Endoscopic endonasal approach for loco-regional recurrent clivus chordomas

Introduction. Role of surgery for loco-regional recurrences of clivus chordomas (CCs) is still debated. It has been proposed in selected cases with a curative or with palliative intent, eventually followed by radiation or chemo/radiation treatments. Only limited data on the endoscopic endonasal approach (EEA) are available. Research question. To assess the role of EEA for loco-regional recurrent CCs. Materials and Methods. All consecutive loco-regional recurrent CCs operated by EEA at our Institution from 1998 to 2021 were identified. The extension of tumor resection, symptoms control, overall survival (OS), and progression free survival (PFS) were assessed. Results. Series includes 54 patients (53.7% females, mean age 55± 14 years). Surgery was planned with a resective aim in 35 (64.8%) patients, while it was palliative in 19 (35.2%). Gross tumor removal was achieved in 24 cases (44.4%). Main complications consisted of 2 (3.7%) CSF leaks. Further local relapses were observed in 30 (55.5%) patients after 25± 24 months; 29 (53.7%) patients deceased after 34 ± 31 months. OS and PFS were lower in these cases than primary surgeries (p<0.001 and p<0.001), but cases undergone surgery with a resective aim had a significant better OS and PFS than for those treated for palliation (p<0.001). Determinants of recurrences were tumoral size (p=0.48) and previous radiotherapy (p=009). Discussion and Conclusions. EEA has proven to be effective for loco-regional recurrent CCs alleviating patients symptoms and preserving their quality of life with limited morbidities. However, because overall prognosis is poor, EEA should be reserved to selected recurrent cases

Clinical-Pathological Evaluation and Prognostic Analysis of 228 Merkel Cell Carcinomas Focusing on Tumor-Infiltrating Lymphocytes, MCPYV Infection and ALK Expression

Merkel cell carcinoma is a rare and aggressive primary neuroendocrine carcinoma of the skin, whose pathogenesis can be traced back to UV radiation damage or Merkel cell polyomavirus (MCPyV) infection. Despite some improvements on the characterization of the disease partly due to its increased incidence, crucial pathogenetic and prognostic factors still need to be refined. A consecutive series of 228 MCC from three hospitals in Turin was collected with the aim of both analyzing the apparent increase in MCC incidence in our area and investigating the distribution and prognostic role of clinical-pathological parameters, with a focus on MCPyV status, ALK tumor expression and tumor infiltrating lymphocytes (TILs). Review of morphology and conventional immunohistochemical staining was possible in 191 cases. In 50 cases, the expression of the novel neuroendocrine marker INSM1 was additionally assessed. Fourteen cases of MCC of unknown primary skin lesion were identified and separately analyzed. While confirming an exponential trend in MCC incidence in the last decades and providing a description of histological and cytological features of a large series of MCC, the present study concludes that 1) INSM1 is a highly sensitive marker in both skin and lymph node primary MCC; 2) positive MCPyV status, brisk TILs and lower tumor size and thickness are independent positive prognostic parameters, and the combination of the former two may provide a novel tool for prognostic stratification; 3) ALK is expressed 87% of MCC and associated with positive viral status, and could represent a prognostic biomarker, if validated in larger series

Role of endoscopic endonasal approach for craniopharyngiomas extending into the third ventricle in adults

Introduction. Recent advancements in endoscopic endonasal approach (EEA) have favored its adoption for craniopharyngiomas extended to 3rd ventricle (3VCPs). However, for lack of extensive series, its outcome, limits, and indications remain debated. Research question. To assess the EEA results of for 3VCPs and identify those factors determining the choice of this approach. Material and Methods. Records of patients with 3VCPs, consecutively operated through an EEA at our Institution were retrospectively analyzed. Demographic and clinico-radiological data, rate of tumor resection, complications and outcome at follow-up were collected. Results. Thirty-six patients (19 females, mean age: 51.1 ± 15.9 yrs) were included. Extended transplanum-transtuberculum approach was performed in all cases Radical resection was achieved in 33 patients (91.7%). At follow-up, visual deficits improved/normalized in 21 cases (58.3%), and 35 (97.2%) presented with panhypopituitarism and DI. Anatomical (displacement of the chiasm and hypothalamus), clinical (age and pre-operative visual and endocrinological function) and tumoral (consistency, presence of hydrocephalus) parameters resulted relevant in determining the choice of this approach. Discussion and Conclusion. EEA offers a valid and direct route for 3VCPs, which permits to safely manage these tumors. In our series, EEA was chosen for tubero-infundibular forms with chiasm displaces antero-superiorly, and preferred in younger patients, with visual disturbances, comprimesed endocrinological function and no hydrocephalus. It requires a specific training and should be reserved in dedicated centers. Because no single approach is ideal for every 3VCP, all surgical options should be considered as complementary and selected basing on clinical, anatomical and tumoral features of each case

Machine learning-based clinical outcome prediction in surgery for acromegaly

Purpose Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. Methods Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. Results The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. Conclusions Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization

A complex of α6 integrin and E-cadherin drives the liver metastasis of colorectal cancer cells by a physical and functional interaction with hepatic angiopoietin-like 6

Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α(6) integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α(6) integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α(6) integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC

Late Quaternary sea-level change and early human societies in the central and eastern Mediterranean Basin : an interdisciplinary review

This article reviews key data and debates focused on relative sea-level changes since the Last Interglacial (approximately the last 132,000 years) in the Mediterranean Basin, and their implications for past human populations. Geological and geomorphological landscape studies are critical to archaeology. Coastal regions provide a wide range of resources to the populations that inhabit them. Coastal landscapes are increasingly the focus of scholarly discussions from the earliest exploitation of littoral resources and early hominin cognition, to the inundation of the earliest permanently settled fishing villages and eventually, formative centres of urbanisation. In the Mediterranean, these would become hubs of maritime transportation that gave rise to the roots of modern seaborne trade. As such, this article represents an original review of both the geo-scientific and archaeological data that specifically relate to sea-level changes and resulting impacts on both physical and cultural landscapes from the Palaeolithic until the emergence of the Classical periods. Our review highlights that the interdisciplinary links between coastal archaeology, geomorphology and sea-level changes are important to explain environmental impacts on coastal human societies and human migration. We review geological indicators of sea level and outline how archaeological features are commonly used as proxies for measuring past sea levels, both gradual changes and catastrophic events. We argue that coastal archaeologists should, as a part of their analyses, incorporate important sea-level concepts, such as indicative meaning. The interpretation of the indicative meaning of Roman fishtanks, for example, plays a critical role in reconstructions of late Holocene Mediterranean sea levels. We identify avenues for future work, which include the consideration of glacial isostatic adjustment (GIA) in addition to coastal tectonics to explain vertical movements of coastlines, more research on Palaeolithic island colonisation, broadening of Palaeolithic studies to include materials from the entire coastal landscape and not just coastal resources, a focus on rescue of archaeological sites under threat by coastal change, and expansion of underwater archaeological explorations in combination with submarine geomorphology. This article presents a collaborative synthesis of data, some of which have been collected and analysed by the authors, as the MEDFLOOD (MEDiterranean sea-level change and projection for future FLOODing) community, and highlights key sites, data, concepts and ongoing debates

Le consulenze psichiatriche ripetute al Policlinico di Modena ed al SSM di Reggio Emilia: due esperienze a confronto.

aspetti comuni e specifici di due attività di psichiatria di consultazione, intra- ed extra-ospedalier

P63 EXPRESSION AS A NEW PROGNOSTIC MARKER IN MERKEL CELL CARCINOMA.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor, mostly affecting elderly individuals. Histogenesis of this rare tumor as well as prognostic criteria are a matter of dispute. Several prognostic indicators have been proposed for MCC. Gender (male), tumour size >5 cm or > 2 cm, location in the buttock, thigh, trunk or head & neck, advanced clinical stage, small cell size, high mitotic index, diffuse pattern as well as mutation of TP53 gene family, have all been reported as indicators of poor prognosis. The p63 protein is a member of the p53 family, and it can be frequently amplified and/or overexpressed in human tumours including carcinoma of head & neck, lung, skin, esophagus, mammary glands, urothelia, cervix, prostate glands, oral squamous cell carcinomas and in odontogenic tumours. Although p63 per se is not general indicator of poor prognosis, nevertheless it is often associated to poorly differentiated basaloid carcinoma. Recently Fukushima et al. suggested that p63 expression is a disadvantageous factor for prognosis in a subgroups of B-cell lymphomas. Our study will show that the same statement can be made in MCC. METHODS: An immunohistochemical analysis of markers of proliferation (Ki67/MIB1), neuroendocrine differentiation (chromogranin A and synaptophisin) and basal cell differentiation (p63) was performed in a series of 47 cases of MCC. Significance of pathological data and of immunoreactivity with different markers was evaluated by chi-squared test. Survival curves were calculated by Kaplan-Meyer method. The difference of survival was estimated using Wilcoxon or Mantel-Cox test. RESULTS: Immunohistochemical evidence of neuroendocrine differentiation and immunopositivity for cytokeratin 20 were observed in all cases, while p63 positivity (10 of neoplastic cell) was detected in approximately half (25/47; 53.2%) of the cases. Cases positive for p63 showed a more aggressive clinical course than the negative ones (Z =2.93; P=.0003; HR=22.22). CONCLUSIONS: Our data indicate that p63 expression is associated with a worse prognosis in MCC and it represents a new independent marker of clinical evolution with a better predictive power than the other prognostic parameters