Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition".

PURPOSE: Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." METHODS: Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. RESULTS: Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. CONCLUSIONS: One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.

Communication, understanding and engagement of patients with pancreatic cancer at time of diagnosis.

BACKGROUND: Objectives: To investigate communication clarity and understanding at the time of pancreatic adenocarcinoma (PDAC) diagnosis and whether they can influence patient engagement and compliance. METHODS: Consecutive PDAC patients were enrolled at the time of diagnosis after obtaining informed consent in a single-center study. The patients completed a validated scale (PHE-s®), and the understanding rate was assessed using standardized tools. Patient compliance was evaluated, and the correlation between the PHE-s®, understanding, and compliance was calculated. RESULTS: Thirty patients were enrolled (15 female) with a mean age 64.4, 13 were metastatic. The mean visit time was 31 min, being longer if visiting doctor was an oncologist (p = 0.002). The engagement level was high in 70% of the patients, and all but one were compliant. The analysis of doctor-patient interactions showed a median of 121 conversational turns for doctors, 75 for patients, and 20 for caregivers (p < 0.0001), and the median percentage of speaking time was 77% for doctors, 13% for patients, and 2% for caregivers (p < 0.0001). Female caregivers spent more time speaking than did male caregivers (median 11.6% vs. 1.3%; p = 0.06). There were 290 instances of problematic understanding, most of which occurred during the taking of patients' personal medical history for doctors, while for patients and caregivers, these occurred mainly during the discussion of diagnosis/treatment (p < 0.0001). In a multivariable analysis, only origin from central or southern Italy was associated with high engagement (p = 0.0087). CONCLUSION: In this first attempt to measure clarity of communication and engagement in patients with PDAC, typical features of conversation and problematic understanding emerged, which deserves further investigation.

Recovery of health-related quality of life after laparoscopic versus open distal pancreatectomy.

BACKGROUND: Limited data comparing recovery of health-related quality of life (HRQoL) after laparoscopic (LDP) versus open distal pancreatectomy (ODP) are available. The aim of this study was to assess the impact of laparoscopy on postoperative HRQOL after DP using the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: Data from consecutive patients who underwent DP (2020-2022) enrolled in a prospective clinical trial were reviewed. Patients completed PROMIS-29 plus 2 profile preoperatively, at postoperative day (POD) 15, 30, 90, and 180. Linear regression analysis adjusting for confounders including preoperative PROMIS scores, age, gender, ASA score, diagnosis, and multivisceral resection was used to estimate mean between-group differences (MD) in postoperative PROMIS domains T scores. RESULTS: Overall, 202 patients (118 laparoscopic, 86 open) underwent DP (median age 66 years, pancreatic cancer 41%, multivisceral resection 10%, median LOS 6 days). At POD15, LDP was associated with higher physical function (MD 5.6) and participation in social roles and activities scores (MD 3.8), reduced fatigue (MD - 2.7) and sleep disturbance (MD - 3.8) compared to ODP. At POD30, LDP patients had higher physical function (MD 5.2) and participation in social roles and activities scores (MD 6.0), reduced fatigue (MD - 3.5), and anxiety (MD - 4.0) compared to ODP. No between-group differences were found in HRQoL domains at POD90 and 180. Six months after surgery, the proportions of patients who had not recovered to preoperative physical function, participation in social roles and activities, fatigue, pain interference, sleep disturbance, cognitive function, depression, and anxiety were 31%, 31%, 28%, 20%, 15%, 14%, 8%, and 7%, respectively. CONCLUSIONS: According to PROMIS, LDP resulted in improved physical and social functioning and reduced anxiety and fatigue up to 30 days after surgery compared to ODP. At 6 months after surgery, recovery of physical domains is still incomplete in up to 30% of patients.

Validation of the PROMIS-29 Questionnaire as a Measure of Recovery After Pancreatic Surgery.

OBJECTIVE: To contribute evidence for the reliability, construct validity, and responsiveness of the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) profile questionnaire as a measure of recovery after pancreatic surgery. BACKGROUND: PROMIS questionnaires have been recommended to evaluate postdischarge recovery after surgery. Evidence supporting their measurement properties in pancreatic surgery is missing. METHODS: An observational validation study designed according to the COSMIN checklist was conducted including data from a prospective clinical trial. Patients undergoing pancreatectomy completed PROMIS-29 preoperatively and on postoperative days (PODs) 15, 30, 90, and 180. Reliability was assessed by internal consistency using Cronbach α. Construct validity was assessed by known-groups comparison. Responsiveness was evaluated hypothesizing that scores would be higher (1) preoperatively versus POD15, (2) on POD30 versus POD15, (3) on POD90 versus POD30, and (4) on POD180 versus POD90. RESULTS: Overall, 510 patients were included in the study. Reliability was good to excellent (α values ranged from 0.82 to 0.97). Data supported 4 of 5 hypotheses tested for construct validity for 5 domains (physical function, anxiety, depression, fatigue, and ability to participate in social roles) at most time points. Responsiveness hypotheses 1, 2, and 3 were supported by the data for physical function, fatigue, sleep disturbance, pain interference, and ability to participate in social roles domains. CONCLUSIONS: PROMIS had excellent reliability, discriminated between most groups expected to have different recovery trajectories and was responsive to the expected trajectory of recovery up to 90 days after surgery. Our findings support the use of PROMIS-29 profile as a patient-reported outcome measure of postdischarge recovery after pancreatectomy.

Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial.

OBJECTIVE: To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF). BACKGROUND: Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences. METHODS: Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery. RESULTS: Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT ( P =0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P =0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P =0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P <0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P <0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time. CONCLUSIONS: TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted.

Prognostic Significance and Predictors of Nodal Recurrence After Surgery for Non-Functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: The prognosis of nodal recurrence after surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs) and its predictors have been poorly investigated. This study aimed to compare clinicopathologic features and survival between patients with nodal relapse and those with distant relapse and to identify predictors of nodal relapse after surgery for NF-PanNETs. METHODS: All patients (n = 321) submitted to surgery for NF-PanNETs were included. Nodal recurrence was defined as the presence of one or more enlarged LNs at high-quality radiologic examinations and always confirmed by 68Ga-DOTA-PET or biopsy. RESULTS: Altogether, 21 patients (6 %) experienced nodal (± distant) relapse, and 35 patients (11 %) had distant recurrence alone. Isolated nodal recurrence occurred for 23 % of patients with recurrence. Overall, 11 patients died of disease, one of whom (pT3N1G3) had an isolated nodal relapse. The rate of LN metastases (81 % vs 54 %; p = 0.044) and median number of positive LNs (PLN) (3 vs 0; p = 0.019) both were significantly higher for the patients with nodal (± distant) relapse than for those with distant relapse alone. Microvascular invasion (p = 0.046), T stage (p = 0.004), N stage (N1 [p = 0.049]; N2 [p = 0.001]), M stage (p < 0.001), and necrosis (p = 0.011) independently predicted nodal relapse. After distal pancreatectomy (n = 182), 13 patients experienced nodal recurrence, 9 of whom had left paraortic LNs involvement. DISCUSSION: Lymph nodes are not rare sites of recurrence after surgery for NF-PanNETs. Lymph node involvement is a powerful determinant of nodal relapse. Nodal relapse frequently involves LNs that are not removed during standard lymphadenectomy.

Development of a predictive model for unplanned intensive care unit admission after pancreatic resection within an enhanced recovery pathway.

BACKGROUND: It is unclear whether routine postoperative admission to the intensive care unit (ICU) can improve outcomes for patients undergoing elective pancreatic surgery. Aim of the study was to determine preoperative and intraoperative predictors of unplanned ICU access in patients undergoing pancreatectomy treated within an established enhanced recovery pathway (ERP) and compare outcomes between direct and late ICU admission. METHODS: A retrospective observational study was conducted on adult patients who underwent pancreatic resection (2015-2019) within an ERP. Patients with preoperatively planned ICU admission were excluded from the study. Multiple multivariate logistic regression models were constructed to verify the association of preoperative and intraoperative variables with study outcomes. RESULTS: The study included 1486 consecutive patients (cancer diagnosis 60%, pancreaticoduodenectomy 60%; laparoscopic approach 20%; vascular resection 9%). Sixty-six (4.4%) patients had an unplanned ICU admission. Direct admission occurred in 22 (33%) patients and late ICU admission in 44 (67%) patients. Mortality was significantly lower in direct admission group (n = 3, 14%) compared to late admission (n = 25, 57%; p > 0.001). A comprehensive model including preoperative and intraoperative variables identified ASA score ≥ 3 (OR 5.59, p value < 0.001), history of hypertension (OR 2.29, p = 0.029), chronic obstructive pulmonary disease (OR 3.05, p = 0.026), proximal pancreatic resection (OR 2.79, p value 0.046), multivisceral resection (OR 8.86, p value < 0.001), high intraoperative blood loss (OR 1.01 per ml, p < 0.001), and increased serum lactate at the end of surgery (OR 1.25, p = 0.017) as independent factors associated with ICU admission. Area under the ROC curve was 0.891. CONCLUSION: Patient comorbidities, surgical complexity, and lactic acidosis at the end of surgery were associated with unplanned postoperative ICU admission. Late ICU admission had very high mortality rates compared to direct admission. Our findings suggest that patients with a combination of preoperative and intraoperative risk factors could benefit from upfront postoperative ICU admission to potentially improve postoperative outcomes.

Management of clinically relevant postoperative pancreatic fistula-related fluid collections after distal pancreatectomy.

BACKGROUND: Distal pancreatectomy is burdened by a high rate of clinically relevant postoperative pancreatic fistula (CR-POPF). The presence of a fistula-related abdominal collection often requires additional treatment such as antibiotics, percutaneous drainage, and endoscopic drainage thus prolonging patient recovery. Aim of this study was to describe the management of abdominal collections related to CR-POPF and identify variables associated with the need for invasive procedures. METHODS: A retrospective review of clinical data for patients who underwent distal pancreatectomy between 2015 and 2020 was conducted. All postoperative CT-scan imaging performed for clinical signs related to POPF was reviewed. The main outcome of the study was the need for procedural management (percutaneous or endoscopic) of CR-POPF-related fluid collections at 90 days after surgery. A multivariate regression analysis was adopted to analyze factors influencing procedural management of the collection. RESULTS: Five hundred sixteen patients were included in the study. Laparoscopic resection was performed in 290 patients (56%). At 90 days after surgery, CR-POPF occurred in 207 (40.1%) patients. A symptomatic collection related to fistula was observed in 130 patients (25.2%). Factors associated with fluid collections were increased body mass index (BMI) (25.5 versus 24, p = 0.001) and intraoperative blood loss (median of 250 versus 200 ml, p < 0.001). Procedural management was required in 70 patients (13.6%); 52 patients required interventional radiology and 18 endoscopic drainage. At multivariate analysis, risk factors for invasive procedures were the following CT-scan parameters: fluid collection diameter greater than 5 cm (OR 6.366, 95%CI 2.29-17.66, p = 0.001), presence of blood in the fluid collection (OR 10.618, 95%CI 1.94-58.09, p = 0.006), and enhancement of its walls (OR 4.073, 95%CI 1.22-13.57, p = 0.022). CONCLUSION: CR-POPF-related fluid collections affect about a quarter of patients undergoing distal pancreatectomy. CT-scan provides important information which can guide the management of the collection in a "step-up" fashion.

The Impact of CT-Assessed Liver Steatosis on Postoperative Complications After Pancreaticoduodenectomy for Cancer.

INTRODUCTION: Liver steatosis (LS) has been increasingly described in preoperative imaging of patients undergoing pancreaticoduodenectomy (PD). The aim of this study was to assess the impact of preoperative LS on complications after PD and identify possible contributors to LS development in this specific cohort. METHODS: Pancreatic head adenocarcinoma (PDAC) patients scheduled for PD, with preoperative CT-imaging available were included in the study. LS was defined as mean liver density lower than 45 Hounsfield units. Patients showing preoperative LS were matched for patient age, gender, BMI, ASA score, neoadjuvant treatment, and vascular and multivisceral resections, based on propensity scores in a 1:2 ratio to patients with no LS. The primary outcome was postoperative complication severity at 90 days as measured by the comprehensive complication index (CCI) RESULTS: Overall, 247 patients were included in the study. Forty-three (17%) patients presented with LS at preoperative CT-scan. After matching, the LS group included 37 patients, whereas the non-LS group had 74 patients. LS patients had a higher mean (SD) CCI, 29.7 (24.5) versus 19.5 (22.5), p = 0.035, and a longer length of hospital stay, median [IQR] 12 [8-26] versus 8 [7-13] days, p = 0.006 compared with non-LS patients. On multivariate analysis, variables independently associated with CCI were: LS (16% increase, p = 0.048), male sex (19% increase, p = 0.030), ASA score ≥ 3 (26% increase, p = 0.002), fistula risk score (FRS) (28% increase for each point of FRS, p = 0.001) and vascular resection (20% increase, p = 0.019). CONCLUSION: Preliminary evidence suggests that preoperative LS assessed by CT-scan influences complication severity in patients undergoing PD for PDAC.

Impact of enhanced recovery protocols after pancreatoduodenectomy: meta-analysis.

BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.

Enhanced recovery protocols consist of interdisciplinary interventions aimed at standardizing care and reducing the impact of surgical stress. They often include a short period of preoperative fasting during the night before surgery, early removal of lines and surgical drains, early food intake and mobilization out of bed on the day of surgery. This study gives a summary of reports assessing such care protocols in patients undergoing pancreatic head surgery, and assesses the impact of these protocols on functional recovery in an analysis of individual-patient data. The study revealed the true benefits of enhanced recovery protocols, including shorter time to food intake, earlier bowel activity, fewer complications after surgery, and a shorter hospital stay compared with conventional care.

Early biochemical predictors of clinically relevant pancreatic fistula after distal pancreatectomy: a role for serum amylase and C-reactive protein.

BACKGROUND: Recent evidence suggests that pancreatic inflammation plays a pivotal role in the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy but few data are available for distal pancreatectomy (DP). The aim of this study was to evaluate the impact of early biochemical markers on the occurrence of CR-POPF after DP. METHODS: Clinical and laboratory data for 432 consecutive DP patients were reviewed. Serum amylase was evaluated on postoperative day (POD) 1, and drain fluid amylase (DFA) and C-reactive protein (CRP) were evaluated on POD 2 and 3. Receiver operator characteristic (ROC) curves were performed for all biochemical markers and an area under the curve (AUC) was computed. Multivariable regression analyses to identify the factors associated with CR-POPF and severe postoperative morbidity (Clavien-Dindo grade ≥ 3) were performed. RESULTS: At 90 days after surgery, CR-POPF occurred in 155 (36%) patients, severe complications in 66 (15%) patients. ROC curve analyses showed that DFA on POD2 had the largest AUC (0.753, p < 0.001), followed by serum amylase on POD 1 (0.651, p < 0.001), serum CRP on POD3 (0.644, p < 0.001), and CRP change between POD 2 and POD 3 (0.644, p < 0.001). Multivariable analysis identified male gender (OR 2.29, 95% CI 1.36-3.86; p = 0.002), DFA ≥ 1500 U/L on POD2 (OR 4.63, 95% CI 2.72-7.89; p < 0.001), serum amylase ≥ 100 U/L on POD 1 (OR 1.72, 95% CI 1.01-2.93; p = 0.046), and CRP increase by at least 25 mg/L on POD 3 compared to the previous day (OR 1.89, 95% CI 1.11-3.21; p = 0.019) as independent predictors of CR-POPF, yielding a valid regression model (AUC 0.765, 95% CI 0.714-0.816, p < 0.001). CONCLUSIONS: Postoperative serum amylase and CRP trajectory represent useful early biochemical markers for CR-POPF in addition to DFA. Our findings suggest that these laboratory tests should be incorporated into clinical practice to aid postoperative patient and drain management.

Construct validity and responsiveness of the Duke Activity Status Index (DASI) as a measure of recovery after colorectal surgery.

BACKGROUND: Returning to preoperative levels of physical function is highly valued by patients recovering from surgery. The Duke Activity Status Index (DASI, a 12-item questionnaire) may be a simple yet robust tool to assess postoperative recovery of functional capacity. This study assessed construct validity and responsiveness of the DASI as a measure of recovery after colorectal surgery. METHODS: Data from a trial on early mobilization after colorectal surgery were analyzed. Patients completed the DASI questionnaire preoperatively and at postoperative weeks (POW) 2 and 4. Construct validity was assessed by testing the primary a priori hypotheses that postoperative DASI scores (1) are higher in patients without vs with postoperative complications and (2) correlate with six-minute walk test distance (6MWD). Exploratory analyses assessed the association between DASI scores and (1) preoperative physical status [higher (ASA ≤ 2) vs lower (ASA > 2)], (2) stoma creation (no stoma vs stoma), (3) age [younger (≤ 75 years) vs older (> 75 years)], (4) time to readiness for discharge [shorter (≤ 4 days) vs longer (> 4 days)], and (5) surgical approach (laparoscopic vs open). Responsiveness was assessed by testing a priori hypotheses that DASI scores are higher (1) preoperatively vs at POW2 and (2) at POW4 vs POW2. Mean differences in DASI scores were obtained using linear regression. The association between DASI and 6MWD was assessed via Pearson correlation. RESULTS: We analyzed data from 100 patients undergoing colorectal surgery (mean age 65; 57% male; 81% laparoscopic). Mean DASI scores were 47.9 ± 12.1 preoperatively, 22.4 ± 12.7 at POW2, and 33.2 ± 15.7 at POW4. The data supported our two primary construct validity hypotheses, as well as 3/5 exploratory hypotheses. Both responsiveness hypotheses were supported. CONCLUSIONS: Our findings support that the DASI questionnaire can be a useful tool to assess postoperative recovery of functional capacity in research and clinical practice.

The impact of preoperative anemia on pancreatic resection outcomes.

BACKGROUND: Preoperative anemia is a risk factor for blood transfusions and delayed postoperative recovery, but few data are available for pancreatic surgery. Aim of the study was to analyze the impact of preoperative anemia on outcomes after pancreatic resection. METHODS: Retrospective review of 1107 patients resected at San Raffaele Hospital (2015-2018). Preoperative anemia was defined as hemoglobin lower than 130 g/L for men and 120 g/L for women. Primary outcome was 90-day comprehensive complication index (CCI). Analysis was stratified according to type of surgery; proximal resections (pancreaticoduodenectomy and total pancreatectomy) versus distal pancreatectomy. RESULTS: In 776 proximal resection patients, preoperative anemia was associated with increased CCI (24 ± 25 vs. 19 ± 23, p = 0.018) and perioperative allogenic blood transfusions (n = 124, 46% vs. n = 129, 26%; p < 0.001). Multivariate analysis showed that anemia was associated with a 7% (95%CI 0.02-0.57 p = 0.047) increase in CCI, and was an independent factor associated with perioperative blood transfusion (OR 2.762, 95%CI 1.72-4.49, p < 0.001). In 331 distal pancreatectomies, anemia was not associated to increased morbidity but only to an increased risk of perioperative blood transfusion. CONCLUSION: Preoperative anemia is an independent risk factor for increased complication severity and blood transfusion in patients undergoing major pancreatic resection.

Pain management, fluid therapy and thromboprophylaxis after pancreatoduodenectomy: a worldwide survey among surgeons.

BACKGROUND: The aim of this survey was to assess practices regarding pain management, fluid therapy and thromboprophylaxis in patients undergoing pancreatoduodenectomy on a global basis. METHODS: This survey study among surgeons from eight (inter)national scientific societies was performed according to the CHERRIES guideline. RESULTS: Overall, 236 surgeons completed the survey. ERAS protocols are used by 61% of surgeons and respectively 82%, 93%, 57% believed there is a relationship between pain management, fluid therapy, and thromboprophylaxis and clinical outcomes. Epidural analgesia (50%) was most popular followed by intravenous morphine (24%). A restrictive fluid therapy was used by 58% of surgeons. Chemical thromboprophylaxis was used by 88% of surgeons. Variations were observed between continents, most interesting being the choice for analgesic technique (transversus abdominis plane block was popular in North America), restrictive fluid therapy (little use in Asia and Oceania) and duration of chemical thromboprophylaxis (large variation). CONCLUSION: The results of this international survey showed that only 61% of surgeons practice ERAS protocols. Although the majority of surgeons presume a relationship between pain management, fluid therapy and thromboprophylaxis and clinical outcomes, variations in practices were observed. Additional studies are needed to further optimize, standardize and implement ERAS protocols after pancreatic surgery.

Impact of Facilitation of Early Mobilization on Postoperative Pulmonary Outcomes After Colorectal Surgery: A Randomized Controlled Trial.

OBJECTIVE: To estimate the extent to which staff-directed facilitation of early mobilization impacts recovery of pulmonary function and 30-day postoperative pulmonary complications (PPCs) after colorectal surgery. SUMMARY BACKGROUND DATA: Early mobilization after surgery is believed to improve pulmonary function and prevent PPCs; however, adherence is low. The value of allocating resources (eg, staff time) to increase early mobilization is unknown. METHODS: This study involved the analysis of a priori secondary outcomes of a pragmatic, observer-blind, randomized trial. Consecutive patients undergoing colorectal surgery were randomized 1:1 to usual care (preoperative education) or facilitated mobilization (staff dedicated to assist transfers and walking during hospital stay). Forced vital capacity, forced expiratory volume in 1 second (FEV1), and peak cough flow were measured preoperatively and at 1, 2, 3 days and 4 weeks after surgery. PPCs were defined according to the European Perioperative Clinical Outcome Taskforce. RESULTS: Ninety-nine patients (57% male, 80% laparoscopic, median age 63, and predicted FEV1 97%) were included in the intention-to-treat analysis (usual care 49, facilitated mobilization 50). There was no between-group difference in recovery of forced vital capacity [adjusted difference in slopes 0.002 L/d (95% CI -0.01 to 0.01)], FEV1 [-0.002 L/d (-0.01 to 0.01)] or peak cough flow [-0.002 L/min/d (-0.02 to 0.02)]. Thirty-day PPCs were also not different between groups [adjusted odds ratio 0.67 (0.23-1.99)]. CONCLUSIONS: In this randomized controlled trial, staff-directed facilitation of early mobilization did not improve postoperative pulmonary function or reduce PPCs within an enhanced recovery pathway for colorectal surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02131844.

R Status is a Relevant Prognostic Factor for Recurrence and Survival After Pancreatic Head Resection for Ductal Adenocarcinoma.

BACKGROUND: The prognostic role of resection margins in pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to investigate the impact that global and individual resection margin status after pancreatic head resection for PDAC has on disease-free survival (DFS) and disease-specific survival (DSS). METHODS: Surgical specimens of pancreaticoduodenectomy/total pancreatectomy performed for PDAC were examined with a standardized protocol. Surgical margin status (biliary, pancreatic neck, duodenal, anterior and posterior pancreatic, superior mesenteric vein groove and superior mesenteric artery margins) was classified as the presence of malignant cells (1) directly at the inked surface (R1 direct), (2) within less than 1 mm (R1 ≤ 1 mm), or (3) with a distance greater than 1 mm (R0). Patients with a positive neck margin at the final histology were excluded from the study. RESULTS: Of the 362 patients included in the study, 179 patients (49.4 %) had an R0 resection, 123 patients (34 %) had an R1 ≤ 1 mm resection, and 60 patients (16.6 %) had an R1 direct resection. The independent predictors of DFS were R1 direct resection (hazard ratio [HR], 1.49), R1 ≤ 1 mm resection (HR, 1.38), involvement of one margin (HR, 1.36), and involvement of two margins or more (HR, 1.55). When surgical margins were analyzed separately, only R1 ≤ 1 mm superior mesenteric vein margin (HR, 1.58) and R1 direct posterior margin (HR, 1.69) were independently associated with DFS. CONCLUSIONS: Positive R status is an independent predictor of DFS (R1 direct and R1 ≤ 1 mm definitions) and of DSS (R1 direct). The presence of multiple positive margins is a risk factor for cancer recurrence and poor survival. Different surgical margins could have different prognostic roles.

The impact of minimally invasive surgery on hospital readmissions, emergency department visits and functional recovery after distal pancreatectomy.

BACKGROUND: A recent RCT showed similar postoperative outcomes and a reduced time to functional recovery in patients undergoing minimally invasive distal pancreatectomy (DP) compared to open approach. However, it reported very-high post-discharge readmission rates, calling for further investigation. The aim of our study was to evaluate the extent to which minimally invasive surgery impacts on postoperative readmissions following DP. METHODS: Clinical data for patients undergoing DP between 2011 and 2018 were reviewed. Primary outcome was hospital readmission at 90 days after surgery. Secondary outcomes included post-discharge emergency department (ED) visits and time to functional recovery. Regression analyses were performed to evaluate the impact of the laparoscopic approach and other perioperative factors. RESULTS: Overall, 376 consecutive patients underwent DP during the study period. Laparoscopy was successfully performed in 219 (58%) patients. Overall, 62 patients (16.5%) returned to the ED after discharge, 41 (18.7%) of laparoscopically operated patients, and 21 (13.4%) of those undergoing open surgery (p = 0.162). Forty-six (12.2%) of them required readmission, 31 (14.2%) after laparoscopic, and 15 (9.6%) after open procedures (p = 0.179). At multivariate regression, a low preoperative physical status (OR 2.3, 95% CI 1.2-4.7; p = 0.017), occurrence of pancreatic fistula (OR 6.8, 95% CI 2.9-15.9; p < 0.001), and post-pancreatectomy hemorrhage (OR 3.9, 95% CI 1.2-13.1; p = 0.025) were significantly associated with 90-day readmission, while laparoscopy had no impact. Median time to reach functional recovery was 5 (IQR 4-6) days. At multivariate analysis, laparoscopy reduced time to functional recovery by 13% (95% CI - 19 to - 6%; p < 0.001), time to adequate oral intake by 19% (95% CI - 27 to - 10%; p < 0.001), and time to adequate pain control by 12% (95% CI - 18 to - 5%; p < 0.001). CONCLUSION: Hospital readmissions and ED visits following DP were not influenced by the surgical approach. A low preoperative physical status, occurrence of postoperative pancreatic fistula and hemorrhage were significantly associated with post-discharge readmission within 90 days. Laparoscopy reduced time to functional recovery.

Prognostic value of the Duke Activity Status Index (DASI) in patients undergoing colorectal surgery.

BACKGROUND: Complications are common after colorectal surgery and remain a target for quality improvement. Lower preoperative physical functioning is associated with poor postoperative outcomes, but assessment often relies on subjective judgment or resource-intensive tests. Recent literature suggests that self-reported functional capacity, measured using the Duke Activity Status Index (DASI), is a strong predictor of postoperative outcomes. This study aimed to estimate the extent to which DASI predicts 30-day complications after colorectal surgery. METHODS: In this observational study, 100 patients undergoing colorectal resection [median age 63, 57% men, 81% laparoscopic, 37% rectal surgery] responded to DASI two weeks preoperatively. Complications were classified according to Clavien-Dindo and quantified using the comprehensive complication index (CCI). Our primary analysis targeted the relationship between preoperative DASI and odds of complications. Secondary analyses focused on 30-day severe complications, CCI, readmissions, and length of stay (LOS). We also explored the predictive ability of DASI with scores dichotomized based on a previously validated threshold (≤ 34). RESULTS: Mean preoperative DASI was 48 ± 12. Forty-six patients (46%) experienced 30-day complications (8% severe, CCI 9.6 ± 15). Lower DASI scores were associated with higher odds of complications (OR 1.08, 95%CI 1.03-1.14; p = 0.001). Preoperative DASI was also an independent predictor of severe complications, CCI, and readmissions. The predictive ability was supported when scores were dichotomized at ≤ 34. CONCLUSION: DASI is a significant predictor of postoperative complications after colorectal surgery. This questionnaire can be easily implemented in clinical practice to identify patients with low preoperative functional capacity and target interventions to those at higher risk.

A four-step method to centralize pancreatic surgery, accounting for volume, performance and access to care.

BACKGROUND: Adequate criteria for pancreatic surgery centralization are debated. This retrospective study aimed to define a reproducible method for complex care centralization, accounting for hospital performance and access to care. METHODS: The method consisted in: 1. Analysis of overall outcome and mortality-related factors. 2. Assessment of volume and adjusted mortality of each hospital. 3. Definition of different centralization models. 4. Final adjustments to guarantee access to care, evaluating travel times and waiting lists. This method was tested on Lombardy, the most populous Italian region (about 10 million inhabitants, 24 000 km2). RESULTS: According to Ministry of Health data, 79 hospitals performed 3037 resections in 2014-2016. Mean overall mortality was 5.0%, increasing from 2.3%, of seven high-volume facilities (>30 resections/year) to 10.7% of 56 low-volume facilities (<10 resections/year). Five centralization models were tested (range: 7-23 hospitals): the best performing model included seven high-volume facilities, providing both low mortality (<2%), and easy access to care, namely reasonable travel time (≤60 min for >90% of the population), and limited impact on waiting list (1.1 extra-resection/hospital/week). CONCLUSION: The four-step method appears as a flexible tool to centralize pancreatic surgery, allowing regulatory institutions to estimate the effect of different models.

Impact of care pathway adherence on recovery following distal pancreatectomy within an enhanced recovery program.

BACKGROUND: In bowel surgery, adherence to enhanced recovery program (ERP) has been associated with improved recovery. The objective of this study was to evaluate the impact of adherence to ERP elements on outcomes, and identify factors associated with successful recovery following distal pancreatectomy (DP). METHODS: Data for 376 patients who underwent DP managed within an ERP including 16 perioperative elements were reviewed. Primary endpoint was successful recovery, a composite outcome defined as length of hospital stay≤7 days, no severe complications nor readmissions. RESULTS: Patients had a mean (SD) overall adherence of 76 (14)%. Overall, 166 (44%) patients had a successful recovery. There was a positive association between overall adherence and successful recovery (OR 1.19, 95%CI 1.08-1.31 for every additional element, p = 0.001), while an inverse relationship was found with comprehensive complication index (8% reduction, 95%CI -15 to -2%, p = 0.011). Adherence to postoperative phase interventions had the greatest impact on recovery (OR 1.29, 95%CI 1.13-1.47 for every additional postoperative element; p < 0.001). At multivariable regression, early termination of IV fluids was the only ERP element associated with successful recovery (OR 2.80, 95%CI 1.73-4.54; p < 0.001). CONCLUSION: Increased adherence to ERP elements was associated with successful early recovery and reduction of postoperative complication severity.