Genetic abnormalities in pancreatic cancer

The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16(INK4), DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers

Analytic semigroup generated by an elliptic operator with discontinuous coefficients

We consider the generation of analytic semigroups by elliptic operators with discontinuous coefficients

ASRS Questionnaire and Tobacco Use: Not Just a Cigarette. A Screening Study in an Italian Young Adult Sample

Young adults exhibit greater sensitivity than adults to nicotine reinforcement, and Attention Deficit Hyperactivity Disorder (ADHD) increases the risk for early-onset smoking. We investigated the correlation between ADHD Self-Report Scale (ASRS) scores and smoking, evaluated the prevalence of ADHD symptomatology (not diagnoses) in smokers and non-smokers and its comorbidity with benzodiazepine and gambling addictions. A total of 389 young adults from 14 schools in Northern Italy fill out a survey and the Adult ADHD Self-Report Scale (ASRS). A total of 15.2% of subjects tested positive at the ASRS, which correlated with smoking; moreover, smokers had twice the probability of testing positive at the ASRS. ADHD symptomatology, especially when comorbid with tobacco abuse, is an important condition to monitor because early nicotine exposure could be a gateway for other addictive behaviors

Forest therapy using virtual reality in the older population: a systematic review

IntroductionAs life expectancy increases, more attention needs to be paid to their mental and physical condition. Many older patients are also bedridden, which makes some treatments, like in vivo exposure to natural environments, more difficult to be applied. This study aimed to systematically review articles that include interventions combining virtual reality and forest environment, targeting a sample of older people.MethodsBased on PRISMA guidelines, we conducted a literature search in three databases (EBSCO, PubMed, and Scopus), plus gray literature (OpenGrey). We considered only studies that used forest settings via virtual reality and included a sample with age ≥ 65.ResultsAfter the screening and eligibility stages, 7 articles have been included.DiscussionThe study underlines the need to implement research in this direction to standardize effective procedures that can be used to improve the mental and physical health of the older people and caregivers, while also reducing social costs

PD-L1 expression heterogeneity in non-small cell lung cancer: Evaluation of small biopsies reliability

Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in \ue2\u89\ua5 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in \ue2\u89\ua51% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohen's \uce\uba value of 0.53 (moderate) and 0,48 (moderate) for \ue2\u89\ua5 1% and \ue2\u89\ua5 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification

Mucinous Cystic Neoplasm of the Pancreas is Not an Aggressive Entity

Objective: Mucinous cystic neoplasms (MCNs) of the pancreas have often been confused with intraductal papillary mucinous neoplasms. We evaluated the clinicopathologic characteristics, prevalence of cancer, and prognosis of a large series of well-characterized MCNs in 2 tertiary centers. Methods: Analysis of 163 patients with resected MCNs, defined by the presence of ovarian stroma and lack of communication with the main pancreatic duct. Results: MCNs were seen mostly in women (95%) and in the distal pancreas (97%); 25% were incidentally discovered. Symptomatic patients typically had mild abdominal pain, but 9% presented with acute pancreatitis. One hundred eighteen patients (72%) had adenoma, 17 (10.5%) borderline tumors, 9 (5.5%) in situ carcinoma, and 19 (12%) invasive carcinoma. Patients with invasive carcinoma were significantly older than those with noninvasive neoplasms (55 vs. 44 years, P = 0.01). Findings associated with malignancy were presence of nodules (P = 0.0001) and diameter ≥60 mm (P = 0.0001). All neoplasms with cancer were either ≥40 mm in size or had nodules. There was no operative mortality and postoperative morbidity was 49%. Median follow-up was 57 months (range, 4 –233); only patients with invasive carcinoma had recurrence. The 5-year disease-specific survival for noninvasive MCNs was 100%, and for those with invasive cancer, 57%. Conclusions: This series, the largest with MCNs defined by ovarian stroma, shows a prevalence of cancer of only 17.5%. Patients with invasive carcinoma are older, suggesting progression from adenoma to carcinoma. Although resection should be considered for all cases, in low-risk MCNs (≤4 cm/no nodules), nonradical resections are appropriate

Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis

Background and aims: Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy. Methods: Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay. Results: One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of −7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome. Conclusion: Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome

Micellar drug nanocarriers and biomembranes: how do they interact?

Pluronic based formulations are among the most successful nanomedicines and block-copolymer micelles including drugs that are undergoing phase I/II studies as anticancer agents. Using coarse-grained models, molecular dynamics simulations of large-scale systems, modeling Pluronic micelles interacting with DPPC lipid bilayers, on the μs timescale have been performed. Simulations show, in agreement with experiments, the release of Pluronic chains from the micelle to the bilayer. This release changes the size of the micelle. Moreover, the presence of drug molecules inside the core of the micelle has a strong influence on this process. The picture emerging from the simulations is that the micelle stability is a result of an interplay of drug–micelle core and block-copolymer–bilayer interactions. The equilibrium size of the drug vector shows a strong dependency on the hydrophobicity of the drug molecules embedded in the core of the micelle. In particular, the radius of the micelle shows an abrupt increase in a very narrow range of drug molecule hydrophobicity