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.

Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.

IMPORTANCE: Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients. OBJECTIVE: To evaluate clinical outcomes when HAI chemotherapy is combined with systemic chemotherapy in patients with unresectable IHC. DESIGN, SETTING, AND PARTICIPANTS: A single-institution, phase 2 clinical trial including 38 patients was conducted with HAI floxuridine plus systemic gemcitabine and oxaliplatin in patients with unresectable IHC at Memorial Sloan Kettering Cancer Center between May 20, 2013, and June 27, 2019. A confirmatory phase 1/2 study using the same therapy was conducted during the same time period at Washington University in St Louis. Patients with histologically confirmed, unresectable IHC were eligible. Resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted. Patients with distant metastatic disease were excluded. INTERVENTIONS: Hepatic arterial infusion of floxuridine and systemic administration of gemcitabine and oxaliplatin. MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival (PFS) of 80% at 6 months. RESULTS: For the phase 2 clinical trial at Memorial Sloan Kettering Cancer Center, 42 patients with unresectable IHC were included and, of these, 38 patients were treated (13 [34%] men; median [range] age at diagnosis, 64 [39-81] years). The median follow-up was 30.5 months. Twenty-two patients (58%) achieved a partial radiographic response, and 32 patients (84%) achieved disease control at 6 months. Four patients had sufficient response to undergo resection, and 1 patient had a complete pathologic response. The median PFS was 11.8 months (1-sided 90% CI, 11.1) with a 6-month PFS rate of 84.1% (90% CI, 74.8%-infinity), thereby meeting the primary end point (6-month PFS rate, 80%). The median OS was 25.0 months (95% CI, 20.6-not reached), and the 1-year OS rate was 89.5% (95% CI, 80.2%-99.8%). Patients with resectable regional lymph nodes (18 [47%]) showed no difference in OS compared with patients with node-negative disease (24-month OS: lymph node negative: 60%; 95% CI, 40%-91% vs lymph node positive: 50%; 95% CI, 30%-83%; P = .66). Four patients (11%) had grade 4 toxic effects requiring removal from the study (1 portal hypertension, 2 gastroduodenal artery aneurysms, 1 infection in the pump pocket). Subgroup analysis showed significant improvement in survival in patients with IDH1/2 mutated tumors (2-year OS, 90%; 95% CI, 73%-99%) vs wild-type (2-year OS, 33%; 95% CI, 18%-63%) (P = .01). In the Washington University in St Louis confirmatory cohort, 9 patients (90%) achieved disease control at 6 months; the most common grade 3 toxic effect was elevated results of liver function tests, and median PFS was 12.8 months (1-sided 90% CI, 6.4). CONCLUSIONS AND RELEVANCE: Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable IHC; further evaluation is warranted.

Surgeon Variation in Intraoperative Supply Cost for Pancreaticoduodenectomy: Is Intraoperative Supply Cost Associated with Outcomes?

BACKGROUND: With increased scrutiny on the quality and cost of health care, surgeons must be mindful of their outcomes and resource use. We evaluated surgeon-specific intraoperative supply cost (ISC) for pancreaticoduodenectomy and examined whether ISC was associated with patient outcomes. STUDY DESIGN: Patients undergoing open pancreaticoduodenectomy between January 2012 and March 2015 were included. Outcomes were tracked prospectively through postoperative day 90, and ISC was defined as the facility cost of single-use surgical items and instruments, plus facility charges for multiuse equipment. Multivariate logistic regression was used to test associations between ISC and patient outcomes using repeated measures at the surgeon level. RESULTS: There were 249 patients who met inclusion criteria. Median ISC was $1,882 (interquartile range [IQR] $1,497 to $2,281). Case volume for 6 surgeons ranged from 18 to 66. Median surgeon-specific ISC ranged from $1,496 to $2,371. Greater case volume was associated with decreased ISC (p < 0.001). Overall, ISC was not predictive of postoperative complications (p = 0.702) or total hospitalization expenditures (p = 0.195). At the surgeon level, surgeon-specific ISC was not associated with the surgeon-specific incidence of severe complication or any wound infection (p > 0.227 for both), but was associated with delayed gastric emptying (p = 0.004) and postoperative pancreatic fistula (p < 0.001). CONCLUSIONS: In a single-institution cohort of 249 pancreaticoduodenectomies, high-volume surgeons tended to be low-cost surgeons. Across the cohort, ISC was not associated with outcomes. At the surgeon level, associations were noted between ISC and complications, but these may be attributable to unmeasured differences in the postoperative management of patients. These findings suggest that quality improvement efforts to restructure resource use toward more cost-effective practice may not affect patient outcomes, although prospective monitoring of safety and effectiveness must be of the utmost concern.

Comparing the burden of pancreatic fistulas after pancreatoduodenectomy and distal pancreatectomy.

BACKGROUND: Differences in the behavior of postoperative pancreatic fistulas (POPF) have been described after various pancreatic resections. Here, we compare POPFs after pancreatoduodenectomy (PD) and distal pancreatectomy (DP) using the average complication burden (ACB), a quantitative measure of complication burden. METHODS: From 2001 to 2014, 837 DPs and 1,533 PDs were performed by 14 surgeons at 4 institutions. POPFs were categorized by International Study Group on Pancreatic Fistula standards as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). ACB values were derived from fistula severity scores based on the Modified Accordion Severity Grading. The ACB of POPFs was compared between PD and DP. RESULTS: POPFs were more common after DP compared with PD (34.5 vs 27.2%; P < .001); however, the incidence of any complication was greater after PD (64.9 vs 53.2%; P < .001). When POPFs occurred, they were more likely to be the highest-graded complication after DP compared with PD (65.1 vs 51.6%; P < .001). ACB significantly varied between PDs and DPs for grade C POPFs (0.804 vs 0.611; P < .001). POPFs accounted for 31.2% of the overall complication burden after DP compared with 17.5% of the burden after PD. ACB differed significantly across both institutions and surgeons in terms of POPFs, nonfistulous complications, and overall complications (all P < .05). CONCLUSION: Although POPFs occur less frequently after PD, they are associated with a greater complication burden compared with DP. ACB varies significantly between health care providers, suggesting the need for risk-adjusted comparisons of complication severity. Using ACB to evaluate a distinct morbidity has the potential to aid in assessing the impact of procedure-specific complications.

Cost variation in a laparoscopic cholecystectomy and the association with outcomes across a single health system: implications for standardization and improved resource utilization.

BACKGROUND: Payers and regulatory bodies are increasingly placing emphasis on cost containment, quality/outcome measurement and transparent reporting. Significant cost variation occurs in many operative procedures without a clear relationship with outcomes. Clear cost-benefit associations will be necessary to justify expenditures in the era of bundled payment structures. METHODS: All laparoscopic cholecystectomies (LCCKs) performed within a single health system over a 1-year period were analysed for operating room (OR) supply cost. The cost was correlated with American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) outcomes. RESULTS: From July 2013 to June 2014, 2178 LCCKs were performed by 55 surgeons at seven hospitals. The median case OR supply cost was $513 ± 156. There was variation in cost between individual surgeons and within an individual surgeon's practice. There was no correlation between cost and ACS NSQIP outcomes. The majority of cost variation was explained by selection of trocar and clip applier constructs. CONCLUSIONS: Significant case OR cost variation is present in LCCK across a single health system, and there is no clear association between increased cost and NSQIP outcomes. Placed within the larger context of overall cost, the opportunity exists for improved resource utilization with no obvious risk for a reduction in the quality of care.

The impact of recent hospitalization on surgical site infection after a pancreatectomy.

BACKGROUND: Surgical site infections (SSI) are a major cause of increased morbidity and cost after a pancreatectomy. Patients undergoing a pancreatectomy frequently have had recent inpatient hospital admissions prior to their surgical admission (recent pre-surgical admission, RPSA), which could increase the risk of SSI. METHODS: The 2009-2011 Healthcare Cost Utilization Project California State Inpatient Database was used. Chi-square tests, Student's t-tests and multivariable logistic regression were used. RESULTS: Three thousand three hundred and seventy-six patients underwent a pancreatectomy, and 444 (13.2%) had RPSA. One hundred and eighty (40.5%) RPSAs were to different hospitals other than where patients' pancreatectomy took place. In univariate analysis, patients with RPSA had a significantly higher rate of post-operative SSIs, and this was associated with a longer length of post-operative stay, higher post-operative hospital costs and increased postoperative 30-day readmission rates (Table 1). In Multivariate analysis, RPSA was an independent predictor of post-operative SSI [odds ratio (OR) = 1.68, P = 0.013], and the risk of SSI increased with increasing RPSA length of stay (OR = 1.07 per day, P = 0.001). CONCLUSIONS: Recent pre-surgical admission is an important risk factor for SSI after a pancreatectomy. Many patients with RPSA are not admitted pre-operatively to the same hospital where the pancreatectomy occurs; in such circumstances, SSI rates may not be a sole reflection of the care provided by operating hospitals.

Cost benefit analysis of mesh reinforcement of stapled left pancreatectomy.

OBJECTIVES: Pancreatic leak is a morbid complication following left pancreatectomy, which results in prolonged hospitalization, additional diagnostic testing and invasive procedures. The present authors have previously demonstrated that mesh reinforcement of stapled left pancreatectomy results in fewer pancreatic leaks. This study was conducted to investigate whether mesh reinforcement also results in cost benefits for the health care system. METHODS: A cost benefit model was developed to estimate net cost savings from the payer's perspective. The model is based on the results of a randomized, single-blinded trial of mesh versus no mesh reinforcement of the pancreatic remnant after left pancreatectomy. A two-way sensitivity analysis was conducted to determine the model's sensitivity to fluctuations in the cost of mesh and the effectiveness of the mesh in reducing clinically significant leaks. RESULTS: Average total costs for an episode of care were US$13 337 and US$15 505 for patients who did and did not receive mesh, respectively, which indicates savings of US$2168. Two-way sensitivity analysis showed that, given a probability of 1.9% for developing a clinically significant leak in patients in whom mesh reinforcement was used, the strategy would continue to save costs if mesh were priced at ≤US$1804. CONCLUSIONS: Mesh reinforcement decreases clinically significant pancreatic leaks. Despite the additional cost of mesh reinforcement, the use of mesh reinforcement results in overall cost savings for the health care system because of the resultant decrease in the occurrence of clinically significant leaks.

New diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo Guidelines.

BACKGROUND: The Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were published in 2007 as the world's first guidelines for acute cholangitis and cholecystitis. The diagnostic criteria and severity assessment of acute cholecystitis have since been widely used all over the world. A validation study of TG07 has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. In addition, considerable new evidence referring to acute cholecystitis as well as evaluations of TG07 have been published. Consequently, we organized the Tokyo Guidelines Revision Committee to evaluate TG07, recognize new evidence, and conduct a multi-center analysis to revise the guidelines (TG13). METHODS AND MATERIALS: We retrospectively analyzed 451 patients with acute cholecystitis from multiple tertiary care centers in Japan. All 451 patients were first evaluated using the criteria in TG07. The "gold standard" for acute cholecystitis in this study was a diagnosis by pathology. The validity of TG07 diagnostic criteria was investigated by comparing clinical with pathological diagnosis. RESULTS: Of 451 patients evaluated, a total of 227 patients were given a diagnosis of acute cholecystitis by pathological examination (prevalence 50.3 %). TG07 criteria provided a definite diagnosis of acute cholecystitis in 224 patients. The sensitivity of TG07 diagnostic criteria for acute cholecystitis was 92.1 %, and the specificity was 93.3 %. Based on the preliminary results, new diagnostic criteria for acute cholecystitis were proposed. Using the new criteria, the sensitivity of definite diagnosis was 91.2 %, and the specificity was 96.9 %. The accuracy rate was improved from 92.7 to 94.0 %. In regard to severity grading among 227 patients, 111 patients were classified as Mild (Grade I), 104 as Moderate (Grade II), and 12 as Severe (Grade III). CONCLUSION: The proposed new diagnostic criteria achieved better performance than the diagnostic criteria in TG07. Therefore, the proposed criteria have been adopted as new diagnostic criteria for acute cholecystitis and are referred to as the 2013 Tokyo Guidelines (TG13). Regarding severity assessment, no new evidence was found to suggest that the criteria in TG07 needed major adjustment. As a result, TG07 severity assessment criteria have been adopted in TG13 with minor changes.

New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo Guidelines.

BACKGROUND: The Tokyo Guidelines for the management of acute cholangitis and cholecystitis were published in 2007 (TG07) and have been widely cited in the world literature. Because of new information that has been published since 2007, we organized the Tokyo Guidelines Revision Committee to conduct a multicenter analysis to develop the updated Tokyo Guidelines (TG13). METHODS/MATERIALS: We retrospectively analyzed 1,432 biliary disease cases where acute cholangitis was suspected. The cases were collected from multiple tertiary care centers in Japan. The 'gold standard' for acute cholangitis in this study was that one of the three following conditions was present: (1) purulent bile was observed; (2) clinical remission following bile duct drainage; or (3) remission was achieved by antibacterial therapy alone, in patients in whom the only site of infection was the biliary tree. Comparisons were made for the validity of each diagnostic criterion among TG13, TG07 and Charcot's triad. RESULTS: The major changes in diagnostic criteria of TG07 were re-arrangement of the diagnostic items and exclusion of abdominal pain from the diagnostic list. The sensitivity improved from 82.8 % (TG07) to 91.8 % (TG13). While the specificity was similar to TG07, the false positive rate in cases of acute cholecystitis was reduced from 15.5 to 5.9 %. The sensitivity of Charcot's triad was only 26.4 % but the specificity was 95.6 %. However, the false positive rate in cases of acute cholecystitis was 11.9 % and not negligible. As for severity grading, Grade II (moderate) acute cholangitis is defined as being associated with any two of the significant prognostic factors which were derived from evidence presented recently in the literature. The factors chosen allow severity assessment to be performed soon after diagnosis of acute cholangitis. CONCLUSION: TG13 present a new standard for the diagnosis, severity grading, and management of acute cholangitis.

Evaluation and stages of surgical innovations.

Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.

No surgical innovation without evaluation: the IDEAL recommendations.

Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

Challenges in evaluating surgical innovation.

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.