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OBJECTIVE: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers. BACKGROUND: Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking. METHODS: Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing ≥10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing ≥10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo ≥3). RESULTS: Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%, P = 0.526), mortality (4.0% vs 3.3%, P = 0.576), percutaneous drainage (12% vs 12%, P = 0.809), reoperation (11% vs 13%, P = 0.329), and hospital stay (mean 17 vs 17 days, P > 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%, P < 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95, P < 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF (24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%, P < 0.001). CONCLUSIONS: In the early experience of 14 European centers performing ≥10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed.

Background Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, the present study aims to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. Methods Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. Results Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of non-immediate cutaneous eruptions, and 17 of bronchospasm related to ASA/NSAID intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, 7 at doses up to 500 mg, 3 at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. Conclusions In patients with stable CIHD and histories of non-severe hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization. This article is protected by copyright. All rights reserved.

Background Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000–2016) and three very-high-volume international centers in the United States and Japan (model validation 2004–2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2–11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9–30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15–25 months). Conclusions When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor. Electronic supplementary material The online version of this article (10.1245/s10434-018-07101-0) contains supplementary material, which is available to authorized users.

START-Register - Survey on anTicoagulated pAtients RegisTer - is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) 80 years with high prevalence of renal failure.

Background Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. Methods Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007–2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. Results Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien–Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14–39) versus 31 months (95% CI 19–42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18–53) versus 20 months (95% CI 15–24), P = 0.049], as compared with upfront resection. Conclusion In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.

Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.

Management for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug–drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was assessed for each patient; drug–drug interactions (DDI) and de-prescribing process were carried out appropriately. Within 414 patients included, percentage rates of women treated was higher than males, BMI was lower and cirrhosis was frequently reported in patients older than 75 years. Hypertension, diabetes mellitus, dyslipidemia (p p p p

MacroH2A1 has two splice isoforms, macroH2A1.1 and macroH2A1.2, that have been studied in several form of cancer. In the literature there are not many scientific papers dealing with the role of macroH2A1 in breast cancer. Breast cancer is the most frequent form of malignancy in females. It tend to metastasize to the bone in ~70% of patients. Despite treatment, new bone metastases will still occur in 30–50% of cases with advanced disease. Overall 5-year survival after the diagnosis of bone metastasis is ~20%. Osteoclasts and osteoblasts of the bone microenvironment are engaged by soluble factors released by neoplastic cells, resulting in bone matrix breakdown. This malfunction enhances the proliferation of the cancer cells, creating a vicious cycle. We investigated immunohistochemical expression of macroH2A1 in primitive breast cancer, focusing on the comparison of metastatic and non-metastatic cases. Furthermore, the immunohistochemical expression of macroH2A1 has been evaluated both in all cases of nodal metastases and in distant metastases. Our data demonstrated that macroH2A1 expression was higher expressed in metastatic breast cancer (77%) vs. non-metastatic breast cancer (32%). Also in analyzed metastases cases, a high macroH2A1 expression was detected: 85 and 80% in nodal and distant metastases cases, respectively. These results supported the fact that macroH2A1 is more highly expressed in breast cancer with worst prognosis.

Sleep problems during pregnancy are prevalent and could be linked to negative outcomes during pregnancy or post-partum. However, these complaints are often underdiagnosed and undertreated. This review aimed to systematically assess the effectiveness of different interventions to ameliorate poor sleep quality and insomnia during pregnancy. Pubmed, PsycINFO and Medline databases were systematically searched without publication period restriction until 3rd May 2019. Eligible studies had to: include pregnant women of any age and gestational age; use clinical intervention designs targeted at improving sleep outcome; report pre- and post-treatment data for one or more sleep-related outcomes; be published in English, Italian, German, Spanish, or French. Sixteen studies were selected including 1252 expecting mothers. Studies evaluated the efficacy of various interventions: cognitive behavioral interventions for insomnia (4); pharmacotherapy (1); acupuncture (1); mindfulness and yoga (3); relaxation (5) and herbal medication (2). Only six were randomized controlled trials, and only four evaluated longitudinal outcomes. Preliminary support was found for all interventions, but our knowledge is still too limited by lack of evidence. There is an utmost urgency to perform high-quality randomized controlled trials for insomnia interventions during pregnancy and to implement effective programs in standard gynecological care.

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Short and long sleep duration have been associated with risk of obesity in children and adolescents. Evidence in adults is more mixed, with biological and psychosocial factors underlying these relationships mostly unknown. This review aimed at qualitatively and quantitatively summarizing previous studies on sleep duration as a predictor of obesity in adults in order to provide an update of the state of art in this field and clarify these relationships. Odds ratios at 95% Confidence Intervals (CI) were estimated using random-effects models. Heterogeneity of effects distribution and publication bias were tested. Twelve articles were selected for short sleep (n = 154,936) and eight for long sleep duration (n = 152,192). Results indicated that short sleep duration (OR: 1.412; 95% CI: 1.177–1.694) was significantly associated with the risk of future obesity, and that long sleep duration (OR: 0.995; 95% CI: 0.889–1.114) was not associated. Heterogeneity was high and lowered to non-significant values when considering gender and extremes of short/long sleep duration. Results seem to confirm a potential role of short sleep duration in predicting but results on long sleep are still mixed. Future investigations on potential mediators of such relationships are needed.

International audience; OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200?mL (60-400) vs 300?mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P \textless 0.001] were lower after MIDP. Clavien-Dindo grade >=3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P \textgreater 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P \textless 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P \textless 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

Purpose: The progressive immune dysfunctions that occur in patients with advanced melanoma make them unlikely to efficiently respond to cancer vaccines. A multicenter randomized phase II trial was conducted to test whether immunization with modified HLA class I tumor peptides in the context of adjuvant therapy results in better immunologic responses and improved clinical outcomes in patients with early melanoma (stages IIB/C-III). Experimental Design: Forty-three patients were enrolled to undergo vaccination (n = 22) or observation (n = 21). The vaccine included four HLA-A*0201–restricted modified peptides (Melan-A/MART-1[27L], gp100[210M], NY-ESO-1[165V], and Survivin[97M]) emulsified in Montanide ISA51 and injected subcutaneously in combination with cyclophosphamide (300 mg/m2) and low-dose IL-2 (3 × 106 IU). The immune responses were monitored using ex vivo IFN-γ–ELISpot, HLA/multimer staining, and in vitro short-term peptide sensitization assays. Results: Vaccination induced a rapid and persistent increase in specific effector memory CD8+ T cells in 75% of the patients. However, this immunization was not associated with any significant increase in disease-free or overall survival as compared with the observation group. An extensive immunologic analysis revealed a significantly reduced cross-recognition of the corresponding native peptides and, most importantly, a limited ability to react to melanoma cells. Conclusions: Adjuvant setting is an appealing approach for testing cancer vaccines because specific CD8+ T cells can be efficiently induced in most vaccinated patients. However, the marginal antitumor activity of the T cells induced by modified peptides in this study largely accounts for the observed lack of benefit of vaccination. These findings suggest reconsidering this immunization strategy, particularly in early disease. Clin Cancer Res; 18(23); 6485–96. ©2012 AACR.

We evaluated the incidence of and predisposing factors for an incisional hernia after kidney transplantation. Numerous techniques have been used to repair postoperative fascial dehiscences or simple incisional hernias, but no clear treatment exists for giant hernias. Our aim was to obtain (1) a safe procedure to repair a large abdominal defect and reinforce the surrounding, fragile zones and (2) a simple, rapid technique to reduce the operative time. Herein we have described the surgical repair of a giant incisional hernia using intraperitoneal Gore ePTFE dual-mesh plus (Gore-Tex; W. L. Gore, Flagstaff, Ariz, USA) in a 55-year-old man status-post renal transplantation. Total necrosis of distal graft ureter had caused a giant urinoma. The patient was reexplored on day 2 posttransplantation with a primary fascial approximation. Thirty days after transplantation we discovered a large incisional hernia and performed a repair. No drain was used. The patient continued immunosuppressive therapy (cyclosporine, mycophenolate mofetil, prednisolone) and was discharged on postoperative day 4 with no complications. An ultrasonographic follow-up at 1 year revealed the prosthesis to be correctely positioned. Incisional hernia is not rare after renal transplantation but the real incidence is unknown. Immunosuppressive therapy, prolonged pretransplantation dialysis, obesity, and diabetes are probably the major causes of incisional hernias in these patients. Surgical complications of renal transplantation surgery, such as wound hematoma, urinoma, and lymphocele, are the most important predisposing factors for an incisional hernia. The use of intraperitoneal ePTFE dual-mesh is feasible, safe, and easy to repair a large incisional hernia in a kidney transplant patient.

Early diagnosis of persistent hyperparathyroidism (HP) following kidney transplantation may prevent worsening of osteodystrophy and potential damage to the graft. We evaluated the utility of collagen pyridinoline (PYD) and deoxypyridinoline (DPD) urinary cross-links beyond the common HP markers to evaluate 70 selected stable recipients between 1997 and 2006 who were divided into 2 group depending on the immunosuppressive protocol. All patients showed elevated levels of urinary cross-links even though calcemia and phosphoremia values were normal. Their mean creatinine level was slightly increased. Data were assessed as mean values +/- SD. All variables underwent a correlation matrix analysis and a stepwise regression, with posttransplant intact parathyroid hormone (iPTH) as the dependent variable and other variables as regressors. A statistically significant correlation was observed between PYD and alkaline phosphatase (ALP; P = .0026, r = .41); PYD and DPD (P = .015, r = .34); pre- and posttransplant iPTH (P = .024, r = .31); and creatinine and ALP (P = .024, r = .31). Taking the groups separately, there were significant correlations between PYD and ALP (P = .0076, r = .42); PYD and DPD (P = .017, r = .38); ALP and posttransplant iPTH (P = .038, r = .33); osteocalcin (OC) and posttransplant iPTH (P = .048, r = .32); and pre- and posttransplant iPTH (P = .019, r = .37) among subjects in the first group, whereas subjects in the second group showed a correlation between posttransplant iPTH and age at transplantation (P = .032, r = .61). In conclusion, we showed that urinary cross-links may be helpful to reveal bone resorption in kidney recipients when usual bone metabolism parameters do not demonstrate hyperparathyroidism.

Purpose The aim of this study was to demonstrate the effectiveness of a new kind of disposable surgical retractor in arteriovenous fistula (AVF) procedures in order to achieve an easier, faster and safer surgical intervention. Methods Between January and June 2008, 22 AVF procedures were performed using the 3PAWS ReeTrakttrade; (Insightra Inc. - Irvine, Ca., USA) a self-retaining, low profile retractor. An equivalent patient sample, in which an AVF was performed using conventional retraction devices, was considered for comparison of the intra- and post-operative results. Results In all of the 22 AVF procedures performed, the ReeTrakt™ system has simplified the performance of the surgical team. The retractors were very easy to place. The view of the operating field was always optimal. The introduction of the surgical instruments was at all times extremely easy and unrestricted. We also noted a reduction in the operating time (from an average of 67 min in controls to 43 min). There were no intraoperative complications. No post-operative complications related to the use of this kind of device occurred. Conversely, the amount of intra- and post-operative complications in the control group managed with conventional retraction devices was marginally higher than in the ReeTrakt™ patient group. Conclusion The ReeTrakt™ system is a very simple and useful low profile retractor for AVF procedures. Its ultra low profile allows a much improved view of the operating field, an unhindered insertion of the surgical instruments and a shortening of intervention time, avoiding the problems which arise as a result of standard retractors typically used during this kind of procedure. Due to absolute perpendicular retraction it offers a highly atraumatic performance, avoiding swelling and marks on the insertion sites. Therefore, in our opinion, it has the potential to reduce the risk of wound oedema, hematomas or infection associated with the AVF procedure. This is important as many patients are elderly with fragile tissues.