1,721,019 research outputs found
CELL OF ORIGIN MARKERS IDENTIFY DIFFERENT PROGNOSTIC SUBGROUPS OF LUNG ADENOCARCINOMA PATIENTS
No full textPur essendo il carcinoma del polmone la causa principale di morte per cancro a livello mondiale, non ci sono ancora marcatori affidabili in grado di stratificare da un punto di vista prognostico i pazienti affetti da adenocarcinoma del polmone. Né l’aspetto istologico né fingerprint genetici sono in grado di fornire una stratificazione prognostica dei pazienti che sia riproducibile e clinicamente utile. Per questo motivo, abbiamo costruito un pannello ad hoc di 6 marcatori immunoistochimici (TTF1, SP-A, Napsin A, MUC5AC, CDX2 e CK5). Testando questi marcatori, che sono fortemente correlati con le "cellule di origine" putative dell’adenocarcinoma polmonare (TTF1, SP-A e Napsin A indicano un'origine alveolare, mentre MUC5AC, CDX2 e CK5 indicano un'origine bronchiolare), ci proponiamo di identificare diversi sottogruppi prognostici tra i pazienti affetti da adenocarcinoma del polmone. Come secondo obiettivo, abbiamo correlato l’espressione di questi marcatori con le comuni mutazioni genetiche e l’aspetto istologico degli adenocarcinomi polmonari testati. A tal fine, abbiamo raccolto un'ampia coorte di pazienti sottoposti a intervento chirurgico per adenocarcinoma polmonare e, usando i tessuti fissati in formalina e inclusi in paraffina , abbiamo studiato: i) il pattern di crescita istologico (lepidico, acinare, papillare, micropapillare, solido e mucinoso) al microscopio ottico, ii) la presenza di mutazioni "hot spot" di geni candidati (ad esempio EGFR, KRAS, PI3K) tramite tecnologia Sequenom e iii) il pannello di 6 marcatori immunoistochimici. Le differenze tra i gruppi così ottenuti sono state valutate con il test di Mann-Whitney per le variabili continue e il test del chi-quadrato o test esatto di Fisher per le variabili categoriali. Per rilevare possibili fattori predittivi di sopravvivenza, abbiamo usato il modello di rischio proporzionale di Cox per descrivere rischi proporzionali con intervalli di confidenza al 95%. Come importante risultato, abbiamo identificato 4 sottogruppi differenti basati sull’espressione del pannello immunoistochimico: alveolari, bronchiolari, misti e tipo "nullo", che risultano fortemente correlati con diversi parametri clinico-patologici e soprattutto con la sopravvivenza globale. In particolare, se gli adenocarcinomi a fenotipo alveolare sorgono con maggiore frequenza nei pazienti giovani e nel sesso femminile e presentano più frequentemente mutazioni del gene EGFR, le neoplasie a fenotipo bronchiolare sono maggiormente associate alla presenza di invasione vascolare, istologia mucinosa e mutazioni del gene KRAS; infine, i fenotipi bronchiolari e “nulli” sono associati con una prognosi peggiore. In assenza di marcatori prognostici clinici, la stratificazione prognostica basata sulla "cellula di origine" è risultata più predittiva della prognosi dei parametri isto-morfologici e del fingerprint genetico e rappresenta un parametro predittivo indipendente di sopravvivenza nell'analisi multivariataLung carcinoma is the leading cause of cancer related-death worldwide, but reliable prognostic markers to correctly stratify the prognosis of patients with lung adenocarcinoma are still lacking. Neither morphology nor genetic fingerprints can fully achieve consistent and clinically informative stratifications. We aimed to evaluate a new immunohistochemical panel composed by 6 markers (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5). Using these markers, that are strongly correlated with the two possible putative “cell of origin” of lung adenocarcinoma (TTF1, SP-A and Napsin A indicate an alveolar origin, whereas MUC5AC, CDX2 and CK5 indicate a bronchiolar origin), we aim at identifying different prognostic subgroups among patients with such tumors. As a second aim, we have correlated these markers with common genetic mutations and classical morphology. We collected a large cohort of adenocarcinoma patients and, using formalin-fixed paraffin-embedded tissue, we have studied: i) the morphological appearance (lepidic, acinar, papillary, micropapillary, solid and mucinous) by light microscopy, ii) the presence of “hot spot” mutations of candidate genes (i.e. EGFR, KRAS, PI3K) by Sequenom technology and iii) the 6 immunohistochemical markers panel. Between-group differences were evaluated using the Mann–Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. To detect possible predictors of survival, we used the Cox proportional hazard model to describe proportional hazards with 95% confidence intervals. As major finding, we identified 4 different subgroups based on markers’ expression: “alveolar” type, “bronchiolar” type, “mixed” type and “null” type, that resulted strongly correlated with different clinic-pathological parameters and above all with Overall Survival (OS). Particularly, if the alveolar-type arose more in young and female patients, and harbor typically EGFR mutations, bronchiolar-type tumors were more frequently associated with vascular invasion, a mucinous histology and KRAS mutations; at last, Bronchiolar and Null types were associated with a worse prognosis. In the absence of reliable prognostic markers, our 6 “cell of origin” markers’ classifier appears more predictable than the classical morphologic parameters and the genetic fingerprint, and is an independent predictor of survival in a multivariate analysis
The Roles of Chromatin Remodeling Genes in Pancreatic-Biliary Malignancies
No full textRecent studies have definitively established that chromatin remodeling is a crucial epigenetic mechanism not only in physiological conditions but also in influencing cancer biology. It is a dynamic process in which the chromatin, the functional entity of DNA, can undergo specific modifications by obtaining transcriptional activation or transcriptional silencing. One of the most important recent discoveries in cancer genetics and genomics is that the genes involved in the establishment of chromatin structure, the so called chromatin remodelers, are frequently mutated in different types of human cancer. This review aims to summarize the main novelties related to this topic, describing also the contribution of such genes during oncogenesis. Particularly, we focus on the switch/sucrose non-fermentable complexes and on three of the most important chromatin remodeling genes in biliary and pancreatic cancer: ARID1A, PBRM1, and BAP1
Basic Elements of Artificial Intelligence Tools in the Diagnosis of Cutaneous Melanoma
No full text: Cutaneous melanoma (CM) incidence has dramatically increased in the last years. Early diagnosis is of paramount importance in terms of prognosis. Artificial Intelligence (AI) tools are being proposed for clinicians and pathologists as an adjunct support in the diagnostic process. We described herein an overview of the most important parameters that a potential AI tool should take into consideration in histopathology to evaluate a skin lesion. First of all, recognition of a melanocytic or non-melanocytic nature. Furthermore, melanocytic lesions should be stratified according to at least four parameters: silhouette and asymmetry; identification and spatial distribution of the cells; mitosis count; presence of ulceration. According to the number of parameters the AI tools might stratify the risk of CM and prioritize the pathologist's work
Complete Cerebrospinal Fluid Response to T-DM1 in HER2 Positive Metastatic Breast Cancer: A Case Report
No full textLeptomeningeal carcinomatosis is a rare but serious consequence of pre-existing tumors, such as breast, lung, and gastrointestinal carcinomas. Further, leptomeningeal carcinomatosis is more frequently diagnosed with breast cancers, if only because breast cancers are diagnosed far more often than any other carcinomas. In this paper, we present the case of a leptomeningeal carcinomatosis patient who experienced complete remission following therapy targeted at the Her-2 (human epidermal growth factor receptor 2-positive) receptor. This patient’s diagnosis was complicated by the fact that brain and column MRI imaging were clear, but analysis of the cerebrospinal fluid led to the conclusion of leptomeningeal carcinomatosis. The tests were requested because the patient, under chemotherapy for advanced breast cancer at the time, reported some neurological symptoms. Following the diagnosis of leptomeningeal carcinomatosis and subsequent T-DM1 Her-2 receptor therapy, the patient showed a complete response to leptomeningeal carcinomatosis within 30 days and survived for another 16 months. This case offers compelling evidence that the effect TDM1 Her-2 receptor therapy has on a patient’s remission and long-term survivability is considerably better than other therapies for similar pre-existing conditions diagnosed with leptomeningeal carcinomatosis. Further prospective studies should confirm these findings
Intra-operative frozen section technique for breast cancer: end of an era.
No full textData on 2436 primary breast carcinomas diagnosed between 1992 and 2006 were collected to evaluate the rate of frozen section procedures performed over time. Frozen section procedures performed to evaluate resection margins for conservative surgery or sentinel node status were excluded. Over time, there was a decrease in the use of frozen sections indistinctly extended to all pT cancer categories. The rate of cancers diagnosed with frozen sections was 51.2% in 1999, and 0% in 2005-2006. In the same period, the adoption of core biopsyand core biopsy for breast cancer diagnosis increased from 40% in 1992 to more than 90% since 1999. In an audited diagnostic activity on breast pathology, the routine use of frozen sections on primary lesions was considered inappropriate, particularly in assessment of clinically non-palpable lesions, and should be limited to cases with inadequate pre-surgical sampling
Laparoscopic partial resection and mucosectomy of pyloric duplication cyst
No full textThe Authors describe the laparoscopic procedure in the tratement of pyloric suplication cyst in childre
Comparative efficacy and safety of trastuzumab biosimilars to the reference drug: a systematic review and meta-analysis of randomized clinical trials
No full textPurpose To assess efficacy and safety of trastuzumab biosimilars in comparison to the reference drug through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods A comprehensive search was conducted using PubMed, Web of Science, Cochrane library, Open Grey and ClinicalTrials.gov databases. Dichotomous data for efficacy and safety outcomes were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs). Meta-analysis was performed with the Mantel-Haenszel method using Revman 5.3 software. Results Eight phase III RCTs including a total of 3913 patients with HER2 + breast cancer were identified that met the inclusion criteria. The pooled results for the comparison of trastuzumab biosimilars to the reference drug showed no differences of objective response rate (ORR) (RR 1.05, 95% CI 0.98-1.12,P = 0.20) or overall survival (RR 0.82, 95% CI 0.61-1.09,P = 0.17) in the intention-to-treat population, as well as no difference of ORR (RR 1.03, 95% CI 0.97-1.10,P = 0.30) in the per-protocol population. Similarly, no significant difference was detected in any type of adverse event reported in at least three RCTs, including any serious treatment-emergent adverse effects (RR 0.97, 95% CI 0.76-1.25,P = 0.83), heart failure (RR 1.47, 95% CI 0.69-3.14,P = 0.32), neutropenia (RR 1.05, 95% CI 0.96-1.15,P = 0.26), and infusion-related reaction (RR 1.10, 95% CI 0.89-1.36,P = 0.38). Conclusion This meta-analysis provides compelling evidence of clinical comparability between trastuzumab biosimilars and the originator product in terms of both efficacy and safety for the treatment of HER2 + breast cancer
Pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies: a case report and review of the literature
No full textA pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies is reported. A 63-year-old woman presented with an invasive ductal carcinoma of the breast and a lung adenocarcinoma. After multidisciplinary discussion, the patient underwent pulmonary left lower lobectomy followed by radio-chemotherapy with cisplatin and vinorelbine and started hormone therapy with letrozole. Ten months later, a left mastectomy with axillary lymph nodes dissection was performed. Histologically, a pathological complete response (pCR) was documented. With a review of the Literature, we discuss the issue of multiple primary malignancies, with its diagnostic and therapeutic implications. In cases of multiple synchronous malignancies it has been highlighted the importance of the choice of the best therapeutic approach for both the malignancies, reducing collateral individual effects
Laparoscopic partial resection and mucosectomy of pyloric duplication cyst
No full textThe Authors describe the laparoscopic procedure in the tratement of pyloric suplication cyst in childre
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