Survival rate of head and neck squamous cell carcinomas (HNSCC) patients are still to date very poor, and the application of innovative clinical approaches are urgently needed. Cold atmospheric plasmas (CAPs) are partially ionized gases that have shown anti-tumor effectiveness over a wide range of cancer types with potential application into clinics. However, the comprehension of the mechanisms underlying indirect CAP effects plays a key role for the prediction of treatment outcomes. In our work, we assessed the potential application of indirect CAP, by using plasma activated media (PAM) and plasma-treated liquids (PTL), as therapeutic strategies for HNSCC treatment. The impact of PAM obtained from exposure to CAP for different times was evaluated in three head and neck cancer (HNC) cell lines (HSC3, FaDu, CAL-27). Cytotoxic effects as inhibition of proliferation, apoptosis rate and cell cycle modifications were tested for the different PAM, showing a time- and cell culture media-dependence tightly related to the chemical composition of PAM considered. In addition, cytotoxic effects were also observed on HNC, two bladder cancer models and one breast cancer cell line when considering PTL, paving the way for their application into a clinical setting.

During the first year of life, development and balance of newborn gut microbiota are strongly influenced by external factors such as delivery mode, breastfeeding, duration of pregnancy, mother diet and lifestyle, siblings and pets, environment, and antibiotics administration. Gut microbiota colonization starts with facultative anaerobes and continues with the establishment of anaerobic genera of which Bifidobacteria are the gold standard of a healthy gut neonatal microbiota. Scientific literature traditionally describes the fetus as sterile in the womb and identifies the membranes rupture as the beginning of microbial colonization. Vaginal delivery is an important source for the onset of infant colonization which will then continue with the transfer of a new selection of intestinal bacteria with breastfeeding. During cesarean delivery a direct contact of the mouth of newborn with the vaginal and intestinal microbiota is absent, and environmental bacteria play an important role for infants intestinal colonization. Nature has ensured that newborns receive other specific maternal bacteria, through a subsequent method of transfer: breastfeeding. We present a brief and comprehensive state-of-the-art in order to encourage natural childbirth and breastfeeding whenever possible and discuss innovative directions for develop new ad hoc personalized treatments in order to restore physiological microbiota.

Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of death by cancer in the world. What makes this pathological condition particularly lethal is a combination of clinical and molecular heterogeneity, lack of early diagnostic indexes, and underwhelming results from current therapeutic protocols. A major cause of PDAC chemoresistance seems to lie in the ability of cancer cells to spread out and fill the pancreatic parenchyma, exchanging nutrients, substrates, and even genetic material with cells from the surrounding tumor microenvironment (TME). Several components can be found in the TME ultrastructure, including collagen fibers, cancer-associated fibroblasts, macrophages, neutrophils, mast cells, and lymphocytes. Cross-talk between PDAC and TME cells results in the latter being converted into cancer-favoring phenotypes; this behavior could be compared to an influencer guiding followers into supporting his activity. Moreover, TME could be a potential target for some of the newest therapeutic strategies; these include the use of pegvorhyaluronidase-α and CAR-T lymphocytes against HER2, FAP, CEA, MLSN, PSCA, and CD133. Other experimental therapy options are being currently studied, aiming to interfere with the KRAS pathway, DNA-repairing proteins, and apoptosis resistance in PDAC cells. Hopefully these new approaches will grant better clinical outcomes in future patients.

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide. Helicobacter pylori (Hp) infection is an important risk factor for GC. However, the etiology of the tumor is multifactorial, since only 1-3% of infected patients develop cancer. Therefore, attention should be focused on the role of microbiota in gastric tumorigenesis since in some studies an alteration of the microbiota in GC has been shown. Fusobacterium nucleatum (Fn) has been found in biopsies of patients with GC. However, since its role is not clearly established, this study investigated the effects of Fn infection on the human gastric adenocarcinoma cell line AGS. Our results showed that Fn co-localized at level of the plasma membrane demonstrating the ability of Fn to adhere to AGS cells. In addition, increases in incubation times were associated with its intra-cellular localization with loss of the classic curved rod shape. Interestingly, Fn determined a greater capacity of cell migration compared to untreated AGS cells. Moreover, IL-4 expression significantly increased in Fn infected GC cells. Since cancer cell migration is an integral component of the metastatic process, additional studies are needed to better understand the mechanisms underlying the Fn/host interaction.

Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients' death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.

Worldwide, gastric cancer (GC) represents the fifth cancer for incidence, and the third as cause of death in developed countries. Indeed, it resulted in more than 780,000 deaths in 2018. Helicobacter pylori appears to be responsible for the majority of these cancers. On the basis of recent studies, and either alone or combined with additional etiological factors, H. pylori is considered a “type I carcinogen.” Over recent decades, new insights have been obtained into the strategies that have been adopted by H. pylori to survive the acidic conditions of the gastric environment, and to result in persistent infection, and dysregulation of host functions. The multistep processes involved in the development of GC are initiated by transition of the mucosa into chronic non-atrophic gastritis, which is primarily triggered by infection with H. pylori. This gastritis then progresses into atrophic gastritis and intestinal metaplasia, and then to dysplasia, and following Correa’s cascade, to adenocarcinoma. The use of antibiotics for eradication of H. pylori can reduce the incidence of precancerous lesions only in the early stages of gastric carcinogenesis. Here, we first survey the etiology and risk factors of GC, and then we analyze the mechanisms underlying tumorigenesis induced by H. pylori, focusing attention on virulence factor CagA, inflammation, oxidative stress, and ErbB2 receptor tyrosine kinase. Moreover, we investigate the relationships between H. pylori eradication therapy and other diseases, considering not only cardia (upper stomach) cancers and Barrett’s esophagus, but also asthma and allergies, through discussion of the “hygiene hypothesis. ” This hypothesis suggests that improved hygiene and antibiotic use in early life reduces microbial exposure, such that the immune response does not become primed, and individuals are not protected against atopic disorders, asthma, and autoimmune diseases. Finally, we overview recent advances to uncover the complex interplay between H. pylori and the gut microbiota during gastric carcinogenesis, as characterized by reduced bacterial diversity and increased microbial dysbiosis. Indeed, it is of particular importance to identify the bacterial taxa of the stomach that might predict the outcome of gastric disease through the stages of Correa’s cascade, to improve prevention and therapy of gastric carcinoma.

Improvements to diagnostic techniques, medical surveillance and screening have allowed early detection of small asymptomatic thyroid lesions, although incidence of large thyroid cancers has increased. The role of environmental, lifestyle, medical and hormonal factors in thyroid cancer development remain under discussion. The aim of this study was to define associations between environmental, lifestyle, medical history and hormonal factors and thyroid tumors. This retrospective cross-sectional population-based study evaluated 246 patients admitted to the ‘SS. Annunziata’ Hospital in Chieti (Italy) for total thyroidectomy or lobectomy. Twenty-eight variables were collected using questionnaires and clinical records. Logistic regression analysis was used to analyze associations between these patient variables and thyroid histology, to identify novel risk factors, and to generate a multivariate model for thyroid tumour risk assessment. Univariate logistic regression analysis showed significant difference in median age for goiter versus thyroid tumour (Odds Ratio [OR]: 0.980; 95% Confidence Interval [CI], 0.962-0.998; P=0.033). Multivariate logistic regression analysis showed hyperthyroidism significantly associated with lower risk of thyroid tumour (hyperthyroidism versus hypothyroidism: OR: 0.174; 95% CI, 0.044-0.694; euthyroidism vs. hypothyroidism: OR: 1.760; 95% CI, 0.678-4.560; P<0.001). These data are supported by significant association with the respective thyroid treatments (in therapy: OR: 0.242; 95% CI, 0.128-0.458; P<0.001). Higher risk of thyroid tumour was significantly associated with single nodule versus multinodular lesions (uninodular: OR: 4.910; 95% CI, 2.240-10.800; P<0.001). Our results suggest that hyperthyroidism and the presence of multinodular lesions represent conditions infrequently associated with thyroid tumors. Mariangela Mazzone1, Maria Carmela Di Marcantonio1, Emira D'Amico2, Luisa Stellin3,4, Margherita Legnini2,5, Alberto D’Aulerio1,5, Luca Napolitano2,5, Roberto Cotellese2,5, Raffaella Muraro1, Anna Chiara Frigo6 and Gabriella Mincione1* 1Department of Innovative Technologies in Medicine and Dentistry, ‘G. d’Annunzio’ University of Chieti-Pescara, Italy 2Department of Medical, Oral and Biotechnological Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, Italy 3Department of Medicine and Aging Sciences, G. d’Annunzio’ University of Chieti-Pescara, Italy 4Division of Emergency Surgery, ‘SS Annunziata’ Hospital, Italy 5Division of General Surgery, ‘SS Annunziata’ Hospital, Italy 6Department of Cardiac-Thoracic-Vascular Sciences, University of Padua, Italy