Preoperative Anxiety in Patients with Pancreatic Cancer: What Contributes to Anxiety Levels in Patients Waiting for Surgical Intervention.

Pancreatic cancer is one of the most lethal malignancies. Currently, the only treatment is surgical resection, which contributes to significant preoperative anxiety, reducing quality of life and worsening surgical outcomes. To date, no standard preventive or therapeutic methods have been established for preoperative anxiety in pancreatic patients. This observational study aims to identify which patients' socio-demographic, clinical and psychological characteristics contribute more to preoperative anxiety and to identify which are their preoperative concerns. Preoperative anxiety was assessed the day before surgery in 104 selected cancer patients undergoing similar pancreatic major surgery, by administering the STAI-S (State-Trait Anxiety Inventory Form) and the APAIS (Amsterdam Preoperative Anxiety and Information Scale). Our data suggest that patients with high STAI-S showed higher levels of APAIS and that major concerns were related to surgical aspects. Among psychological characteristics, depressive symptoms and trait anxiety appeared as risk factors for the development of preoperative anxiety. Findings support the utility of planning a specific psychological screening to identify patients who need more help, with the aim of offering support and preventing the development of state anxiety and surgery worries in the preoperative phase. This highlights also the importance of good communication by the surgeon on specific aspects related to the operation.

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 Surface Plasmon Resonance Plastic Optical Fiber Biosensor for the Detection of Pancreatic Amylase in Surgically-Placed Drain Effluent.

Postoperative pancreatic fistula (POPF), the major driver of morbidity and mortality following pancreatectomy, is caused by an abnormal communication between the pancreatic ductal epithelium and another epithelial surface containing pancreas-derived, enzyme-rich fluid. There is a strong correlation between the amylase content in surgically-placed drains early in the postoperative course and the development of POPF. A simple and cheap method to determine the amylase content from the drain effluent has been eagerly advocated. Here, we developed an amylase optical biosensor, based on a surface plasmon resonance (SPR) plastic optical fiber (POF), metallized with a 60 nm layer of gold and interrogated with white light. The sensor was made specific by coupling it with an anti-amylase antibody. Each surface derivatization step was optimized and studied by XPS, contact angle, and fluorescence. The POF-biosensor was tested for its response to amylase in diluted drain effluents. The volume of sample required was 50 µL and the measurement time was 8 min. The POF-biosensor showed selectivity for amylase, a calibration curve log-linear in the range of 0.8-25.8 U/L and a limit of detection (LOD) of ~0.5 U/L. In preliminary tests, the POF-biosensor allowed for the measurement of the amylase content of diluted surgically-placed drain effluents with an accuracy of >92% with respect to the gold standard. The POF-biosensor allows for reliable measurement and could be implemented to allow for a rapid bedside assessment of amylase value in drains following pancreatectomy.

Negative pressure wound therapy for prevention of surgical site infection in patients at high risk after clean-contaminated major pancreatic resections: A single-center, phase 3, randomized clinical trial.

BACKGROUND: Surgical site infections are an important burden of pancreatic surgery, prolonging hospitalization and delaying adjuvant treatment. The aim of this study was to compare negative pressure wound therapy with standard sterile dressing in terms of the prevention of non-organ-space surgical site infection (superficial and deep surgical site infection) in the high-risk setting. METHODS: The trial was conducted at the University of Verona Hospital Trust, Verona, Italy, from July 25, 2018, through October 10, 2019, among adults undergoing surgery for periampullary neoplasms. Only patients at high-risk for surgical site infection based on body mass index, diabetes, steroids, neoadjuvant therapy, American Society of Anesthesiologists score, Charlson comorbidity index, duration of surgery, and blood loss were included and randomized. RESULTS: A total of 351 patients were screened, 100 met the inclusion criteria and were 1:1 allocated in the 2 arms. The difference in terms of non-organ-space surgical site infection comparing negative pressure wound therapy with standard sterile dressing was not significant (10.9 vs 12.2%, risk ratio [RR] 1.144, confidence interval [CI] 95% 0.324-4.040, P = 1.000). Hematomas (4.3 vs 2%, RR 1.565, CI 95% 0.312-7.848, P = .609) and organ-space infections (46.7 vs 43.8%, RR 1.059, CI 95% 0.711-1.576, P = .836) were similar. Negative pressure wound therapy prevented the development of seromas (0 vs 12.2%, RR 0.483, CI 95% 0.390-0.599, P = .027). The aesthetic result assessed on postoperative day 7 was better in the negative pressure wound therapy group (visual analogue scale, 8 vs 7, P = .029; Stony Brook Scar Evaluation Scale, 3.2 vs 2.5, P = .009), but it was no more evident on postoperative day 30 after a total number of 23 dropouts. CONCLUSION: Compared with standard sterile dressing, negative pressure wound therapy is not associated with an improved rate of non-organ-space surgical site infection after surgery for periampullary neoplasms in patients at high risk for surgical site infection. Additional studies will help identify the population that could benefit most from this intervention.

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.

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.

PREPARE: PreoPerative Anxiety REduction. One-Year Feasibility RCT on a Brief Psychological Intervention for Pancreatic Cancer Patients Prior to Major Surgery.

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.

Epidemiology, clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey.

INTRODUCTION: A prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines. METHODS: An online data sheet was built. RESULTS: Fifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up. CONCLUSIONS: This prospective study offers a reliable real-life picture of the diagnostic work-up CPN.

"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.

Outcomes of Primary Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma.

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.

Central pancreatectomy for benign or low-grade malignant pancreatic lesions - A single-center retrospective analysis of 116 cases.

BACKGROUND: Central pancreatectomy (CP) is a parenchyma-sparing surgery for benign or low-grade malignant pancreatic tumors. This study aimed to evaluate the safety of the procedure and to analyze the long-term pancreatic function. The age-specific incidence ratio (IR) was calculated based on the incidence of diabetes mellitus in the general Italian population of Italy. MATERIALS AND METHODS: Patients submitted to CP from January 1990 to December 2017 at the Department of General and Pancreatic Surgery of the Pancreas Institute of Verona, Italy, were evaluated. RESULTS: The final population was composed of 116 patients. There was a clear prevalence of females (74.1%), the mean age was 48 ±â€¯15 years and the main indication for surgery was a pancreatic neuroendocrine tumor (45.7%). A pancreojejunal anastomosis was performed more frequently than a pancreogastric anastomosis (78.4% vs 11.6%). The mean length of stay was 20 ±â€¯33 days. The overall abdominal complications rate was 62%. The frequency of clinically relevant postoperative pancreatic fistula (grades B and C) was 26.7%. The mortality rate was 0%. The rate of R1-resection was 0.8%, as was the recurrence rate. After a mean follow-up of 12.8 years ±6.5, 6 patients developed new-onset diabetes (NODM, 7.5%), and the IR was 1.36 (95%CI 0.49-2.96). CONCLUSIONS: CP is associated with high rates of abdominal complications, however, considering the amount of the normal pancreas that was spared, it might be indicated for selected benign or low-malignancy pancreatic tumors. CP patients have the same incidence of diabetes than the general population.

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.

Preoperative surveillance rectal swab is associated with an increased risk of infectious complications in pancreaticoduodenectomy and directs antimicrobial prophylaxis: an antibiotic stewardship strategy?

BACKGROUND: Despite improvements in the perioperative care, the morbidity rate after pancreaticoduodenectomy (PD) is still higher than 50%. The aim of this study was twofold: first, to assess the correlation between preoperative rectal swab (RS) and intraoperative bile cultures; to examine the impact of RS isolates on postoperative course after PD. METHODS: An observational study was conducted analyzing all consecutive PD performed from January 2015 to July 2016. Based on the positivity/negativity of preoperative RS for multi-drug resistant bacteria, two groups of patients were identified (RS+ vs. RS-) and then compared. RESULTS: Three hundred thirty-eight patients were considered for the analysis. RS culture showed a perfect correlation (species and phenotypic antibiotic susceptibility pattern) with bile culture in 157 patients (86.7%). Fifty patients (14.8%) had a RS+. Preoperative biliary drain (PBD) was the single independent preoperative risk factor associated to RS+ (p = 0.021, OR = 2.6, 95% CI = 1.5-11.7). Infective complications (IC) and mortality were independently correlated to RS+ (p = 0.013, OR = 2.9, 95% CI = 1.3-6.7; p = 0.009 OR = 3.4, 95% CI = 1.8-14.9, respectively). CONCLUSIONS: Preoperative surveillance RS-culture's positivity correlates to biliary colonization that occurs after PBD. IC and mortality after PD are associated with RS+. Preoperative RS can direct antibiotic prophylaxis to reduce morbidity and mortality after PD.

Vanishing Pancreatic Cysts during Follow-Up: Another Step Towards De-Emphasizing Cyst Size as a Major Clinical Predictor of Malignancy.

INTRODUCTION: In the management of pancreatic cystic neoplasms (PCN), size plays a crucial role as the expression of disease progression. While many evidences regarding the natural history of growing pancreatic cysts exist, almost no data are available regarding cysts with a reduction in size. METHODS: Radiological and clinical data from patients of the dedicated pancreatic cysts outpatient clinic of the Department of General and Pancreatic Surgery, University of Verona Hospital were retrospectively reviewed. Patients diagnosed with PCNs reducing in size during follow-up were reviewed. RESULTS: From a total of 3,146 patients, we identified 12 (0.38%) vanishing/reducing cysts without a history of pancreatitis. Most of them were presumed IPMN (66.6%). The median follow-up was 69 months and the median cyst's size 30 mm (range 10-49). Most of the patients (75%) experienced a reduction in cyst size (median reduction of 8 mm, range 6-22) after a median time of 12 months (range 6-63), 3 patients experienced a complete disappearance of the cyst. CONCLUSION: Cyst size reduction during follow-up is a rare phenomenon of unknown explanation. It adds to the debate regarding the role of size as a clinical predictor whenever a definite diagnosis of a PCN cannot be reached.

Pancreaticoduodenectomy in patients ≥ 75 years of age: Are there any differences with other age ranges in oncological and surgical outcomes? Results from a tertiary referral center.

AIM: To compare surgical and oncological outcomes after pancreaticoduodenectomy (PD) in patients ≥ 75 years of age with two younger cohorts of patients. METHODS: The prospectively maintained Institutional database of pancreatic resection was queried for patients aged ≥ 75 years (late elderly, LE) submitted to PD for any disease from January 2010 to June 2015. We compared clinical, demographic and pathological features and survival outcomes of LE patients with 2 exact matched cohorts of younger patients [≥ 40 to 64 years of age (adults, A) and ≥ 65 to 74 years of age (young elderly, YE)] submitted to PD, according to selected variables. RESULTS: The final LE population, as well as the control groups, were made of 96 subjects. Up to 71% of patients was operated on for a periampullary malignancy and pancreatic cancer (PDAC) accounted for 79% of them. Intraoperative data (estimated blood loss and duration of surgery) did not differ among the groups. The overall complication rate was 65.6%, 61.5% and 58.3% for LE, YE and A patients, respectively, P = NS). Reoperation and cardiovascular complications were significantly more frequent in LE than in YE and A groups (P = 0.003 and P = 0.019, respectively). When considering either all malignancies and PDAC only, the three groups did not differ in survival. Considering all benign diseases, the estimated mean survival was 58 and 78 mo for ≥ and < 75 years of age (YE + A groups), respectively (P = 0.012). CONCLUSION: Age is not a contraindication for PD. A careful selection of LE patients allows to obtain good surgical and oncological results.

Is there a role for near-infrared technology in laparoscopic resection of pancreatic neuroendocrine tumors? Results of the COLPAN "colour-and-resect the pancreas" study.

BACKGROUND: The intraoperative identification of pancreatic neuroendocrine tumors (PanNETs) is of utmost importance to drive their laparoscopic resection. Near-infrared (NIR) surgery has emerged as a new technique for localizing tumors or neoplastic tissue. This study aimed to explore the results of the application of NIR in the laparoscopic resection of PanNETs. METHODS: Per protocol we enrolled ten subjects undergoing laparoscopic pancreatic surgery for PanNET from March 2016 to October 2016. During surgery, the patients were injected with indocyanine green dye (ICG, 25 mg given in 5 boli of 5 mg each). The switch-activation of NIR was performed to identify PanNETs. An ex-post analysis of the images was realized using ImageJ Software® to calculate the fluorescence signal. RESULTS: NIR imaging identified all ten PanNETs. Nine (90%) laparoscopic distal pancreatectomy with splenectomy and one (10%) laparoscopic enucleation were performed. The mean maximum tumor dimension was 2.4 cm (range 1-4 cm). Eight non-functioning PanNETs (80%) and two insulinomas (20%) were found at the final pathology. Nine out of ten (90%) PanNETs were detected after the second ICG bolus. The mean latency time was 80 s and the mean visibility time was 220 s. The peak of tumor visualization was reached 20 min after the last bolus. This finding was confirmed by the ex-post analysis of the fluorescence signal (mean signal-to-background ratio of 7.7, p = 0.001). NIR identified two additional lesions, which turned out to be normal lymph nodes at final pathology. A fluorescent signal was identified at the bed of the enucleation, and thus, a further exeresis was performed and final pathology revealed that is was residual neoplastic tissue. CONCLUSIONS: This explorative study shows that NIR with ICG can have a role in laparoscopic pancreatic resection of PanNETs. Further studies are needed to assess the proper setting and role of this new and promising technology.

Biliary fistula after pancreaticoduodenectomy: data from 1618 consecutive pancreaticoduodenectomies.

BACKGROUND: Biliary fistula (BF) occurs in 3-8% of patients following pancreaticoduodenectomy (PD). It usually pursues a benign course, but rarely may represent a life-threatening event. STUDY DESIGN: Data from 1618 PDs were collected prospectively. BF was defined as the presence of bile stained fluid from drains by post-operative day 3 and confirmed by sinogram in the majority of cases. Three classifications were validated. RESULTS: BF occurred in 58 (3.6%) patients. In 22 cases was associated with pancreatic fistula (POPF). POPF, PPH, operative time and a smaller common bile duct (CBD) were significantly associated with BF. Only CBD diameter (HR 0.55, CI 95% 0.44-0.7, p < 0.01) was an independent predictor of BF. Patients with smaller CBDs developing concomitant BF and POPF carried the highest mortality rate (34.8%, n = 8/22). All the existing classifications resulted in discrete categories of BFs when considering hospital stay and total cost as dependent variables. CONCLUSIONS: Biliary fistula is rare, but it can be life threatening when associated with POPF. As the sole independent risk factor is the CBD diameter, surgical technique is crucial. Regardless of the existing classification systems, further studies must assess the additive burden of BF when a concomitant POPF is present.

Over 700 Whipples for Pancreaticobiliary Malignancies: Postoperative Morbidity Is an Additional Negative Prognostic Factor for Distal Bile Duct Cancer.

BACKGROUND: Distal cholangiocarcinomas and pancreatic cancers both arise from pancreaticobiliary epithelium. Despite their common origin, there is a possible discrepancy in outcome. We analysed the surgical, pathological and survival outcome of resected distal cholangiocarcinoma compared with pancreatic cancer. METHODS: All cases of resected distal cholangiocarcinoma and pancreatic cancer from 1998 to 2014 were extracted from our database. Outcomes were compared. RESULTS: There were 54 (7.6%) cases of cholangiocarcinoma and 656 (92.4%) pancreatic cancer. Cholangiocarcinoma showed lower T and N stage, lymphatic and perineural invasion (p < 0.05), worse surgical outcome (p < 0.05) and less access to adjuvant therapy if compared with pancreatic cancer (72.7 vs. 83.1%, p = 0.05). Both showed a similar disease-specific survival (35 vs. 29 months, p = 0.3). Independent predictors of prognosis for pancreatic cancer were resection margin, grading, perineural invasion, T and N status, whereas for cholangiocarcinoma were grading and occurrence of POPF. CONCLUSION: Considering a large cohort of resected periampullary cancers, cholangiocarcinoma is extremely rare. An earlier diagnosis is associated with better pathological predictors of outcome but increased postoperative morbidity compared to pancreatic cancer, particularly POPF. Consequent decrease in the access to adjuvant therapy for complicated cholangiocarcinoma might explain why survival is as poor as for pancreatic cancer.

CD45 and multiple sclerosis: the exon 4 C77G polymorphism (additional studies and meta-analysis) and new markers.

We re-evaluated the association with multiple sclerosis (MS) of the C77G splicing regulatory variation in the CD45 gene and screened for new mutations the three alternatively spliced exons (#4, 5 and 6). No association with C77G was detected in two groups of patients (total=448) and controls (total=559) from Northern and Southern Italy. When excluding the first published study indicating a positive association, a meta-analysis of the five further studies conducted to date (including the present one) led to a non-significant combined odds ratio (OR) of 1.11. None of the four newly identified nucleotide substitutions, namely C77T (Pro59Pro) in exon 4, G69C (Asp121His) in exon 5, T127A (Ile187Asn) and A138G (Thr191Ala) in exon 6, was significantly associated to MS.

Mutations in the SPINK1 gene in idiopathic pancreatitis Italian patients.

Idiopathic chronic and acute recurrent pancreatitis (IP) have been associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutations in the serine protease inhibitor Kazal 1 (SPINK1) have been described in some idiopathic chronic patients and it has been suggested that mutations in this gene could be responsible for a loss of trypsin inhibitor function. In this study, the 5'UTR region, and the four exons and exon-intron boundaries of the SPINK1 gene in 32 IP patients have been analyzed. Three IP patients (9.3%) and one control/100 carried the N34S mutation of the SPINK1 gene (Fisher's exact test, P=0.044). No other mutation that could be associated with an altered function of the SPINK1 protein was observed. The N34S mutation was present in two patients who carried the CFTR-IVS8 5T variant and in one who carried the L997F variant in the CFTR gene. The association of SPINK1 with CFTR gene mutations in IP patients is statistically significant (3/32 IP cases and 0/100 control individuals carrying mutations in both genes; Fisher's exact test P=0.01).