still-face (FFSF) paradigm to measure both infants' stress response (i.e., negative emotionality) and maternal sensitivity. Results: Maternal sensitivity did not significantly differ between VPT and FT infants' mothers. In VPT infants, higher SLC6A4 methylation at hospital discharge associates with higher negative emotionality during the FFSF. In FT infants, SLC6A4 methylation and maternal sensitivity significantly interacted to predict stress response: a positive significant association between SLC6A4 methylation and negative emotionality emerged only in FT infants of less-sensitive mothers. Discussion: Although no differences emerged in caregiving behavior in the two groups of mothers, maternal sensitivity was effective in moderating the effects of SLC6A4 methylation in FT infants, but not in VPT infants at 3 months. Speculatively, the buffering effect of maternal sensitivity observed in FT infants was disrupted by the altered early mother-infant contact due to NICU stay of the VPT group. These findings indirectly support that the effects of maternal sensitivity on infants' socio-emotional development might be time dependent, and that mother-infant interventions in the NICU need to be provided precociously within a narrow sensitive period after VPT birth