A case of chronic strongyloidiasis diagnosed by histopathological study

No abstract availabl

Comparison of hormonal receptor and HER-2 status between breast primary tumours and relapsing tumours: clinical implications of progesterone receptor loss

Differences in hormone receptor and HER-2 status between primary tumour and corresponding relapse could have a substantial impact on clinical management of patients. The aim of this study was to evaluate change in expression of hormone receptors and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis. We analysed 140 primary tumours and related recurrent or metastatic samples. Hormone receptors status was evaluated by immunohistochemistry, while HER-2 status by immunohistochemistry and silver in situ hybridisation. A change in HER-2 was rare; 3.7% of cases by immunohistochemistry and only 0.7% by silver in situ hybridisation analysis. A change in estrogen and progesterone receptors was seen in 6.4% and 21.4% of cases, respectively. Estrogen receptor change was not affected by adjuvant therapy, whereas progesterone receptor was influenced by adjuvant chemotherapy associated to hormone therapy (P = 0.0005). A change in progesterone receptor was more frequent in distant metastases than in local recurrences (P = 0.03). In the setting of estrogen receptor positive tumours, patients with progesterone receptor loss in local recurrence had a statistically significant lower median metastasis free survival compared to others patients; progesterone receptor positive, 112 months; progesterone receptor negative, 24 months (P = 0.005). A change between primary tumour and corresponding relapse is frequent for progesterone receptor, infrequent for estrogen receptor and rare for HER-2. In cases with changes in HER-2, it is worthwhile reassessing HER-2 status with both immunohistochemistry and in situ hybridisation analysis. Progesterone receptor loss seems to be influenced by therapy and to correlate with a worse prognosis

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Muc expression and their prognostic value in cholangiocarcinoma

Il colangiocarcinoma (CC) \ue8 un tumore composto da cellule che ricordano quelle dei dotti biliari e rappresenta il secondo tumore epatico come incidenza dopo l\u2019epatocarcinoma, costituendo il 5-10% delle neoplasie primitive epatiche. A livello mondiale il colangiocarcinoma rende conto del 3% di tutti i carcinomi del tratto gastroenterico. Numerosi studi hanno messo in evidenza il fatto che i tassi di incidenza e mortalit\ue0 per il colangiocarcinoma intraepatico (IHCC) stanno aumentando, mentre quelli per il colangiocarcinoma extraepatico (EHCC) stanno globalmente diminuendo. Ad oggi l\u2019unica terapia potenzialmente curativa \ue8 quella chirurgica e questi pazienti hanno una prognosi infausta con una sopravvivenza di pochi mesi. Al momento una delle ragioni per cui questo tumore si presenta tardivamente \ue8 la mancanza di un marcatore diagnostico sensibile e specifico che permetta una diagnosi precoce. Lo scopo del nostro lavoro era trovare un marcatore sensibile e specifico, dosabile nel siero dei pazienti che si correli con il tipo tumorale e con le dimensioni del tumore in quanto la sopravvivenza \ue8 del 70-80% per quei pazienti con tumori piccoli scoperti incidentalmente in corso di trapianto per colangite sclerosante primitiva. Le Mucine sono glicoproteine altamente glicosilate con un ruolo protettivo nelle cellule, servendo in parte da barriera per la superficie delle cellule epiteliali e per le cellule tumorali. Boonla C et al. recentemente hanno dimostrato che la mucina MUC5AC \ue8 presente in concentrazioni significative nel siero dei pazienti con CC. In un lavoro recente, MUC5AC correlava significativamente con l\u2019invasione perineurale e uno stadio avanzato di malattia. Ci sono pochi studi sulla espressione delle mucine, in particolare il tipo gastrico e la loro relazione con la morfologia e la prognosi dei colangiocarcinomi. Abbiamo analizzato mediante immunoistochimica tutti i nostri casi per MUC1, MUC2, MUC6 e MUC5AC. I risultati pi\uf9 significativi sono stati con MUC5AC. Recentemente il Liver Cancer Study Group of Japan ha suddiviso IHCC in tre tipi morfologici: mass-forming (MF), periductal infiltrating (PI) e intraductal growth (IG). Il tipo MF \ue8 caratterizzato dalla presenza di una massa tondeggiante a margini distinti all\u2019interno del parenchima epatico, il tipo PI \ue8 caratterizzato da una infiltrazione tumorale lungo i dotti biliari,che occasionalmente interessa i vasi e/o il parenchima epatico, il tipo IG da una crescita papillare e/o granulare all\u2019interno del lume dei dotti. Il tipo PI \ue8 correlato ad una maggiore incidenza di invasioni perineurali, metastasi linfonodali e recidive extraepatiche rispetto al tipo MF. La sopravvivenza a 5 anni dei pazienti con tumori IG o MF \ue8 significativamente migliore di quelli con tumori MF pi\uf9 PI o solo PI. C\u2019\ue8 sempre pi\uf9 evidenza che i colangiocarcinomi intraepatici debbano essere suddivisi in periferici e periilari su base eziopatogenetica, di comportamento biologico e caratteristiche cliniche. I CC periilari probabilmente derivano dall\u2019epitelio di rivestimento dei rami principali dei dotti epatici di destra e sinistra e dalle ghiandole peribiliari che li circondano e istologicamente sono adenocarcinomi con caratteristiche dei tipi ilari e extraepatici. I CC periferici presumibilmente originano dai piccoli dotti biliari, duttuli e canali di Hering. Probabilmente sono coinvolte nella tumorigenesi le cellule progenitrici epatiche. Distinguere per\uf2 tumori periilari da ilari \ue8 spesso difficile soprattutto in casi avanzati. Nel nostro studio insieme con i chirurghi proponiamo una classificazione di questo tipo: periferici per colangiocarcinomi che si sviluppano nel parenchima epatico, periilari per tumori localizzati nel fegato ma che interessano l\u2019ilo e per i tumori di Klatskin e extraepatici per tumori del tratto biliare distale. Questa classificazione correla bene con la morfologia. La maggior parte (30/35) CC periferici sono di tipo MF con solo 5 casi MF+PI. I tumori periilari e gli extraepatici sono principalmente PI o MF+PI rispecchiando un differente pattern di crescita tra le due forme. Al di l\ue0 di un diverso pattern di crescita c\u2019\ue8 anche una differenza statisticamente significativa rispetto alla espressione di MUC5AC. 30 dei 35 casi (85,7%) di CC periferico erano MUC5AC negativi. 26 di 39 (66,6%) CC periilari erano MUC5AC positivi, con intensit\ue0 variabile ma positivi. 13 casi erano negativi, di questi in 8 c\u2019erano alcune cellule positive anche se non sufficienti a raggiungere il cut-off del 5%, non sappiamo se sia di qualche significato ma \ue8 diverso dalla negativit\ue0 completa che si vede nei MF. Nel nostro studio MUC5AC sembra essere un buon marcatore immunoistochimico che pu\uf2 distinguere colangiocarcinomi periferici da periilari, che correla bene con la morfologia e ha anche un significato prognostico. Questo marcatore pu\uf2 essere misurato nel siero e pu\uf2 essere usato nel pannello dei marcatori tumorali da utilizzare nei colangiocarcinomi che pu\uf2 essere utile anche nel followup.Cholangiocarcinoma (CC) is a malignant tumour composed of cells resembling those of the bile ducts and the second most common primary hepatic tumor after hepatocellular carcinoma, comprising 5-10% of primary liver neoplasms. Worldwide, cholangiocarcinoma accounts for 3% of all gastrointestinal cancers. Several studies have shown that the incidence and mortality rates of intrahepatic CC (IHCC) are rising, and those of extrahepatic cholangiocarcinoma (EHCC) are declining worldwide. To date, radical surgery is the only therapy offering a potential cure for CC patients, whose prognosis is generally poor with survival limited to few months. At present, the lack of a sensitive and specific early diagnostic marker is one of the reasons why CC has a fairly late presentation. Our aim was to find out a sensitive and specific marker which could be detected in patient serum and be correlated with tumor type and tumor burden since the potential survival benefit from early detection is shown by 70-80% survival for patients with early cholangiocarcinoma that was discovered incidentally on transplantation for primary sclerosing cholangitis. Mucins are heavily glycosylated glycoproteins and play a protective role in cells, in part serving as a barrier to the epithelial surface and to tumor cells. Boonla C. et al. recently showed that MUC5AC mucin is present in significant concentrations in serum from patients with CC. In a recent report, MUC5AC significantly correlated with neural invasion and advanced CC stage. Only a few studies have been carried out about mucins expression, in particular the gastric type and their relationship with CC morphology and prognosis. We stained all tissue for MUC1, MUC2, MUC6 and MUC5AC. The only interesting results were with MUC5AC. Recently the Liver Cancer Study Group of Japan divided IHCC into three morphological types: mass-forming (MF), periductal infiltrating (PI) and intraductal growth (IG). MF type is characterized by the presence of a spherical mass with a distinct border in the liver parenchyma, PI type presents tumor infiltration along the bile duct, occasionally involving the surrounding blood vessels and/or hepatic parenchyma, IG is characterized by papillary and/or granular growth into the bile duct lumen. PI type of CC present a significantly higher frequency of perineural invasion, lymph node metastasis and extrahepatic recurrence than MF type. The 5-year survival rates of patients with IG tumors or MF tumors is significantly better than those of patients with MF plus PI tumors or PI type alone. There is increasing evidence that intrahepatic cholangiocarcinoma should be divided in peripheral CC and perihilar CC based on etiopathogenesis, biological behaviour and clinical features. Perihilar CC may evolve from the lining epithelia of the major branches of the right and left hepatic bile duct and also from peribiliary glands around them and histologically is an adenocarcinoma resembling many of the features of hilar or extrahepatic CC. Peripheral CC presumably develop from small bile duct, ductules or canals of Hering. Hepatic progenitor cell may be involved in the tumorigenesis of peripheral CC. Distinguishing perihilar from hilar CC is often difficult, especially in advanced cases. In this study together with the surgeons we propose a different classification: peripheral CC for tumors that growth inside the liver parenchima, perihilar for tumors located in the liver but involving the hilum and for Klatskin tumors and extrahepatic for tumors of the distal biliary tract. This classification correlates well with morphology. Most (30/35) peripheral CC are of the MF type with only 5 cases MF+PI. Perihilar CC and EHCC are mostly PI or MF+PI reflecting a different growth pattern between the two. Beside a different growth pattern there is a statistical difference between the tumor types when comparing MUC5AC expression. 30 out of 35 (85,7%) peripheral CC were MUC5AC negative. 26 out of 39 (66,6%) perihilar CC were MUC5AC positive with different intensities but positive. 13 cases were negative. Of these 13 cases in 8 cases there were same positive cells but not enough to reach 5% of the total (our cut-off value), we don\u2019t know if this positivity is of any significance, but it is something different compared to the true negativity that we see in MF. In our study MUC5AC seems to be a good immunohistochemical marker that can distinguish peripheral from perihilar CC, that correlates well with morphology and has a prognostic significance as well. This marker can be measured in the serum and can be used in the panel of tumor markers to search for in CC and could be useful in the follow-up

Machine Learning Approaches for the Image-Based Identification of Surgical Wound Infections: Scoping Review

BackgroundSurgical site infections (SSIs) occur frequently and impact patients and health care systems. Remote surveillance of surgical wounds is currently limited by the need for manual assessment by clinicians. Machine learning (ML)–based methods have recently been used to address various aspects of the postoperative wound healing process and may be used to improve the scalability and cost-effectiveness of remote surgical wound assessment. ObjectiveThe objective of this review was to provide an overview of the ML methods that have been used to identify surgical wound infections from images. MethodsWe conducted a scoping review of ML approaches for visual detection of SSIs following the JBI (Joanna Briggs Institute) methodology. Reports of participants in any postoperative context focusing on identification of surgical wound infections were included. Studies that did not address SSI identification, surgical wounds, or did not use image or video data were excluded. We searched MEDLINE, Embase, CINAHL, CENTRAL, Web of Science Core Collection, IEEE Xplore, Compendex, and arXiv for relevant studies in November 2022. The records retrieved were double screened for eligibility. A data extraction tool was used to chart the relevant data, which was described narratively and presented using tables. Employment of TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines was evaluated and PROBAST (Prediction Model Risk of Bias Assessment Tool) was used to assess risk of bias (RoB). ResultsIn total, 10 of the 715 unique records screened met the eligibility criteria. In these studies, the clinical contexts and surgical procedures were diverse. All papers developed diagnostic models, though none performed external validation. Both traditional ML and deep learning methods were used to identify SSIs from mostly color images, and the volume of images used ranged from under 50 to thousands. Further, 10 TRIPOD items were reported in at least 4 studies, though 15 items were reported in fewer than 4 studies. PROBAST assessment led to 9 studies being identified as having an overall high RoB, with 1 study having overall unclear RoB. ConclusionsResearch on the image-based identification of surgical wound infections using ML remains novel, and there is a need for standardized reporting. Limitations related to variability in image capture, model building, and data sources should be addressed in the future

Neuroendocrine carcinoma of the breast: Current evidence and future perspectives

: Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer. Anthracycline- and taxane-based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small-cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast

Neuroendocrine differentiation in breast carcinoma: clinicopathological features and outcome

AIMS: Primary neuroendocrine (NE) breast carcinoma (BC) is an entity with a wide range of prevalence and poorly defined clinical behavior. We evaluated the prevalence, clinicopathological features and clinical outcome of NEBC. METHODS AND RESULTS: Immunohistochemical staining for synaptophysin and chromogranin A was performed on whole sections from 1232 consecutive cases of invasive BC. We divided NEBC in focal (10-49% positive cells) and diffuse ( 6550% positive cells) and compared the outcome of patients with NEBC with strictly matched non-NEBC. A total of 128 BC showed NE differentiation (10.4%): 84 diffuse (6.8%) and 44 focal (3.6%). NE differentiation showed a significant association with T4 stage (P=0.001), solid-papillary and mucinous histotype (P<0.0001), G2 grading (P=0.002), positive ER (P=0.003) and PR (P=0.002). Almost 90% of NEBC are ER+/HER2- and more than half ER+/HER2-/Ki-67 6514%. Kaplan-Meier analysis revealed that patients with NEBC showed worse disease-free survival (DFS) (P=0.04) compared to matched non-NEBC. We did not find significant differences regarding clinicopathological features, DFS and CSS between diffuse and focal neuroendocrine BC CONCLUSIONS: This study demonstrates that NEBC represents 7-10% of invasive BC and that NE differentiation does not affect the prognosis of BC in terms of CSS. This article is protected by copyright. All rights reserved