Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy.

INTRODUCTION: Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery. METHODS AND ANALYSIS: This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04549662.

Minimally Invasive Compared to Open Colorectal Cancer Resection for Older Adults: A Population-based Analysis of Long-term Functional Outcomes.

OBJECTIVE: We sought to compare long-term healthcare dependency and time-at-home between older adults undergoing minimally invasive surgery (MIS) for colorectal cancer (CRC) and those undergoing open resection. BACKGROUND: Although the benefits of MIS for CRC resection are established, data specific to older adults are lacking. Long-term functional outcomes, central to decision-making in the care for older adults, are unknown. METHODS: We performed a population-based analysis of patients ≥70years old undergoing CRC resection between 2007 to 2017 using administrative datasets. Outcomes were receipt of homecare and "high" time-at-home, which we defined as years with ≤14 institution-days, in the 5years after surgery. Homecare was analyzed using time-to-event analyses as a recurrent dichotomous outcome with Andersen-Gill multivariable models. High timeat-home was assessed using Cox multivariable models. RESULTS: Of 16,479 included patients with median follow-up of 4.3 (interquartile range 2.1-7.1) years, 7822 had MIS (47.5%). The MIS group had lower homecare use than the open group with 22.3% versus 31.6% at 6 months and 14.8% versus 19.4% at 1 year [hazard ratio 0.87,95% confidence interval (CI) 0.83-0.92]. The MIS group had higher probability ofhigh time-at-home than open surgery with 54.9% (95% CI 53.6%-56.1%) versus 41.2% (95% CI 40.1%-42.3%) at 5years (hazard ratio 0.71, 95% CI 0.68-0.75). CONCLUSIONS: Compared to open surgery, MIS for CRC resection was associated with lower homecare needs and higher probability of high time-at-home in the 5 years after surgery, indicating reduced long-term functional dependence. These are important patient-centered endpoints reflecting the overall long-term treatment burden to be taken into consideration in decision-making.

PATCH-DP: a single-arm phase II trial of intra-operative application of HEMOPATCH™ to the pancreatic stump to prevent post-operative pancreatic fistula following distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the most significant cause of morbidity following distal pancreatectomy. Hemopatch™ is a thin, bovine collagen-based hemostatic sealant. We hypothesized that application of Hemopatch™ to the pancreatic stump following distal pancreatectomy would decrease the incidence of clinically-significant POPF. METHODS: We conducted a prospective, single-arm, multicentre phase II study of application of Hemopatch™ to the pancreatic stump following distal pancreatectomy. The primary outcome was clinically-significant POPF within 90 days of surgery. A sample size of 52 patients was required to demonstrate a 50% relative reduction in Grade B/C POPF from a baseline incidence of 20%, with a type I error of 0.2 and power of 0.75. Secondary outcomes included incidence of POPF (all grades), 90-day mortality, 90-day morbidity, re-interventions, and length of stay. RESULTS: Adequate fixation Hemopatch™ to the pancreatic stump was successful in all cases. The rate of grade B/C POPF was 25% (95%CI: 14.0-39.0%). There was no significant difference in the incidence of grade B/C POPF compared to the historical baseline (p = 0.46). The 90-day incidence of Clavien-Dindo grade ≥3 complications was 26.9% (95%CI: 15.6-41.0%). CONCLUSION: The use of Hemopatch™ was not associated with a decreased incidence of clinically-significant POPF compared to historical rates. (NCT03410914).

Determining the Independent Risk Factors for Worse SCAR-Q Scores and Future Scar Revision Surgery.

BACKGROUND: Scar revisions have been increasing in number. Patient-reported outcome measures are one tool to aid scar modulation decision-making. The aims of this study were to determine patient, scar, and clinical risk factors for (1) low SCAR-Q Appearance, Symptom, and Psychosocial Impact scores and how this differs for children; and (2) the potential need for future scar revision surgery to better identify such patients in a clinical setting. METHODS: A multicenter international cross-sectional cohort study based on survey data of participants with traumatic, surgical, and burn scars attending plastic, hand, and burn clinics in four countries was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Univariate analysis to identify risk factors and multivariable logistic analysis to select risk factors were completed. Collinearity for nonindependent factors and C statistic for model discrimination were also calculated. RESULTS: Seven hundred thirty-one participants completed the study booklet, and 546 participants (74.7 percent) had full data. Independent risk factors were determined to be a bothersome scar and perception of scarring badly for all three scales. Risk factors for self-reporting the need for future surgery included a health condition, scarring badly, scar diagnosis, prior scar revision, and low Psychosocial Impact scores. We did not identify evidence of multicollinearity. C statistics were high (0.81 to 0.84). CONCLUSIONS: This study is the first multicenter international study to examine independent risk factors for low patient-reported outcome measure scores and the potential need for future scar revision surgery. Patients that perceive themselves as scarring badly and having a bothersome scar were at a higher risk of scar appearance concern, an increased symptom burden, and poorer psychosocial impact scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Hospital-level Variation in the Management and Outcomes of Patients With Adhesive Small Bowel Obstruction: A Population-Based Analysis.

OBJECTIVE: Determine the association between the rate of early operative management for adhesive small bowel obstruction (aSBO) at the hospital-level and the incidence of morbidity and mortality. BACKGROUND: Mounting evidence of the benefits of early operation in patients with aSBO has translated to both an increase in the proportion of patients treated operatively, and the proportion of patients who undergo early operative management. However, variation in practice remains. METHODS: We identified a population-based cohort of patients (18-80 years) who were admitted with their first episode of aSBO (2005-2014). The exposures of interest were hospital characteristics and the primary outcome measure was 30-day mortality. Hierarchical logistic regression models were used to evaluate hospital-level variation on 30-day mortality, serious complications, and bowel resection. RESULTS: A total of 27,026 patients were admitted to 122 hospitals, 23% (n = 6090) were managed operatively, 7% (n = 1845) had a serious complication, and 30-day mortality was 4.2% (n = 1146). The proportion of patients managed with early operation ranged from 0% to 33% [median 10% (interquartile range: 5%-14%)]. There was a 17% lower likelihood of 30-day mortality for every 10% increase in proportion of patients managed with an early operation at the hospital-level (odds ratio: 0.83, 95% confidence interval: 0.70-0.99). CONCLUSIONS: Hospitals with a higher proportion of aSBO patients treated with an early operation had a lower likelihood of serious complications, bowel resection, and death, independent of hospital type and volume of aSBO admissions. Early operative intervention rates likely are a proxy for additional structures and processes of care focused on aSBO patients that may facilitate patient selection.

The impact of tranexamic acid on administration of red blood cell transfusions for resection of colorectal liver metastases.

BACKGROUND: Red blood cell transfusions (RBCT) remain a concern for patients undergoing hepatectomy. The effect of tranexamic acid (TXA), an anti-fibrinolytic, on receipt of RBCT in colorectal liver metastases (CRLM) resection was examined. METHODS: Hepatectomies for CRLM over 2009-2014 were included. Primary outcome was 30-day receipt of RBCT. Secondary outcomes were 30-day major morbidity (Clavien-Dindo III-V) and 90-day mortality. Multivariable modelling examined the adjusted association between TXA and outcomes. RESULTS: Of 433 included patients, 146 (34%) received TXA. TXA patients were more likely to have inflow occlusion (41.8% vs. 23.1%; p < 0.01) and major hepatectomies (56.1% vs. 45.6%; p = 0.0193). TXA was independently associated with lower risk of RBCT (Relative risk (RR) 0.59; 95% confidence interval (95%CI): 0.42-0.85), but not with 30-day major morbidity (adjusted RR 1.02; 95%CI: 0.64-1.60) and 90-day mortality (univariable RR 0.99; 95%CI: 0.95-1.03). CONCLUSION: Intraoperative TXA was associated with a 41% reduction in risk of 30 -day receipt of RBCT after hepatectomy for CRLM. This finding is important to potentially improve healthcare resource allocation and patient outcomes. Pending further evidence, intraoperative TXA may be an effective method of reducing RBCT in hepatectomy for CRLM.

Longer Trials of Non-operative Management for Adhesive Small Bowel Obstruction Are Associated with Increased Complications.

BACKGROUND: Current guidelines for the management of adhesive small bowel obstruction suggest a limited trial of non-operative management, often of 3-5 days. A longer delay to operation may worsen post-operative outcomes in patients who ultimately require operation. Our objective was to evaluate the impact of time to operation on post-operative outcomes in patients who undergo operation following a trial of non-operative management for adhesive small bowel obstruction. METHODS: We used health administrative data to identify patients with adhesive small bowel obstruction who underwent operative management following a trial of non-operative management from 2005 to 2014 in the province of Ontario, Canada. We used multivariable logistic regression to examine the relationship between the time from admission to operation with rates of 30-day mortality, serious complication, and bowel resection. RESULTS: Three thousand five hundred sixty-three patients underwent operation after a trial of non-operative management for adhesive small bowel obstruction. Older patients, patients with a high comorbidity burden, and patients with a lower socioeconomic status were more likely to experience a longer pre-operative period. After adjusting for covariates, each additional day from admission to operation increased odds of serious complication (OR = 1.07, 95% CI = 1.03-1.11) and bowel resection (OR = 1.06, 95% CI = 1.03-1.98). Longer times to operation were not associated with greater adjusted odds of 30-day mortality. CONCLUSION: Each additional day from admission to operation is associated with greater odds of adverse outcomes. Clinical practice guidelines should emphasize strategies that identify patients who will ultimately require operation.

Surgery for adhesive small-bowel obstruction is associated with improved long-term survival mediated through recurrence prevention: A population-based, propensity-matched analysis.

BACKGROUND: Adhesive small-bowel obstruction (aSBO) is among the most common reasons for admission to a surgical service. While operative intervention for aSBO is associated with a lower risk of recurrence, current guidelines continue to advocate a trial of nonoperative management. The impact of the increased risk for recurrence on long-term survival is unknown. We sought to explore the potential for improved survival with operative management through the prevention of admissions for recurrence of aSBO and the associated risks. METHODS: This is a population-based retrospective cohort study using administrative data. We identified patients admitted to hospital for their first episode of aSBO from 2005 to 2014 and created a propensity-matched cohort to compare survival of patients managed operatively with those managed nonoperatively. To test whether survival differences were mediated by recurrence prevention, a competing risk regression was used to model the subdistribution hazard of death when accounting for the risk of recurrence. An instrumental variable approach was used as a secondary analysis to compare survival while accounting for unmeasured confounding. RESULTS: There were 27,904 patients admitted for their first episode of aSBO between 2005 and 2014. The mean age was 61.2 years (std dev, 13.6), and 51% were female. Operative management was associated with a significantly lower risk of death (hazard ratio, 0.80; 95% confidence interval, 0.75-0.86), which was robust to instrumental variable analyses, and a lower risk of recurrence (hazard ratio, 0.59; 95% confidence interval, 0.54-0.65). When adjusting for the risk of recurrence, operative intervention was not associated with improved survival, suggesting that the survival benefit is mediated through prevention of recurrences of aSBO. CONCLUSION: In patients admitted for their first episode of aSBO, operative intervention is associated with a significant long-term survival benefit. This survival benefit appears to be mediated through the prevention of recurrences of aSBO. STUDY TYPE: Retrospective cohort study. LEVEL OF EVIDENCE: Therapeutic study, Level II.

Association of Surgical Intervention for Adhesive Small-Bowel Obstruction With the Risk of Recurrence.

Importance: Adhesive small-bowel obstruction (aSBO) is a potentially chronic, recurring surgical illness. Although guidelines suggest trials of nonoperative management, the long-term association of this approach with recurrence is poorly understood. Objective: To compare the incidence of recurrence of aSBO in patients undergoing operative management at their first admission compared with nonoperative management. Design, Setting, and Participants: This longitudinal, propensity-matched, retrospective cohort study used health administrative data for the province of Ontario, Canada, for patients treated from April 1, 2005, through March 31, 2014. The study population included adults aged 18 to 80 years who were admitted for their first episode of aSBO. Patients with nonadhesive causes of SBO were excluded. A total of 27 904 patients were included and matched 1:1 by their propensity to undergo surgery. Factors used to calculate propensity included patient age, sex, comorbidity burden, socioeconomic status, and rurality of home residence. Data were analyzed from September 10, 2017, through October 4, 2018. Exposures: Operative vs nonoperative management for aSBO. Main Outcomes and Measures: The primary outcome was the rate of recurrence of aSBO among those with operative vs nonoperative management. Time-to-event analyses were used to estimate hazard ratios of recurrence while accounting for the competing risk of death. Results: Of 27 904 patients admitted with their first episode of aSBO, 6186 (22.2%) underwent operative management. Mean (SD) patient age was 61.2 (13.6) years, and 51.1% (14 228 of 27 904) were female. Patients undergoing operative management were younger (mean [SD] age, 60.2 [14.3] vs 61.5 [13.4] years) with fewer comorbidities (low burden, 382 [6.2%] vs 912 [4.2%]). After matching, those with operative management had a lower risk of recurrence (13.0% vs 21.3%; hazard ratio, 0.62; 95% CI, 0.56-0.68; P < .001). The 5-year probability of experiencing another recurrence increased with each episode until surgical intervention, at which point the risk of subsequent recurrence decreased by approximately 50%. Conclusions and Relevance: According to this study, operative management of the first episode of aSBO is associated with significantly reduced risk of recurrence. Guidelines advocating trials of nonoperative management for aSBO may assume that surgery increases the risk of recurrence putatively through the formation of additional adhesions. The long-term risk of recurrence of aSBO should be considered in the management of this patient population.

Evolving Management Strategies in Patients with Adhesive Small Bowel Obstruction: a Population-Based Analysis.

BACKGROUND: In patients with adhesive small bowel obstruction (aSBO), the decision to operate as well as the timing and technique of surgery have significant impacts on clinical outcomes. Trends in the management of aSBO have not been described at the population level and guideline adherence is unknown. We sought to evaluate the secular trends in the management of aSBO in a large North American population. METHODS: We used administrative data to identify patients admitted to hospital for their first episode of aSBO over 2005-2014. We evaluated temporal trends in admission for aSBO and in management practices using Cochran-Armitage tests. Multivariable logistic regressions were used to assess trends when controlling for potential confounders. RESULTS: Patients (40,800) were admitted with their first episode of aSBO. The mean age was 68.5 years and 55% of patients were female. The population-based rate of admission for aSBO decreased over the study period, from 39.1 to 38.1 per 100,000 persons per year. There was a significant increase in the proportion of patients who underwent surgery for aSBO (19 to 23%, p < 0.0001). Among those who underwent surgery, there were significant increases in the proportions of patients who underwent laparoscopic procedures (4 to 14%, p < 0.0001) and who underwent surgery within 1 day of admission (51 to 60%, p < 0.0001). CONCLUSION: Between 2005 and 2014, there was a decrease in the population-based rate of aSBO, which may reflect increased utilization of minimally invasive techniques. There were significant trends towards increased operative intervention, with surgery occurring earlier and increasingly using laparoscopic approach.

Medial Open Transversus Abdominis Plane (MOTAP) Catheters Reduce Opioid Requirements and Improve Pain Control Following Open Liver Resection: A Multicenter, Blinded, Randomized Controlled Trial.

OBJECTIVE: Conventional management of pain following open liver resection involves intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. The objective of this trial was to assess the efficacy of a regional technique called Medial Open Transversus Abdominis Plane (MOTAP) catheter analgesia compared with IV PCA. METHODS: This was a blinded, randomized, controlled parallel-arm trial conducted at 2 high-volume centers. Patients undergoing liver resection through a subcostal incision were enrolled. Using a standardized technique, 2 catheters were placed after resection: one in the plane between internal oblique and transversus abdominis and the other in the posterior rectus sheath. Patients were randomized to receive ropivacaine 0.2% (ROP) or saline (NS) through both catheters for 72 hours. All patients received IV PCA with hydromorphone as part of a multimodality analgesia program. Primary outcome was opioid use over the first 48 hours. RESULTS: One hundred fifty-three patients were included in the analysis (71 ROP, 82 NS). Patients receiving ROP used significantly less opioid than patients with NS at 48 hours (median 39.6 mg morphine-equivalent vs 49.2 mg, P = 0.033) and at 72 hours (median 50.0 vs 66.4 mg, P = 0.046). Pain scores at rest and with coughing were significantly lower at all time points in patients who received ROP (P = 0.002). Median length of hospital stay was 5 days in patients receiving ROP and 6 days in patients who received NS (P = 0.035). There was no difference between groups in complications [ROP 20 (28.2%) vs NS 26 (31.7%), P = 0.63]. CONCLUSION: MOTAP catheter analgesia reduces opioid requirements, pain, and length of hospital stay compared with IV PCA following open liver resection with subcostal incisions.

Approach to asymptomatic paraesophageal hernia: watchful waiting or elective laparoscopic hernia repair?

BACKGROUND: There is no consensus on whether asymptomatic paraesophageal hernia (PEH) should be operated. Some argue that surgery is necessary prophylaxis against potentially catastrophic consequences of acute complications in untreated PEH. Others reason that the acute complications are rare and emergent operations have relatively low mortality. In the laparoscopic era, elective operations have become safer and less morbid. However, recent studies report high incidence of recurrent hernia, some of which affect quality of life and require further interventions. In light of these new findings, we investigated whether asymptomatic PEH should receive elective laparoscopic hernia repair (ELHR) or watchful waiting (WW). METHODS: A Markov Monte Carlo microsimulation decision analysis model followed a hypothetical cohort of asymptomatic PEH patients who have predominantly female gender and normally distributed mean age of 62.5 years for the lifetime. Accrued health benefits expressed in quality-adjusted life months (QALM) were compared between two strategies: WW and ELHR. Two-dimensional simulations were performed to account for uncertainties in the model. Deterministic sensitivity analyses were performed to test key assumptions. RESULTS: After considering both individual- and parameter-level uncertainties in the two-dimensional simulations, WW was the superior strategy in 82% of the simulations, accumulating mean 5 QALM more than ELHR (168 vs. 163). Our model was robust to deterministic sensitivity analyses and was internally validated, which supported the validity of our results. CONCLUSIONS: Patients with asymptomatic PEH are more likely to achieve greater health outcomes if they undergo WW as initial treatment than ELHR.

Elevated Lactate is Independently Associated with Adverse Outcomes Following Hepatectomy.

BACKGROUND: Arterial lactate is frequently monitored to indicate tissue hypoxia and direct therapy. We sought to determine whether early post-hepatectomy lactate (PHL) is associated with adverse outcomes and define factors associated with PHL. METHODS: Hepatectomy patients at a single institution from 2003 to 2012 with PHL available were included. Univariable and multivariable analyses examined factors associated with PHL and the relationship between PHL and 30-day major morbidity (Clavien grade III-V), 90-day mortality, and length of stay (LOS). RESULTS: Of 749 hepatectomies, 490 were included of whom 71.4% had elevated PHL (≥2 mmol/L). Cirrhosis (coefficient 0.31, p = 0.039), Charlson comorbidity index (coefficient 0.05, p < 0.001), major resections (coefficient 0.34, p < 0.001), procedure time (coefficient 0.08, p < 0.001), and blood loss (coefficient 0.11, p < 0.001) were associated with PHL. As lactate increased from <2 to ≥6 mmol/L, morbidity rose from 11.6 to 40.6%, and mortality from 0.7 to 22.7%. PHL was independently associated with 90-day mortality (OR 1.52 p < 0.001) and 30-day morbidity (OR 1.19, p = 0.002), but not LOS (rate ratio 1.03, p = 0.071). CONCLUSION: Patients with elevated PHL in the initial postoperative period should be carefully monitored due to increased risk of major morbidity and mortality. Further research on the impact of lactate-directed fluid therapy is warranted.

Laparoscopic Surgery for Adhesive Small Bowel Obstruction Is Associated With a Higher Risk of Bowel Injury: A Population-based Analysis of 8584 Patients.

OBJECTIVE: We set out to compare the incidence of bowel repair and/or resection in a large cohort of patients with adhesive small bowel obstruction (SBO) managed operatively. BACKGROUND: Laparoscopic lysis of adhesions for adhesive SBO (aSBO) is becoming more common, yet might increase the risk of bowel injury given the distended and/or potentially compromised small bowel. METHODS: We used administrative discharge data derived from a large geographic region, identifying patients who underwent surgery for their first episode of aSBO during 2005 to 2014. Procedure codes were used to determine the exposure: either an open approach or a laparoscopic approach (including procedures converted to open). The primary outcome was incidence of bowel intervention, defined as intraoperative enterotomy, suture repair of intestine, or bowel resection. We estimated the odds of bowel intervention after adjusting for patient and clinical factors. RESULTS: A total of 8584 patients underwent operation for aSBO. Patients undergoing laparoscopic procedures were younger with fewer comorbid conditions. The rate of laparoscopic approaches increased more than 3-fold during the study period (4.3%-14.3%, P < 0.0001). The incidence of bowel intervention was 53.5% versus 43.4% in laparoscopic versus open procedures (P < 0.0001). After adjustment for potential confounders, the odds of bowel intervention among patients treated laparoscopically versus open was 1.6 (95% confidence interval: 1.4-1.9). CONCLUSIONS: Laparoscopic procedures for aSBO are associated with a greater likelihood of intervention for bowel injury and/or repair. This increase might be due to challenges inherent with laparoscopic approaches in patients with distended small bowel. Surgeons should approach laparoscopic lysis of adhesions with a higher level of awareness and use strategies to mitigate this risk.

Pasireotide for the Prevention of Pancreatic Fistula Following Pancreaticoduodenectomy: A Cost-effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of perioperative administration of pasireotide for reduction of pancreatic fistula (PF). SUMMARY: PF is a major complication following pancreaticoduodenectomy (PD), associated with significant morbidity and healthcare-related costs. Pasireotide is a novel multireceptor ligand somatostatin analogue, which has been demonstrated to reduce the incidence of PF following pancreas resection; however, the drug cost is significant. This study sought to estimate the cost-effectiveness of routine administration of pasireotide to patients undergoing PD, compared with no intervention from the perspective of the hospital system. METHODS: A decision-analytic model was developed to compare costs for perioperative administration of pasireotide versus no pasireotide. The model was populated using an institutional database containing all PDs performed 2002 to 2012 at a single institution, including data regarding clinically significant PF (International Study Group on Pancreatic Fistula Grade B or C) and hospital-related inpatient costs for 90 days following PD, converted to 2014 $USD. Relative risk of PF associated with pasireotide was estimated from the published literature. Deterministic and probabilistic sensitivity analyses were performed to test robustness of the model. RESULTS: Mean institutional cost of index admissions was $67,417 and $31,950 for patients with and without PF, respectively. Pasireotide was the dominant strategy, associated with savings of $1685, and a mean reduction of 1.5 days length of stay. Univariate sensitivity analyses demonstrated cost-savings down to a PF rate of 5.6%, up to a relative risk of PF of 0.775, and up to a drug cost of $2817. Probabilistic sensitivity analysis showed 79% of simulations were cost saving. CONCLUSIONS: Pasireotide appears to be a cost-saving treatment following PD across a wide variation of clinical and cost scenarios.

Impact of fluid resuscitation on major adverse events following pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy remains a major undertaking with substantial perioperative morbidity and mortality. Previous studies in the colorectal population have noted a correlation between excessive postoperative fluid resuscitation and anastomotic complications. This study sought to assess the relationship between perioperative fluid management and clinical outcomes in patients undergoing pancreaticoduodenectomy. METHODS: Data from a single institution, prospective database over a 10-year period (2002 to 2012) were reviewed. Patients were compared for perioperative fluid balance and postoperative outcomes. Multivariable analysis was performed to assess the relationship between perioperative fluid administration and incidence of major adverse events. RESULTS: Higher positive fluid balance on postoperative day 0, postoperative day 1, and postoperative day 2 was associated with increased incidence of major adverse events, increased postoperative intensive care unit admission, and longer hospital stay. Higher positive fluid balance on postoperative day 0 was most strongly associated with postoperative morbidity (odds ratio 1.39, confidence interval 1.16 to 1.66, P = .0003). Fluid balance on postoperative day 3 was not associated with adverse events. CONCLUSIONS: Increased early perioperative fluid resuscitation is associated with major adverse events in patients undergoing pancreaticoduodenectomy. More restrictive fluid administration may improve postoperative outcomes; further prospective clinical trials focused on fluid resuscitation and goal-directed therapy are needed.

The Effect of Early Postoperative Non-Steroidal Anti-Inflammatory Drugs on Pancreatic Fistula Following Pancreaticoduodenectomy.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are used commonly for postoperative analgesia but can potentially impair healing. Their effect on pancreaticoduodenectomy (PD) outcomes is unknown. We sought to examine the impact of early postoperative NSAIDs on pancreatic fistula (PF) after PD. METHODS: We reviewed our prospective pancreatectomy database supplemented by medication administration records, including all PDs from 2002 to 2012. Primary outcome was occurrence of clinically significant (grade B-C) PF. Secondary outcomes included major morbidity (Clavien grade III-V) and 90-day mortality. Patients were compared based on early postoperative NSAID use (first 3 days following surgery) using univariate and multivariate analyses. Subgroup analyses were conducted based on NSAID type (COX-2 inhibitors and non-selective inhibitors). RESULTS: We included 251 PDs, of whom 127 (50.6%) patients received NSAIDs postoperatively (35.5% COX-2 inhibitors, 18.3% non-selective inhibitors, and 4.4% both). Use of any NSAIDs was associated with a non-significant increase in PF (16.5 vs 11.3%%; p = 0.23), and no difference in major morbidity and mortality. Use of non-selective inhibitors was not associated with an increase in PF (8.7 vs 15.1%; p = 0.256). COX-2 inhibitors were associated with increased PF (20.2 vs 10.5 %; p = 0.033), but no difference in major morbidity or mortality. After adjusting for Charlson comorbidity and estimated blood loss, use of COX-2 inhibitors was independently associated with PF (odds ratio 2.12; p = 0.044). CONCLUSIONS: COX-2 inhibitors are associated with PF in the early postoperative period. While non-selective inhibitors appear safe in this setting, caution is warranted with the use of COX-2 inhibitors.

Adherence to Guidelines for Adjuvant Imatinib Therapy for GIST: A Multi-institutional Analysis.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy improves recurrence-free and overall survival following surgery for patients with high-risk GIST; however, the factors associated with use of adjuvant imatinib therapy are unclear, and adherence to adjuvant imatinib has not been investigated. We sought to determine the clinicopathologic predictors of therapy with adjuvant imatinib following surgical resection for GIST and to determine the utilization of adjuvant imatinib in patients who underwent surgical resection of primary GIST in 2009 or later as recommended by National Comprehensive Cancer network (NCCN) guidelines. METHODS: A multi-institutional cohort including 171 patients who underwent surgery for primary GIST at seven high-volume cancer centers in the USA and Canada between January 2009-December 2012 was used in this study. Receipt of adjuvant imatinib therapy was ascertained, and factors associated with imatinib therapy were analyzed. RESULTS: Following surgery for primary GIST, tumor size (<5.0 cm: ref; 5.0-9.9 cm: odds ratio (OR) 2.36, 95 % confidence interval (CI) 0.74-7.55; >10.0 cm: OR 9.15, 95 % CI 2.28-36.75; p = 0.007), mitotic rate (≤5/50 mitoses per 50 high powered field [HPF]: ref; 6-10/50 HPF: OR 24.91, 95 % CI 3.64-170.35; >10/50 HPF: OR 5.80, 95 % CI 3.64-170.35; p < 0.001), and neoadjuvant therapy (OR 9.52; 95 % CI 2.51-36.14; p = 0.001) were associated with receipt of adjuvant imatinib therapy. Overall, 75 % of patients received appropriate treatment, 23 % of patients were undertreated, and 2 % of patients were overtreated as compared to NCCN guidelines. Adjuvant imatinib therapy was administered in only 53 % of patients for which the NCCN guidelines recommended adjuvant therapy. CONCLUSION: The clinicopathologic factors associated with use of adjuvant imatinib therapy in patients following resection of primary GIST are consistent with established risk factors for recurrence. Adjuvant imatinib therapy remains underutilized in patients with intermediate and high-risk GIST and in patients who receive neoadjuvant therapy. Barriers to adjuvant imatinib therapy in this group of patients needs to be further explored.