Total pancreatectomy and islet cell autotransplantation: a 10-year update on outcomes and assessment of long-term durability.

BACKGROUND: Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years. METHODS: Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively. RESULTS: Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months. CONCLUSION: This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.

Intraoperative Pancreatic Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in the Era of Neoadjuvant Therapy: A Multi-institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting. The impact of neoadjuvant therapy on this practice and its relationship with overall survival (OS) is incompletely understood. METHODS: We reviewed PDAC patients (80% borderline resectable/locally advanced [BR/LA]) undergoing pancreaticoduodenectomy after neoadjuvant therapy at seven, academic, high-volume centers (2010-2018). Multivariable models examined the association of PS:R0, PS:R1, and converted-R0 margins with OS. RESULTS: Of 272 patients receiving at least 2 (median 4) cycles of neoadjuvant chemotherapy (71% mFOLFIRINOX or gemcitabine/nab-paclitaxel) and undergoing pancreaticoduodenectomy with intraoperative frozen-section assessment of the transected pancreatic neck margin, PS:R0 (n = 220, 80.9%) was observed in a majority of patients; 18 patients (6.6%) had converted-R0 margins following additional resection, whereas 34 patients (12.5%) had persistently positive PS:R1 margins. At a median follow-up of 42 months, PS:R0 resection was associated with improved OS compared with either converted-R0 or PS:R1 resection (median 25 vs. 14 vs. 16 months, respectively; p = 0.023), with no survival difference between the converted-R0 and PS:R1 groups (p = 0.9). On Cox regression, SMA margin positivity (hazard ratio 2.2, p = 0.012), but not neck margin positivity (hazard ratio 1.2, p = 0.65), was associated with worse OS. CONCLUSIONS: In this multi-institutional cohort of predominantly BR/LA PDAC patients undergoing pancreaticoduodenectomy following modern neoadjuvant therapy, pursuing a negative neck margin intraoperatively if the initial margin is positive does not appear to be associated with improved survival.

A National Assessment of T2 Staging for Intrahepatic Cholangiocarcinoma and the Poor Prognosis Associated with Multifocality.

BACKGROUND: T2 intrahepatic cholangiocarcinoma (ICC) is defined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC. The patients were grouped based on T2 staging, multifocality, and lymph node involvement. RESULTS: The study enrolled and classified 4887 patients into clinical (c) stage groups as follows: 15.2% with solitary T2N0 (sT2N0) tumors, 21.3% with multifocal T2N0 (mT2N0) tumors, and 63.5% with node-positive (TxN1) disease. Patients with (c)sT2N0 tumors had higher rates of surgical resection than those with (c)mT2N0 or (c)TxN1 disease (33.5% vs 19.7% vs 15.0%; p < 0.01). Median overall survival (OS) was better for the patients with (c)sT2N0 tumors than for those with multifocal and node-positive disease (15.4 vs 10.4 vs 10.4 months; p < 0.01). On multivariate analysis, (c)sT2N0 tumors were associated with better OS than (c)mT2N0 tumors [hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.17-1.46; p < 0.01] or (c)TxN1 disease (HR,1.41; 95% CI 1.28-1.56; p < 0.01). In a subset analysis based on pathologic (p) staging of patients who underwent surgical resection with regional lymphadenectomy, multivariate analysis demonstrated that (p)sT2N0 tumors were associated with better OS than (p)mT2N0 tumors (HR,1.40; 95% CI 1.03-1.92; p = 0.03) or (p)TxN1 disease (HR, 2.05; 95% CI 1.62-2.58; p < 0.01). CONCLUSIONS: Multifocal T2N0 ICC is associated with poor OS and has a disparate prognosis compared with solitary T2N0 disease, even among patients who undergo resection. Future staging criteria should account for the poor outcomes associated with multifocal ICC.

Variability in blood transfusions after pancreaticoduodenectomy: A national analysis of the University HealthSystem Consortium.

BACKGROUND: Variability in blood use after pancreaticoduodenectomy and the associated impact on readmission, mortality, and cost is not well understood at the national level. METHODS: The University HealthSystem Consortium database was queried for all pancreaticoduodenectomies performed between the years 2011-2013 (n = 9,582). Patients were grouped according to transfusion requirements into none (0 units, 64%), low (1-2 units, 15%), medium (3-5 units, 13%), and high (>5 units, 8%). Multivariable analyses were used to determine predictors of increased transfusions, readmission, in-hospital mortality, and cost. RESULTS: Of the patients undergoing pancreaticoduodenectomy, 36% received blood perioperatively. Patients with high transfusion requirements were less often white, more often male, and had a higher severity of illness (all P < .01). High transfusion requirements correlated with higher readmission rates (OR 1.23, P = .03), cost (RR 1.84, P < .01), length of stay (18 vs. 13 vs. 10 vs. 8 days, P < .01), and in-hospital mortality (12.5% vs. 3.1% vs. 0.5% vs. 0.4%, P < .01). Higher-volume surgeons demonstrated lower transfusion requirements (OR 0.61, P < .01). CONCLUSION: Significant variability exists nationally in transfusion practices for patients undergoing pancreaticoduodenectomy, which may be driven most by severity of illness and surgeon volume. Efforts to reduce such variability could lead to improved outcomes and healthcare cost savings.

Equivalent Treatment and Survival after Resection of Pancreatic Cancer at Safety-Net Hospitals.

BACKGROUND: Due to disparities in access to care, patients with Medicaid or no health insurance are at risk of not receiving appropriate adjuvant treatment following resection of pancreatic cancer. We have previously shown inferior short-term outcomes following surgery at safety-net hospitals. Subsequently, we hypothesized that safety-net hospitals caring for these vulnerable populations utilize less adjuvant chemoradiation, resulting in inferior long-term outcomes. METHODS: The American College of Surgeons National Cancer Data Base was queried for patients diagnosed with pancreatic adenocarcinoma (n = 32,296) from 1998 to 2010. Hospitals were grouped according to safety-net burden, defined as the proportion of patients with Medicaid or no insurance. The highest quartile, representing safety-net hospitals, was compared to lower-burden hospitals with regard to patient demographics, disease characteristics, surgical management, delivery of multimodal systemic therapy, and survival. RESULTS: Patients at safety-net hospitals were less often white, had lower income, and were less educated. Safety-net hospital patients were just as likely to undergo surgical resection (OR 1.03, p = 0.73), achieving similar rates of negative surgical margins when compared to patients at medium and low burden hospitals (70% vs. 73% vs. 66%). Thirty-day mortality rates were 5.6% for high burden hospitals, 5.2% for medium burden hospitals, and 4.3% for low burden hospitals. No clinically significant differences were noted in the proportion of surgical patients receiving either chemotherapy (48% vs. 52% vs. 52%) or radiation therapy (26% vs. 30% vs. 29%) or the time between diagnosis and start of systemic therapy (58 days vs. 61 days vs. 53 days). Across safety-net burden groups, no difference was noted in stage-specific median survival (all p > 0.05) or receipt of adjuvant as opposed to neoadjuvant systemic therapy (82% vs. 85% vs. 85%). Multivariate analysis adjusting for cancer stage revealed no difference in survival for safety-net hospital patients who had surgery and survived > 30 days (HR 1.02, p = 0.63). CONCLUSION: For patients surviving the perioperative setting following pancreatic cancer surgery, safety-net hospitals achieve equivalent long-term survival outcomes potentially due to equivalent delivery of multimodal therapy at non-safety-net hospitals. Safety-net hospitals are a crucial resource that provides quality long-term cancer treatment for vulnerable populations.

Prophylactic pasireotide administration following pancreatic resection reduces cost while improving outcomes.

BACKGROUND AND OBJECTIVES: Pasireotide decreases leak rates after pancreatic resection, though significant drug cost may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile. METHODS: A cost-effectiveness model compared pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify influential clinical components of the model. RESULTS: With the cost of pasireotide included, per patient costs of pancreatectomy, including those for readmission, were lower in the intervention arm (41,769 versus 42,159$; net savings of 390$, or 1%). This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A; 21.9-9.2%). Pasireotide cost would need to increase by over 15.4% to make the intervention strategy more costly than usual care. Sensitivity analyses exploring variability of key model inputs demonstrated that the three strongest drivers of cost were (i) cost of pasireotide; (ii) probability of readmission; and (iii) probability of PF/PL/A. CONCLUSIONS: Prophylactic pasireotide administration following pancreatectomy is cost savings, reducing expensive post-operative sequealae (major complications and readmissions). Pasireotide should be utilized as a cost-saving measure in pancreatic resection. J. Surg. Oncol. 2016;113:784-788. © 2016 Wiley Periodicals, Inc.

How Much Should We Pay to Minimize Pancreatic Leak? The Cost-effectiveness of Pasireotide in Pancreatic Resection: RETRACTED.

INTRODUCTION: Pasireotide was recently shown to decrease leak rates after pancreatic resection, though the significant cost of the drug may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile by improving outcomes. METHODS: A cost-effectiveness model was constructed to compare pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a recent randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify the most influential clinical components of the model. RESULTS: Without considering pasireotide cost, prophylactic use of the drug saved an average of $8,109 per patient. However, when the cost of pasireotide was included, per patient costs increased from $42,159 to $77,202. This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A) (21.9% to 9.2%). The resultant cost per PF/PL/A avoided was $301,628. Threshold analysis demonstrated that for this intervention to be cost neutral, either the purchase price of pasireotide ($43,172) must be reduced by 92.3% (to $3324) or drug reimbursement must be $39,848. Sensitivity analyses exploring variable perioperative mortality, rate of PF/PL/A, and readmission rates did not significantly alter model outcomes. CONCLUSIONS: Our analyses demonstrate that when prophylactic pasireotide is administered, the cost per PF/PL/A avoided is approximately $300,000. Aggressive pricing negotiation, payer reimbursement for the drug, high-volume use, and consensus among the public, payers, and surgical community regarding the value of reducing morbidity will ultimately determine the utility of widespread pasireotide application in pancreatic resection.

Cost-Effectiveness in Hepatic Lobectomy: the Effect of Case Volume on Mortality, Readmission, and Cost of Care.

OBJECTIVE(S): Higher-volume centers demonstrate better perioperative outcomes for complex surgical interventions, though resource utilization implications of this hospital-level variation are unclear. We hypothesized that for hepatic lobectomy, higher operative volume correlates with better outcomes and lower costs. METHODS: From 2009 to 2011, 4163 patients undergoing hepatic lobectomy were identified from the University HealthSystems Consortium database. Univariate, multivariate logistic regression, and decision analytic models were constructed to identify differences in hospital utilization and cost. Cost included both index and readmission hospitalizations, when applicable. RESULTS: The annual number of hepatic lobectomies performed by the institutions within the study ranged from 1 to 86. The median age of the 4163 patients was 58 years with a roughly equal gender split (M/F 49 %:51 %) and a racial breakdown which reflected that of the general US population. For all patients, the overall perioperative mortality rate was 2.3 % and the 30-day readmission rate was 13.4 %. Hospitals performing >30 hepatic lobectomies per year had significantly lower mortality and readmission rates than those hospitals performing ≤15 lobectomies annually (both p < 0.05). On multivariate analysis, higher severity of illness (odd ratio (OR) 2.13, 95 % confidence interval (CI) [1.48-3.07], p < 0.001), discharge to rehab (OR 1.84, [1.28-2.64], p < 0.001), home with home health care (OR 1.38, [1.08-1.76], p = 0.01), and surgery at a low-volume hospital (OR 1.49, [1.18-1.88], p < 0.001) were significant predictors of readmission. Conversely, surgical intervention at high-volume centers was associated with decreased risk of readmission (OR 0.67, [0.53-0.85], p < 0.001). When both index and readmission costs were considered, per-patient cost at low-volume centers was 21.9 % higher than at high-volume centers ($19,669 vs. $16,137). Sensitivity analyses adjusting for perioperative mortality and readmission at all centers did not significantly change the analysis. CONCLUSIONS: These data, for the first time, demonstrate that hospital volume in hepatic lobectomy is an important, modifiable risk factor for readmission and cost. To optimize resource utilization, patients undergoing complex hepatic surgery should be directed to higher-volume surgical institutions.

Resource utilization in esophagectomy: When higher costs are associated with worse outcomes.

INTRODUCTION: Care of the esophagectomy patient requires significant resources. We sought to determine which patient and provider variables contribute to resource utilization and their association with clinical outcomes. METHODS: 6,737 patients undergoing esophagectomy were identified from the University Healthsystem Consortium (UHC). Linear and logistic regression models were used to determine whether characteristics, including age, severity of illness (SOI) and procedural volume were associated with mortality, length of stay (LOS), discharge disposition, readmission rates, and cost. RESULTS: Older patients were twice as likely to suffer post-operative death (OR 2.12; 95%CI 1.7-2.7), three times more likely to be discharged to extended care facilities (31.9% vs. 10.6%, P < 0.001), and cost 8.4% more ($27,628 vs. $25,481, P < 0.001). Similarly, patients with higher SOI were more likely to suffer post- operative death (OR 14.6; 4.7-45.9), be readmitted (OR 1.3; 1.1-1.6), and have longer hospital stays (RR 1.3; 1.8-2.1). Patients with the highest index hospital costs were five times more likely to be discharged to an extended care facility (P < 0.001). CONCLUSION: Older patients and those with a higher SOI have higher perioperative mortality, readmission rates, hospital costs, and require more post- operative care. With increasingly scrutinized health care costs, these data provide guidance for more careful patient selection.

Readmission After Pancreaticoduodenectomy: The Influence of the Volume Effect Beyond Mortality.

BACKGROUND: As increased focus is placed on quality of care in surgery, readmission is an increasingly important metric by which hospital and surgeon quality is measured. For complex pancreatic surgery, we hypothesized that increased pancreaticoduodenectomy (PD) volume may mitigate readmission rates. METHODS: The University Healthsystems Consortium database was queried for all patients (n = 9805) undergoing PD from 2009 to 2011. Hospitals were stratified into quintiles based on number of cases performed annually. Univariate and multivariate logistic regression analyses were performed to identify factors associated with 30-day readmission. RESULTS: The 30-day readmission rate for patients undergoing PD was 19.1 %. Stratified by volume, hospitals performing the highest two quintiles of PDs annually (≥56 cases) had a significantly lower unadjusted readmission rate than those hospitals performing the lowest quintile (n ≤ 23 cases; 16.7 and 18.0 % vs. 20.9 %, p < 0.05). On univariate analysis, readmitted patients tended to have higher severity of illness (p < 0.01) and longer index admission (10 vs. 9 days, p < 0.01). Age and insurance status had no significant association with readmission. Multivariate analysis demonstrated that higher severity of illness (odds ratio [OR] 1.36, 95 % confidence interval [CI] 1.04-1.77, p = 0.02), discharge to rehab (OR 1.41, 95 % CI 1.19-1.66, p < 0.001), and surgery at the lowest volume hospitals (OR 1.28, 95 % CI 1.08-1.51, p = 0.004) were factors independently associated with readmission. CONCLUSIONS: Lower hospital volume is a significant risk factor for readmission after PD. To minimize the excess resource utilization that accompanies readmission, patients undergoing complex oncologic pancreatic surgery should be directed to hospitals most experienced in caring for this patient population.

Cost-effectiveness of total pancreatectomy and islet cell autotransplantation for the treatment of minimal change chronic pancreatitis.

INTRODUCTION: The current standard of care for the management of minimal change chronic pancreatitis (MCCP) is medical management. Controversy exists, however, regarding the use of surgical intervention for MCCP. We hypothesized that total pancreatectomy and islet cell autotransplantation (TPIAT) decreases long-term resource utilization and improves quality of life, justifying initial costs and risks. METHODS: Detailed perioperative outcomes from 46 patients with MCCP populated a Markov model comparing medical management to TPIAT. Mortality, complications, readmission rates, insulin and narcotic use, imaging, and endoscopy were included in the model. Outcomes reported were survival, measured in quality-adjusted life years (QALYs), and costs, in 2013 US dollars. RESULTS: In medical patients, annual mean hospital admissions were 1.6 (range = 0-11), endoscopy 1.4 (0-6), and imaging (CT/MRI) 1.5 (0-4). In surgical patients, there were no perioperative deaths, with complication and 30-day readmission rates of 47 and 37%. One year after TPIAT, annual mean admissions, endoscopy, and imaging had decreased to 0.9 (0-4), 0.4 (0-2), and 0.9 (0-5); monthly narcotic use decreased from 138 to 37 morphine equivalents (p = 0.012). Cost and survival for TPIAT versus medical management were $153,575/14.9 QALYs and $196,042/11.5 QALYs, respectively. CONCLUSIONS: In patients with MCCP, TPIAT is associated with decreased cost and increased quality-adjusted survival. Providers and insurers should more enthusiastically embrace TPIAT use as a more effective cost-saving strategy.

Cost effectiveness after a pancreaticoduodenectomy: bolstering the volume argument.

BACKGROUND: The cost implication of variability in pancreatic surgery is not well described. It was hypothesized that for a pancreaticoduodenectomy (PD), lower volume centres demonstrate worse peri-operative outcomes at higher costs. METHODS: From 2009-2011, 9883 patients undergoing a PD were identified from the University HealthSystems Consortium (UHC) database and stratified into quintiles by annual hospital case volume. A decision analytic model was constructed to assess cost effectiveness. Total direct cost data were based on Medicare cost/charge ratios and included readmission costs when applicable. RESULTS: The lowest volume centres demonstrated a higher peri-operative mortality rate (3.5% versus 1.3%, P < 0.001) compared with the highest volume centres. When both index and readmission costs were considered, the per-patient total direct cost at the lowest volume centres was $23,005, or 10.9% (i.e. $2263 per case) more than at the highest volume centres. One-way sensitivity analyses adjusting for peri-operative mortality (1.3% at all centres) did not materially change the cost effectiveness analysis. Differences in cost were largely recognized in the index admission; readmission costs were similar across quintiles. CONCLUSIONS: For PD, low volume centres have higher peri-operative mortality rates and 10.9% higher cost per patient. Performance of PD at higher volume centres can lead to both better outcomes and substantial cost savings.

Frequency and intensity of postoperative surveillance after curative treatment of pancreatic cancer: a cost-effectiveness analysis.

BACKGROUND: Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy. METHODS: We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars). RESULTS: The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies' absolute costs but not the relative ranks of their ICERs. CONCLUSIONS: Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.

Cost-effectiveness of staging computed tomography of the chest in patients with T2 soft tissue sarcomas.

BACKGROUND: Published practice guidelines recommend routine chest computed tomography (CT) scanning as part of the staging evaluation for patients with T2 soft tissue sarcomas (STS), although there is no direct evidence to support this practice. The objective of this study was to determine the yield and cost-effectiveness of routine versus selective chest CT scanning for the staging of patients with T2 STS and to identify any subgroups for whom a more selective approach to chest CT scanning could be considered. METHODS: Six hundred consecutive patients with primary, nonthoracic, T2 (> 5 cm) STS underwent both chest X-ray (CXR) and chest CT scanning to evaluate the presence of pulmonary metastatic disease (M1). The authors constructed a decision tree that modeled the outcomes of diagnostic testing for two hypothetical diagnostic strategies: 1) routine chest CT (rCT) or 2) CXR and selective chest CT (sCT). The yield and cost of each strategy were determined; the incremental cost-effectiveness ratio (ICER) was calculated as the cost per additional patient with pulmonary metastases identified by rCT versus sCT. RESULTS: The yield of rCT was higher than that of sCT (M1 disease identified in 19.2% vs. 16.0% of patients, respectively), but rCT was more costly ($1301 vs. $418 per patient, respectively). The ICER of rCT compared with sCT was $27,594 per patient identified with pulmonary metastasis. The expected yields, costs, and ICERs of the diagnostic strategies varied across patient subgroups based on grade, anatomic site, and tumor size. CONCLUSIONS: For patients with T2 STS, rCT was most cost-effective in patients with high-grade lesions or extremity lesions. The findings of this study do not support the routine use of chest CT scanning in all patients with T2 STS.