Recovery of health-related quality of life after laparoscopic versus open distal pancreatectomy.

BACKGROUND: Limited data comparing recovery of health-related quality of life (HRQoL) after laparoscopic (LDP) versus open distal pancreatectomy (ODP) are available. The aim of this study was to assess the impact of laparoscopy on postoperative HRQOL after DP using the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: Data from consecutive patients who underwent DP (2020-2022) enrolled in a prospective clinical trial were reviewed. Patients completed PROMIS-29 plus 2 profile preoperatively, at postoperative day (POD) 15, 30, 90, and 180. Linear regression analysis adjusting for confounders including preoperative PROMIS scores, age, gender, ASA score, diagnosis, and multivisceral resection was used to estimate mean between-group differences (MD) in postoperative PROMIS domains T scores. RESULTS: Overall, 202 patients (118 laparoscopic, 86 open) underwent DP (median age 66 years, pancreatic cancer 41%, multivisceral resection 10%, median LOS 6 days). At POD15, LDP was associated with higher physical function (MD 5.6) and participation in social roles and activities scores (MD 3.8), reduced fatigue (MD - 2.7) and sleep disturbance (MD - 3.8) compared to ODP. At POD30, LDP patients had higher physical function (MD 5.2) and participation in social roles and activities scores (MD 6.0), reduced fatigue (MD - 3.5), and anxiety (MD - 4.0) compared to ODP. No between-group differences were found in HRQoL domains at POD90 and 180. Six months after surgery, the proportions of patients who had not recovered to preoperative physical function, participation in social roles and activities, fatigue, pain interference, sleep disturbance, cognitive function, depression, and anxiety were 31%, 31%, 28%, 20%, 15%, 14%, 8%, and 7%, respectively. CONCLUSIONS: According to PROMIS, LDP resulted in improved physical and social functioning and reduced anxiety and fatigue up to 30 days after surgery compared to ODP. At 6 months after surgery, recovery of physical domains is still incomplete in up to 30% of patients.

Validation of the PROMIS-29 Questionnaire as a Measure of Recovery After Pancreatic Surgery.

OBJECTIVE: To contribute evidence for the reliability, construct validity, and responsiveness of the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) profile questionnaire as a measure of recovery after pancreatic surgery. BACKGROUND: PROMIS questionnaires have been recommended to evaluate postdischarge recovery after surgery. Evidence supporting their measurement properties in pancreatic surgery is missing. METHODS: An observational validation study designed according to the COSMIN checklist was conducted including data from a prospective clinical trial. Patients undergoing pancreatectomy completed PROMIS-29 preoperatively and on postoperative days (PODs) 15, 30, 90, and 180. Reliability was assessed by internal consistency using Cronbach α. Construct validity was assessed by known-groups comparison. Responsiveness was evaluated hypothesizing that scores would be higher (1) preoperatively versus POD15, (2) on POD30 versus POD15, (3) on POD90 versus POD30, and (4) on POD180 versus POD90. RESULTS: Overall, 510 patients were included in the study. Reliability was good to excellent (α values ranged from 0.82 to 0.97). Data supported 4 of 5 hypotheses tested for construct validity for 5 domains (physical function, anxiety, depression, fatigue, and ability to participate in social roles) at most time points. Responsiveness hypotheses 1, 2, and 3 were supported by the data for physical function, fatigue, sleep disturbance, pain interference, and ability to participate in social roles domains. CONCLUSIONS: PROMIS had excellent reliability, discriminated between most groups expected to have different recovery trajectories and was responsive to the expected trajectory of recovery up to 90 days after surgery. Our findings support the use of PROMIS-29 profile as a patient-reported outcome measure of postdischarge recovery after pancreatectomy.

Curcumin and Andrographolide Co-Administration Safely Prevent Steatosis Induction and ROS Production in HepG2 Cell Line.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination.

Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma.

OBJECTIVE: To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in ''early stage disease'' (PDAC ≤20 mm, R0/ N0 PDAC). METHODS: This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models. RESULTS: PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis ( P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤ 20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 >37 and pain. CONCLUSIONS: PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression.

Main Duct Thresholds for Malignancy Are Different in Intraductal Papillary Mucinous Neoplasms of the Pancreatic Head and Body-Tail.

BACKGROUND & AIMS: The risk of malignancy is uncertain for intraductal papillary mucinous neoplasms (IPMNs) with main pancreatic duct (MPD) of 5-9 mm. No study has correlated MPD size and malignancy considering the anatomic site of the gland (head versus body-tail). Our aim was to analyze the significance of MPD in pancreatic head/body-tail as a predictor of malignancy in main-duct/mixed IPMNs. METHODS: Retrospective analysis of resected patients between 2009-2018 was performed. Malignancy was defined as high-grade dysplasia and invasive carcinoma. MPD diameter was measured with magnetic resonance imaging. Receiver operating characteristic curve (ROC) analysis was utilized to identify optimal MPD cut-off for malignancy. Independent predictors of malignancy were searched. RESULTS: Malignancy was detected in 74% of 312 identified patients. 213 patients (68.3%) had IPMNs of the pancreatic head and 99 (31.7%) of the body-tail. ROC analysis identified 9 and 7 mm as the optimal MPD cut-offs for malignancy in IPMNs of head and body-tail of the pancreas, respectively. Multivariate analysis confirmed that MPD ≥9 mm (pancreatic head) and ≥7 mm (body-tail) were independent predictors of malignancy along with macroscopic solid components, positive cytology and elevated CA 19-9. The risk of malignancy was low for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) unless high-risk stigmata or multiple worrisome features were present. CONCLUSIONS: Different thresholds of MPD dilation are associated with malignancy in IPMNs of the head and body-tail of the pancreas. The risk of malignancy for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) lacking high-risk stigmata or multiple worrisome features is low.

A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO). METHODS: Five hundred and eighty-two consecutive patients with biopsy-proven NAFLD or a clinical diagnosis of NAFLD-related compensated cirrhosis were classified as hepatocellular (H), C and mixed (M) patterns, by using the formula (ALT/ALT Upper Limit of Normal-ULN)/(ALP/ALP ULN). MALO were recorded during follow-up. An external cohort of 1281 biopsy-proven NAFLD patients was enrolled as validation set. RESULTS: H, M and C patterns were found in 153 (26.3%), 272 (46.7%) and 157 (27%) patients respectively. During a median follow-up of 78 months, only 1 (0.6%) patient with H pattern experienced MALO, whilst 15 (5.5%) and 38 (24.2%) patients in M and C groups had MALO. At multivariate Cox regression analysis, age >55 years (HR 2.55, 95% CI 1.17-5.54; p = .01), platelets <150 000/mmc (HR 0.14, 95% CI 0.06-0.32; p < .001), albumin <4 g/L(HR 0.62, 95% CI 0.35-1.08; p = .09), C versus M pattern (HR 7.86, 95% CI 1.03-60.1; p = .04), C versus H pattern(HR 12.1, 95% CI 1.61-90.9; p = .01) and fibrosis F3-F4(HR 35.8, 95% CI 4.65-275.2; p < .001) were independent risk factors for MALO occurrence. C versus M pattern(HR 14.3, 95% CI 1.90-105.6; p = .008) and C versus H pattern (HR 15.6, 95% CI 2.10-115.1; p = .0068) were confirmed independently associated with MALO occurrence in the validation set. The immunohistochemical analysis found a significantly higher prevalence of moderate-high-grade ductular metaplasia combined with low-grade ductular proliferation in C pattern when compared with the biochemical H pattern. Gene expression analysis showed a lower expression of NR1H3, RXRα and VCAM1 in patients with the C pattern. CONCLUSIONS: The presence of a cholestatic pattern in patients with NAFLD predicts a higher risk of MALO independently from other features of liver disease.

Water and Soil Pollution: Ecological Environmental Study Methodologies Useful for Public Health Projects. A Literature Review.

Health risks at population level may be investigated with different types of environmental studies depending on access to data and funds. Options include ecological studies, case-control studies with individual interviews and human sample analysis, risk assessment or cohort studies. Most public health projects use data and methodologies already available due to the cost of ad-hoc data collection. The aim of the article is to perform a literature review of environmental exposure and health outcomes with main focus on methodologies for assessing an association between water and/or soil pollutants and cancer. A systematic literature search was performed in May 2019 using PubMed. Articles were assessed by four independent reviewers. Forty articles were identified and divided into four groups, according to the data and methods they used, i.e.: (1) regression models with data by geographical area; (2) regression models with data at individual level; (3) exposure intensity threshold values for evaluating health outcome trends; (4) analyses of distance between source of pollutant and health outcome clusters. The issue of exposure assessment has been investigated for over 40 years and the most important innovations regard technologies developed to measure pollutants, statistical methodologies to assess exposure, and software development. Thanks to these changes, it has been possible to develop and apply geo-coding and statistical methods to reduce the ecological bias when considering the relationship between humans, geographic areas, pollutants, and health outcomes. The results of the present review may contribute to optimize the use of public health resources.

[Excess deaths for haematological tumours in Falconara Marittima (Marche Region, Central Italy): short story from the epidemiological survey up to now]. / EPICHANGE/3. Eccesso di morti per tumori ematologici a Falconara Marittima: breve storia dall'indagine epidemiologica a oggi.

API is a company refining petroleum products located in Falconara Marittima (Ancona Province, Marche Region, Central Italy). Thanks to the pressure made by citizens' committees, which considered the plant as a risk source for the population residing in the surroundings municipalities, Marche Region as institution asked for an epidemiological survey. This survey found a significative excess in deaths for haematological tumours in women and in a sub-group of retired and elderly. The results were published in one report and two scientific journals, and were also presented during a public meeting. It was urgent to made public health intervention, which were called for, but up to now nothing has been done. Here, the reconstruction of this affair, from the start of the epidemiological survey up to the more recent development in terms of public health.

Out-of-pocket costs for cancer survivors between 5 and 10 years from diagnosis: an Italian population-based study.

PURPOSE: To illustrate the out-of-pocket (OOP) costs incurred by a population-based group of patients from 5 to 10 years since their cancer diagnosis in a country with a nationwide public health system. METHODS: Interviews on OOP costs to a sample of 5-10 year prevalent cases randomly extracted from four population-based cancer registries (CRs), two in the north and two in the south of Italy. The patients' general practitioners (GPs) gave assurance about the patient's physical and psychological condition for the interview. A zero-inflated negative binomial model was used to analyze OOP cost determinants. RESULTS: Two hundred six cancer patients were interviewed (48 % of the original sample). On average, a patient in the north spent €69 monthly, against €244 in the south. The main differences are for transport, room, and board (TRB) to reach the hospital and/or the cancer specialist (north €0; south €119). Everywhere, OOP costs without TRB costs were higher for patients with a low quality of life. CONCLUSIONS: Despite the limited participation, our study sample's characteristics are similar to those of the Italian cancer prevalence population, allowing us to generalize the results. The higher OOP costs in the south may be due to the scarcity of oncologic structures, obliging patients to seek assistance far from their residence. Implications for cancer survivors Cancer survivors need descriptive studies to show realistic data about their status. Future Italian and European descriptive studies on cancer survivorship should be based on population CRs and involve GPs in order to approach the patient at best.

Spatial variation in mortality risk for hematological malignancies near a petrochemical refinery: A population-based case-control study.

INTRODUCTION: The study investigated the geographic variation of mortality risk for hematological malignancies (HMs) in order to identify potential high-risk areas near an Italian petrochemical refinery. MATERIAL AND METHODS: A population-based case-control study was conducted and residential histories for 171 cases and 338 sex- and age-matched controls were collected. Confounding factors were obtained from interviews with consenting relatives for 109 HM deaths and 267 controls. To produce risk mortality maps, two different approaches were applied and compared. We mapped (1) adaptive kernel density relative risk estimation for case-control studies which estimates a spatial relative risk function using the ratio between cases and controls' densities, and (2) estimated odds ratios for case-control study data using Generalized Additive Models (GAMs) to smooth the effect of location, a proxy for exposure, while adjusting for confounding variables. RESULTS: No high-risk areas for HM mortality were identified among all subjects (men and women combined), by applying both approaches. Using the adaptive KDE approach, we found a significant increase in death risk only among women in a large area 2-6 km southeast of the refinery and the application of GAMs also identified a similarly-located significant high-risk area among women only (global p-value<0.025). Potential confounding risk factors we considered in the GAM did not alter the results. CONCLUSION: Both approaches identified a high-risk area close to the refinery among women only. Those spatial methods are useful tools for public policy management to determine priority areas for intervention. Our findings suggest several directions for further research in order to identify other potential environmental exposures that may be assessed in forthcoming studies based on detailed exposure modeling.

Risk of death for hematological malignancies for residents close to an Italian petrochemical refinery: a population-based case-control study.

PURPOSE: We investigated the risk of death for hematological malignancies (HMs) in the area surrounding an Italian petrochemical refinery, where atmospheric concentrations of benzene (known carcinogen) had not been adequately monitored in the past. METHODS: We performed a population-based case-control study, using conditional logistic regression to estimate odds ratios (ORs) of HM death, with 95 % confidence intervals (CIs), and p trends, in relation to tertiles of time-weighted average residential proximity to the refinery. We identified 177 HM deaths and 349 sex- and age-matched controls from municipal files. Confounding factors were investigated from interviews with consenting relatives for 109 HM deaths and 178 matched controls. RESULTS: For males and females combined, risk of HM death was unrelated to residential proximity. For females, ORs of HM death by increasing tertiles of proximity were 1, 2.74 (95 % CI 1.48-5.09, significant) and 1.49 (95 % CI 0.76-2.92) (p trend 0.184). For the subgroup of persons who plausibly spent most of their time at home (long-term retired, homemakers or unemployed, 53 cases, 79 controls), the ORs of leukemia plus non-Hodgkin lymphoma death (38 cases, 56 controls) by increasing tertiles of proximity were 1, 3.44 (95 % CI 1.04-11.37, significant) and 3.25 (95 % CI 0.82-12.87) (p trend 0.083). CONCLUSIONS: No increased risk of HM death for males and females combined living close to the refinery was found. However, the findings for females and a subgroup plausibly spending most of their time at home suggest a relation between increased risk of HM death and residential proximity to the refinery.

The Exercise aNd hEArt transplant (ENEA) trial - a registry-based randomized controlled trial evaluating the safety and efficacy of cardiac telerehabilitation after heart transplant.

BACKGROUND: Heart transplant (HTx) is gold-standard therapy for patients with end-stage heart failure. Cardiac rehabilitation (CR) is a multidisciplinary intervention shown to improve cardiovascular prognosis and quality of life. The aim in this randomized controlled trial is to explore the safety and efficacy of cardiac telerehabilitation after HTx. In addition, biomarkers of rehabilitation outcomes will be identified, as data that will enable treatment to be tailored to patient phenotype. METHODS: Patients after HTx will be recruited at IRCCS S. Maria Nascente - Fondazione Don Gnocchi, Milan, Italy (n = 40). Consenting participants will be randomly allocated to either of two groups (1:1): an intervention group who will receive on-site CR followed by 12 weeks of telerehabilitation, or a control group who will receive on-site CR followed by standard homecare and exercise programme. Recruitment began on 20th May 2023 and is expected to continue until 20th May 2025. Socio-demographic characteristics, lifestyle, health status, cardiovascular events, cognitive function, anxiety and depression symptoms, and quality of life will be assessed, as well as exercise capacity and muscular endurance. Participants will be evaluated before the intervention, post-CR and after 6 months. In addition, analysis of circulating extracellular vesicles using Surface Plasmon Resonance imaging (SPRi), based on a rehabilomic approach, will be applied to both groups pre- and post-CR. CONCLUSION: This study will explore the safety and efficacy of cardiac telerehabilitation after HTx. In addition, a rehabilomic approach will be used to investigate biomolecular phenotypization in HTx patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05824364.

A method for differentiating cancer prevalence according to health status, exemplified using a population-based sample of Italian colorectal cancer cases.

UNLABELLED: Cancer prevalence is the proportion of a population diagnosed with cancer. We present a method for differentiating prevalence into the proportions expected to survive without relapse, die of cancer within a year, and die of cancer within 10 years or survive with relapse at the end of the 10th year. MATERIAL AND METHODS: The method was applied to samples of colorectal cancer cases, randomly extracted from four Italian cancer registries (CRs). The CRs collected data on treatments, local relapses, distant relapses, and causes of death: 1) over the entire follow-up to 31 December 2007 for 601 cases diagnosed in 2002 (cohort approach); 2) over a single year (2007) for five cohorts of cases defined by year of diagnosis (from 1997 to 2001), alive at 1 January 2007 (total 298 cases). The cohorts were combined into a fictitious cohort with 10 years survival experience. For each year j after diagnosis the health status of cases alive at the beginning of j was estimated at the end of the 10th year. From these estimates the 10-year colorectal cancer prevalence was differentiated. RESULTS: We estimated: 74.7% alive without relapse or not undergoing treatment at the end of 10 years; 8.1% had died of colorectal cancer within a year; 11.4% had died of colorectal cancer 1-10 years after diagnosis or had relapsed or were undergoing treatment at the end of the 10th year; and 5.8% had died of other causes. CONCLUSIONS: We have introduced a new method for estimating the healthcare and rehabilitation demands of cancer survivors based on CR data plus treatment and relapse data specifically collected for samples of cases archived by CRs.

Quantification of perineural invasion in pancreatic ductal adenocarcinoma: proposal of a severity score system.

Perineural invasion (PNI) is a common feature in pancreatic ductal adenocarcinoma (PDAC) and correlates with an aggressive tumor behavior already at early stages of disease. PNI is currently considered as a "present vs. absent" feature, and a severity score system has not yet been established. The aim of the present study was thus to develop and validate a score system for PNI and to correlate it with other prognostic features. In this monocentric retrospective study, 356 consecutive PDAC patients (61.8% upfront surgery patients, 38.2% received neoadjuvant therapy) were analyzed. PNI was scored as follows: 0: absent; 1: the presence of neoplasia along nerves < 3 mm in caliber; and 2: neoplastic infiltration of nerve fibers ≥ 3 mm and/or massive perineural infiltration and/or the presence of necrosis of the infiltrated nerve bundle. For every PNI grade, the correlation with other pathological features, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed. Uni- and multivariate analysis for DFS and DSS were also performed. PNI was found in 72.5% of the patients. Relevant trends between PNI score and tumor differentiation grade, lymph node metastases, vascular invasion, and surgical margins status were found. The latter was the only parameter statistically correlated with the proposed score. The agreement between pathologists was substantial (Cohen's K 0.61). PNI severity score significantly correlated also with decreased DFS and DSS at univariate analysis (p < 0.001). At multivariate analysis, only the presence of lymph node metastases was an independent predictor of DFS (HR 2.235 p < 0.001). Lymph node metastases (HR 2.902, p < 0.001) and tumor differentiation grade (HR 1.677, p = 0.002) were independent predictors of DSS. Our newly developed PNI score correlates with other features of PDAC aggressiveness and proved to have a prognostic role though less robust than lymph nodes metastases and tumor differentiation grade. A prospective validation is needed.

Mer Tyrosine Kinase (MERTK) modulates liver fibrosis progression and hepatocellular carcinoma development.

MerTK is a tyrosine kinase receptor that belongs to the TAM (Tyro3/Axl/Mer) receptor family. It is involved in different processes including cellular proliferation/survival, cellular adhesion/migration, and release of the inflammatory/anti-inflammatory cytokines. Although it is reported that MERTK polymorphisms affect the severity of viral and metabolic liver diseases, being able to influence fibrosis progression and hepatocellular carcinoma development, the mechanisms remain unknown. METHODS: using a microarray approach, we evaluated the liver expression of genes involved in fibrogenesis and hepatocarcinogenesis in patient with chronic hepatitis C (CHC), stratified for MERTK genotype and MERTK expression. RESULTS: we found that the rs 4374383 AA homozygosity is associated with lower MERTK expression in CHC patients and that, depending on MERTK genotype, Matrix Metallopeptidase 9 (MMP9), Matrix Metallopeptidase 7 (MMP7), Secreted Frizzled Related Protein 1 (SFRP1) and WNT gene family 11(WNT11) show differential expression in patients with CHC with or without neoplastic progression. CONCLUSIONS: our results confirm that MERTK represents a genetic biomarker for progression of liver disease and are suggestive of translational relevance for the study of downstream pathways involved in fibrogenesis and hepatocarcinogenesis.

Portal vein resection during pancreaticoduodenectomy for pancreatic neuroendocrine tumors. An international multicenter comparative study.

BACKGROUND: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. METHODS: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. RESULTS: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). CONCLUSION: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

A combined physical-chemical and microbiological approach to unveil the fabrication, provenance, and state of conservation of the Kinkarakawa-gami art.

Kinkarakawa-gami wallpapers are unique works of art produced in Japan between 1870 and 1905 and exported in European countries, although only few examples are nowadays present in Europe. So far, neither the wallpapers nor the composing materials have been characterised, limiting the effective conservation-restoration of these artefacts accounting also for the potential deteriogen effects of microorganisms populating them. In the present study, four Kinkarakawa-gami wallpapers were analysed combining physical-chemical and microbiological approaches to obtain information regarding the artefacts' manufacture, composition, dating, and their microbial community. The validity of these methodologies was verified through a fine in blind statistical analysis, which allowed to identify trends and similarities within these important artefacts. The evidence gathered indicated that these wallpapers were generated between 1885 and 1889, during the so-called industrial production period. A wide range of organic (proteinaceous binders, natural waxes, pigments, and vegetable lacquers) and inorganic (tin foil and pigments) substances were used for the artefacts' manufacture, contributing to their overall complexity, which also reflects on the identification of a heterogeneous microbiota, often found in Eastern environmental matrices. Nevertheless, whether microorganisms inhabiting these wallpapers determined a detrimental or protective effect is not fully elucidated yet, thus constituting an aspect worth to be explored to deepen the knowledge needed for the conservation of Kinkarakawa-gami over time.

Italian performance in cancer research.

AIMS AND BACKGROUND: Italian performance in cancer research from 2000 to 2007 was assessed and compared to that of the other 19 wealthiest countries in the world which carry out the bulk of cancer research. METHODS: Performance was evaluated quantitatively as the number of publications in 125 journals indexed as 'oncological' by Journal Citation Reports and qualitatively as the total impact factor (TIF). Number of publications and TIF were adjusted for the population and gross domestic product (GDP) of each country. The Scopus database was used as publication source. RESULTS: Italy ranked 5th, with the US ranking 1st, over the entire study period for number of cancer publications, which increased over that period. Italy ranked 4th in 2006-2007 for GDP-adjusted and 5th for population-adjusted publication number, loosing ground in the GDP-adjusted ranking and gaining ground in the population-adjusted ranking over the study period. When the quality of research publications was considered, in 2006-2007 Italy was in 5th place for crude TIF (US 1st), in 4th place for GDP-adjusted TIF (Sweden 1st), and in 6th place for population-adjusted TIF (Sweden 1st). Over the study period, Italy was stable for crude and population-adjusted TIF but declined somewhat for GDP-adjusted TIF. CONCLUSIONS: Italy's performance in cancer research over the eight years to 2008 was better than expected considering its GDP and population. Nevertheless, the slight decline evidenced by the present study should induce scientists and policy makers to find ways to reverse the situation.

Postoperative Outcomes and Functional Recovery After Preoperative Combination Chemotherapy for Pancreatic Cancer: A Propensity Score-Matched Study.

Introduction: Previous studies show encouraging oncologic outcomes for neoadjuvant chemotherapy (NACT) in the setting of pancreatic ductal adenocarcinoma (PDAC). However, recent literature reported an increased clinical burden in patients undergoing pancreaticoduodenectomy (PD) following NACT. Therefore, the aim of our study was to assess the impact of NACT on postoperative outcomes and recovery after PD. Methods: A retrospective propensity score-matched study was performed including all patients who underwent PD for PDAC in a single center between 2015 and 2018. Patients treated with NACT for resectable, borderline resectable or locally advanced PDAC were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients who underwent upfront resection. Propensity scores were calculated using 7 perioperative variables, including gender, age, BMI, ASA score, Charlson-Deyo comorbidity score, fistula risk score (FRS), vascular resection. Primary outcome was the number and severity of complications at 90-days after surgery measured by the comprehensive complication index (CCI). Data are reported as median (IQR) or number of patients (%). Results: Of 283 resected patients, 95 (34%) were treated with NACT. Before matching, NACT patients were younger, had less comorbidities (Charlson-Deyo score 0 vs. 1, p = 0.04), similar FRS [2 (0-3) for both groups], and more vascular resections performed [n = 28 (30%) vs. n = 26 (14%), p < 0.01]. After propensity-score matching, preoperative and intraoperative characteristics were comparable. Postoperatively, CCI was similar between groups [8.7 (0-29.6) for both groups, p = 0.59]. NACT patients had a non-statistically significant increase in superficial incisional surgical site infections [n = 12 (13%) vs. 6 (6%), p = 0.14], while no difference was found for overall infectious complications and organ-space SSI. The occurrence of clinically-relevant pancreatic fistula was similar between groups [10 (11%) vs. 13 (14%), p = 0.51]. No difference was found between groups for length of hospital stay [8 (7-15) vs. 8 (7-14) days, p = 0.62], and functional recovery outcomes. Conclusion: After propensity score adjustment for perioperative risk factors, NACT did not worsen postoperative outcomes and functional recovery following PD for PDAC compared to upfront resection.

Impact of diet-induced obesity on the mouse brain phosphoproteome.

Obesity is closely associated to several diseases such as type 2 diabetes, cardiovascular disease, hepatic steatosis, airway disease, neurodegeneration, biliary diseases and certain cancers. It is, therefore, of importance to assess the role of nutrition in disease prevention as well as its effect in the course of such pathologies. In the present study, we addressed the impact of the exposure to different obesogenic diets in the mice brains phosphoproteome. To analyze if the obesity could be able to modify the protein pattern expression of brain neurons, obesity was induced in two different groups of mice. One group of mice was fed with hyperglycemic diet (HGD) and the other one was fed with high-fat diet (HFD), both for 12 weeks. A control group of lean mice was fed with a standard diet (SD). Metabolic parameters were measured before sacrifice, and brains were harvested for label-free phosphoproteomic analysis. Mice brains were analyzed to find differences, if any, in protein phosphorylation. Interestingly, the changes were independent of the obesogenic diet as no changes were detected between the two obese groups. Dephosphorylation of proteins involved in neuronal development (among others SYNGAP1 and PPP1R9B), in vesicle trafficking (for example SNAP91 and AMPH) and in cytoskeletal functions (for example, CLASP2 and GSK3B) was identified, while increased phosphorylation was detected for microtubule proteins (such as MAP2 and MAPT). Phospho site analysis of the mouse brain proteome reveals important changes that point to a connection between diet-induced obesity and impairment of neuronal functions and signaling.