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Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene‐disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case–control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58–0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21–0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19–0.89, and OR = 0.73, 95%CI 0.53–1.00, respectively). Several inflammatory‐related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

Resection is the gold standard in the treatment of liver metastases from colorectal cancer. An internal cooled radiofrequency electrode was described to achieve tissue coagulation to a greater margin width. The aim of this study is to determinate if a RFassisted transection device (RFAT) has any effect on local hepatic recurrence (LHER) compared to conventional technologies. A study population of 103 patients who had undergone a hepatic surgical resection was retrospectively analysed. Patients were classified into two groups according to the device used: a RF-assisted device (RFAT group; n=45) and standard conventional devices (control group; n=58). LHER was defined as any growing or enhancing tumour in the margin of hepatic resection during follow-up. Cox proportional models were constructed and variables were eliminated only if p>0.20 to protect against residual confounding. To assess the stability of Cox’s regression model and its internal validity, a bootstrap investigation was also performed. Baseline and operative characteristics were similar in both groups. With a mean followup of 28.5 months (range 2-106), in patients with positive margins, we demonstrated 0% of LHER in RFAT vs. 27% in control group (p=0.032). In the multivariate analysis five factors demonstrated significant influence on the final model of LHER: RFAT group, size of the largest metastases, number of resected metastases, positive margin and usage of Pringle-manoeuvre. This study suggests that parenchymal transection using a RFAT able to create deep thermal lesions may reduce LHER especially in case of margin invasion during transection

Background: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. Methods: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. Results: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01–12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11–2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36–0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9–16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29–2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. Conclusions: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis b

Purpose: To evaluate the impact of using monopolar thermal coagulation based on radiofrequency (RF) currents on intraoperative blood loss during liver resection. Materials and methods: A prospective randomized controlled trial was planned. Patients undergoing hepatectomy were randomized into two groups. In the Control group (n=10), hemostasis was obtained with a combination of stitches, vessel-sealing bipolar RF systems, sutures or clips. In the monopolar radiofrequency coagulation (MRFC) group (n=18), hemostasis was mainly obtained using an internally cooled monopolar RF electrode. Results: No differences in demographic or clinical characteristics were found between groups. Mean blood loss during liver resection in the Control group was more than twice that of the MRFC group (556±471 ml vs. 225±313 ml, p=0.02). The adjusted mean bleeding/transection area was also significantly higher in the Control group (7.0±3.3 ml/cm2 vs. 2.8±4.0 ml/cm2 , p=0.006). No significant differences were observed in the rate of complications between the groups. Conclusions: The findings suggest that the monopolar electrocoagulation created with an internally-cooled RF electrode considerably reduces intraoperative blood loss during liver resection.

Purpose: To assess the capacity of two methods of surgical pancreatic stump closure in terms of reducing the risk of pancreatic fistula formation (POPF): radiofrequencyinduced heating versus mechanical stapler. Materials and Methods: Sixteen pigs underwent a laparoscopic transection of the neck of the pancreas. Pancreatic anastomosis was always avoided in order to work with an experimental model prone to pancreatic fistula formation (POPF). Pancreatic stump closure was conducted either by stapler (ST Group, n=8) or radiofrequency energy (RF Group, n=8). Both groups were compared for incidence of POPF and histopathologic alterations of the pancreatic remnant. Results: Six animals (75%) in the ST Group and one (14%) in the RF Group were diagnosed of POPF (p=0.019). One animal in the RF Group and three animals in the ST Group had a pseudocyst in close contact with both pancreas stumps. On day 30 postoperative, almost complete atrophy of the exocrine distal pancreas was observed when the main pancreatic duct was efficiently sealed. Conclusions: Our findings suggest that RF-induced heating is more effective at closing the pancreatic stump than mechanical stapler and leads to the complete atrophy of the distal remnant pancreas.

The aim of this study was to assess the capacity of two methods of surgical pancreatic stump closure in terms of reducing the risk of pancreatic fistula formation (POPF): radiofrequency-induced heating versus mechanical stapler. Sixteen pigs underwent a laparoscopic transection of the neck of the pancreas. Pancreatic anastomosis was always avoided in order to work with an experimental model prone to POPF. Pancreatic stump closure was conducted either by stapler (ST group, n = 8) or radiofrequency energy (RF group, n = 8). Both groups were compared for incidence of POPF and histopathological alterations of the pancreatic remnant.

[EN] Background Although radiofrequency-assisted devices have sometimes been used in partial splenectomy, this is not a common technique. This report describes the first case of laparoscopic partial splenectomy using an RF-assisted device (Coolinside) which allows both coagulation and transection of the parenchyma and eventually the protective coagulation of the remnant side. Case presentation A 27-year-old woman was found to have a giant hydatic cyst measuring 12.0¿×¿14.0¿×¿16.6 cm that mainly occupied the lower pole of the spleen and retroperitoneal space. The patient underwent a laparoscopic partial splenectomy using an RF-based device designed to accomplish both the coagulation and dissection of the splenic tissue. The estimated blood loss was less than 200 mL. Conclusions Even though RF ablation has traditionally been used for hepatic parenchymal transection, it seems equally suited to partial splenectomy. This device seems to provide good results, minimizing blood loss during partial splenectomy; however, randomized trials will be necessary to see if the results are superior to those of other techniques.

[EN] Postoperative pancreatic fistula (PPF) is the most frequent and serious complication after laparoscopic distal pancreatectomy (LDP). Our goal was to compare the performance, in terms of PPF prevention, and safety of a radiofrequency (RF)-assisted transection device versus a stapler device in a porcine LDP model. Thirty-two animals were randomly divided into two groups to perform LDP using a RF-assisted device (RF group; n = 16) and stapler device (ST group; n = 16) and necropsied 4 weeks after surgery. The primary endpoint was the incidence of PPF. Secondary endpoints were surgery/transection time, intra/postoperative complications/deaths, postoperative plasmatic amylase and glucose concentration, peritoneal liquid amylase and interleukin 6 (IL-6) concentrations, weight variations, and histopathological changes. Two clinical and one biochemical PPF were observed in the ST and RF groups respectively. Peritoneal amylase concentration was significantly higher in the RF group 4 days after surgery, but this difference was no longer present at necropsy. Both groups presented a significant decrease in peritoneal IL-6 concentration during the postoperative follow-up, with no differences between the groups. RF group animals showed a higher postoperative weight gain. In the histopathological exam, all RF group animals showed a common pattern of central coagulative necrosis of the parenchymal surface, surrounded by a thick fibrosis, which sealed main and secondary pancreatic ducts and was not found in ST group. The fibrosis caused by an RF-assisted device can be at least as safe and effective as stapler compression to achieve pancreatic parenchyma sealing in a porcine LDP model.

[EN] Purpose: To track the saline during infusion with a 15 G needle into healthy pig livers at high and low infusion rates for 300 s. Methods: In each experiment, the needle was inserted into a single lobe of the liver to a depth of at least 2 cm following its longer axis. Two sets of experiments were defined: 1) low infusion rate of 0.1 mL/min (n = 6) and 2) high infusion rate of 1 mL/min (n = 6). Cine CT scans were carried out and three transverse planes were defined around the infusion point (IP), which corresponds with needle tip. Two assessments were performed: 1) a dynamic plane study focused on the time progress of the saline distribution on a single plane, which provided the Mean Percentage of Grayscale Intensity (MPG!): and 2) a volumetric study focused on the three dimensional distribution of the saline around IP at the end of the experiment, which provided the High Intensity Volume Ratio (HIVR). Results: The saline solution was conspicuous around the IP and shortly after heterogeneously inside the vessels. At the high infusion rate, the saline became conspicuous not only much sooner (evident at 20 s) but farther away (mean value of MPGI over 2%, up to 17 mm from the IP) and at a much higher intensity (mean value of MPGI over 10% up to 4 mm from the IP). The lower the radial distance to the IP, the greater the difference in HIVR between both groups. Conclusions: The high infusion rate leads to a faster, wider and a more marked presence of saline than the low rate. The rapid drainage into the hepatic veins may explain the heterogeneous distribution. (C) 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

This is a copy of an article published in the Journal of Laparoendoscopic and Advanced Surgical Techniques © 2012 [copyright Mary Ann Liebert, Inc.]; Journal of Laparoendoscopic and Advanced Surgical Techniques is available online at: http://online.liebertpub.com., Background and Aim: Despite technological improvements in pancreatic surgery, the incidence and morbidity of pancreatic leak after resection of distal pancreas are persistently high in most series. Laparoscopic distal pancreatectomy (LDP) is today the gold standard procedure for benign and certain malignant neoplasms of the pancreatic body and tail in specialized centers. This study evaluated safety and feasibility of a radiofrequency (RF)-assisted transection device in a porcine model of LDP. Materials and Methods: LDP was performed on 10 pigs (median weight, 39.6 kg) using a new device based on an internally cooled RF-assisted electrode (Coolinside (R), Apeiron Medical, Valencia, Spain). The animals were subjected to daily observation and then sacrificed and necropsied at 4 weeks postoperatively. Primary end points were the development of postoperative pancreatic fistula using the Pancreatic Anastomotic Leak Study Group definition and/or the presence of abdominal amylase-rich fluid collections or abscesses during necropsy and pathological study and/or dye extravasation from the pancreatic remnant duct. Secondary end points were intra- or postoperative complications, surgery, and transection duration. Results: No clinically relevant postoperative pancreatic fistulas were observed. In one case a grade A postoperative fistula was diagnosed due to amylase drain concentration of more than 6200 IU/mL on postoperative day 4. Median peritoneal liquid amylase concentration on postoperative day 4 was 2399.0 IU/L (range, 819.2-7122.0 IU/L), similar to the median plasma amylase level of 1520.8 IU/L (range, 1015.3-4056.6 IU/L). Median surgery time was 93.5 minutes (range, 46.0-140.0 minutes), and median transection time was 4.5 minutes (range, 2.0-26.0 minutes). There was one postoperative wound infection. There were no postoperative deaths or major complications. During the histopathological study, the surgical margin of the remaining pancreas showed a common pattern with a c

[ES] El instrumento ideal para realizar la transección hepática debería aunar en una sola herramienta hemostasia segura y rápida. Presentamos nuestra investigación multidisciplinar encaminada al desarrollo de un dispositivo de transección hepática asistido por radiofrecuencia (RF); la investigación incluye: modelado teórico por computador, estudio experimental y ensayo clínico de este dispositivo. El modelado teórico se realizó por computador basado en el Método de Elementos Finitos (MEF) con objeto de estudiar la distribución de energía eléctrica y temperatura en el tejido y valorar el efecto de las características del instrumento. El estudio experimental basado en un modelo in vivo porcino sugiere que el nuevo instrumento permitiría aumentar la velocidad de transección del parénquima hepático con una menor hemorragia por área de transección al compararlo con otras técnicas ampliamente extendidas en la cirugía hepática. Estos datos permitieron afrontar la realización de la primera fase de un ensayo clínico, cuyos resultados preliminares sugieren que el nuevo instrumento es seguro y eficaz., [EN] The ideal instrument for performing hepatic transection should combine safe and rapid haemostasis in a single tool. We present a new multidisciplinary investigation designed to develop a hepatic transection device assisted by radiofrequency (RF); the investigation included: a computerised theoretical model, and experimental study and a clinical trial of this device. The theoretic modelling was performed by computer, based on the Finite Elements Method (FEM), with the objective of studying the distribution of electrical energy and temperature in the tissue, and to assess the effect of the characteristics of the instrument. The experimental study, based on an in vivo porcine model, suggested that the new instrument would allow the transection velocity of the hepatic parenchyma to be increased with lower bleeding per transection area compared with other techniques extensively used in liver surgery. These data should enable the first phase of clinical trial to be conducted, with preliminary results that suggest that the new device is safe and effective.

OBJECTIVE. Our aim was to evaluate the capability of a Cool-tip electrode to create larger coagulation volumes combined with a low-flow (0.1 mL/min) perfusion of hypertonic saline at a distance of 2 mm (hybrid applicator) without reducing either predictability or sphericity of the coagulation zone. MATERIALS AND METHODS. A total of 48 radiofrequency ablations were performed on a total of 12 adult pigs: 24 with the Cool-tip (group 1) and 24 with the hybrid applicator (group 2). Volumes and diameters were assessed both macroscopically and with imaging techniques (ultrasound and MRI). Digital reconstruction techniques were also used. Reproducibility of the coagulations was assessed by means of the coefficient of variation. RESULTS. The macroscopic assessment showed a significantly larger coagulation zone in group 2 than in group 1, both with (19.40 ± 11.38 cm3 vs 9.16 ± 5.62 cm3; p < 0.001) and without (19.54 ± 11.39 cm3 vs 9.21 ± 5.74 cm3; p < 0.001) digital reconstruction. Differences were also significant in the MRI assessment. The minimum transverse diameter was also significantly (p < 0.01) larger in group 2 than group 1: 2.46 ± 0.61 versus 1.86 ± 0.55 cm for macroscopic assessment, 2.33 ± 0.96 versus 1.69 ± 0.53 cm for ultrasound, and 2.41 ± 0.58 versus 1.8 ± 0.52 cm for MRI. The coefficient of variation was similar in both groups. CONCLUSION. The results suggest that low-flow perfusion of hypertonic saline at 2 mm from a Cool-tip electrode could increase coagulation zone volume without reducing predictability.

[EN] The objective of this study was to evaluate the clinical feasibility of a new technique for liver resection based on a radiofrequency-assisted (485 kHz) device that has shown high performance in the animal setting in both transection speed and blood loss per transection area. Eight patients with colorectal hepatic metastasis underwent 11 partial hepatectomies using the proposed technique for both parenchyma division and hemostasis. Main outcome measures were blood loss per transection area and transection speed. No other instruments (including sutures or clips) were used in any of the cases; temporary vascular occlusion performed was not performed. No blood transfusions were required and no mortality or morbidity linked to the hepatic procedure were observed. The median blood loss per transection area and the median transection speed were .79 mL/cm2 (range, .05–7.37 mL/cm2) and 1.28 cm2/min (range, .49–1.87 mL/cm2), respectively. During the follow-up period (range, 4–12 mo) no late complications were detected and postoperative patients were free from hepatic recurrence. The proposed radiofrequency-assisted device was shown to achieve parenchymal division and hemostasis simultaneously, resulting in extremely reduced blood loss.

In this article some recent data concerning the approach on radiofrequency ablation (RFA) of liver tumors are reviewed. Specifically, several critical statements between surgical and percutaneous approach are raised and discussed: (1) Open approach may lead to a higher complication rate; (2) Temporary occlusion of hepatic inflow during surgical approach may lead to a higher rate of ablation of the liver tumors; (3) Surgical approach may permit better targeting of the tumor to be ablated. (4) Surgical approach may discover additional liver tumors. Finally, several conclusions and recommendations are also addressed.