Molecular Subtypes of Extra-pulmonary Neuroendocrine Carcinomas Identified by the Expression of Neuroendocrine Lineage-Specific Transcription Factors

Extra-pulmonary neuroendocrine carcinomas (EPNEC) represent a group of rare and heterogenous neoplasms with adverse clinical outcome. Their molecular profile is largely unexplored. Our aim was to investigate if the major transcriptional drivers recently described in high-grade pulmonary neuroendocrine carcinomas characterize distinct molecular and clinical subgroups of EPNEC. Gene expression of ASCL1, NEUROD1, DLL3, NOTCH1, INSM1, MYCL1, POU2F3, and YAP1 was investigated in a series of 54 EPNEC (including 10 cases with mixed components analyzed separately) and in a group of 48 pulmonary large cell neuroendocrine carcinomas (P-LCNEC). Unsupervised hierarchical cluster analysis classified the whole series into four major clusters. P-LCNEC were classified into two major clusters, the first ASCL1/DLL3/INSM1-high and the second (including four EPNEC) ASCL1/DLL3-low but INSM1-high. The remaining EPNEC cases were sub-classified into two other clusters. The first showed INSM1-high and alternative ASCL1/DLL3 or NEUROD1 high expression. The second was characterized mainly by MYCL1 and YAP1 overexpression. In the ten cases with mixed histology, ASCL1, DLL3, INSM1, and NEUROD1 genes were significantly upregulated in the neuroendocrine component. Higher gene-expression levels of NOTCH1 and INSM1 were associated with lower pT stage and negative nodal status. Low INSM1 gene expression was associated with shorter overall survival in the entire case series (p = 0.0017) and with a trend towards significance in EPNEC, only (p = 0.06). In conclusion, our results show that EPNEC possess distinct neuroendocrine-lineage-specific transcriptional profiles; moreover, low INSM1 gene expression represents a novel potential unfavorable prognostic marker in high-grade NECs including those in extra-pulmonary location

The Effect of Adjuvant Radiotherapy on One- and Two-Stage Prosthetic Breast Reconstruction and on Autologous Reconstruction: A Multicenter Italian Study among 18 Senonetwork Breast Centres

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered

Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

<p>Abstract</p> <p>Background</p> <p>Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma.</p> <p>Methods</p> <p>Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m²daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival.</p> <p>Results</p> <p>Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable.</p> <p>Conclusion</p> <p>Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future.</p> <p>Trial registration</p> <p>NCT00953394</p

Apophyseal injuries in children's and youth sports

Introduction: The authors reviewed the current English literature regarding apophyseal injuries affecting young athletes, to highlight the frequency and characteristics of these injuries, to clarify risk factors and specific prevention measures, and to identify future research objectives. Sources of data: The authors performed a comprehensive search of the medical literature, using the Medline database, including all English articles. Various combinations of the Keywords 'injury', 'sports', 'athletic injuries', 'avulsion fractures', 'physeal', 'physis', 'apophysis', 'apophysitis', 'growth plate' were used. Areas of agreement: Growth benefits from a moderate physical activity. Areas of controversy: Growth deficit may occur in young athletes involved in intensive practice of sport following apophysitis. Growing points: Apophyseal injuries occurring during sport are less common than overall rate of injuries affecting the adolescent population. Growth disturbance occurs only rarely after an apophyseal injury. Areas timely for developing research: Further studies should consider analytical as well as descriptive components of apophyseal injuries, to allow the identification of new possible risk factors and preventive measures and to help early detection and proper treatment as well

The effectiveness of conservative and surgical treatment for shoulder stiffness: a systematic review of current literature

Currently, no therapeutic intervention is universally accepted, and the most effective management for restoring motion and diminishing pain in patients with shoulder stiffness has yet to be defined. This systematic review analyses outcomes of conservative and surgical interventions to treat shoulder stiffness

Surgical versus conservative management of Type III acromioclavicular dislocation: a systematic review

The management of Type III acromioclavicular (AC) dislocations is still controversial. We wished to compare the rate of recurrence and outcome scores of operative versus non-operative treatment of patients with Type III AC dislocations

Surgical management of chordoma: A systematic review

Chordomas are rare primary tumors of bone characterized by local aggressiveness and poor prognosis. The surgical exeresis plays a critical role for their management

Conservative and surgical management of acute isolated syndesmotic injuries: ESSKA-AFAS consensus and guidelines

Correct management of syndesmotic injuries is mandatory to avoid scar tissue impingement, chronic instability, heterotopic ossification, or deformity of the ankle. The aim of the present study was to perform a systematic review of the current treatments of these injuries to identify the best non-surgical and surgical management for patients with acute isolated syndesmotic injuries. A review of the literature was performed according to the PRISMA guidelines. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases was performed using the following keywords: "ankle injury", "syndesmotic injury", "chronic", "acute", "treatment", "conservative", "non-operative" "operative", "fixation", "osteosynthesis", "screw", "synostosis", "ligamentoplasties" over the years 1962-2015. The literature search and cross-referencing resulted in a total of 345 references, of which 283 were rejected due to off-topic abstract and/or failure to fulfil the inclusion criteria. After reading the remaining full-text articles, we included four studies, describing non-surgical management, and only two studies investigating surgical management of acute isolated injuries. The ESSKA-AFAS consensus panel provided recommendations to improve the management of patients with isolated acute syndesmotic injury in clinical practice. Non-surgical management is recommended for stable ankle lesions and includes: 3-week non-weight bearing, a below-the-knee cast, rest and ice, followed by proprioceptive exercises. Surgery is recommended for unstable lesions. Syndesmotic screw is recommended to achieve a temporary fixation of the mortise. Suture-button device can be considered a viable alternative to a positioning screw. Partial weight bearing is allowed 6 weeks after surgery. I

Classification and diagnosis of acute isolated syndesmotic injuries: ESSKA-AFAS consensus and guidelines

The aim of the present study was to perform a systematic review of the current classification systems, and the clinical and radiological tests for the acute isolated syndesmotic injuries to identify the best method of classification and diagnosis allowing the surgeon to choose the appropriate management. A systematic review of the literature according to the PRISMA guidelines has been performed. A comprehensive search using various combinations of the keywords "classification", "grading system", "ankle injury", "ligament", "syndesmotic injury", "internal fixation", "acute", "synostosis", "ligamentoplasties", "clinical", "radiological" over the years 1962-2015 was performed. The following databases were searched: MEDLINE, Google Scholar, EMBASE and Ovid. The literature search resulted in 345 references for classification systems and 308 references for diagnosis methods, of which 283 and 295 were rejected due to off-topic abstract and/or failure to fulfil the inclusion criteria. After reading the remaining full-text articles, we included 27 articles describing classification systems and 13 articles describing diagnostic tests for acute isolated syndesmotic injuries. The ESSKA-AFAS consensus panel recommends distinguishing acute isolated syndesmotic injury as stable or unstable. Stable injuries should be treated non-operatively with a short-leg cast or brace, while unstable injuries should be managed operatively. The recommended clinical tests include: tenderness on palpation over the anterior tibiofibular ligament, the fibular translation test and the Cotton test. Radiographic imaging must include an AP view and a mortise view of the syndesmosis to check the tibiofibular clear space, medial clear space overlap, tibial width and fibular width. I

2017 Marathon of Rome: Anthropometry and Sport Profile in 350 Runners and Association With Achilles and Patellar Tendinopathy

Achilles and patellar tendinopathy are common in runners. Despite the relevance of the problem, causative factors remain poorly understood. This cross-sectional study evaluated the association between Achilles and patellar tendinopathy and age, sex, weight, height, number of marathons, and impact profile in runners who participated in the 2017 Marathon of Rome