Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma

Background: We investigated the correlation between pancreatic ductal adenocarcinoma patient progno- sis and the presence of tumour infiltrating lymphocytes and expression of 521 immune sys- tem genes. Methods: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochem- istry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenect- omy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results: Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like recep- tor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell develop- ment); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NF\u3baB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion: Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expres- sion level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy

Obesity is associated with\ua0non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with\ua0chronic liver disease\ua0of different aetiologies (eg\ua0HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery

Phase-contrast breast CT: the effect of propagation distance

X-ray phase imaging has the potential to dramatically improve soft tissue contrast sensitivity, which is a crucial requirement in many diagnostic applications such as breast imaging. In this context, a program devoted to perform in-vivo phase-contrast synchrotron radiation breast computed tomography is ongoing at the Elettra facility (Trieste, Italy). The used phase-contrast technique is the propagation-based configuration, which requires a spatially coherent source and a sufficient object-to-detector distance. In this work the effect of this distance on image quality is quantitatively investigated scanning a large breast surgical specimen at 3 object-to-detector distances (1.6, 3, 9 m) and comparing the images both before and after applying the phase-retrieval procedure. The sample is imaged at 30 keV with a 60 \ub5m pixel pitch CdTe single-photon-counting detector, positioned at a fixed distance of 31.6~m from the source. The detector fluence is kept constant for all acquisitions. The study shows that, at the largest distance, a 20-fold SNR increase can be obtained by applying the phase-retrieval procedure. Moreover, it is shown that, for phase-retrieved images, changing the object-to-detector distance does not affect spatial resolution while boosting SNR (4-fold increase going from the shortest to the largest distance). The experimental results are supported by a theoretical model proposed by other authors, whose salient results are presented in this paper

Multicenter research into the quality of life of patients with advanced oropharyngeal carcinoma with long-term survival associated with human papilloma virus

The treatment of advanced-stage oropharyngeal squamous cell carcinoma may utilize various modes, including combining surgery with chemoradiotherapy (CTRT), or primary CTRT followed by rescue surgery. In previous literature it has been revealed how patients treated with combined modes report a low quality of life (QoL) and severe consequences following surgery, radiotherapy and chemotherapy, in the short and in the long-term. The decrease in the QoL of patients treated with high-intensity multi-modal strategies highlights the necessity of modifying treatments, particularly for young HPV-positive patients, where an increased survival rate has already been reported. The modified treatment for HPV-positive tumors in the tonsils and at the base of the tongue is based on the deintensification of therapies aiming to reduce toxicity and thereby improve QoL in the long term, whilst still maintaining therapeutic effectiveness. The aim of the present study was to evaluate the QoL in patients with a long-term survival, who were treated with combined therapy for squamous cell tumors in the tonsils and at the base of the tongue, and to compare the results observed in HPV-positive and HPV-negative patients. According to statistical analysis, differences in the general QoL and in the single scales of the European Organization for the Research and Treatment of Cancer questionnaires were not correlated with the type of therapy selected for the particular patient. QoL considered the presence of HPV, the type of treatment, the subregion of the tonsils vs. the base of the tongue and the disease stage at the time of diagnosis, and was determined to be non-influential with regard to these specific variables

Is the complement protein C1q a pro- or anti-tumorigenic factor? Bioinformatics analysis involving human carcinomas

C1q is the first subcomponent of the classical pathway of the complement system and belongs to the C1q/Tumor Necrosis Factor superfamily. C1q can perform a diverse range of immune and non-immune functions in a complement-dependent as well as -independent manner. Being a pattern recognition molecule of the innate immunity, C1q can recognize a number of self, non-self and altered-self ligands and bring about effector mechanisms designed to clear pathogens via opsonisation and inflammatory response. C1q is locally synthesized by macrophages and dendritic cells, and thus, can get involved in a range of biological processes, such as angiogenesis and tissue remodeling, immune modulation, and immunologic tolerance. The notion of C1q involvement in the pathogenesis of cancer is still evolving. C1q appears to have a dual role in cancer: tumor promoting as well as tumor-protective, depending on the context of the disease. In the current study, we performed a bioinformatics analysis to investigate whether C1q can serve as a potential prognostic marker for human carcinoma. We used the Oncomine database and the survival analysis platforms Kaplan-Meier plotter. Our results showed that high levels of C1q have a favorable prognostic index in basal-like breast cancer for disease-free survival, and in HER2-positive breast cancer for overall survival, while it showed a pro-tumorigenic role of C1q in lung adenocarcinoma, and in clear cell renal cell carcinoma. This in silico study, if validated via a retrospective study, can be a step forward in establishing C1q as a new tool as a prognostic biomarker for various carcinoma.Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Ital

A simple in silico strategy identifies candidate biomarkers for the diagnosis of liver fibrosis in morbidly obese subjects

Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis. Methods: Seventy-one morbidly obese (MO) subjects with biopsy-proven NAFLD were enrolled, and the cohort was subdivided according to minimal (F0/F1) or moderate (F2/F3) fibrosis. The plasmatic level of CD44 antigen (CD44), secreted protein acidic and rich in cysteine (SPARC), epidermal growth factor receptor (EGFR) and insulin-like growth factor 2 (IGF2) were determined by ELISA. Significant associations between plasmatic levels and histological fibrosis were determined by correlation analysis and the diagnostic accuracy by the area under receiver operating characteristic curves (AUROC). Results: Eighty-two percentage of the subjects had F0/F1 and 18% with F2/F3 fibrosis. Plasmatic levels of IGF2, EGFR and their ratio (EGFR/IGF2) were associated with liver fibrosis, correlating inversely for IGF2 (P < .006) and directly (P < .018; P < .0001) for EGFR and EGFR/IGF2 respectively. The IGF2 marker had the best diagnostic accuracy for moderate fibrosis (AUROC 0.83), followed by EGFR/IGF2 ratio (AUROC 0.79) and EGFR (AUROC 0.71). Conclusions: Our study supports the potential utility of IGF2 and EGFR as non-invasive diagnostic biomarkers for liver fibrosis in morbidly obese subjects.Facultad de Ciencias Exacta

Gestione delle pazienti con tumore fillode della mammella: esperienza triestina nel periodo 2006-2014

La diagnosi e la gestione dei tumori fillodi della mammella \ue8 complessa a causa del basso tasso di incidenza e dell\u2019imprevedibilit\ue0 del comportamento di questo tipo di neoplasie (meno dell\u20191% tra tutti i tumori della mammella [1]). L\u2019obiettivo di questo studio \ue8 analizzare i casi di tumori filloidi diagnosticati a Trieste nel periodo 2006-2014 al fine di contestualizzare il comportamento particolarmente aggressivo di un tumore fillode maligno insorto in una paziente con pregressi fillodi benigni

Menstruation-related disseminated intravascular coagulation in an adenomyosis patient: case report and review of the literature

Disseminated intravascular coagulation (DIC) is a high mortality coagulopathy that leads to simultaneous thrombotic and bleeding problems. It occurs as a complication in different disease as malignancies, obstetrical catastrophes, bacterial sepsis and traumas. We report on an extremely rare case of acute DIC in a patient with misdiagnosed adenomyosis and massive methrorragia which led to acute kidney failure. The patient was successfully treated with hysterectomy and blood product transfusions; however, a slight reduction of renal function persisted. We were able to confirm the cause-consequence link between adenomyosis and consumptive DIC since we saw the thrombi in the adenomyotic uterus from early hysterectomy specimen. Moreover, this is the first case, for the best of our knowledge, in which systemic consequences persist in an adenomyosis patient who developed a DIC. Early diagnose and treatment of acute DIC is essential for patient's survival and to prevent severe complications: adenomyosis should be kept in mind as a possible cause of DIC when a patient shows up with massive bleeding

Usefulness of core needle biopsy for the diagnosis of thyroid Burkitt’s lymphoma: a case report and review of the literature

Abstract Background Thyroid lymphomas are an exceptional finding in patients with thyroid nodules. Burkitt’s lymphoma is one of the rarest and most aggressive forms of thyroid lymphomas, and its prognosis depends on the earliness of medical treatment. Given the rarity of this disease, making a prompt diagnosis can be challenging. For instance, fine-needle aspiration (FNA) cytology, which is the first-line diagnostic test that is performed in patients with thyroid nodules, is often not diagnostic in cases of thyroid lymphomas, with subsequent delay of the start of therapy. Case presentation Here we report the case of a 52-year-old woman presenting with a rapidly enlarging thyroid mass. Thyroid ultrasonography demonstrated a solid hypoechoic nodule. FNA cytology was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. It is core needle biopsy (CNB) that helped us to overcome the limitations of routine FNA cytology, showing the presence of thyroid Burkitt’s lymphoma. Subsequent staging demonstrated bone marrow involvement. The early start of an intensive multi-agent chemotherapy resulted in complete disease remission. At 60 months after the diagnosis, the patient is alive and has not had any recurrence. Conclusions Clinicians should be aware that thyroid Burkitt’s lymphoma is an aggressive disease that needs to be treated with multi-agent chemotherapy as soon as possible. To diagnose it promptly, they should consider to order/perform a CNB in any patient with a rapidly enlarging thyroid mass that is suspicious for lymphoma