Adjuvant chemotherapy omission after pancreatic cancer resection: a French nationwide study.

BACKGROUND: Adjuvant chemotherapy (AC) improves the prognosis after pancreatic ductal adenocarcinoma (PDAC) resection. However, previous studies have shown that a large proportion of patients do not receive or complete AC. This national study examined the risk factors for the omission or interruption of AC. METHODS: Data of all patients who underwent pancreatic surgery for PDAC in France between January 2012 and December 2017 were extracted from the French National Administrative Database. We considered "omission of adjuvant chemotherapy" (OAC) all patients who failed to receive any course of gemcitabine within 12 postoperative weeks and "interruption of AC" (IAC) was defined as less than 18 courses of AC. RESULTS: A total of 11 599 patients were included in this study. Pancreaticoduodenectomy was the most common procedure (76.3%), and 31% of the patients experienced major postoperative complications. OACs and IACs affected 42% and 68% of the patients, respectively. Ultimately, only 18.6% of the cohort completed AC. Patients who underwent surgery in a high-volume centers were less affected by postoperative complications, with no impact on the likelihood of receiving AC. Multivariate analysis showed that age ≥ 80 years, Charlson comorbidity index (CCI) ≥ 4, and major complications were associated with OAC (OR = 2.19; CI95%[1.79-2.68]; OR = 1.75; CI95%[1.41-2.18] and OR = 2.37; CI95%[2.15-2.62] respectively). Moreover, age ≥ 80 years and CCI 2-3 or ≥ 4 were also independent risk factors for IAC (OR = 1.54, CI95%[1.1-2.15]; OR = 1.43, CI95%[1.21-1.68]; OR = 1.47, CI95%[1.02-2.12], respectively). CONCLUSION: Sequence surgery followed by chemotherapy is associated with a high dropout rate, especially in octogenarian and comorbid patients.

Practice Patterns of Pancreatic Surgery Within the Military.

INTRODUCTION: Pancreatic surgery is technically challenging, with mortality rates at high-volume centers ranging from 0% to 5%. An inverse relationship between surgeon volume and perioperative mortality has been reported suggesting that patients benefit from experienced surgeons at high-volume centers. There is little published on the volume of pancreatic surgeries performed in military treatment facilities (MTF) and there is no centralization policy regarding pancreatic surgery. This study evaluates pancreatic procedures at MTFs. We hypothesize that a small group of MTFs perform most pancreatic procedures, including more complex pancreatic surgeries. METHODS: This is a retrospective review of de-identified data from MHS Mart (M2) from 2014 to 2020. The database contains patient data from all Defense Health Agency treatment facilities. Variables collected include number and types of pancreatic procedures performed and patient demographics. The primary endpoint was the number and type of surgery for each MTF. RESULTS: Twenty-six MTFs performed pancreatic surgeries from 2014 to 2020. There was a significant decrease in the number of cases from 2014 to 2020. Nine hospitals performed one surgery over eight years. The most common surgery was a distal pancreatectomy, followed by a pancreaticoduodenectomy. There was a decrease in the number of pancreaticoduodenectomies and distal pancreatectomies performed over this period. CONCLUSIONS: Pancreatic surgery is being performed at few MTFs with a downward trajectory over time. Further studies would be needed to assess the impact on patient care regarding postoperative complications, barriers to timely patient care, and impact on readiness of military surgeons.

Comparing oncologic and surgical outcomes of robotic and laparoscopic pancreatoduodenectomy in patients with pancreatic cancer: a propensity-matched analysis.

INTRODUCTION: Minimally invasive Pancreatoduodenectomy (MIPD), or the Whipple procedure, is increasingly utilized. No study has compared laparoscopic (LPD) and robotic (RPD) approaches, and the impact of the learning curve on oncologic, technical, and post-operative outcomes remains relatively understudied. METHODS: The National Cancer Database was queried for patients undergoing LPD or RPD from 2010 to 2020 with a diagnosis of pancreatic cancer. Outcomes were compared between approaches using propensity-score matching (PSM); the impact of annual center-level volume of MIPD was also assessed by dividing volume into quartiles. RESULTS: A total of 3,342 patients were included. Most (n = 2,716, 81.3%) underwent LPD versus RPD (n = 626, 18.7%). There was a high rate (20.2%, n = 719) of positive margins. Mean length-of-stay (LOS) was 10.4 ± 8.9 days. Thirty-day mortality was 2.8% (n = 92) and ninety-day mortality was 5.7% (n = 189). PSM matched 625 pairs of patients receiving LPD or RPD. After PSM, there was no differences between groups based on age, sex, race, CCI, T-stage, neoadjuvant chemo/radiotherapy, or type of PD. After PSM, there was a higher rate of conversion to open (HR = 0.68, 95%CI = 0.50-0.92)., but there was no difference in LOS (HR = 1.00, 95%CI = 0.92-1.11), 30-day readmission (HR = 1.08, 95% CI = 0.68-1.71), 30-day (HR = 0.78, 95% CI = 0.39-1.56) or 90-day mortality (HR = 0.70, 95% CI = 0.42-1.16), ability to receive adjuvant therapy (HR = 1.15, 95% CI = 0.92-1.44), nodal harvest (HR = 1.01, 95%CI = 0.94-1.09) or positive margins (HR = 1.19, 95% CI = 0.89-1.59). Centers in lower quartiles of annual volume of MIPD demonstrated reduced nodal harvest (p = 0.005) and a higher rate of conversion to open (p = 0.038). Higher-volume centers had a shorter LOS (p = 0.012), higher rate of initiation of adjuvant therapy (p = 0.042), and, most strikingly, a reduction in 90-day mortality (p = 0.033). CONCLUSION: LPD and RPD have similar surgical and oncologic outcomes, with a lower rate of conversion to open in the robotic cohort. The robotic technique does not appear to eliminate the "learning curve", with higher volume centers demonstrating improved outcomes, especially seen at minimum annual volume of 5 cases.

The aborted Whipple: Why, and what happens next?

BACKGROUND: For patients with periampullary adenocarcinoma (PAC), pancreatoduodenectomy (PD) provides the best survival. Surgery on a subset of patients is aborted during PD. We analyzed these patients. METHODS: Patients who underwent laparotomy for planned PD for PAC were identified (2006-2019). From operative notes, we identified the subset with intraoperative decision to abort. Patient, treatment, and outcome data were analyzed. The subset with pancreatic ductal adenocarcinoma (PDAC) was analyzed for survival. RESULTS: Only 6.7% (n = 55/819) of cases were aborted. Majority 78% (n = 43) had pathologically-confirmed diagnoses at time of surgery, and 18.2% (n = 10) received preoperative chemotherapy. Reasons for aborted PD included: distant metastases (65.5%, n = 36) and local invasion (34.5%, n = 19). Of patients with metastatic disease, 75% (n = 27) had liver metastases. Eighty-nine percent (n = 49) of patients underwent at least one palliative bypass procedure and 81.8% (n = 45) had both gastric and biliary bypass. Patients with computed tomography (CT) scans before surgery more commonly had missed metastatic disease (79.2% CT compared to 54.8% magnetic resonance imaging [MRI], χ2 = 3.54, p = 0.059). In PDAC, 61.4% (n = 27/44) were aborted for metastatic disease and 38.7% (n = 17/44) for local invasion. Median overall survival for all PDAC patients after aborted PD was 334 days. CONCLUSION: Majority of pancreatoduodenectomies for periampullary adenocarcinoma are done to completion. Liver metastases is the most common reason for aborting. Preoperative MRI may help identify hepatic metastases.

Outcomes of laparoscopic, robotic, and open pancreatoduodenectomy: A network meta-analysis of randomized controlled trials and propensity-score matched studies.

BACKGROUND: This network meta-analysis was performed to determine the optimal surgical approach for pancreatoduodenectomy by comparing outcomes after laparoscopic pancreatoduodenectomy, robotic pancreatoduodenectomy and open pancreatoduodenectomy. METHODS: A systematic search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify eligible randomized controlled trials and propensity-score matched studies. RESULTS: Four randomized controlled trials and 23 propensity-score matched studies comprising a total of 4,945 patients were included for analysis. Operation time for open pancreatoduodenectomy was shorter than both laparoscopic pancreatoduodenectomy (mean difference -57.35, 95% CI 26.25-88.46 minutes) and robotic pancreatoduodenectomy (mean difference -91.08, 95% CI 48.61-133.56 minutes), blood loss for robotic pancreatoduodenectomy was significantly less than both laparoscopic pancreatoduodenectomy (mean difference -112.58, 95% CI 36.95-118.20 mL) and open pancreatoduodenectomy (mean difference -209.87, 95% CI 140.39-279.36 mL), both robotic pancreatoduodenectomy and laparoscopic pancreatoduodenectomy were associated with reduced rates of delayed gastric emptying compared with open pancreatoduodenectomy (odds ratio 0.59, 95% CI 0.39-0.90 and odds ratio 0.69, 95% CI 0.50-0.95, respectively), robotic pancreatoduodenectomy was associated with fewer wound infections compared with open pancreatoduodenectomy (odds ratio 0.35, 95% CI 0.18-0.71), and laparoscopic pancreatoduodenectomy patients enjoyed significantly shorter length of stay compared with open pancreatoduodenectomy (odds ratio 0.43, 95% CI 0.28-0.95). There were no differences in other outcomes. CONCLUSION: This network meta-analysis of high-quality studies suggests that when laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy are performed in high-volume centers, short-term perioperative and oncologic outcomes are largely comparable, if not slightly improved, compared with traditional open pancreatoduodenectomy. These findings should be corroborated in further prospective randomized studies.

Short-term outcomes after pancreatoduodenectomy in octogenarians: multicentre case-control study.

BACKGROUND: Pancreatoduodenectomy (PD) is frequently the surgical treatment indicated for a number of pathologies. Elderly patients may be denied surgery because of concerns over poor perioperative outcomes. The aim of this study was to evaluate postoperative clinical outcomes and provide evidence on current UK practice in the elderly population after PD. METHODS: This was a multicentre retrospective case-control study of octogenarians undergoing PD between January 2008 and December 2017, matched with younger controls from seven specialist centres in the UK. The primary endpoint was 90-day mortality. Secondary endpoints were index admission mortality, postoperative complications, and 30-day readmission rates. RESULTS: In total, 235 octogenarians (median age 81 (range 80-90) years) and 235 controls (age 67 (31-79) years) were included in the study. Eastern Cooperative Oncology Group performance status (median 0 (range 0-3) versus 0 (0-2); P = 0.010) and Charlson Co-morbidity Index score (7 (6-11) versus 5 (2-9); P = 0.001) were higher for octogenarians than controls. Postoperative complication and 30-day readmission rates were comparable. The 90-day mortality rate was higher among octogenarians (9 versus 3 per cent; P = 0.030). Index admission mortality rates were comparable (4 versus 2 per cent; P = 0.160), indicating that the difference in mortality was related to deaths after hospital discharge. Despite the higher 90-day mortality rate in the octogenarian population, multivariable Cox regression analysis did not identify age as an independent predictor of postoperative mortality. CONCLUSION: Despite careful patient selection and comparable index admission mortality, 90-day and, particularly, out-of-hospital mortality rates were higher in octogenarians.

Glucose Tolerance after Pancreatectomy: A Prospective Observational Follow-Up Study of Pancreaticoduodenectomy and Distal Pancreatectomy.

BACKGROUND: Effects of pancreatectomy on glucose tolerance have not been clarified, and evidence regarding the difference in postoperative glucose tolerance between pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is lacking. STUDY DESIGN: This prospective, single-center observational study analyzed 40 patients undergoing PD and 29 patients undergoing DP (Clinical trial registry number UMIN000008122). Glucose tolerance, including insulin secretion (Δ C-peptide immunoreactivity, ΔCPR) and insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) were assessed before and 1 month after pancreatectomy using the oral glucose tolerance test (OGTT) and glucagon stimulation test. We assessed long-term hemoglobin A1c (HbA1c) levels in patients, with a follow-up time of 3 years. RESULTS: Percentages of patients diagnosed with abnormal OGTT decreased after PD (from 12 [30%] to 7 [17.5%] of 40 patients, p = 0.096); however, they increased after DP (from 4 [13.8%] to 8 [27.6%] of 29 patients, p = 0.103), although the changes were not statistically significant. ΔCPR decreased after both PD (from 3.2 to 1.0 ng/mL, p < 0.001) and DP (from 3.3 to 1.8 ng/mL, p < 0.001). HOMA-IR decreased after PD (from 1.10 to 0.68, p < 0.001), but did not change after DP (1.10 and 1.07, p = 0.42). Median HbA1c level was higher after DP than after PD for up to 3 years, but the differences were not statistically significant. CONCLUSIONS: In comparisons of pre- and 1 month post-pancreatectomy data, glucose tolerance showed improvement after PD, whereas it worsened after DP. Insulin secretion decreased after both PD and DP. Insulin resistance improved after PD, but did not change after DP. Further studies are warranted to clarify mechanisms of improved insulin resistance after PD.

Does drainage or resection predict subsequent interventions and long-term quality of life in patients with Grade IV pancreatic injuries: A population-based analysis.

BACKGROUND: Clinical equipoise remains significant for the treatment of Grade IV pancreatic injuries in stable patients (i.e., drainage vs. resection). The literature is poor in regards to experience, confirmed main pancreatic ductal injury, nuanced multidisciplinary treatment, and long-term patient quality of life (QOL). The primary aim was to evaluate the management and outcomes (including long-term QOL) associated with Grade IV pancreatic injuries. METHODS: All severely injured adult patients with pancreatic trauma (1995-2020) were evaluated (Grade IV injuries compared). Concordance of perioperative imaging, intraoperative exploration, and pathological reporting with a main pancreatic ductal injury was required. Patients with resection of Grade IV injuries were compared with drainage alone. Long-term QOL was evaluated (Standard Short Form-36). RESULTS: Of 475 pancreatic injuries, 36(8%) were confirmed as Grade IV. Twenty-four (67%) underwent a pancreatic resection (29% pancreatoduodenectomy; 71% extended distal pancreatectomy [EDP]). Patient, injury and procedure demographics were similar between resection and drainage groups (p > 0.05). Pancreas-specific complications in the drainage group included 92% pancreatic leaks, 8% pseudocyst, and 8% walled-off pancreatic necrosis. Among patients with controlled pancreatic fistulas beyond 90 days, 67% required subsequent pancreatic operations (fistulo-jejunostomy or EDP). Among patients whose fistulas closed, 75% suffered from recurrent pancreatitis (67% eventually undergoing a Frey or EDP). All patients in the resection group had fistula closure by 64 days after injury. The median number of pancreas-related health care encounters following discharge was higher in the drainage group (9 vs. 5; p = 0.012). Long-term (median follow-up = 9 years) total QOL, mental and physical health scores were higher in the initial resection group (p = 0.031, 0.022 and 0.017 respectively). CONCLUSION: The immediate, intermediate and long-term experiences for patients who sustain Grade IV pancreatic injuries indicate that resection is the preferred option, when possible. The majority of drainage patients will require additional, delayed pancreas-targeted surgical interventions and report poorer long-term QOL. LEVEL OF EVIDENCE: Epidemiology/Prognostic, Level III.

Optimal extent of lymphadenectomy for radical surgery of pancreatic head adenocarcinoma: 2-year survival rate results of single-center, prospective, randomized controlled study.

BACKGROUND: Radical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma. METHODS: A total of 240 patients were assessed for eligibility in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy. RESULT: The demography, histopathology and clinical characteristics were similar between the 2 groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; P = .034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; P = .021). There was no significant difference in the overall incidence of complications between the 2 groups (P = .502). The overall recurrence rate in the SG and EG (70.7% vs 77.5%; P = .349), and the patterns of recurrence between 2 groups were no significant differences. CONCLUSION: In multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be 1 of the reasons why extended lymphadenectomy did not result in survival benefits. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/.

Impact of Postoperative Glycemic Control on Postoperative Morbidity in Patients Undergoing Open Pancreaticoduodenectomy.

OBJECTIVE: To evaluate the impact of postoperative glycemic control on postoperative morbidity in patients undergoing a pancreaticoduodenectomy. METHODS: A retrospective study was performed on patients at The Johns Hopkins Hospital between April 2015 and April 2016. Data were collected on postoperative insulin regimens, blood glucose, rates of hyperglycemia and hypoglycemia, and postoperative complications and were evaluated. RESULTS: Out of 244 patients, 114 (46.7%) experienced at least 1 hyperglycemic (>180 mg/dL) episode and 16 (6.6%) experienced at least 1 hypoglycemic episode (<70 mg/dL) during the first postoperative 24 hours. Early postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of surgical site infections (15.7% vs 7%; P = 0.031). Late postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of fistulas (4.3% vs 14.6%; P = 0.021). CONCLUSIONS: Early hyperglycemia (>180 mg/dL) is associated with a higher risk of surgical site infections while late hyperglycemia is associated with a higher risk of fistulas. Intensive glucose control (<150 mg/dL) was not demonstrated to decrease the risk of postoperative complications. Similar to other critically ill populations, targeting a glucose goal of <180 mg/dL may be an appropriate target to reduce morbidity without increasing the risk of hypoglycemia.

Validation study of the ACS NSQIP surgical risk calculator for two procedures in Japan.

INTRODUCTION: The ACS NSQIP Surgical Risk Calculator (SRC) assesses risk to support goal-concordant care. While it accurately predicts US outcomes, its performance internationally is unknown. This study evaluates SRC accuracy in predicting mortality following low anterior resection (LAR) and pancreaticoduodenectomy (PD) in NSQIP patients and accuracy retention when applied to native Japanese patients (National Clinical Database, NCD). METHODS: NSQIP (41,260 LAR; 15,114 PD) and NCD cases (61,220 LAR; 27,901 PD) from 2015 to 2017 were processed through the SRC mortality model. Country-specific calibration and discrimination were assessed with and without an intercept correction applied to the Japanese data. RESULTS: The SRC exhibited acceptable calibration for LAR and PD when applied to NSQIP data but miscalibration for NCD data. A simple correction to the model intercept, motivated by lower mortality rates in the Japanese data, successfully remediated the miscalibration. CONCLUSIONS: The SRC may inaccurately predict surgical risk when applied to the native Japanese population. An intercept correction method is suggested when miscalibration is encountered; it is simple to implement and may permit effective international use of the SRC.

Pancreatic resections: 30 and 90-day outcomes in octogenarians.

BACKGROUND: Pancreatic tumors are frequently found in a geriatric population. Given that the median age of patients with pancreatic cancer is 70 years at diagnosis and the ubiquity of CT and MRI imaging has increased the detection of pancreas masses, pancreatic surgeons often find themselves operating on patients of advanced age. This study sought to evaluate the outcomes of pancreatic resection in an octogenarian population at a single institution with a dedicated surgical oncology team. STUDY DESIGN: A retrospective chart review was performed for all patients undergoing pancreatic resection over a 13-year period at an academic community cancer center. Patient characteristics and operative outcomes were compared between patients aged 80 and older, and those younger than 80. Student t-tests, Fisher's exact test, and Kruskal-Wallis tests were used for univariate analyses. RESULTS: Over the 13-year period, a total of 48 patients of 403 undergoing pancreatic resections were aged 80 or older. Of these 48 patients, 35 underwent pancreaticoduodenectomy (Whipple) and 13 underwent distal pancreatectomy. Patient characteristics including ASA classification were similar among the two age groups. The procedures themselves were equally complicated with similar operative times, transfusion requirements, estimated blood losses, and portal vein resections. The number and severity of complications such as delayed gastric emptying and pancreatic leak were not statistically different between the two groups. Additionally, the 30-day reoperation, readmission, and mortality rates were not statistically different. Outcomes at 90-days revealed an increased rate of readmission amongst octogenarians who underwent Whipple without an increase in rates of major complications. The total number of deaths in the octogenarian group was 3 (6.2%) vs. 6 (1.7%) in the non-octogenarian group (p = 0.080). The median length of stay was similar amongst the two age groups. CONCLUSIONS: At a large-volume academic community cancer center with a dedicated surgical oncology team, highly selected octogenarians can undergo pancreatic resection safely with outcomes that do not differ significantly from their younger counterparts.

Prognostic Nomogram for patients undergoing radical Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head.

BACKGROUND: Radical pancreaticoduodenectomy is the most common treatment strategy for patients diagnosed with adenocarcinoma of the pancreatic head. Few studies have reported the clinical characteristics and treatment efficacies of patients undergoing radical pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. METHODS: A total of 177 pancreatic head cancer patients who underwent radical pancreaticoduodenectomy and were pathologically confirmed as having pancreatic ductal adenocarcinoma were screened in the West China Hospital of Sichuan University. The multivariate analysis results were implemented to construct a nomogram. The concordance index (c-index), the area under the curve (AUC) and calibration were utilized to evaluate the predictive performance of the nomogram. RESULTS: The prognostic nutritional index (PNI), the lymph node ratio (LNR) and the American Joint Committee on Cancer (AJCC) staging served as independent prognostic factors and were used to construct the nomogram. The c-indexes of the nomogram were 0.799 (confidence interval (CI), 0.741-0.858) and 0.732 (0.657-0.807) in the primary set and validation set, respectively. The AUCs of the nomogram at 1 and 3 years were 0.832 and 0.783, which were superior to the AJCC staging values of 0.759 and 0.705, respectively. CONCLUSIONS: The nomogram may be used to predict the prognosis of radical resection for adenocarcinoma of the pancreatic head. These findings may represent an effective model for the developing an optimal therapeutic schedule for malnourished patients who need early effective nutritional intervention and may promote the treatment efficacy of resectable adenocarcinoma of the pancreatic head.

Inability to manage non-severe complications on an outpatient basis increases non-white patient readmission rates after pancreaticoduodenectomy: A large metropolitan tertiary care center experience.

BACKGROUND: Pancreaticoduodenectomy (PD) has a high rate of readmission, and racial disparities in care could be an important contributor. METHODS: Patients undergoing PD were prospectively followed, and their complications graded using the Modified Accordion Grading System (MAGS). Patient factors and perioperative outcomes for patients with and without postoperative readmission were compared in univariate and multivariate analysis by severity. RESULTS: 837 patients underwent PD, the overall 90-day readmission rate was 27.5%. Non-white race was independently associated with readmission (OR 1.83, p = 0.007). 51.3% of readmissions were for non-severe complications (MAGS <3). Non-white race was independently associated with MAGS non-severe readmission (OR 2.13, p = 0.006), but not MAGS severe readmission. CONCLUSIONS: Non-white patients are more likely to be readmitted, particularly for non-severe complications. Follow up protocols should be tailored to address race disparities in the rates of readmission as readmission for less severe complications could potentially be avoidable.

Non-arbitrary minimum threshold of yearly performed pancreatoduodenectomies: National multicentric study.

BACKGROUND: Annual hospital volume of pancreatoduodenectomies could influence postoperative outcomes. The aim of this study is to establish with a non-arbitrary method the minimum threshold of yearly performed pancreatoduodenectomies in order to improve several postoperative quality outcomes. METHOD: Prospective follow-up of patients submitted to pancreatoduodenectomy in participating hospitals during 1 year. The influence of hospital volume on quality outcomes was analyzed by univariable and multivariable models. The minimum threshold of yearly performed pancreatoduodenectomies to improve outcomes was established by Akaike's information criteria. RESULTS: Data from 877 patients operated in 74 hospitals were analyzed. Of 12 quality outcomes, 9 were influenced by hospital pancreatoduodenectomy volume on multivariable analysis. To decrease the risk of complications and the risk of retrieving an insufficient number of lymph nodes at least 31 pancreatoduodenectomies per year should be performed. To decrease the risk of prolonged length of stay, postoperative death, and affected surgical margins, at least 37, 6, and 14 pancreatoduodenectomies per year should be performed, respectively. CONCLUSION: Several postoperative quality outcomes are influenced by the number of yearly performed pancreatoduodenectomies and could be improved by establishing a minimum threshold of procedures. Number of procedures needed to improve quality outcomes has been established by a non-arbitrary method.

Is Improved Survival in Early-Stage Pancreatic Cancer Worth the Extra Cost at High-Volume Centers?

BACKGROUND: Volume of operative cases may be an important factor associated with improved survival for early-stage pancreatic cancer. Most high-volume pancreatic centers are also academic institutions, which have been associated with additional healthcare costs. We hypothesized that at high-volume centers, the value of the extra survival outweighs the extra cost. STUDY DESIGN: This retrospective cohort study used data from the California Cancer Registry linked to the Office of Statewide Health Planning and Development database from January 1, 2004 through December 31, 2012. Stage I-II pancreatic cancer patients who underwent resection were included. Multivariable analyses estimated overall survival and 30-day costs at low- vs high-volume pancreatic surgery centers. The incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) were estimated, and statistical uncertainty was characterized using net benefit regression. RESULTS: Of 2,786 patients, 46.5% were treated at high-volume centers and 53.5% at low-volume centers. There was a 0.45-year (5.4 months) survival benefit (95% CI 0.21-0.69) and a $7,884 extra cost associated with receiving surgery at high-volume centers (95% CI $4,074-$11,694). The ICER was $17,529 for an additional year of survival (95% CI $7,997-$40,616). For decision-makers willing to pay more than $20,000 for an additional year of life, high-volume centers appear cost-effective. CONCLUSIONS: Although healthcare costs were greater at high-volume centers, patients undergoing pancreatic surgery at high-volume centers experienced a survival benefit (5.4 months). The extra cost of $17,529 per additional year is quite modest for improved survival and is economically attractive by many oncology standards.

The use and clinical outcome of total pancreatectomy in the United States, Germany, the Netherlands, and Sweden.

BACKGROUND: Total pancreatectomy has high morbidity and mortality and differences among countries are currently unknown. This study compared the use and postoperative outcomes of total pancreatectomy among 4 Western countries. METHODS: Patients who underwent one-stage total pancreatectomy were included from registries in the United States, Germany, the Netherlands, and Sweden (2014-2018). Use of total pancreatectomy was assessed by calculating the ratio total pancreatectomy to pancreatoduodenectomy. Primary outcomes were major morbidity (Clavien Dindo ≥3) and in-hospital mortality. Predictors for the primary outcomes were assessed in multivariable logistic regression analyses. Sensitivity analysis assessed the impact of volume (low-volume <40 or high-volume ≥40 pancreatoduodenectomies annually; data available for the Netherlands and Germany). RESULTS: In total, 1,579 patients underwent one-stage total pancreatectomy. The relative use of total pancreatectomy to pancreatoduodenectomy varied up to fivefold (United States 0.03, Germany 0.15, the Netherlands 0.03, and Sweden 0.15; P < .001). Both the indication and several baseline characteristics differed significantly among countries. Major morbidity occurred in 423 patients (26.8%) and differed (22.3%, 34.9%, 38.3%, and 15.9%, respectively; P < .001). In-hospital mortality occurred in 85 patients (5.4%) and also differed (1.8%, 10.2%, 10.8%, 1.9%, respectively; P < .001). Country, age ≥75, and vascular resection were predictors for in-hospital mortality. In-hospital mortality was lower in high-volume centers in the Netherlands (4.9% vs 23.1%; P = .002), but not in Germany (9.8% vs 10.6%; P = .733). CONCLUSION: Considerable differences in the use of total pancreatectomy, patient characteristics, and postoperative outcome were noted among 4 Western countries with better outcomes in the United States and Sweden. These large, yet unexplained, differences require further research to ultimately improve patient outcome.

Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data.

Factors for overall survival after pancreatic ductal adenocarcinoma (PDAC) seem to be nodal status, chemotherapy administration, UICC staging, and resection margin. However, there is no consensus on the definition for tumor free resection margin. Therefore, univariate OS as well as multivariate long-term survival using cancer center data was analyzed with regards to two different resection margin definitions. Ninety-five patients met inclusion criteria (pancreatic head PDAC, R0/R1, no 30 days mortality). OS was analyzed in univariate analysis with respect to R-status, CRM (circumferential resection margin; positive: ≤1mm; negative: >1mm), nodal status, and chemotherapy administration. Long-term survival >36 months was modelled using multivariate logistic regression instead of Cox regression because the distribution function of the dependent data violated the requirements for the application of this test. Significant differences in OS were found regarding the R status (Median OS and 95%CI for R0: 29.8 months, 22.3-37.4; R1: 15.9 months, 9.2-22.7; p = 0.005), nodal status (pN0 = 34.7, 10.4-59.0; pN1 = 17.1, 11.5-22.8; p = 0.003), and chemotherapy (with CTx: 26.7, 20.4-33.0; without CTx: 9.7, 5.2-14.1; p < .001). OS according to CRM status differed on a clinically relevant level by about 12 months (CRM positive: 17.2 months, 11.5-23.0; CRM negative: 29.8 months, 18.6-41.1; p = 0.126). A multivariate model containing chemotherapy, nodal status, and CRM explained long-term survival (p = 0.008; correct prediction >70%). Chemotherapy, nodal status and resection margin according to UICC R status are univariate factors for OS after PDAC. In contrast, long-term survival seems to depend on wider resection margins than those used in UICC R classification. Therefore, standardized histopathological reporting (including resection margin size) should be agreed upon.

Risk of conversion to open surgery during robotic and laparoscopic pancreatoduodenectomy and effect on outcomes: international propensity score-matched comparison study.

BACKGROUND: Minimally invasive pancreatoduodenectomy (MIPD) is increasingly being performed because of perceived patient benefits. Whether conversion of MIPD to open pancreatoduodenectomy worsens outcome, and which risk factors are associated with conversion, is unclear. METHODS: This was a post hoc analysis of a European multicentre retrospective cohort study of patients undergoing MIPD (2012-2017) in ten medium-volume (10-19 MIPDs annually) and four high-volume (at least 20 MIPDs annually) centres. Propensity score matching (1 : 1) was used to compare outcomes of converted and non-converted MIPD procedures. Multivariable logistic regression analysis was performed to identify risk factors for conversion, with results presented as odds ratios (ORs) with 95 per cent confidence intervals (c.i). RESULTS: Overall, 65 of 709 MIPDs were converted (9.2 per cent) and the overall 30-day mortality rate was 3.8 per cent. Risk factors for conversion were tumour size larger than 40 mm (OR 2.7, 95 per cent c.i.1.0 to 6.8; P = 0.041), pancreatobiliary tumours (OR 2.2, 1.0 to 4.8; P = 0.039), age at least 75 years (OR 2.0, 1.0 to 4.1; P = 0.043), and laparoscopic pancreatoduodenectomy (OR 5.2, 2.5 to 10.7; P < 0.001). Medium-volume centres had a higher risk of conversion than high-volume centres (15.2 versus 4.1 per cent, P < 0.001; OR 4.1, 2.3 to 7.4, P < 0.001). After propensity score matching (56 converted MIPDs and 56 completed MIPDs) including risk factors, rates of complications with a Clavien-Dindo grade of III or higher (32 versus 34 per cent; P = 0.841) and 30-day mortality (12 versus 6 per cent; P = 0.274) did not differ between converted and non-converted MIPDs. CONCLUSION: Risk factors for conversion during MIPD include age, large tumour size, tumour location, laparoscopic approach, and surgery in medium-volume centres. Although conversion during MIPD itself was not associated with worse outcomes, the outcome in these patients was poor in general which should be taken into account during patient selection for MIPD.

Cost Analysis of Pancreaticoduodenectomy at a High-Volume Robotic Hepatopancreaticobiliary Surgery Program.

BACKGROUND: The robotic approach to pancreaticoduodenectomy is thought by many to be associated with increased financial burden for hospitals. We undertook this study to analyze and compare the cost of "open" pancreaticoduodenectomy with that associated with the application of the robotic surgical system to pancreaticoduodenectomy in our hepatobiliary program. STUDY DESIGN: With IRB approval, all patients undergoing pancreaticoduodenectomy at our institution, from August 2012 to November 2019, were prospectively followed. Cost, including total, variable, fixed-direct, fixed-indirect, and profitability for robotic and "open" pancreaticoduodenectomy were analyzed and compared. Data are presented as median (mean ± SD). RESULTS: There were 386 patients who underwent pancreaticoduodenectomy; 205 patients underwent robotic pancreaticoduodenectomy and 181 underwent "open" pancreaticoduodenectomy. Costs are presented as mean ± SD. Overall, the cost of care for robotic pancreaticoduodenectomy was $31,389 ($36,611 ± $20,545.40) vs $23,132 ($31,323 ± $28,885.50) for "open" pancreaticoduodenectomy (p = 0.04); total variable cost was $20,355 ($22,747 ± $11,127.60) vs $11,680 ($16,032 ± $14,817.20) (p = 0.01), total fixed direct cost was $1,999 ($2,330 ± $1,363.10) vs $2,073 ($2,983 ± $3,209.00) (p = 0.01), and total indirect cost was $7,217 ($9,354 ± $6,802.40) vs $6,802 ($9,505 ± $9,307.20) (p = 0.86), for robotic vs "open" pancreaticoduodenectomy, respectively. Since 2016, profitability was achieved in 29% of patients undergoing robotic pancreaticoduodenectomy. CONCLUSIONS: Robotic pancreaticoduodenectomy had lower estimated blood loss and shorter length of stay. Cost of care for robotic pancreaticoduodenectomy was greater across all categories, except for total indirect cost, than "open" pancreaticoduodenectomy. For our institution, profitability was accomplished in less than one-third of patients undergoing robotic pancreaticoduodenectomy. The role of the robotic platform for pancreaticoduodenectomy needs to be discussed among all stakeholders.