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BACKGROUND: The European registry for minimally invasive pancreatic surgery (E-MIPS) collects data on laparoscopic and robotic MIPS in low- and high-volume centers across Europe.METHODS: Analysis of the first year (2019) of the E-MIPS registry, including minimally invasive distal pancreatectomy (MIDP) and minimally invasive pancreatoduodenectomy (MIPD). Primary outcome was 90-day mortality.RESULTS: Overall, 959 patients from 54 centers in 15 countries were included, 558 patients underwent MIDP and 401 patients MIPD. Median volume of MIDP was 10 (7-20) and 9 (2-20) for MIPD. Median use of MIDP was 56.0% (IQR 39.0-77.3%) and median use of MIPD 27.7% (IQR 9.7-45.3%). MIDP was mostly performed laparoscopic (401/558, 71.9%) and MIPD mostly robotic (234/401, 58.3%). MIPD was performed in 50/54 (89.3%) centers, of which 15/50 (30.0%) performed ≥20 MIPD annually. This was 30/54 (55.6%) centers and 13/30 (43%) centers for MIPD respectively. Conversion rate was 10.9% for MIDP and 8.4% for MIPD. Overall 90 day mortality was 1.1% (n = 6) for MIDP and 3.7% (n = 15) for MIPD.CONCLUSION: Within the E-MIPS registry, MIDP is performed in about half of all patients, mostly using laparoscopy. MIPD is performed in about a quarter of patients, slightly more often using the robotic approach. A minority of centers met the Miami guideline volume criteria for MIPD.

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/β1 integrin complex. First, using the scDb (scDb-hERG1-β1) in immunohistochemistry (IHC), Western blot (WB) analysis and immunofluorescence (IF), we confirmed the presence of the hERG1/β1 integrin complex in primary PDAC samples and PDAC cell lines. Combining Gemcitabine with scDb-hERG1-β1 improved its cytotoxicity on all PDAC cells tested in vitro. We also tested the combination treatment in vivo, using an orthotopic xenograft mouse model involving ultrasound-guided injection of PDAC cells. We first demonstrated good penetration of the scDb-hERG1-β1 conjugated with indocyanine green (ICG) into tumour masses by photoacoustic (PA) imaging. Next, we tested the effects of the combination at either therapeutic or sub-optimal doses of Gemcitabine (25 or 5 mg/kg, respectively). The combination of scDb-hERG1-β1 and sub-optimal doses of Gemcitabine reduced the tumour masses to the same extent as the therapeutic doses of Gemcitabine administrated alone; yielded increased survival; and was accompanied by minimised side effects (toxicity). These data pave the way for a novel therapeutic approach to PDAC, based on the combination of low doses of a chemotherapeutic drug (to minimize adverse side effects and the onset of resistance) and the novel scDb-hERG1-β1 targeting the hERG1/β1 integrin complex as neoantigen.

Simultaneous detection of multiple analytes from a single biological sample is gaining more attention in the development of more reliable and point-of-care diagnostic devices. We developed a multiplexed strategy that combined outcomes of clinical biomarkers with analysis of the protein corona that forms around graphene oxide sheets upon exposure to patient&rsquo, s plasma. As a paradigmatic case study, we selected pancreatic ductal adenocarcinoma (PDAC), mainly because of the absence of effective detection strategies that resulted in an extremely low five-year survival rate after diagnosis (&lt, 10%). Association of protein corona analysis and haemoglobin levels discriminated PDAC patients from healthy volunteers in up to 90% of cases. If further confirmed in larger-cohort studies, this approach may be used in the detection of PDAC.

Background: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative biliary cultures, and related complications after PD. Methods: An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF). Results: Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for E. coli, Klebsiella pneumoniæ and Enterococcus fæcalis (p &lt, 0.001) was detected. Prevalences of polymicrobial biliary cultures with Escherichia coli, Klebsiella pneumoniæ, Enterococcus fæcalis and Enterococcus fæcium were significantly associated with POPF (p &lt, 0.001). Biliary culture positive for Escherichia coli, Enterococcus fæcalis and Enterococcus fæcium showed a higher prevalence of intra-abdominal collection and DGE (p &lt, 0.001). Notably, Escherichia coli was significantly associated with DGE as a unique complication (OR = 2.94 (1.30–6.70), p &lt, 0.01). Conclusions: Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial Escherichia coli bacterobilia is associated with DGE as a unique complication after PD.

BackgroundThe choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC.MethodsPreoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction.ResultsIncreased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p 418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059).ConclusionsIn R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.

Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD), consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance, the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. Results. One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively, with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p &gt, 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. Conclusions. The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.

The rhythmic control of the lower limb muscles influences the cycle-to-cycle variability during a walking task. The benefits of insoles, commonly used to improve the walking gait, have been little studied. Therefore, the aim of this study was to assess the walking gait variability and stability on different walking conditions (without shoes, WTS, with shoes, WS, with shoes and insoles, WSI) related to brain activity. Twelve participants randomly (WTS/WS/WSI) walked on a treadmill at 4 km/h for 10 min. Kinematic analysis (i.e., footstep and gait variability), brain activation (beta wave signal), rating of perceived exertion (RPE, CR-10 scale), and time domain measures of walking variability were assessed. The maximum Lyapunov exponent (LyE) on the stride cycle period&rsquo, s datasets was also calculated. Stride length and cycle calculated for all walking conditions were 61.59 &plusmn, 2.53/63.38 &plusmn, 1.43/64.09 &plusmn, 2.40 cm and 1.11 &plusmn, 0.03/1.14 &plusmn, 0.03/1.15 &plusmn, 0.04 s (F1,10 = 4.941/p = 0.01, F1,10 = 4.938/p = 0.012) for WTS, WS, WSI, respectively. Beta wave (F1,10 = 564.201/p = 0.0001) was higher in WTS compared to WS and WSI. Analysis of variance&rsquo, s (ANOVA) LyE showed a F1,10 = 3.209/p = 0.056, while post hoc analysis showed a significant effect between WS and WSI with p = 0.023, and nonsignificant effects between WTS and WS/WSI (p = 0.070/0.607), respectively. Small perturbations of the foot can influence the control of gait rhythmicity by increasing the variability in a dissipative deterministic regimen.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level &gt, 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66&ndash, 19.47, p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64&ndash, 57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9&ndash, 10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (&gt, 90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.

The PROCESS Guidelines were first published in 2016 and were last updated in 2018. They provide a structure for reporting surgical case series in order to increase reporting robustness and transparency, and are used and endorsed by authors, journal editors and reviewers alike. In order to drive forwards reporting quality, they must be kept up to date. As such, we have updated these guidelines via a DELPHI consensus exercise.The updated guidelines were produced via a DELPHI consensus exercise. Members from the previous DELPHI group were again invited, alongside editorial board members and peer reviewers of the International Journal of Surgery and the International Journal of Surgery Case Reports. An online survey was completed by this expert group to indicate their agreement with proposed changes to the checklist items.A total of 53 surgical experts agreed to participate and 49 (92%) completed the survey. The responses and suggested modifications were incorporated into the previous 2018 guidelines. There was a high degree of agreement amongst the PROCESS Group, with all but one of the PROCESS items receiving over 70% of scores ranging 7-9.A DELPHI consensus exercise was completed and an updated and improved PROCESS Checklist is now presented.

Physical education allows children to develop motor skills, but it has an impact on affective domain too. The aim of this study was to analyse the effects of two different teaching approaches on the levels of enjoyment of 9-year-old pupils who attended the fourth grade of the primary school. A pre- post- repost design was used as a mean of a longitudinal study. The participants involved were divided into two groups: Teaching skill group (TS) and Teaching games group (TGM). The TS group followed a protocol using the traditional skill-based approach, while the TGM group followed the Tactical Game Model approach, highlighting tactical problems and awareness. The level of enjoyment was assessed by administering the PACES questionnaire. The results show no statistically significant difference, but it can be seen that the TGM group had a more positive trend in enjoyment levels than the TS group. Furthermore, carrying out an analysis by gender it was seen that the females of the TGM group had increases in the scores on the positive scale in the post intervention. In this respect, the physical education teacher has to account for affective learning outcomes when they identify the teaching methods for their courses.

To asses drains amylase (DA) cut-offs for the risk of clinically relevant postoperative pancreatic fistula (POPF) and define the optimal timing of drains removal based on daily DA assay and abdominal CT scan finding after pancreatoduodenectomy (PD). Different algorithms able to identify patients at higher risk of POPF and to assess the optimal time for drains removal after PD have been proposed. The most accurate DA cut-offs in the assessment of the risk of clinically relevant POPF were retrospectively identified. Data from a prospective trial for optimal timing of drains removal were analyzed. Then, to validate the cut-offs identified in the first phase, they were applied to the patients enrolled in the prospective trial. Patients with POD1 DA ≥ 666 U/L were at higher risk of clinically relevant POPF (p 0.0001). POD3 DA value ≥ 252 U/L predicted 88% of clinical relevant fistulas. POD3 DA level ≥ 207 U/L was able to predict 68% of biliary fistulas. Patients with abdominal collection ≥ 5 cm, showed a significantly higher rate (60% vs. 23%, p

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6–10 cases in 38.9% of the centers, 11–20 cases in 16.7%, 21–30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.

Objectives Treatment of aortic valve stenosis is evolving, indications for transcatheter approach (TAVI) have increased but also surgical valve replacement has changed with the use of minimally invasive approaches. Comparisons between TAVI and surgery have rarely been done with minimally invasive techniques (mini-SAVR) in the surgical arm. Aim of the present study is to compare mini-SAVR and TAVI in a multicenter recent cohort. Methods Evaluated were 2904 patients undergone mini-SAVR (2407) or TAVI (497) in 10 different centers in the period 2011–2016. The Heart Team approved treatment for complex cases. The primary outcome is the incidence of 30-day mortality following mini-SAVR and TAVI. Secondary outcomes are the occurrence of major complications following both procedures. Propensity matched comparisons was performed based on multivariable logistic regression model. Results In the overall population TAVI patients had increased surgical risk (median EuroSCORE II 3.3% vs. 1.7%, p ≤ 0.001) and 30-day mortality was higher (1.5% and 2.8% in mini-SAVR and TAVI respectively, p = 0.048). Propensity score identified 386 patients per group with similar baseline profile (median EuroSCORE II ~3.0%). There was no difference in 30-day mortality (3.4% in mini-SAVR and 2.3% in TAVI; p = 0.396) and stroke, surgical patients had more blood transfusion, kidney dysfunction and required longer ICU and hospital length of stay while TAVI patients had more permanent pace maker insertion. Conclusions Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities. A joint evaluation by the heart-team is essential to direct patients to the proper approach., Highlights • A comparison between TAVI and minimally invasive techniques has rarely been done • In a propensity-matched comparison from 10 different hospitals, TAVI and mini-SAVR provided optimal short-term outcome. • 30-day mortality was 3.4% in mini-SAVR and 2.3% in TAVI (p = 0.396) • Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities.

Background Surgical-site infections (SSIs) remain a serious complication of colorectal surgery, causing a significant financial burden to the health care system. The aim of this study is to investigate whether the use of an O-ring retractor can be effective in preventing the incidence of wound infections after elective laparoscopic colorectal surgery. Methods A retrospective case-control study from January 2014 to June 2018 was performed. Data were analyzed from a retrospective colorectal database. SSI was defined according to criteria published by the European Centre for Disease Prevention and Control and analyzed as a primary outcome. Results Three hundred twelve consecutive patients (n = 312) were enrolled in our study. Among them, 158 patients (Group A) in which an O-ring retractor device was used during surgery was compared with a control group of 154 patients (Group B) in which an O-ring retractor device was not used. Primary outcome was to determine SSIs rates among the 2 groups. No statistically differences were observed with regard to baseline characteristics between both groups. A total of 9 patients (5.69%) and 24 (15.58%) with SSIs were identified in Group A and B, respectively, and the difference was statistically significant (OR, 0.32; 95% CI, 0.14-0.72; P = .0045). The median postoperative hospital stay length was 6.7 days in group A and 7.6 days in group B (P ≤ .05). Conclusions SSIs infections rates were significantly higher in patients in which an O-ring retractor device was not used. This study suggests that the use of a wound protector device can be considered for routine use in elective colorectal surgery.

It is well established the relationship between the enjoyment within the physical activities and the personal motivation to follow up a healthy lifestyle. Therefore, the aim of this study was to assess the level of enjoinment during and after the practice of physical and sport activities in school sector. The sample was recruited from a primary school in the south of Italy and the participants had the following characteristics: male: 75; female: 75; mean age: 9.45. The participants were divided into two groups: control group (children did not practice any physical activities) and experimental group (children performed structured physical and sport activities). Two scales have been used for assessing the level of enjoy in such groups: the Italian version of the Physical Activity Enjoyment Scale (PACES-IT) and the Enjoy Scale. The scales provided valid and interesting data for comparing the differences between the two groups. The obtained notes will be useful for supporting the work of the physical education teachers.

Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified. The aim of this observational study was to investigate genotype-phenotype correlation in these three members, with attention to GPE-NETs behavior over the years. The genetic and clinical data obtained and the follow-up screening program (2012–2016) were according to the International Guidelines in a multidisciplinary academic reference center. The familial history collected strongly suggested MEN1 GEP-NETs in at least other four members from different generations. Three MEN1 patients (aged 30–69 years at MEN1 diagnosis) were clinically screened for MEN1 GEP-NETs, both functioning and nonfunctioning. Biochemical, imaging, and nuclear medicine tests and fine-needle agobiopsy were performed, depending on found/emerging clinical symptoms/biochemical abnormalities, and made when necessary. Our clinical survey found strong genotype-phenotype correlation with aggressive MEN1 GEP-NETs (G1, G2-NETs, and multiple ZES/gastrinomas) over the years. The familial history strongly suggested ZES/gastrinoma in progenitors from previous generations. This novel MEN1 truncating mutation correlates with an aggressive evolution and behavior of MEN1 GEP-NETs in studied affected subjects, confirming the need for MEN1 individuals to be evaluated by a skilled multidisciplinary team, as also stated by International Guidelines.

Carbapenems resistant Enterobacteriaceae infections are increasing worldwide representing an emerging public health problem. The application of phylogenetic and phylodynamic analyses to bacterial whole genome sequencing (WGS) data have become essential in the epidemiological surveillance of multi-drug resistant nosocomial pathogens. Between January 2012 and February 2013, twenty-one multi-drug resistant K. pneumoniae strains, were collected from patients hospitalized among different wards of the University Hospital Campus Bio-Medico. Epidemiological contact tracing of patients and Bayesian phylogenetic analysis of bacterial WGS data were used to investigate the evolution and spatial dispersion of K. pneumoniae in support of hospital infection control. The epidemic curve of incident K. pneumoniae cases showed a bimodal distribution of cases with two peaks separated by 46 days between November 2012 and January 2013. The time-scaled phylogeny suggested that K. pneumoniae strains isolated during the study period may have been introduced into the hospital setting as early as 2007. Moreover, the phylogeny showed two different epidemic introductions in 2008 and 2009. Bayesian genomic epidemiology is a powerful tool that promises to improve the surveillance and control of multi-drug resistant pathogens in an effort to develop effective infection prevention in healthcare settings or constant strains reintroduction.

Pancreatic cancer is a very aggressive malignancy that is often diagnosed in the advanced stages, with the implication that long-term survivors are extremely rare. Thus, developing new methods for the early detection of pancreatic cancer is an urgent task for current research. To date, nanotechnology offers unprecedented opportunities for cancer therapeutics and diagnosis. The aim of this study is the development of a new pancreatic cancer diagnostic technology based on the exploitation of the nano-bio-interactions between nanoparticles and blood samples. In this study, blood samples from 20 pancreatic cancer patients and 5 patients without malignancy were allowed to interact with designed lipid nanoparticles, leading to the formation of a hard “protein corona” at the nanoparticle surface. After isolation, the protein patterns were characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE). We found that the protein corona of pancreatic cancer patients was much more enriched than that of healthy individuals. Statistical analysis of SDS-PAGE results allowed us to discriminate between healthy and pancreatic cancer patients with a total discriminate correctness rate of 88%.

K. pneumoniae isolates carrying blaKPC-3 gene were collected to perform Bayesian phylogenetic and selective pressure analysis and to apply homology modeling to the KPC-3 protein. A dataset of 44 blakpc-3 gene sequences from clinical isolates of K. pneumoniae was used for Bayesian phylogenetic, selective pressure analysis and homology modeling. The mean evolutionary rate for blakpc-3 gene was 2.67×10-3 substitution/site/year (95% HPD: 3.4×10-4-5.59×10-3). The root of the Bayesian tree dated back to the year 2011 (95% HPD: 2007-2012). Two main clades (I and II) were identified. The population dynamics analysis showed an exponential growth from 2011 to 2013 and the reaching of a plateau. The phylogeographic reconstruction showed that the root of the tree had a probable common ancestor in the general surgery ward. Selective pressure analysis revealed twelve positively selected sites. Structural analysis of KPC-3 protein predicted that the amino acid mutations are destabilizing for the protein and could alter the substrate specificity. Phylogenetic analysis and homology modeling of blaKPC-3 gene could represent a useful tool to follow KPC spread in nosocomial setting and to evidence amino acid substitutions altering the substrate specificity.

Objectives Aortic valve replacement through conventional sternotomy still represents the gold-standard surgical approach for aortic valve disease. However, given the increasing number of patients with comorbidities, strategies that can improve operative results are always sought. Minimally invasive aortic valve surgery, although related to a steep learning curve, might be associated with improved postoperative outcomes. The main aim of this study was to assess whether significant differences exist in terms of operative and early results between a mini-sternotomy and a right mini-thoracotomy approach for isolated aortic valve replacement without sutureless technologies. Methods This is an observational retrospective multicentre study from nine Italian cardiac centres that analyses prospectively collected data of patients who underwent isolated minimally invasive aortic valve replacement between January 2010 and December 2014. Two approaches are considered (mini-sternotomy and mini-thoracotomy) and compared in terms of operative and early outcomes. Results After interrogation of the centralized database, a total of 1130 patients were retrieved (854 mini-sternotomy and 276 mini-thoracotomy). Patients in the mini-sternotomy group had a higher risk profile. There was no difference in terms of early mortality; cardiopulmonary bypass and cross-clamp time did not differ significantly between the groups; and a significantly higher number of reoperations for bleeding was observed in the right mini-thoracotomy group. Conclusions Both mini-sternotomy and mini-thoracotomy could be performed safely, with low mortality and postoperative morbidity. The mini-thoracotomy approach was associated with a significantly higher rate of reoperation for bleeding. Uptake among cardiac centres was low. Sutureless technologies could potentially increase surgical volume by simplifying the mini-thoracotomy procedure.

The minimally invasive approach is becoming the standard-of-care for surgery of the mitral valve. As any less invasive strategy, it entails an increased surgical complexity. Standard-of-care mitral repair using the totally videoscopic approach is indeed reproducible; however, few specific data on patients with complex mitral valve disease are available in the published literature. The purpose of the present paper is to provide an overview of the current state-of-the-art in minimally invasive cardiac surgery, and a summary of recent evidence on the topic, with particular regard to the surgical techniques and comparisons with conventional surgery. The experience of the GVM Care and Research network in the field is also briefly reported.

Background Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease. Materials and methods From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m2 and Cetuximab were given weekly during radiation therapy. Results Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3–4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3–4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months. Conclusions The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients’ selection is crucial in order to treat patients appropriately.

Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.

When nanoparticles (NPs) enter a biological environment, proteins bind to their surface forming a protein coating, which alters NP features giving it a biological identity, which controls its physiological response. The NP biological identity (size, charge and aggregation state) does strictly correlate with its physicochemical properties and the nature of the biological environment. While the former relationship has been extensively investigated, whether and how alterations in the physiological environment affect the biological identity of the NPs remains unclear. In this work we enrolled healthy and histologically proven pancreatic cancer patients. A statistically significant reduction in the level of clinically relevant proteins in cancer patients occurred. Positively and negatively charged lipid nanoparticles with two different surface chemistries (plain and PEGylated) were incubated with human plasma from both groups and characterized thoroughly by dynamic light scattering and zeta potential measurements. Only when plain positively charged NPs were tested, significant difference in zeta-potential between healthy and pancreatic cancer groups was found. This result implies that pooling human plasma from healthy volunteers might lead to a bias and thus unpredictable consequences in regard to previously optimized targeting profile.

Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

We present a case of a transsexual patient who underwent a partial pelvectomy and genital reconstruction for anal cancer after chemoradiation. This is the first case in literature reporting on the occurrence of anal cancer after male-to-female sex reassignment surgery. We describe the surgical approach presenting our technique to avoid postoperative complications and preserve the sexual reassignment.

Introduction: Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumor. The present study investigated the prognostic role of MUC2 and MUC5 apomucin expression in a series of surgically resected pancreatic cancer patients. Results: By univariate analysis, survival was influenced by MUC2 expression but not by MUC5 expression. The MUC2 overexpression was associated with better prognosis (p = 0.003). By a multivariate Cox regression analysis, MUC2 overexpression maintained the prognostic statistical value. In particular, patients with high MUC2 staining showed a longer survival. Moreover the present study does report the absence of a prognostic role of MUC5 expression in this type of cancer. Material and methods: All patients affected by pancreatic ductal adenocarcinoma and treated with surgical resection from 1988-2003 were considered for the study. MUC2 and MUC5 expression were evaluated by immunohistochemical staining. Tumor specimens of 59 resected patients were included in the study. Conclusions: the study demonstrated the prognostic relevance of MUC2 expression in pancreatic cancer and underlined its potential role as target gene in the field of therapy research. ©2009 Landes Bioscience.

BACKGROUND: The aim of the current study was the investigation of the value of bevacizumab + 5-fluorouracil(5–FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options. METHODS: The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27-79 years) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy, an irinotecan-based second-line regimen, and a third-line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5-FU/folinic acid was administered according to the de Gramont schedule. RESULTS: The response rate was 6.25%, and 30.4% of patients demonstrated stable disease as the best response. The median time to disease progression was 3.5 months (95% confidence interval [95% CI], 2.3-6.9 months), and the median survival time was 7.7 months (95% CI, 3.9-11.9 months). The most common grade 3 to 4 side toxicities (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) were: diarrhea (20.8%), fatigue (14.5%), and stomatitis (12.5%). Grade 3 to 4 hemorrhage occurred in 8 patients (16.6%), including 4 cases of bleeding in the gastrointestinal tract. Other relatively common adverse events such as hypertension, thrombosis, and bowel perforation were reported in 50%, 18.7%, and 4.16%, of patients respectively. CONCLUSIONS: The data from the current study suggest a modest but significant clinical benefit of bevacizumab + de Gramont schedule in heavily pretreated colorectal cancer patients. Cancer 2009. © 2009 American Cancer Society.

Objectives: We compared two different approaches to right laparoscopic transperitoneal adrenalectomy for large tumors (>5 cm): the anterior transperitoneal (AT) and lateral transperitoneal (LT) approaches. Methods: 40 patients with a right large adrenal mass >5 cm underwent right adrenalectomy: 20 patients underwent the AT procedure and 20 patients the LT procedure. Preoperative characteristics were similar for both groups: mean tumor size for the AT and LT groups was 6.52 cm (range 5.2–8.5) and 6.59 cm (range 5.4–8.1), respectively. Mean patient’s age was 53 years (23–75 in the AT group and 20–77 in the LT group). AT and LT approaches were compared in terms of operative time, intraoperative blood loss, time to first oral intake and postoperative convalescence. Results: No difference was found between two groups in terms of estimated blood (100 ml for the AT group and 105.3 ml for the LT group), time to first oral intake (2.0 days for both groups) and convalescence (3.5 and 3 days, respectively). The mean operative times of the AT and LT procedures were 75.25 and 84.75 min, respectively: this difference was statistically significant at the Student’s t test (p = 0.0423). Conclusions: Both approaches proved to be safe and minimally invasive. We believe that the shorter operative time of AT procedures was related to the better visibility of familiar anatomic landmarks, easier access to the vessels and a larger operative field. For these reasons, we prefer the AT approach in the management of large adrenal masses.

Background Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors. Materials and methods We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes. Results In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor–node–metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05). Conclusions hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.

Deaths after percutaneous ethanol injection (PEI) into hepatocellular carcinoma (HCC) may occur within a few hours to a few days following the procedure because of hemoperitoneum and haemorrhage from oesophageal varices or hepatic insufficiency. Pancreatitis has been recently reported as a rare lethal complication of intra-arterial PEI, another modality for treating HCCs. In this minireview, we analyze the literature concerning the development of acute pancreatitis after PEI. Pathogenesis of pancreatitis from opioids and ethanol is also addressed. Treatment with opioids to reduce the patient's abdominal pain after PEI in combination with the PEI itself may lead to direct toxic effects, thus favouring the development of pancreatitis.