Surveillance of Individuals at High Risk of Developing Pancreatic Cancer: A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery.

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.

Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

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.

Adjuvant Therapy After Upfront Resection of Resectable Pancreatic Cancer: Patterns of Omission and Use-A Prospective Real-Life Study.

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.

Dental plaque microbiota sequence counts for microbial profiling and resistance genes detection.

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.

Prevalence of FMS Diagnosis According to ACR 2016 Revised Criteria in a Pain Therapy Centre in Italy: Observational Study.

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.

Modified Frailty Index to Assess Risk in Elderly Patients Undergoing Distal Pancreatectomy: A Retrospective Single-Center Study.

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.

Pancreatoduodenectomy in obese patients: surgery for nonmalignant tumors might be deferred.

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.

A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma.

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.

Prevalence of depression in a cohort of 400 patients with pancreatic neoplasm attending day hospital for major surgery: Role on depression of psychosocial functioning and clinical factors.

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.

Laser Treatment of Pancreatic Cancer with Immunostimulating Interstitial Laser Thermotherapy Protocol: Safety and Feasibility Results From Two Phase 2a Studies.

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.

Cost-effectiveness and quality of life analysis of laparoscopic and robotic distal pancreatectomy: a propensity score-matched study.

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.

Prognostic Impact of Preoperative Nutritional Risk in Patients Who Undergo Surgery for Pancreatic Adenocarcinoma.

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/m2(± 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.

Psychological distress in patients under surveillance for intraductal papillary mucinous neoplasms of the pancreas: The "Sword of Damocles" effect calls for an integrated medical and psychological approach a prospective analysis.

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.

The emotional impact of surveillance programs for pancreatic cancer on high-risk individuals: A prospective analysis.

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.

"Trivial" Cysts Redefine the Risk of Cancer in Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Potential Target for Follow-Up Discontinuation?

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.

The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis.

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.

Adjuvant chemotherapy is associated with improved postoperative survival in specific subtypes of invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas: it is time for randomized controlled data.

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.

Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results.

BACKGROUND/OBJECTIVES: Screening/surveillance programs for pancreatic cancer (PC) in familial high-risk individuals (FPC-HRI) have been widely reported, but their merits remain unclear. The data reported so far are heterogeneous-especially in terms of screening yield. We performed a systematic review and meta-analysis of currently available data coming from screening/surveillance programs to evaluate the proportion of screening goal achievement (SGA), overall surgery and unnecessary surgery. METHODS: We searched MEDLINE, Embase, PubMed and the Cochrane Library database from January 2000 to December 2016to identify studies reporting results of screening/surveillance programs including cohorts of FPC-HRI. The main outcome measures were weighted proportion of SGA, overall surgery, and unnecessary surgery among the FPC-HRI cohort, using a random effects model. SGA was defined as any diagnosis of resectable PC, PanIN3, or high-grade dysplasia intraductal papillary mucinous neoplasm (HGD-IPMN). Unnecessary surgery was defined as any other final pathology. RESULTS: In a meta-analysis of 16 studies reporting on 1551 FPC-HRI cases, 30 subjects (1.82%), received a diagnosis of PC, PanIN3 or HGD-IPMNs. The pooled proportion of SGA was 1.4%(95% CI 0.8-2, p < 0.001, I2 = 0%). The pooled proportion of overall surgery was 6%(95% CI 4.1-7.9, p < 0.001, I2 = 60.91%). The pooled proportion of unnecessary surgery was 68.1%(95% CI 59.5-76.7, p < 0.001, I2 = 4.05%); 105 subjects (6.3%) received surgery, and the overall number of diagnoses from non-malignant specimens was 156 (1.5 lesion/subject). CONCLUSIONS: The weighted proportion of SGA of screening/surveillance programs published thus far is excellent. However, the probability of receiving surgery during the screening/surveillance program is non-negligible, and unnecessary surgery is a potential negative outcome.

Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients.

PURPOSE: SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. METHODS: Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). CONCLUSIONS: Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation.

Impact of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: An analysis of 1500 consecutive cases.

BACKGROUND AND AIM: Implications of preoperative biliary drain on morbidity and mortality after pancreatoduodenectomy are still controversial. The present study aims to assess the impact of preoperative biliary drain on postoperative outcome and to define optimal serum bilirubin cut-off to recommend biliary drainage in patients undergoing pancreatoduodenectomy. METHODS: All consecutive pancreatoduodenectomies carried out at Verona Hospital from 2005 to 2016 were retrospectively analyzed. The study population was divided into three groups: preoperative biliary drained (Stented Group), preoperative jaundice without drainage (Jaundiced Group) and the control group of non-jaundiced, non-stented patients (Control Group). RESULTS: A total of 1500 patients were included. Seven hundred and fourteen patients (47.6%) received biliary drain (stented group), 258 (17.2%) patients did not (jaundiced group) and 528 (35.2%) patients represented the (control group). Major complications and mortality rates did not differ between groups. Conversely, the risk of developing surgical site infections doubled in the stented group (18.1%) (OR = 2.1, 95% CI = 1.5-2.8). In jaundiced patients, a preoperative bilirubin value greater than 7.5 mg/dL (128 µmol/L) accurately predicted the likelihood of postoperative complications. CONCLUSION: Preoperative biliary drain does not increase major complications and mortality rates after pancreatoduodenectomy, but it is associated with higher surgical site infection rates. In jaundiced patients, a bilirubin value greater than 7.5 mg/dL (128 µmol/L) should indicate biliary drainage.