Laparoscopic-assisted ERCP following RYGB: a 12-year assessment of outcomes and learning curve at a high-volume pancreatobiliary center.

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

International Validation of Reduced Major Morbidity After Minimally Invasive Distal Pancreatectomy Compared With Open Pancreatectomy.

OBJECTIVE: To quantify the nationwide impact of minimally invasive distal pancreatectomy (MIDP) on major morbidity as compared with open distal pancreatectomy (ODP). BACKGROUND: A recent randomized controlled trial (RCT) demonstrated significant reduction in time to functional recovery after MIDP compared with ODP, but was not powered to assess potential risk reductions in major morbidity. METHODS: International cohort study using the American College of Surgeons' National Quality Improvement Program (ACS-NSQIP) (88 centers; 2014-2016) to evaluate the association between surgical approach (MIDP vs ODP) and 30-day composite major morbidity (CMM; death or severe complications) with external model validation using Dutch Pancreatic Cancer Group data (17 centers; 2005-2016). Multivariable logistic regression assessed the impact of nationwide MIDP rates between 0% and 100% on postoperative CMM at conversion rates between 0% and 25%, using estimated marginal effects. A sensitivity analysis tested the impact at various scenarios and patient populations. RESULTS: Of 2921 ACS-NSQIP patients, 1562 (53%) underwent MIDP with 18% conversion, and 1359 (47%) underwent ODP. MIDP was independently associated with reduced CMM [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.42-0.60, P < 0.001], confirmed by external model validation (n = 637, P < 0.003). The association between rising MIDP implementation rates and falling postoperative morbidity was linear between 0% (all ODP) and 100% (all MIDP). The absolute risk reduction for CMM was 11% (95% CI 7.3%-15%) at observed conversion rates and improved to 14% (95% CI 11%-18%) as conversion approached 0%. Similar effects were seen across subgroups. CONCLUSION: This international study predicted a nationwide 11% risk reduction for CMM after MIDP versus ODP, which is likely to improve as conversion rates decrease. These findings confirm secondary outcomes of the recent LEOPARD RCT.

500 Minimally Invasive Robotic Pancreatoduodenectomies: One Decade of Optimizing Performance.

OBJECTIVES: This study aims to present the outcomes of our decade-long experience of robotic pancreatoduodenectomy and provide insights into successful program implementation. BACKGROUND: Despite significant improvement in mortality over the past 30 years, morbidity following open pancreatoduodenectomy remains high. We implemented a minimally invasive pancreatic surgery program based on the robotic platform as one potential method of improving outcomes for this operation. METHODS: A retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent robotic pancreatoduodenectomy (RPD) between 2008 and 2017 at the University of Pittsburgh. RESULTS: In total, 500 consecutive RPDs were included. Operative time, conversion to open, blood loss, and clinically relevant postoperative pancreatic fistula improved early in the experience and have remained low despite increasing complexity of case selection as reflected by increasing number of patients with pancreatic cancer, vascular resections, and higher Charlson Comorbidity scores (all P<0.05). Operating room time plateaued after 240 cases at a median time of 391 minutes (interquartile rang 340-477). Major complications (Clavien >2) occurred in less than 24%, clinically relevant postoperative pancreatic fistula in 7.8%, 30- and 90-day mortality were 1.4% and 3.1% respectively, and median length of stay was 8 days. Outcomes were not impacted by integration of trainees or expansion of selection criteria. CONCLUSIONS: Structured implementation of robotic pancreatoduodenectomy can be associated with excellent outcomes. In the largest series of RPD, we establish benchmarks for the surgical community to consider when adopting this approach.

Procedure-specific Training for Robot-assisted Distal Pancreatectomy.

OBJECTIVE: To train practicing surgeons in robot-assisted distal pancreatectomy (RADP) and assess the impact on 5 domains of healthcare quality. BACKGROUND: RADP may reduce the treatment burden compared with open distal pancreatectomy (ODP), but studies on institutional training and implementation programs are scarce. METHODS: A retrospective, single-center, cohort study evaluating surgical performance during a procedure-specific training program for RADP (January 2006 to September 2017). Baseline and unadjusted outcomes were compared "before training" (ODP only; June 2012). Exclusion criteria were neoadjuvant therapy, vascular- and unrelated organ resection. Run charts evaluated index length of stay (LOS) and 90-day comprehensive complication index. Cumulative sum charts of operating time (OT) assessed institutional learning. Adjusted outcomes after RADP versus ODP were compared using a secondary propensity-score-matched (1:1) analysis to determine clinical efficacy. RESULTS: After screening, 237 patients were included in the before-training (133 ODP) and after-training (24 ODP, 80 RADP) groups. After initiation of training, mean perioperative blood loss decreased (-255 mL, P<0.001), OT increased (+65 min, P < 0.001), and median LOS decreased (-1 day, P < 0.001). All other outcomes remained similar (P>0.05). Over time, there were nonrandom (P < 0.05) downward shifts in LOS, while comprehensive complication index was unaffected. We observed 3 learning curve phases in OT: accumulation (<31 cases), optimization (case 31-65), and a steady-state (>65 cases). Propensity-score-matching confirmed reductions in index and 90-day LOS and blood loss with similar morbidity between RADP and ODP. CONCLUSION: Supervised procedure-specific training enabled successful implementation of RADP by practicing surgeons with immediate improvements in length of stay, without adverse effects on safety.

Mentorship and formal robotic proficiency skills curriculum improve subsequent generations' learning curve for the robotic distal pancreatectomy.

BACKGROUND: Minimally invasive distal pancreatectomy is the accepted standard of care. The robotic distal (RDP) learning curve is 20-40 surgeries with operating time (ORT) as the most significant factor. This study evaluates how formal mentorship and a robotic skills curriculum impact the learning curve for subsequent generation surgeons. METHODS: Consecutive RDP from 2008 to 2017 were evaluated. First Generation was two surgeons who started program without training or mentorship. Second Generation was the two surgeons who joined the program with mentorship. Third Generation was fellows who benefited from both formal training and mentorship. Multivariable models (MVA) were performed for ORT, clinically relevant pancreatic fistula (CR-POPF), and major complications (Clavien≥3). RESULTS: A total of 296 RDP were performed of which 187 did not include other procedures: First Generation (n = 71), Second Generation (n = 50), and Third Generation (n = 66). ORT decreased by generation (p < 0.001) without any differences in CR-POPF or Clavien≥3. On MVA, earlier generation (p = 0.019), pre-operative albumin (p = 0.001) and pancreatic adenocarcinoma (p = 0.019) were predictive of ORT. Increased BMI (p = 0.049) and neoadjuvant therapy (p = 0.046) were predictive of CR-POPF. Fellow participation at the console increased over time. CONCLUSION: Formal mentorship and a skills curriculum decreased the learning curve and complications were largely dependent on patient factors.

Biliary palliation for unresectable pancreatic adenocarcinoma: surgical bypass or self-expanding metal stent?

BACKGROUND: Standard of care guidelines endorse self-expanding metal stents (SEMS) rather than open surgical biliary bypass (OSBB) for biliary palliation in the setting of unresectable pancreatic ductal adenocarcinoma (PDAC). This study used competing risk analysis to compare short- and long-term morbidity and overall survival among patients undergoing SEMS or OSBB after unresectable or metastatic disease is identified at the time of exploration. METHODS: Single institution retrospective cohort study (n = 127) evaluating outcomes after OSBB and SEMS for biliary palliation in patients found to have unresectable PDAC at exploration. Short-term, long-term, and lifetime risk of biliary occlusion and survival were compared after adjustment for stage and comprehensive complication index (CCI). RESULTS: Baseline demographics and tumor characteristics were equivalent between cohorts. Short-term complications were more frequent after OSBB, whereas late complications were greater after SEMS. The cumulative incidence of recurrent biliary obstruction was greater after SEMS, but lifetime complication burden and median survival were equivalent. CONCLUSION: OSBB was associated with longer hospital stays and more short-term complications, and SEMS was associated with a higher risk of recurrent biliary obstruction among surgical patients with unresectable PDAC. Patient preference should be defined pre-operatively in the case the unresectable disease is encountered during attempted resection.

Outcomes and Risk Score for Distal Pancreatectomy with Celiac Axis Resection (DP-CAR): An International Multicenter Analysis.

BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. METHODS: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. RESULTS: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15-25 months). CONCLUSIONS: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor.

Incidental pulmonary embolism in pancreatic ductal adenocarcinoma: Impact of tumor and AJCC stages at initial staging CT.

BACKGROUND/OBJECTIVES: To determine the prevalence of incidental pulmonary embolism (PE) detected during initial staging CT among patients with newly diagnosed pancreatic ductal adenocarcinoma (PDAC) and assess their association with underlying tumor burden. MATERIALS AND METHODS: This retrospective cohort study evaluated staging chest CT scans (2013-2017) to identify PE among patients with treatment naïve, biopsy-proven PDAC. Data included age, sex, T stage, AJCC stage, presence/absence of metastases and their location at diagnosis. The association of PE with tumor (T1-T4) and AJCC stage were assessed using Pearson Chi-square and Fischer's exact test. A threshold p-value of <0.05 indicated statistical significance. RESULTS: A total of 174 patients (90 female, mean age, 68 years; range: 34-93) were identified, of which 10 patients harbored incidental PE (prevalence, 5.7%). In the PE group, two patients presented with distant metastasis (liver, 20%), while eight patients had T4 tumors (80%). No statistical association was detected between PE and age, sex, and the presence/absence or location of distant metastasis (p = 0.065, p = 0.59, p = 0.687 and p = 0.933, respectively). Patients with T4 tumors and higher AJCC stages (stage III/IV) were significantly more likely to present with PE than those with lower T stage (p = 0.045) and AJCC stage (stage I/II; p = 0.017). CONCLUSION: The prevalence of incidental PE among PDAC patients undergoing initial CT staging is 5.7%. Patients with T4 and AJCC stages III/IV are at higher risk of PE. Caution should be exercised during radiographic interpretation of initial staging chest CTs, as incidental PE may be lurking and require treatment.

DWI of Pancreatic Ductal Adenocarcinoma: A Pilot Study to Estimate the Correlation With Metastatic Disease Potential and Overall Survival.

OBJECTIVE: The purpose of this study is to analyze the relationship between the apparent diffusion coefficient (ADC) of pancreatic ductal adenocarcinoma (PDAC) and the presence or development of metastasis and overall survival (OS). MATERIALS AND METHODS: Of 290 consecutive patients with histopathologically proven PDAC from January 2013 to December 2014, staging DWI was performed for 124 patients. Image quality was adequate in 112 studies. Sixty-five patients were treatment naïve, but 17 of the 65 were excluded because of the presence of other associated pancreatic pathologic abnormalities. Data for the remaining 48 patients (24 men and 24 women; median age, 65.5 years; interquartile range, 56-77 years) were obtained during a 4-year follow-up period (mean [± SD], 397 ± 415.1 days). The correlation between ADC and the presence or development of metastasis was assessed using descriptive statistics. OS was determined and mortality analysis was performed using Pearson correlation and Kaplan-Meier curves. RESULTS: Of 48 patients, 10 had metastases at staging MRI, and 12 later developed metastatic disease. Among the latter, the mean time from staging MRI to metastasis was 258 ± 274.1 days. Most (86%) metastases were hepatic (n = 19). During the follow-up period, the remaining 26 patients (54%) never developed metastases. Patients with metastatic disease (n = 22) had significantly lower mean ADCs than did those without metastases (1.27 × 10-3 vs 1.43 × 10-3 mm2/s; p = 0.047). The ADC of PDAC had a positive correlation with survival: patients with PDAC with lower ADCs (< 1.36 × 10-3 mm2/s) had significantly worse 4-year OS rates than did patients with higher ADC values (p = 0.036). CONCLUSION: Pretreatment ADC values of PDAC may be significantly lower in patients who have or will develop metastatic disease and may correlate with worse OS.

Does surgical approach affect outcomes of enucleation for benign and low-grade pancreatic tumors? An ACS-NSQIP evaluation.

BACKGROUND: Enucleation of low-grade pancreatic tumors achieves oncological outcomes equivalent to resection but conserves parenchyma. Given strict selection criteria, we hypothesized that minimally-invasive (MI) enucleation is associated with decreased composite major morbidity (CMM) compared to open. METHODS: Pancreas-targeted ACS NSQIP (2014 -2016) was queried for enucleation (CPT code: 48120) and analyzed by intended surgical approach regardless of conversion. The primary outcome was CMM, a validated 30-day composite metric of adverse events. RESULTS: Enucleation was performed using an open (n = 71; 62.3%) or MI (n = 43; 37.7%) approach with 7 conversions (16.2%). Both cohorts had interchangeable baseline characteristics. No selection factors governing MI were identified. MI-enucleation reduced median length of stay (4 vs. 5 days; p = 0.003), whereas rates of CMM after open (24; 34%) and MIenucleation (12; 28%) were equivalent (p = 0.541). Multivariable analysis demonstrated an association between CMM and prolonged operative time (OR 2.7, 95% CI 1.14 -6.74), female sex (OR 0.38, 95% CI 0.16 -0.94), and ASA score <3 (OR 0.39, 95% CI 0.16 -0.96) but not surgical approach. CONCLUSION: MI-enucleation was not associated with reduced 30-day CMM compared to open, whereas prolonged operating time and unmodifiable patient factors were correlated with adverse outcomes.

Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma.

BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3-generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC-associated gene mutations did not meet currently established genetic testing criteria. According to guideline-based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population.

Multicenter outcomes of robotic reconstruction during the early learning curve for minimally-invasive pancreaticoduodenectomy.

BACKGROUND: Perceived excess morbidity during the early learning curve of minimally-invasive pancreaticoduodenectomy (MIPD) has limited widespread adoption. It was hypothesized that robot-assisted reconstruction (RA) after MIPD allows anastomotic outcomes equivalent to open pancreaticoduodenectomy (PD). METHODS: Intent to treat analysis of centrally audited data accrued during early adoption of RA-MIPD at five centers. RESULTS: CUSUM analysis of operating times at each center identified 92 RA-MIPD during the early learning curve. Mean age was 65 ± 12 years with body mass index 25.8 ± 5.0. Surgical indications included malignant (60%) and premalignant (38%) lesions. Median operating time was 504 min (interquartile range 133) with 242 ml median estimated blood loss (IQR 398) and twelve (13%) conversions to open PD. Major complication rate (Clavien-Dindo III/IV) was 24% with 2 (2.2%) deaths and ten (10.9%) reoperations. Nine (9.9%) clinically significant pancreatic fistulae were observed (4 grade B; 5 grade C). Margin negative resection rate for malignancy was 90% (75% for PDA) with mean harvest of 16 ± 8 lymph nodes. CONCLUSIONS: These multicenter data during the early learning curve for RA-MIPD do not demonstrate excess anastomotic morbidity compared to open. Further studies are required to determine whether surgeon proficiency and evolving technique improve anastomotic outcomes compared to open.

Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma.

BACKGROUND: Resection margin status is an important prognostic factor in pancreatic cancer; however, the impact of positive resection margins in those who received neoadjuvant therapy remains unclear. The current study investigates the prognostic impact of resection margin status after neoadjuvant therapy and pancreaticoduodenectomy for patients with pancreatic adenocarcinoma. METHODS: Patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma between 2006 and 2013 were identified from the National Cancer Database. Multivariable logistic regression analysis was utilized to examine the predictive value of neoadjuvant therapy for resection margin status. Long-term outcomes were compared using a Cox proportional hazards model. RESULTS: 7917 patients were identified in total: 1077 (13.6%) and 6840 (86.4%) patients received neoadjuvant therapy and upfront surgery, respectively. Upfront surgery was independently predictive of a positive margin (25.7% vs. 17.7%; OR, 1.54) compared to neoadjuvant therapy. After receipt of neoadjuvant therapy, positive margins (median overall survival, 18.5 vs. 25.9 months; HR, 1.58) remained significantly associated with poor survival on multivariable analysis. DISCUSSION: While neoadjuvant therapy is associated with decreased R1/R2-resection rates after pancreaticoduodenectomy, the poor prognostic impact of positive margins is not abrogated by neoadjuvant therapy, stressing the need for complete tumor clearance and postoperative treatment even after neoadjuvant therapy.

Unique predictors and economic burden of superficial and deep/organ space surgical site infections following pancreatectomy.

BACKGROUND: Surgical site infections (SSIs) are common following pancreatectomy and associated with significant morbidity and economic burden. We sought to identify distinct predictors for superficial versus deep/organ space SSIs and their effects on surgical outcomes. METHODS: ACS-NSQIP targeted pancreatectomy 2014 and 2015 databases were queried. Univariate and multivariate models were developed for both types of SSI, length of stay (LOS), and readmission. Costs were estimated based on Centers for Medicare & Medicaid Services (CMS) recommendations. RESULTS: Of 8093 patients, there were 422 (5.2%) superficial and 1005 (12.4%) deep/organ space SSIs. On multivariate analyses, preoperative biliary stenting was predictive only for superficial SSI (OR: 2.21), while BMI of 25-29.9 (OR: 1.25) and BMI ≥30 kg/m2 (OR: 1.53), pancreatic duct size <3 mm (OR: 1.30), and intermediate (OR: 1.67) versus hard gland texture were predictors of deep/organ-space SSI. Superficial and deep/organ space SSIs were independent predictors of prolonged LOS (OR: 1.74 vs 1.80) and readmission (OR: 2.59 vs 6.57). Additional readmission costs per patient secondary to superficial SSI and deep/organ space SSI were $7661.37 and $18,409.42, respectively. CONCLUSION: Deep/organ space SSI contributes more profoundly to prolonged hospital stay, readmission, and additional costs, suggesting that strategies should focus on preferential prevention of deep/organ space infections.

Nationwide Evaluation of Patient Selection for Minimally Invasive Distal Pancreatectomy Using American College of Surgeons' National Quality Improvement Program.

OBJECTIVE: To assess current nationwide case selection factors for minimally invasive distal pancreatectomy (MIDP) and identify actual risk factors for adverse outcomes compared with open distal pancreatectomy (ODP). BACKGROUND: Patient selection criteria that predict outcomes after MIDP remain unknown. As a result, widespread adoption of this surgical technique may have been delayed and its potential benefits possibly under-exploited. METHODS: Retrospective cohort study of elective ODP and MIDP performed at 106 centers in 2014, using the pancreas-targeted American College of Surgeons' National Quality Improvement Program (ACS-NSQIP) database. Exclusion criteria were neoadjuvant treatment or pancreatitis as only diagnosis. Primary outcome includes a composite major morbidity metric, reflecting adverse events including mortality and reoperation. Multivariable modeling was used to detect current selection factors and to identify actual risk factors of composite major morbidity. RESULTS: A total of 928 patients underwent ODP (n = 472) or MIDP (n = 456) using a laparoscopic or robot-assisted approach, 24% for pancreatic ductal adenocarcinoma (PDAC). Current selection factors for MIDP were benign disease (odds ratio: OR: 1.56, CI: 1.10-2.21) and body mass index (BMI) 30-40 (OR: 1.41, CI: 1.04-1.91). Current selection factors for ODP were PDAC (OR: 0.45, CI: 0.31-0.64), benign tumor size >5 centimeters (OR: 0.40, CI: 0.23-0.67), and multivisceral procedures (OR: 0.39, CI: 0.26-0.59). Risk factors for composite major morbidity did not differ between ODP and MIDP. A trend was observed between MIDP and a lower risk of composite major morbidity compared with ODP (OR: 0.43, CI: 0.17-1.07). CONCLUSIONS: Current selection factors for ODP or MIDP (benign disease, tumor size, and BMI) do not mitigate the risk of major morbidity. We found no evidence that MIDP should be avoided based on tumor etiology or size, BMI, or patient physical status.

Training in Minimally Invasive Pancreatic Resections: a paradigm shift away from "See one, Do one, Teach one".

BACKGROUND: Increased incorporation of minimally invasive pancreatic resections (MIPR) has emerged into hepato-pancreato-biliary practice, however, no standardization exists for its safe adoption. Novel strategies are presented for dissemination of safe MIPR. METHODS: An international State-of-the-Art conference evaluating multiple aspects of MIPR was conducted by a panel of pancreas experts in Sao Paulo, Brazil on April 20, 2016. Training and education issues were discussed regarding the introduction of novel strategies for safe dissemination of MIPR. RESULTS: The low volume of pancreatic resections per institution poses a challenge for surgeons to overcome their MIPR learning curve without deliberate training. A mastery-based simulation and biotissue curriculum can improve technical proficiency and allow for training of surgeons before the operating room. Video-based platforms allow for performance reporting and feedback necessary for coaching and surgical quality improvement. Centers of excellence with training involving a standardized approach and proctorship are important concepts that can be utilized in various formats internationally. DISCUSSION: Surgical volume is not sufficient to ensure quality and patient safety in MIPR. Safe adoption of these complex procedures should consider innovative mastery-based training outside of the operating room, novel video based coaching techniques and prospective reporting of patient data and outcomes using standardized definitions.

Hemorrhage after pancreaticoduodenectomy: does timing matter?

BACKGROUND: Hemorrhage after pancreaticoduodenectomy is a potentially fatal complication. We retrospectively reviewed state-wide data to evaluate incidence, type of hemorrhage, treatment modalities, and outcomes. METHODS: Healthcare Cost and Utilization Project's Florida State Inpatient Database was queried 2007-2011 for patients undergoing pancreaticoduodenectomy. Characteristics and outcomes were compared by χ2. Multivariate logistic regression model was generated for risk of hemorrhage during index visit. RESULTS: Of 2548 patients, 217 (8.5%) developed post-operative hemorrhage during their index visit with 139 (64.0%) requiring angiographic, endoscopic, or operative intervention. Overall mortality during index visit was 5.7% (146) - significantly higher in those patients who had post-operative hemorrhage (24.9%) vs not (4.0%) (p < 0.0001). Mortality was significantly higher when post-operative hemorrhage occurred during the second (POD 8-14) vs first (POD 0-7) week at 15/28 vs 16/74, respectively (p = 0.007). On multivariate analysis, male sex (OR 1.56, p = 0.003), vascular resection (OR 1.88, p = 0.017), very low hospital volume (≤7 PD/year; OR 1.62, p = 0.016), and post-operative intra-abdominal/wound infection (OR 2.31, p < 0.0001) were independent predictors for risk of hemorrhage during index visit. CONCLUSIONS: Hemorrhage following pancreaticoduodenectomy remains common, resulting in significantly increased mortality. Hemorrhage during the second post-operative week carries approximately double the mortality of early bleeding, suggesting different etiologies requiring differing treatment approaches.

Early surgical bypass versus endoscopic stent placement in pancreatic cancer.

INTRODUCTION: The optimal treatment for biliary obstruction in pancreatic cancer remains controversial between surgical bypass and endoscopic stenting. METHODS: Retrospective analysis of unresected pancreatic cancer patients in the Healthcare Cost and Utilization Project Florida State Inpatient and Ambulatory Surgery databases (2007-2011). Propensity score matching by procedure. Primary outcome was reintervention, and secondary outcomes were readmission, overall length of stay (LOS), discharge home, death and cost. Multivariate analyses performed by logistic regression. RESULTS: In a matched cohort of 622, 20.3% (63) of endoscopic and 4.5% (14) of surgical patients underwent reintervention (p < 0.0001) and 56.0% (174) vs. 60.1% (187) were readmitted (p = 0.2909). Endoscopic patients had lower median LOS (10 vs. 19 days, p < 0.0001) and cost ($21,648 vs. $38,106, p < 0.0001) as well as increased discharge home (p = 0.0029). No difference in mortality on index admission. On multivariate analysis, initial procedure not predictive of readmission (p = 0.1406), but early surgical bypass associated with lower odds of reintervention (OR = 0.233, 95% CI 0.119, 0.434). DISCUSSION: Among propensity score-matched patients receiving bypass vs. stenting, readmission and mortality rates are similar. However, candidates for both techniques may experience fewer subsequent procedures if offered early biliary bypass with the caveats of decreased discharge home and increased cost/LOS.

Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma.

PURPOSE: Autophagy is a cell survival mechanism that plays a critical role in pancreatic carcinogenesis. Murine studies have previously demonstrated that treatment with the late-autophagy inhibitor chloroquine in combination with chemotherapy limited tumor growth. METHODS: In this phase 1/2 trial, we examined treatment with hydroxychloroquine (HCQ) and gemcitabine for patients with pancreatic adenocarcinoma. The primary endpoints were safety and tolerability, evaluated by Storer's dose escalation design. Secondary endpoints were CA 19-9 biomarker response, R0 resection rates, survival, and correlative studies of autophagy. RESULTS: Thirty-five patients were enrolled. There were no dose-limiting toxicities and no grade 4/5 events related to treatment. Nineteen patients (61 %) had a decrease in CA 19-9 after treatment. Twenty-nine patients (94 %) underwent surgical resection as scheduled, with a 77 % R0 resection rate. Median overall survival was 34.8 months (95 % confidence interval, 11.57 to not reached). Patients who had more than a 51 % increase in the autophagy marker LC3-II in circulating peripheral blood mononuclear cells had improvement in disease-free survival (15.03 vs. 6.9 months, p < 0.05) and overall survival (34.83 vs. 10.83 months, p < 0.05). No outcome differences were demonstrated in the 81 % of patients with abnormal p53 expression assessed by immunohistochemistry in the resected specimens. CONCLUSIONS: Preoperative autophagy inhibition with HCQ plus gemcitabine is safe and well tolerated. Surrogate biomarker responses (CA 19-9) and surgical oncologic outcomes were encouraging. p53 status was not associated with adverse outcomes.