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Background and Aims: Patients undergoing pancreatic resection are commonly malnourished. It is still unclear whether nutritional scores reliably predict postoperative outcomes after pancreatic resection. This study evaluated whether five commonly used preoperative nutritional screening scores predicted severe complications and length of stay., Methods: Patients scheduled for pancreatic resection (pancreatoduodenectomy, distal and total pancreatectomy) at a national referral center for pancreatic surgery from September 2022 to June 2023 were prospectively screened for malnutrition with MNA, MUST, SGA, SNAQ, and NRS2002 scores. Postoperative complications were classified using the Clavien-Dindo classification. #NCT05608538., Results: Three hundred patients were enrolled, including 168 pancreatoduodenectomies (56%), 102 distal pancreatectomies (34%), and 30 total pancreatectomies (10%). Final pathology revealed malignancy in 203 cases (67.7%). When applying the scores, the proportion of patients malnourished or at risk of malnutrition ranged from 21.7% for SGA to 79.3% for NRS2002. After adjusting for selected confounders, only an MNA <17 was associated with severe postoperative complications (OR 8.39, 95%CI [1.95-32.31], p = 0.01). MNA, SGA, and SNAQ predicted the length of stay (all p < 0.01), while MNA and SGA also correlated with a higher probability of having a greater heterogeneity in the length of stay (p = 0.04 and 0.002, respectively)., Discussion: We promote using MNA to detect malnourished patients at risk of severe postoperative complications and longer hospitalization after pancreatic surgery. SGA and SNAQ may also have value in predicting patients who will be hospitalized longer. More prospective studies will be needed to corroborate these findings., Competing Interests: Declaration of competing interest SP and ES receive consultancy honoraria from AlphaTau., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Screening programs for early detection and treatment of pancreatic cancer (PC) and its precursor lesions are increasingly implemented worldwide to reduce disease-specific lethality. Given the relatively low prevalence of the disease, the ideal target of such approaches is an enriched cohort of individuals harboring a lifetime risk of developing PC significantly higher compared to the general population, given either a substantial aggregation of PC cases in their family (i.e. familial pancreatic cancer) or a genomic landscape enriched with pathogenic variants associated with pancreatic carcinogenesis (i.e. mutation carriers). In Italy, a national registry for the census and surveillance of high-risk individuals for PC was launched in 2015, enrolling some 1200 subjects as of today. In this perspective, the scientific background, multi-level structure, and evolution of IRFARPC are outlined, as well as its long-term results, future developments, and areas for improvement., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Shotgun metagenomics sequencing experiments are finding a wide range of applications. Nonetheless, there are still limited guidelines regarding the number of sequences needed to acquire meaningful information for taxonomic profiling and antimicrobial resistance gene (ARG) identification. In this study, we explored this issue in the context of oral microbiota by sequencing with a very high number of sequences (~ 100 million), four human plaque samples, and one microbial community standard and by evaluating the performance of microbial identification and ARGs detection through a downsampling procedure. When investigating the impact of a decreasing number of sequences on quantitative taxonomic profiling in the microbial community standard datasets, we found some discrepancies in the identified microbial species and their abundances when compared to the expected ones. Such differences were consistent throughout downsampling, suggesting their link to taxonomic profiling methods limitations. Overall, results showed that the number of sequences has a great impact on metagenomic samples at the qualitative (i.e., presence/absence) level in terms of loss of information, especially in experiments having less than 40 million reads, whereas abundance estimation was minimally affected, with only slight variations observed in low-abundance species. The presence of ARGs was also assessed: a total of 133 ARGs were identified. Notably, 23% of them inconsistently resulted as present or absent across downsampling datasets of the same sample. Moreover, over half of ARGs were lost in datasets having less than 20 million reads. This study highlights the importance of carefully considering sequencing aspects and suggests some guidelines for designing shotgun metagenomics experiments with the final goal of maximizing oral microbiome analyses. Our findings suggest varying optimized sequence numbers according to different study aims: 40 million for microbiota profiling, 50 million for low-abundance species detection, and 20 million for ARG identification. KEY POINTS: • Forty million sequences are a cost-efficient solution for microbiota profiling • Fifty million sequences allow low-abundance species detection • Twenty million sequences are recommended for ARG identification., (© 2024. The Author(s).)

Background: Little is known about adjuvant therapy (AT) omission and use outside of randomized trials. We aimed to assess the patterns of AT omission and use in a cohort of upfront resected pancreatic cancer patients in a real-life scenario., Methods: From January 2019 to July 2022, 317 patients with resected pancreatic cancer and operated upfront were prospectively enrolled in this prospective observational trial according to the previously calculated sample size. The association between perioperative variables and the risk of AT omission and AT delay was analyzed using multivariable logistic regression., Results: Eighty patients (25.2%) did not receive AT. The main reasons for AT omission were postoperative complications (38.8%), oncologist's choice (21.2%), baseline comorbidities (20%), patient's choice (10%), and early recurrence (10%). At the multivariable analysis, the odds of not receiving AT increased significantly for older patients (odds ratio [OR] 1.1, p < 0.001), those having an American Society of Anesthesiologists score ≥II (OR 2.03, p = 0.015), or developing postoperative pancreatic fistula (OR 2.5, p = 0.019). The likelihood of not receiving FOLFIRINOX as AT increased for older patients (OR 1.1, p < 0.001), in the presence of early-stage disease (stage I-IIa vs. IIb-III, OR 2.82, p =0.031; N0 vs. N+, OR 3, p = 0.03), and for patients who experienced postoperative major complications (OR 4.7, p = 0.009). A twofold increased likelihood of delay in AT was found in patients experiencing postoperative complications (OR 3.86, p = 0.011)., Conclusions: AT is not delivered in about one-quarter of upfront resected pancreatic cancer patients. Age, comorbidities, and postoperative complications are the main drivers of AT omission and mFOLFIRINOX non-use., Clinicaltrials Registration: NCT03788382., (© 2024. The Author(s).)

Background and Objectives: Fibromyalgia syndrome (FMS) is a multifaceted disease with a strong preference for the female sex. It is characterised by chronic widespread pain, sleep-wake disorders, fatigue, cognitive disturbances, and several other somatic symptoms. Materials and Methods: In this prospective observational study, we analysed data regarding 302 patients who were referred to our pain centre for a first clinical assessment evaluation and were then inspected for the physician-based 2016 revision of the ACR diagnostic criteria for FMS, regardless of the final diagnosis previously made by the pain therapist. Results: Among the 280 patients who adhered to the 2016 ACR questionnaire, 20.3% displayed positive criteria for FMS diagnosis. The level of agreement between the FMS discharge diagnosis made by the pain clinician and the ACR 2016 criteria-positivity was moderate (kappa = 0.599, with moderate agreement set at a kappa value of 0.6). Only four patients (1.7%) diagnosed as suffering from FMS at discharge did not satisfy the minimal 2016 ACR diagnostic criteria. Conclusions : This prospective observational study confirmed the diagnostic challenge with FMS, as demonstrated by the moderate grade of agreement between the FMS diagnosis at discharge and the positivity for 2016 ACR criteria. In our opinion, the use of widely accepted diagnostic guidelines should be implemented in clinical scenarios and should become a common language among clinicians who evaluate and treat patients reporting widespread pain and FMS-suggestive symptoms. Further methodologically stronger studies will be necessary to validate our observation.

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before., Methods: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195)., Results: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported., Discussion: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Migraine is a neurological disorder characterized by attacks of head pain with prevalent unilateral localization, moderate to high intensity and specifically associated accompanying symptoms., Methods: In this retrospective observational study, we analyzed data regarding 209 patients who had previously been diagnosed with migraine and who were prescribed, between 2019 and 2022, subcutaneous injections of anti-CGRP monoclonal antibodies (mAbs) fremanezumab or galcanezumab or anti-CGRP receptors mAb erenumab regardless of the concomitant assumption of any other acute-phase or prophylactic migraine medication., Results: Regarding efficacy, in the 205 analyzed patients, the change from baseline in terms of MIDAS, HIT-6, MMDs and MAD scores was statistically significant for erenumab and galcanezumab, while for fremanezumab a statistical significance was not achieved likely due to the small sample size. In the treated population, 36 patients (17.5%) reported AEs (pain during injection, transient injection site erythema, nausea, constipation and fatigue). Only 5 patients (2.4%) discontinued the treatment for AEs while 15 patients (7.3%) left for lack of efficacy., Conclusions: this retrospective study comes out in favor of both significant efficacy and safety of anti-CGRP and anti-CGRP receptors mAbs in migraine patients. Further methodologically stronger studies are necessary to validate our observation.

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance., Background: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified., Materials and Methods: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408)., Results: Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I2 : 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I2 : 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P <0.01)., Conclusions: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance., Competing Interests: S.P. receives consultancy fees from AlphaTau. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fibromyalgia (FM) is a chronic disease characterized by a heterogeneous set of physical and psychological conditions. The chronic experience of disability felt by patients and the impact on quality of life (QoL) of the disease may worsen the cognitive reappraisal ability and contribute to maintaining an altered pain modulation mechanism. This paper presents the study protocol of an INTEGRated psychotherapeutic interventiOn on the management of chronic pain in patients with fibromyalgia (INTEGRO). The aim of the study is to investigate the efficacy of an integrated psychotherapeutic intervention focused on pain management on QoL and pain perception, in a pilot sample of 45 FM patients with idiopathic chronic pain. The contribution of perceived therapeutic relationship (alliance) and physiological attunement, in both the patient and therapist, will be considered as possible mediators of intervention efficacy. Attachment dimensions, traumatic experiences, difficulties in emotion regulation, mindfulness attitude and psychophysiological profile will also be considered as covariates. The objectives are to evaluate longitudinally if patients will experience an increase in QoL perception (primary endpoint), pain-managing self-efficacy and emotion-regulation abilities as well as a reduction in pain intensity (secondary endpoints), considering the mediating role of perceived therapeutic alliance and physiological attunement in both the patient and therapist.

Background and Aims: Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy., Methods: Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay., Results: One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m 2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of -7.8 cm 2 /m 2 ( p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI ( p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT ( p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications ( p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm 2 /m 2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome., Conclusion: Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paiella, Azzolina, Trestini, Malleo, Nappo, Ricci, Ingaldi, Vacca, De Pastena, Secchettin, Zamboni, Maggino, Corciulo, Sandini, Cereda, Capretti, Casadei, Bassi, Mansueto, Gregori, Milella, Zerbi, Gianotti and Salvia.)

Background: Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain, fatigue, unrefreshing sleep and cognitive dysfunction. Depressive and manic symptoms are often reported in FMS patients' history. The aim of this study was to evaluate the prevalence of bipolar spectrum symptoms (BSS) and to correlate these with quality of life (QoL) scores and antidepressant treatment., Methods: From October 2017 to July 2018, a battery of QoL questionnaires (FIQ, PSQI and SF-12) was administered to 120 FMS patients after a clinical examination. The MOODS-SR lifetime questionnaire was then remotely administered to the patients included in the study., Results: The presence of depressive and manic lifetime symptoms was found, in line with the results of the available literature. A correlation was found between the history of depressive symptoms and the severity of FIQ and SF-12 scores. Despite a low statistical strength, a trend toward a correlation between a history of manic symptoms and SNRI treatment was detected., Conclusions: The correlation between the MOOD-depressive domains and poor QoL is in line with the available literature. Further studies are needed to corroborate these findings and to elucidate the relationship between manic symptoms and SNRI treatment.

Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.

Background: Persistent Idiopathic Facial Pain (PIFP), previously named Atypical Facial Pain (AFP) is a poorly understood condition, often diagnosed after several inconclusive investigations. The aim of this retrospective study was to evaluate the demographic and clinical characteristics of patients with PIFP referred to a Facial Pain Center., Methods: Between May 2011 and September 2014, data on 41 PIFP patients were analyzed regarding temporal, topographical and descriptive pain features, including onset, localization, pain descriptors and intensity. Pharmacological pain treatments were also registered. Finally, the presence and type of previous minor oro-surgery procedures in the painful area were investigated., Results: Demographic and clinical characterization were similar to PIFP patients reported in literature. The presence of previous minor oro-surgery procedures in the painful area was reported in most of these patients, in particular endodontic treatments and tooth extractions., Conclusions: This retrospective analysis showed a high prevalence of minor oro-surgery procedures in our population, while its role in PIFP pathophysiology remains unknown. A new classification of PIFP built around the main discriminant factor of presence of these procedures in the painful area could be considered while available data were still insufficient to define specific diagnostic criteria.

Background: Obesity has traditionally been considered a cause of increased surgical complexity and poor outcomes following pancreatoduodenectomy (PD). This study aimed at evaluating the role of obesity in terms of mortality and failure to rescue (FTR), with a particular focus on nonmalignant tumors., Methods: All patients undergoing elective PD over 10 consecutive years were analyzed. Patients were stratified according to their BMI and categorized into two groups. Predictors of mortality and FTR were assessed through logistic regression., Results: Out of 1865 patients included, 151 were obese (8.1%). Overall mortality and FTR were 3.1% and 14.1%, respectively. In obese patients, mortality was 6.0% and FTR 26.5%, significantly higher compared to nonobese (p < 0.05). In the multivariable analysis, obesity, age > 70 years, and ASA-PS score were independent predictors of mortality and FTR. Postoperative pancreatic fistula (35.8% vs. 25.8%), postpancreatectomy acute pancreatitis (24.5% vs. 12.5%), and chyle leak (6.0% vs. 3.2%) were more frequent among obese patients. In the subgroup of patients with nonmalignant tumors (n = 443), obesity was the only independent predictor of FTR., Conclusion: PD performed in obese patients was associated with higher surgical morbidity and mortality. When dealing with nonmalignant tumors, deferring surgery in obese patients should be strongly considered., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: To compare the postoperative course of elderly patients (≥70 years) submitted to minimally invasive (MIDP) versus open distal pancreatectomy (ODP) and to evaluate if the modified Frailty Index (mFI) predicts the surgical course of elderly patients submitted to DP., Methods: Data of patients aged ≥70 who underwent DP at a single institution between March 2011 and December 2019 were retrospectively retrieved. A 2:1 propensity score matching (PSM) was used to correct for differences in baseline characteristics. Then, postoperative complications were compared between the two groups (MIDP vs. ODP). Additionally, the entire cohort of DP elderly patients was stratified according to the mFI into three groups: non-frail (mFI = 0), mildly frail (mFI = 1/2), or severely frail (mFI = 3) and then compared., Results: A total of 204 patients were analyzed. After PSM, 40 MIDP and 80 ODP patients were identified. The complications considered stratified homogenously between the two groups, with no statistically significant differences. The severity of the postoperative course increased as mFI did among the three groups regarding any complication (p = 0.022), abdominal collection (p = 0.014), pulmonary complication (p = 0.001), postoperative confusion (p = 0.047), Clavien-Dindo severity ≥3 events (p = 0.036), and length of stay (p = 0.018)., Conclusions: Elderly patients can be safely submitted to MIDP. The mFI identifies frail elderly patients more prone to develop surgical and non-surgical complications after DP., (© 2022. The Author(s).)

Background and Aim: We aimed to describe the socio-demographic, behavioral and clinical profiles of adult patients with newly diagnosed celiac disease (CeD) and their possible association with QoL and psychological symptoms., Methods: Adults newly diagnosed with CeD and residents in the Veneto region were included. Their sociodemographic characteristics, clinical presentation, mode of diagnosis, duration of symptoms before diagnosis and comorbidities were recorded. All patients completed the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) and Short Form Health Survey (SF-36) questionnaires., Results: Between 2016 and 2019, 110 CeD patients (81% females, mean age 37.5) were recruited. At diagnosis, patients were categorized into classical (n = 56), nonclassical CeD (n = 49) and asymptomatic (n = 5) groups. Patients with classical presentation had a lower QoL than nonclassical patients, who were found to be more depressed. We observed a diagnosis delay of more than 7 months in more than 60% of patients with both classical and nonclassical presentations and we found that a longer duration of GI symptoms decreased the self-reported SF36 scores in the physical health (p = 0.002), social functioning (p = 0.03) and general health (p = 0.009) domains. Women had an overall lower self-perceived QoL., Conclusions: Symptomatic presentation at CeD diagnosis, diagnostic delay and sex may affect QoL and psychological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to evaluate the effectiveness of piperacillin-tazobactam as antibiotic prophylaxis in patients affected by a peri-ampullary tumor submitted to pancreatic surgery. Methods: A prospective, non-randomized, non-blinded, interventional study was conducted from January 2015 to March 2018. Patients were screened pre-operatively for Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL-PE). During the baseline period (January 2015-October 2016), surgical prophylaxis was performed with ampicillin-sulbactam. In the intervention phase (November 2016-March 2018), patients received piperacillin-tazobactam. Statistical analysis was performed by univariable and multivariable analysis with logistic regression models. Results: Overall, 383 patients were included in the baseline period and 296 in the intervention period. The surveillance strategy identified 47 ESBL-PE carriers (14%) in the baseline phase and 29 (10%) in the intervention phase. In the baseline period, the patients had a higher rate of hospital-acquired infection (43% versus 33%; p = 0.004), superficial surgical site infection (SSI) (11% versus 2%; p < 0.001), and pneumonia (16% versus 9%; p = 0.006). After the logistic regression, the baseline group had an odds ratio to develop superficial SSI and pneumonia of 7.7 (95% confidence interval [CI] 3-20) and 1.8 (95% CI 1-3.3), respectively. The ESBL colonization increased the mortality rate significantly (8% versus 3%; p = 0.017). Conclusions: Adopting antibiotic prophylaxis based on piperacillin-tazobactam is associated with a reduction in post-operative SSI, particularly superficial-SSIs. Further randomized studies would be warranted to evaluate this antibiotic combination more extensively in preventive strategies.

Objective: (1) To determine the prevalence and type of depressive symptoms at day-hospital clinical evaluation, before undergoing major surgery in patients diagnosed with pancreatic neoplasm. (2) To analyze the association between depression and sociodemographic, clinical, and psychosocial variables. (3) To understand how coping strategies, perceived social support, and self-efficacy might affect depressive symptoms in this cohort of patients., Methods: Secondary data analysis collected during the baseline phase of a randomized controlled trial performed at the Pancreas Institute of the University Hospital of Verona, Italy, between June 2017 and June 2018., Results: 18.5% of pancreatic patients had a PHQ-9 score ≥10 (cut-off). Depressed patients were basically more often female (p = 0.07), younger (p = 0.06), and married/with a partner (p = 0.02). Depression was associated to high trait anxiety (p < 0.01), the use of anxiolytics (p < 0.01), sleep-inducing drugs (p < 0.01), and painkillers (p < 0.01). Among psychosocial variables, depressed patients showed lower perceived self-efficacy (p < 0.01) and family and friends' social support (p < 0.01) and used significantly more often dysfunctional coping strategies (p < 0.01), compared to nondepressed. A logistic multivariate model using psychosocial variables as explanatory and depression as dependent was calculated and post hoc analyses were conducted to describe the contribution of each psychosocial variable on depression., Conclusions: Our study advocates the need for screening for distress and depression in cancer surgery units and recommends to strengthen patients' adaptive coping, social support, and sense of effectiveness in facing the challenges related to the medical condition and treatment process., (© 2020 John Wiley & Sons Ltd.)

Background: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP)., Method: All patients who underwent LDP or RDP from 2011 to 2017 and with a minimum postoperative follow-up of 12 months were included in the study. To minimize bias, a propensity score-matched analysis (1:2) was performed. Two different questionnaires (EORTC QLQ-C30 and EQ-5D) were completed by the patients. The mean differential cost and mean differential Quality Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane., Results: The study population consisted of 152 patients. After having applied the propensity score matching, the final population included 103 patients divided into RDP group (n = 37, 36%) and LDP (n = 66, 64%). No differences were found between groups regarding the baseline, intraoperative, postoperative, and pathological variables (p > 0.05). The QoL analysis showed a significant improvement in the RDP group on the postoperative social function, nausea, vomiting, and financial status (p = 0.010, p = 0.050, and p = 0.030, respectively). As expected, the crude costs analysis confirmed that RDP was more expensive than LDP (12,053 Euros vs. 5519 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay of more than 4800 Euros/QALY was accepted., Conclusion: RDP was associated with QoL improvement in specific domains. Crude costs were higher relative to LDP. Cost-effectiveness threshold resulted to be 4800 euros/QALY. The increasing worldwide diffusion of the robotic technology, with easier access and possible cost reduction, could increase the sustainability of this procedure.

Purpose: Ablative techniques have emerged as new potential therapeutic options for patients with locally advanced pancreatic cancer (LAPC). We explored the safety and feasibility of using TRANBERG|Thermal Therapy System (Clinical Laserthermia Systems AB, Lund, Sweden) in feedback mode for immunostimulating Interstitial Laser Thermotherapy (imILT) protocol, the newest ablative technique introduced for the treatment of LAPC., Methods: The safety and feasibility results after the use of imILT protocol treatment in 15 patients of a prospective series of postsystemic therapy LAPC in two high-volume European institutions, the General and Pancreatic Unit of the Pancreas Institute, of the University of Verona, Italy, and the Department of Surgical Oncology of the Institut Paoli-Calmettes of Marseille, France, were assessed., Results: The mean age was 66 ± 5 years, with a mean tumor size of 34.6 (±8) mm. The median number of cycles of pre-imILT chemotherapy was 6 (6-12). The procedure was performed in 13 of 15 (86.6%) cases; indeed, in two cases, the procedure was not performed; in one, the procedure was considered technically demanding; in the other, liver metastases were found intraoperatively. In all treated cases, the procedure was completed. Three late pancreatic fistulas developed over four overall adverse events (26.6%) and were attributed to imILT. Mortality was nil. A learning curve is necessary to interpret and manage the laser parameters., Conclusions: Safety, feasibility, and device handling outcomes of using TRANBERG|Thermal Therapy System with temperature probes in feedback mode and imILT protocol on LAPC were not satisfactory. The metastatic setting may be appropriate to evaluate the hypothetic abscopal effect.#NCT02702986 and #NCT02973217., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes., Methods/design: In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a "total neoadjuvant" therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting., Trial Registration: NCT04090463 at clinicaltrials.gov.

Background: Nutritional derangements are common hallmarks of pancreatic cancer (PC). Their early detection and management are usually overlooked in routine practice. This study aimed to explore preoperative nutritional status and its prognostic value in patients undergoing surgery for PC., Methods: Data from 73 patients who underwent surgery for PC from November 2015 to January 2018 at the General and Pancreatic Surgery Unit, The Pancreas Institute, University Hospital of Verona Hospital, Verona, Italy, were retrospectively evaluated. The Nutritional Risk Screening (NRS)-2002 was used to evaluate the preoperative nutritional risk. Body composition was assessed using bioimpedance vectorial analysis (BIVA) on the day prior to surgery. The effect of clinical, pathological, and nutritional characteristics on overall survival (OS) was investigated using a Cox and logistic regression model. Kaplan-Meier curves were compared using the log-rank test., Results: Most patients (80.8%) were at preoperative risk of malnutrition (NRS-2002 ≥ 3) despite a mean BMI of 24.1 kg/m 2 (± 4.3). Twenty-four patients (32.9%) received neoadjuvant therapy prior to surgery. Preoperative NRS-2002 was significantly higher in this subset of patients (p = 0.026), with a significant difference by chemotherapy regimens (in favor of FOLFIRINOX, p = 0.035). In a multivariate analysis, the only independent prognostic factor for OS was the NRS-2002 score (HR 5.24, p = 0.013). Particularly, the likelihood of 2-year survival was higher in NRS < 3 (p = 0.009)., Conclusions: Our analysis confirms that preoperative malnutrition has a detrimental impact on OS in PC patients undergoing radical surgery for PC. Careful preoperative nutritional evaluation of PC patients should be mandatory, especially in those who are candidates for neoadjuvant therapy.

Pancreatic cancer is one of the main causes of cancer-related death worldwide, with a survival rate around 9%. In Italy 13,500 new cases of pancreatic cancer occurred in 2019. It is estimated that at least 5% have a hereditary background. Surveillance is advisable for healthy individuals with specific genetic syndromes with or without family history of pancreatic cancer or members of families with multiple cases of pancreatic cancer, irrespective of genetic syndromes. In 2010 the Italian Association for the Study of the Pancreas (AISP) defined criteria to include individuals in such surveillance programs with the first-round results published in 2019. In order to include other categories at high-risk and increase the diagnostic yield of surveillance, these criteria have recently been modified. The present position paper presents the updated criteria of the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) with their diagnostic yield calculation. Also, AISP priority projects concerning: (a) increasing awareness of citizens and primary care physicians through a dedicated App; (b) increasing access to germline testing to personalize surveillance; (c) measuring psychological impact of surveillance; (d) investigating the role of risk-modifiers and (e) evaluating the cost-effectiveness and ability to save lives of the program are briefly presented., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Literature shows that emotional status can influence participation in screening/surveillance programs, and that screening/surveillance programs may alter the psychological well-being of subjects examined. This study aims to assess if participating in a surveillance program for pancreatic cancer early detection is associated with abnormal levels of psychological distress in high-risk individuals (HRIs), compared to the general population., Methods: Fifty-four HRIs participating in a magnetic resonance cholangiopancreatography (MRCP)-based surveillance program completed several psychological assessment questionnaires, investigating global functioning, self-efficacy, perceived stress, coping abilities, and social support. The questionnaires were administered by a clinical psychologist after the MRCP but before the subjects were informed about the results of the scans. The HRIs were subjects with strong familiarity of pancreatic cancer and/or carriers of known genetic mutations related to cancer susceptibility. The psychological assessment was made at the time of the first examination., Results: The population was characterized by an overall good psychological status. Scoring of our sample was comparable to the general population norms. The HRIs showed decent global functioning, high self-efficacy levels, low perceived stress in the last month prior to examination, efficient emotion-focused coping strategies, and an adequate social support system. The younger subjects' subpopulation only revealed higher levels of stress., Conclusions: From a psychological point of view, an MRCP-based pancreatic cancer annual surveillance seemed not to influence the HRIs' psychological well-being, unless in young people. Further studies are needed to better establish if there are any changes in distress levels over time and how emotional status influences participation in surveillance programs., (© 2020 John Wiley & Sons, Ltd.)

Introduction: Most intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can be safely surveilled. Their psychological impact is not known. The aim of this study is to obtain a psychological profile of patients under surveillance and compare the results to patients undergoing surgery., Methods: Patients under surveillance for IPMNs evaluated between 2017 and 2019 at the pancreatic cysts clinic of The Pancreas Institute of Verona were compared to patients undergoing surgery for the same disease. Patients with high-risk stigmata were excluded in both groups. Patients were profiled with the Barratt Simplified Measure of Socio-Economic Status (BSMSS), the Brief Coping Orientation to Problems Experienced (Brief-COPE), the Perceived Stress Scale (PSS), the Symptom Checklist-90 and the Short Form Health Survey (SF-36). Age, sex, BSMSS and Brief-COPE were used to match patients with the propensity score as potential sources of bias., Results: Two hundred patients were profiled. After the matching, 74 patients under surveillance were compared to 74 patients who underwent surgery. Patients under surveillance reported significantly increased scores for symptoms such as somatization (0.71 vs. 0.54, p = 0.032), depression (0.45 vs 0.31, p = 0.047) and anxiety (0.45 vs. 0.27, p = 0.002). They also reported a reduced health perception in the domain of physical role functioning (54 vs. 68, p = 0.046)., Conclusion: Patients under surveillance for a presumed IPMN experience anxiety and stress and feel less healthy than do patients undergoing surgery. This reduction in quality of life should always be taken into account and warrants an integrated medical-psychological approach in selected cases., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Fibromyalgia syndrome (FMS) is a chronic clinical condition characterized by pain, fatigue, altered sleep, and cognitive disturbances. The purpose of this study was to compare two alternative treatments (nutraceutical and acupuncture) in FMS patients through a randomized clinical trial., Research Methods: A total of 60 FMS female patients were randomized for treatment with a nutritional combination containing coenzyme Q10, vitamin D, alpha-lipoic acid, magnesium, and tryptophan (Migratens ® Group) or acupuncture treatment (Acupuncture Group) performed according the principles of traditional Chinese medicine (TCM), both for 3 months. Changes in pain and in quality of life (QoL) measured with a Fibromyalgia Impact Questionnaire Score-Revised (FIQ-R) and the Fibromyalgia Severity Scale (FSS) were performed at 1, 3, and 6 months after the start of treatments., Results: A total of 55 patient completed the study (21 in the Migratens ® Group and 34 in the Acupuncture Group). Migratens ® treatment shows a statistically significant reduction of pain 1 month after the start of therapy (T1, p = 0.025), strengthened after 3 months with maintenance of treatment (p = 0.012). The efficacy in reducing pain was apparent in the Acupuncture Group at all post-treatment determinations and at follow-up (T1 and T2 p = <0.001). Regarding QoL, improvement in FIQ-R and FSS values was revealed in both groups., Conclusion: The nutraceutical approach with Migratens ® seems to be an effective option to for patients with FMS. Our experience confirmed also the validity of acupuncture in these patients. Considering the complexity of the management of FMS patients, our results suggest a cyclical and sequential, or even concurrent treatment with different approaches, to improve the efficacy and the compliance of patients to long-term treatment., Competing Interests: The authors have no relevant interest to declare.

Introduction: The aim of the present paper is to establish feasibility and required power of a one-session psychological intervention devoted to increasing patient's self-efficacy and awareness in dealing with anxiety symptoms before major pancreatic cancer surgery., Methods: Parallel assignment RCT. All consenting patients listed for pancreatic major surgery during day-hospital visits (T0) between June 2017-June 2018 were assigned randomly in blocks of ten to a psychological intervention vs usual care group to be held the day before surgery (T1). The psychological intervention provided the patient the opportunity to increase self-efficacy in dealing with anxiety by talking with a psychologist about personal concerns and learning mindfulness based techniques to cope with anxiety., Results: 400 patients were randomized into the experimental vs. usual care group. 49 and 65, respectively, completed baseline and post-intervention measures. The dropout rate between day-hospital (T0) and pre-surgery intervention (T1) was high (74.5%) due to several management and organization pitfalls. The main outcome, perceived self-efficacy in managing anxiety, showed a significant increase in the intervention group compared to the control group ( p < 0.001), and was related to a reduction in state anxiety ( p < 0.001). The intervention group perceived also lower emotional pain ( p = 0.03). A power analysis was performed to define the appropriate sample size in a definitive RCT., Conclusion: Beneath the complexity in retaining patients along their trajectory in pancreatic surgery department, when they had the opportunity to follow a brief psychological intervention, most of them adhered, showing a significant reduction in preoperative emotional distress and less emotional pain perception after surgery. Even if results need caution because of the high attrition rate, we can infer that our psychological intervention has the potential to be proposed in surgical setting, being short, easy to learn and applicable to a wide range of patients., Clinical Trial Registration: The trial was registered on ClinicalTrials.gov (identifier: NCT03408002). The full protocol is available from the last author., (Copyright © 2020 Marinelli, Danzi, Mazzi, Secchettin, Tuveri, Bonamini, Rimondini, Salvia, Bassi and Del Piccolo.)

Importance: Chemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood., Objective: To investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy., Design, Setting, and Participants: This prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018., Exposures: The chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center., Main Outcomes and Measures: Rates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival., Results: Of 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy., Conclusions and Relevance: This pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.

Objectives: The management of small and incidental branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) still is of concern. The aim is assessing the safety of a surveillance protocol through the evaluation of their progression to malignancy., Methods: All presumed BD-IPMNs observed from 2000 to 2016 were included. Only patients presenting without worrisome features (WFs) and high-risk stigmata (HRS) at diagnosis were included. Development of WF, HRS, pancreatic cancer (PC), and survival were analyzed. BD-IPMNs were defined as trivial in the continuing absence of WF/HRS after 5 years of surveillance. The age-specific standardized incidence ratio of PC in the general population was used for comparison., Results: A total of 1,036 BD-IPMNs without WF/HRS at diagnosis were included, 4.2% developed WF or HRS, and 1.1% developed PC after a median of 62 months. The median cyst growth rate was 0 mm/yr. A growth rate ≥2.5 mm/yr and the development of WF resulted independent predictors of PC. The standardized incidence ratio of PC for trivial BD-IPMN (n = 378) was 22.45 (95% confidence interval 8.19-48.86), but considering only patients aged >65 years (n = 198), it decreased to 3.84 (95% confidence interval 0.77-11.20)., Discussion: Surveillance of the vast majority of presumed BD-IPMNs is safe, as the risk of PC is comparable to postoperative mortality of pancreatic surgery. A growth rate ≥2.5 mm/yr is the main predictor of PC, reinforcing the role of repeated observations. A trivial BD-IPMN in patients aged >65 years might not increase the risk of developing PC compared with general population, identifying potential targets for follow-up discontinuation.

Background: Very little is known about adjuvant chemotherapy for invasive Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas. The aim was to assess whether adjuvant chemotherapy affects survival., Methods: Retrospective evaluation of invasive IPMNs. Patients treated with surgery alone or followed by adjuvant chemotherapy were compared in terms of survival., Results: A total of 102 invasive IPMNs were analyzed. Median follow-up was 72 (5-318) months and 18.6% received adjuvant chemotherapy. Overall, recurrence rate was 40.2%, while 5-year overall survival and disease specific survival (DSS) were 65.3% and 69.4%, respectively. N1 disease (HR5.58, CI95% 2.49-12.51, p < 0.01), tubular type (HR2.35, CI95% 1.71-4.82, p = 0.05) and G3 tumors (HR4.54, CI95% 2.12-15.49, <0.01) were predictors of reduced DSS. Overall, there was no difference in the 5-year DSS comparing patients treated with adjuvant chemotherapy to surgery alone (61.8 vs. 69.4%, p = 0.8). Adjuvant chemotherapy significantly improved DSS only in N1 (5-years-DSS 76 vs. 35.8%, p = 0.01) and tubular carcinomas (5-years-DSS 88.9 vs. 53%, p = 0.03)., Conclusions: Adjuvant therapy improves survival only in invasive IPMNs with nodal disease or tubular differentiation. Future trials are needed to improve the level of evidence about adjuvant chemotherapy., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance., Methods: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. An identical survey was carried out on a control population matched for age, sex, and comorbidities in which any pancreatic disease was excluded by MRI., Results: Two groups of 184 individuals were compared. Patients with PCNs have a similar prevalence of abdominal pain when compared to controls (35.2 vs. 28.8, p = 0.2). PCNs in the distal pancreas experienced a significantly increased prevalence of abdominal pain (42.3 vs. 28.8%, p = 0.04), whereas size and presumed connection with the ductal system did not affect the prevalence of abdominal pain. PCNs associated with abdominal pain did not differ in terms of clinical and radiological features from asymptomatic ones., Conclusion: Patients with PCNs under surveillance have a similar prevalence of abdominal pain when compared to a matched population of controls. Abdominal pain might not correlate with radiological signs of malignancy., (© 2018 S. Karger AG, Basel.)