Incidence of psychiatric illness in patients with neuroendocrine tumors: a comparative population-based analysis.

PURPOSE: Diversion of tryptophan to tumoral hormonal production has been suggested to result in psychiatric illnesses in neuroendocrine tumors (NET). We measured the occurrence of psychiatric illness after NET diagnosis and compare it to colon cancer (CC). METHODS: We conducted a population-based retrospective cohort study. Adults with NET were matched 1:1 to CC (2000-2019). Psychiatric illness was defined by mental health diagnoses and mental health care use after a cancer diagnosis, categorized as severe, other, and none. Cumulative incidence functions accounted for death as a competing risk. RESULTS: A total of 11,223 NETs were matched to CC controls. Five-year cumulative incidences of severe psychiatric illness for NETs vs. CC was 7.7% (95%CI 7.2-8.2%) vs 7.6% (95%CI 7.2-8.2%) (p = 0.50), and that of other psychiatric illness was 32.9% (95%CI 32.0-33.9%) vs 31.6% (95%CI 30.8-32.6%) (p = 0.005). In small bowel and lung NETs, 5-year cumulative incidences of severe (8.1% [95%CI 7.3-8.9%] vs. 7.0% [95%CI 6.3-7.8%]; p = 0.01) and other psychiatric illness (34.7% [95%CI 33.3-36.1%] vs. 31.1% [95%CI 29.7-32.5%]; p < 0.01) were higher than for matched CC. The same was observed for serotonin-producing NETs for both severe (7.9% [95%CI 6.5-9.4%] vs. 6.8% [95%CI 5.5-8.2%]; p = 0.02) and other psychiatric illness (35.4% [95%CI 32.8-38.1%] vs. 31.9% [95%CI 29.3-34.4%]; p = 0.02). CONCLUSIONS: In all NETs, there was no difference observed in the incidence of psychiatric illness compared to CC. For sub-groups of small bowel and lung NETs and of serotonin-producing NETs, the incidence of psychiatric illness was higher than for CC. These data suggest a signal towards a relationship between those sub-groups of NETs and psychiatric illness.

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).

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.

Benefits of High-Volume Medical Oncology Care for Noncurable Pancreatic Adenocarcinoma: A Population-Based Analysis.

BACKGROUND: Although pancreatic adenocarcinoma (PA) surgery performed by high-volume (HV) providers yields better outcomes, volume-outcome relationships are unknown for medical oncologists. This study examined variation in practice and outcomes in noncurative management of PA based on medical oncology provider volume. METHODS: This population-based cohort study linked administrative healthcare datasets and included nonresected PA from 2005 through 2016. The volume of PA consultations per medical oncology provider per year was divided into quintiles, with HV providers (≥16 patients/year) constituting the fifth quintile and low-volume (LV) providers the first to fourth quintiles. Outcomes were receipt of chemotherapy and overall survival (OS). The Brown-Forsythe-Levene (BFL) test for equality of variances was performed to assess outcome variability between provider-volume quintiles. Multivariate regression models were used to examine the association between management by HV provider and outcomes. RESULTS: A total of 7,062 patients with noncurable PA consulted with medical oncology providers. Variability was seen in receipt of chemotherapy and median survival based on provider volume (BFL, P<.001 for both), with superior 1-year OS for HV providers (30.1%; 95% CI, 27.7%-32.4%) compared with LV providers (19.7%; 95% CI, 18.5%-20.6%) (P<.001). After adjustment for age at diagnosis, sex, comorbidity burden, rural residence, income, and diagnosis period, HV provider care was independently associated with higher odds of receiving chemotherapy (odds ratio, 1.19; 95% CI, 1.05-1.34) and with superior OS (hazard ratio, 0.79; 95% CI, 0.74-0.84). CONCLUSIONS: Significant variation was seen in noncurative management and outcomes of PA based on provider volume, with management by an HV provider being independently associated with superior OS and higher odds of receiving chemotherapy. This information is important to inform disease care pathways and care organization. Cancer care systems could consider increasing the number of HV providers to reduce variation and improve outcomes.

Risk factors for survival following recurrence after first liver resection for colorectal cancer liver metastases.

BACKGROUND: Management of recurrence following liver resection for colorectal cancer metastases is a topic of debate. We determined risk factors for survival following recurrence after liver resection. METHODS: Long-term follow-up of patients in the PETCAM trial who had recurrence following liver resection. Risk groups were created according to their survival risk. Differences in overall survival (OS) between groups were estimated. Disease-free survival (DFS), patterns of disease recurrence and management were determined. Cox proportional hazard models, Kaplan-Meier method, and the log-rank test were used. RESULTS: Among 368 patients who underwent liver resection, 264 (72%) experienced disease recurrence (51% lung and 41% liver). Following liver resection, DFS: 17 months (95% CI, 14-19); OS: 57 months (95% CI, 46-70). In those who recurred, 120 (45%) received chemotherapy only, and 112 (42%) underwent second surgical resection. Among patients who experienced recurrence (n = 264), the high-risk group (more than one site of recurrence or disease-free duration < 5 months and node-positive disease) had median OS: 19 months (95% CI, 15-23) vs 36 months (95% CI, 30-48) for patients in the low-risk group (HR = 2.9, 95% CI, 2.2-3.9). CONCLUSION: Recurrence following liver resection is common. Following recurrence after liver resection, patients should be carefully selected for surgical re-resection based on risk factors.

Patterns of Symptoms Burden in Neuroendocrine Tumors: A Population-Based Analysis of Prospective Patient-Reported Outcomes.

BACKGROUND: How to best support patients with neuroendocrine tumors (NETs) remains unclear. Improving quality of care requires an understanding of symptom trajectories. Objective validated assessments of symptoms burden over the course of disease are lacking. This study examined patterns and risk factors of symptom burden in NETs, using patient-reported outcomes. SUBJECTS, MATERIALS, AND METHODS: A retrospective, population-based, observational cohort study of patients with NETs diagnosed from 2004 to 2015, who survived at least 1 year, was conducted. Prospectively collected patient-reported Edmonton Symptom Assessment System scores were linked to provincial administrative health data sets. Moderate-to-severe symptom scores were presented graphically for both the 1st year and 5 years following diagnosis. Multivariable Poisson regression identified factors associated with record of moderate-to-severe symptom scores during the 1st year after diagnosis. RESULTS: Among 2,721 included patients, 7,719 symptom assessments were recorded over 5 years following diagnosis. Moderate-to-severe scores were most frequent for tiredness (40%-51%), well-being (37%-49%), and anxiety (30%-40%). The proportion of moderate-to-severe symptoms was stable over time. Proportion of moderate-to-severe anxiety decreased by 10% within 6 months of diagnosis, followed by stability thereafter. Changes were below 5% for other symptoms. Similar patterns were observed for the 1st year after diagnosis. Primary tumor site, metastatic disease, younger age, higher comorbidity burden, lower socioeconomic status, and receipt of therapy within 30 days of assessment were independently associated with higher risk of elevated symptom burden. CONCLUSION: Patients with NETs have a high prevalence of moderate-to-severe patient-reported symptoms, with little change over time. Patients remain at risk of prolonged symptom burden following diagnosis, highlighting potential unmet needs. Combined with identified patient and disease factors associated with moderate-to-severe symptom scores, this information is important to support symptom management strategies to improve patient-centered care. IMPLICATIONS FOR PRACTICE: This study used population-level, prospectively collected, validated, patient-reported outcome measures to appraise the symptoms burden and trajectory of patients with neuroendocrine tumors (NETs) after diagnosis. It is the largest and most detailed analysis of patient-reported symptoms for NETs. Patients with NETs present a high burden of symptoms at diagnosis that persists up to 5 years later, highlighting unmet needs. Early and comprehensive symptom screening and management programs are needed. This information should serve to devise pathways and policies to better support patients, evaluate supportive interventions, and assess the effectiveness of symptom management at the provider, institutional, and system levels.

Symptom Burden at the End of Life for Neuroendocrine Tumors: An Analysis of 2579 Prospectively Collected Patient-Reported Outcomes.

BACKGROUND: Given a slow course of disease, end-of-life issues are understudied in neuroendocrine tumors (NETs). To date, there are no data regarding symptoms at the end of life. This study examined symptom trajectories and factors associated with high symptom burden in NETs at the end of life. METHODS: We conducted a retrospective cohort study of NET patients diagnosed from 2004 to 2015 and who died between 2007 and 2016, in Ontario, Canada. Prospectively collected patient-reported Edmonton Symptom Assessment System scores were linked to administrative healthcare datasets. Moderate-to-severe symptom scores (≥ 4 out of 10) in the 6 months before death were analyzed, with multivariable modified Poisson regression identifying factors associated with moderate-to-severe symptoms scores. RESULTS: Among 677 NET decedents, 2579 symptom assessments were recorded. Overall, moderate-to-severe scores were most common for tiredness (86%), wellbeing (81%), lack of appetite (75%), and drowsiness (68%), with these proportions increasing as death approached. For symptoms of lack of appetite, drowsiness, and shortness of breath, the increase was steepest in the 8 weeks before death. On multivariable analyses, the risk of moderate-to-severe symptoms was significantly higher in the last 2 months before death and for patients with shorter survival (< 6 months). Women had higher risks of anxiety, nausea, and pain. CONCLUSION: A high prevalence of moderate-to-severe symptoms was observed for NETs at the end of life, not previously described. The proportion of moderate-to-severe symptoms increases steeply as death nears, highlighting an opportunity for improved management. Combined with identified factors associated with moderate-to-severe symptoms, this information is important to improve patient-centred and personalized supportive care for NETs at the end of life.

Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases.

We integrated clinical, genomic, and transcriptomic data from 224 primaries and 95 metastases from 289 patients to characterize progression of pancreatic ductal adenocarcinoma (PDAC). Driver gene alterations and mutational and expression-based signatures were preserved, with truncations, inversions, and translocations most conserved. Cell cycle progression (CCP) increased with sequential inactivation of tumor suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene variants. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Paired tumor heterogeneity showed cancer cell migration by Halstedian progression. Multiple PDACs arising synchronously and metachronously in the same pancreas were actually intra-parenchymal metastases, not independent primary tumors. Established clinical co-variates dominated survival analyses, although CCP and hypoxia may inform clinical practice.

Reducing repeat imaging in hepato-pancreatico-biliary surgical cancer care through shared diagnostic imaging repositories.

BACKGROUND: With regionalization of care, patients often undergo treatment in institutions other than where the initial investigation is conducted. This study assessed the impact of a shared diagnostic imaging repository (SDIR) on processes of care and outcomes in hepato-pancreatico-biliary (HPB) cancer surgery. METHODS: Provincial administrative datasets were linked to study HPB cancer patients operated at a regional cancer centre (2003-2014). SDIR and non-SDIR groups were based on where initial imaging (CT or MRI) was conducted. Outcomes were repeat imaging before surgery and wait times for surgery from initial imaging and surgical consultation. RESULTS: Of 839 patients, 474 were from SDIR institutions. Fewer SDIR patients underwent any repeat imaging (55.9% vs. 75.3%; p < 0.01) and repeat imaging with same modality and protocol (24.7% vs. 43.0%; p < 0.01). Median wait time to surgery from initial imaging (64 Vs. 79 days; p < 0.01) and surgical consultation (39 Vs. 45 days; p = 0.046) was shorter with SDIR. SDIR patients had lower adjusted odds of any repeat imaging (OR 0.20 [0.14-0.30]), and repeat imaging with same modality and protocol (OR 0.58 [0.41-0.80]). CONCLUSION: Radiology sharing with SDIR reduced repeat imaging for HPB cancer surgery, including potentially redundant repeat imaging with same protocol, and shortened wait time to surgical care.

Outcomes of Non-curative Gastrectomy for Gastric Cancer: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).

BACKGROUND: The surgical care of patients with metastatic gastric cancer (GC) remains debated. Despite level 1 evidence showing lack of survival benefit, surgery may be used for symptoms prevention or palliation. This study examined short-term postoperative outcomes of non-curative gastrectomy performed for metastatic GC. METHODS: A multi-institutional retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry, including gastrectomies for GC (2007-2015). The primary outcome was 30-day major morbidity. Multivariable analysis examined the association between metastatic status and outcomes adjusted for relevant demographic and clinical covariates. RESULTS: Of 5341 patients, 377 (7.1%) had metastases. Major morbidity was more common with metastases (29.4 vs. 19.6%; p < 0.001), driven by a higher rate of respiratory events. Prolonged hospital length of stay (beyond the 75th percentile: 11 days) was more likely with metastases than with no metastases (41.9 vs. 28.3%; p < 0.001). After adjustment, metastatic status was associated with major morbidity (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90). This association remained for respiratory events (OR, 1.58; 95% CI, 1.07-2.33), 30-day mortality (OR, 2.19; 95% CI, 1.38-3.48), and prolonged hospital stay (OR, 1.65; 95% CI, 1.31-2.07). CONCLUSION: Non-curative gastrectomy for metastatic GC was associated with significant major morbidity and mortality as well as a prolonged hospital stay, longer than expected for gastrectomy for non-metastatic GC. These data can inform decision making regarding non-curative gastrectomy, helping surgeons to weigh the risks of morbidity against the potential benefits and alternative therapeutic options.

Outcomes of Cytoreductive Surgery for Metastatic Low-Grade Neuroendocrine Tumors in the Setting of Extrahepatic Metastases.

BACKGROUND: Neuroendocrine tumors (NETs) have a uniquely indolent biology. Management focuses on tumor and hormonal burden reduction. Data on cytoreduction with extrahepatic disease remain limited. OBJECTIVE: We sought to define the outcomes of cytoreduction for metastatic NETs with extrahepatic metastases. METHODS: Patients undergoing cytoreductive surgery for grade 1 or 2 NETs with extrahepatic metastases (with or without intrahepatic disease) were identified from an institutional database (2003-2014). Primary outcomes included postoperative hormonal response (> 50% urinary 5HIAA decrease), progression-free survival (PFS) and overall survival (OS), while secondary outcomes were 30-day postoperative major morbidity (Clavien grade III-V), mortality, and length of stay. RESULTS: Fifty-five patients were identified (median age 59.3 years, 80% small bowel primaries, 56.4% grade 1); 87% of patients presented with combined intra- and extrahepatic metastases. Resection most commonly included the liver (87%), small bowel (22%), mesenteric (25%) and retroperitoneal (11%) lymph nodes, and peritoneum (7%). Thirty-day major morbidity (Clavien III-V) was 18%, with 3.6% mortality, and median length of stay was 7 days [interquartile range (IQR) 5-9]. Liver embolization was performed in 31% of patients after surgery, at a median of 23 months following surgery. Overall, postoperative hormonal response occurred in 70% of patients. At median follow-up of 37 months (IQR range 22-93), 42 (76%) patients were alive and 23 (41.8%) had progressed. Five-year OS was 77% and 5-year PFS was 51%. CONCLUSION: Patients undergoing cytoreduction of metastatic well-differentiated NET in the setting of extrahepatic metastatic disease experience good tumoral control with favorable PFS and OS. Cytoreductive surgery can be safely included in the therapeutic armamentarium for NET with extrahepatic metastases.

Three point transfusion risk score in hepatectomy: an external validation using the American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP).

BACKGROUND: Risk of red blood cell transfusion (RBCT) in partial hepatectomy is 17-27%; strategies to reduce transfusions can be targeted in patients at increased risk. A Three Point Transfusion Risk Score (TRS) was previously developed to predict patients' risk of transfusion during and following hepatectomy. Here, it was subject to external validation using the ACS-NSQIP database. METHODS: TRIPOD guidelines were followed. A validation cohort was created with the ACS-NSQIP dataset. Risk groups for RBCT were created using the TRS: anemia (hematocrit ≤36%), major liver resection (≥4 segments) and primary liver malignancy. Concordance index was used to assess the discrimination. The Hosmer-Lemeshow test for goodness of fit and calibration curves were used to assess calibration. RESULTS: Of 2854 hepatectomies, 18.9% received RBCT. The TRS stratified patients from low (8.5% risk of RBCT) to very high risk (40.6%) of RBCT. The concordance was 0.68 (95% CI 0.66-0.70). Hosmer-Lemeshow test and calibration curves supported good predictive performance of the model. CONCLUSION: The TRS adequately discriminated risk of RBCT in an external sample of patients undergoing hepatectomy. It provides a simple method to identify patients at high transfusion risk. It can be used to tailor patient blood management initiatives and reduce the use of RBCT.

The impact of advanced age on short-term outcomes following gastric cancer resection: an ACS-NSQIP analysis.

BACKGROUND: Evidence on short-term outcomes for GC resection in elderly patients is limited by small samples from single-institutions. This study sought to examine the association between advanced age and short-term outcomes of gastrectomy for gastric cancer (GC). METHODS: Using ACS-NSQIP data, patients undergoing gastrectomy for GC (2007-2013) were identified. Primary outcome was 30-day major morbidity. Outcomes were compared across age categories (<65, 65-70, 71-75, 76-80, >80 years old). Univariable and multivariable regression was used to estimate the morbidity risk associated with age. RESULTS: Of 3637 patients, 60.6% were ≥65 years old. Major morbidity increased with age, from 16.3% (<65 years old) to 21.5% (76-80 years old), and 24.1% (>80 years old) (p < 0.001), driven by higher respiratory and infectious events. Perioperative 30-day mortality increased from 1.2% (<65years old) to 6.5% (>80 years old) (p < 0.0001). After adjustments, age was independently associated with morbidity for 76-80 years of age (RR 1.31, 95% CI, 1.08-1.60) and >80 years old (RR 1.49, 95% CI, 1.23-1.81). Predicted morbidity increased by 18.6% in those 75-80 years old and 27.5% in those >80 years old (compared to <65 years old) for total gastrectomy, and by 11.6% and 17.2% for subtotal gastrectomy, for worst case scenario. Morbidity increased by 5.1% in those 75-80 years old and 7.6% in those >80 years old for total gastrectomy, and by 3.1% and 4.7% for subtotal gastrectomy, for best case scenario. CONCLUSIONS: Advanced age, defined as more than 75 years, was independently associated with increased morbidity after GC resection. The magnitude of this impact is further modulated by clinical scenarios. Increased risk in elderly GC patient should be recognized and considered in indications for resection.

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.

The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society.

Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.

Patient Adherence and Experience with Extended Use of Prophylactic Low-Molecular-Weight Heparin Following Pancreas and Liver Resection.

BACKGROUND: Guidelines recommend 28 days venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) following major abdominal surgery for cancer. Overall adherence with these recommendations is poor, but little is known about feasibility and tolerability from a patient perspective. METHODS: An institution-wide policy for routine administration of 28 days of post-operative LMWH following major hepatic or pancreatic resection for cancer was implemented in April 2013. Patients having surgery from July 2013 to June 2015 were approached to participate in an interview examining adherence and experience with extended duration LMWH. RESULTS: There were 100 patients included, with 81.4 % reporting perfect adherence with the regimen. The most frequent reasons for non-adherence were that a healthcare provider stopped the regimen or because of poor experience with injections. Most patients were able to correctly recall the reason for being prescribed LMWH (82.6 %), and 78.4 % of patients performed all injections themselves. Over half the patients (55.7 %) did not find the injections bothersome. CONCLUSION: Patients reported high adherence and a manageable experience with post-operative extended-duration LMWH in an ambulatory setting following liver or pancreas resection. These findings suggest that patient adherence is not a major contributor to poor compliance with VTE prophylaxis guidelines.

Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid.

BACKGROUND: Hyperfibrinolysis may occur due to systemic inflammation or hepatic injury that occurs during liver resection. Tranexamic acid (TXA) is an antifibrinolytic agent that decreases bleeding in various settings, but has not been well studied in patients undergoing liver resection. METHODS: In this prospective, phase II trial, 18 patients undergoing major liver resection were sequentially assigned to one of three cohorts: (i) Control (no TXA); (ii) TXA Dose I - 1 g bolus followed by 1 g infusion over 8 h; (iii) TXA Dose II - 1 g bolus followed by 10 mg/kg/hr until the end of surgery. Serial blood samples were collected for thromboelastography (TEG), coagulation components and TXA concentration. RESULTS: No abnormalities in hemostatic function were identified on TEG. PAP complex levels increased to peak at 1106 µg/L (normal 0-512 µg/L) following parenchymal transection, then decreased to baseline by the morning following surgery. TXA reached stable, therapeutic concentrations early in both dosing regimens. There were no differences between patients based on TXA. CONCLUSIONS: There is no thromboelastographic evidence of hyperfibrinolysis in patients undergoing major liver resection. TXA does not influence the change in systemic fibrinolysis; it may reduce bleeding through a different mechanism of action. Registered with ClinicalTrials.gov: NCT01651182.

The impact of blood transfusion on perioperative outcomes following gastric cancer resection: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Red blood cell transfusions (RBCT) carry risk of transfusion-related immunodulation that may impact postoperative recovery. This study examined the association between perioperative RBCT and short-term postoperative outcomes following gastrectomy for gastric cancer. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we compared outcomes of patients (transfused v. nontransfused) undergoing elective gastrectomy for gastric cancer (2007-2012). Outcomes were 30-day major morbidity, mortality and length of stay. The association between perioperative RBCT and outcomes was estimated using modified Poisson, logistic, or negative binomial regression. RESULTS: Of the 3243 patients in the entire cohort, we included 2884 patients with nonmissing data, of whom 535 (18.6%) received RBCT. Overall 30-day major morbidity and mortality were 20% and 3.5%, respectively. After adjustment for baseline and clinical characteristics, RBCT was independently associated with increased 30-day mortality (relative risk [RR] 3.1, 95% confidence interval [CI] 1.9-5.0), major morbidity (RR 1.4, 95% CI 1.2-1.8), length of stay (RR 1.2, 95% CI 1.1-1.2), infections (RR 1.4, 95% CI 1.1-1.6), cardiac complications (RR 1.8, 95% CI 1.0-3.2) and respiratory failure (RR 2.3, 95% CI 1.6-3.3). CONCLUSION: Red blood cell transfusions are associated with worse postoperative short-term outcomes in patients with gastric cancer. Blood management strategies are needed to reduce the use of RBCT after gastrectomy for gastric cancer.

CONTEXTE: Les transfusion de globules rouges (TGR) entrainent une immunosuppression qui peut entraver la récupération post-opératoire. Cette étude évalue l'association entre les TGR péri-opératoires et l'issue post-opératoire après gastrectomie pour cancer gastrique (CG). MÉTHODES: Le registre de l'ACS-NSQIP fut utilisé pour comparer l'issue des patients subissant une gastrectomie élective pour CG de 2007 à 2012, selon la TGR. La morbidité majeure et mortalité à 30 jours, et la durée d'hospitalisation furent analysées. L'association entre la TGR et les résultats post-opératoires fut estimée par régressions de Poisson modifiée, logistique, et binomiale. RÉSULTATS: Parmi 3243 gastrectomies, 2884 patients avec des données complètes furent inclus, dont 535 (18,6 %) furent transfusés. La morbidité globale à 30 jours était 20 % et la mortalité 3,5 %. Après avoir contrôlé pour les caractéristiques démographiques et cliniques pertinentes, les TGR démontraient une association indépendante avec une morbidité majeure (risque relatif [RR] 3,1; intervalle de confiance [IC] à 95 % 1,9-5,0), une mortalité (RR 1,4; IC à 95 % 1,2-1,8), et une durée d'hospitalisation (RR 1,2; IC à 95 % 1,1-1,2) accrues. Les TGR étaient aussi associées aux complications infectieuses (RR 1,4; IC à 95 % 1,1-1,6), cardiaques (RR 1,8; IC à 95 % 1,0-3,2), et respiratoires (RR 1,4; IC à 95 % 1,6-3,3). CONCLUSION: Les TGR sont associées à une détérioration de l'issue post-opératoire après gastrectomie pour CG, dont la morbidité majeure, la mortalité, et la durée d'hospitalisation. Des stratégies multidisciplinaires de gestion du risque transfusionnel sont nécessaires afin de limiter l'utilisation des TGRs après gastrectomie pour CG.

Hypophosphatemia and recovery of post-hepatectomy liver insufficiency.

BACKGROUND: Hypophosphatemia (HP) is frequent following liver resection, and thought to represent use of phosphate during liver regeneration. We sought to evaluate the association of post-hepatectomy HP with liver insufficiency and recovery. METHODS: Liver resections were retrospectively reviewed from 2009 to 2012 at a single institution. We explored the relationship between HP (defined as serum phosphate ≤0.65 mmol/L), occurrence of initial liver insufficiency (ILI) [bilirubin >50 µmol/L, international normalized ratio (INR) >1.7 within 72 hours of surgery] and in-hospital recovery of ILI. Secondary outcomes included 30-day post-operative major morbidity (Clavien grade 3 and 4 complications), mortality, and re-admission. RESULTS: Among 402 patients, 223 (55.5%) experienced HP and 64 (15.9%) met our definition of ILI, of which 53 (82.8%) recovered. Length of stay, 30-day post-operative major morbidity, mortality, and re-admission were similar between patients with and without HP. Among patients with ILI, 44 (68.8%) experienced HP. Following ILI, patients with HP recovered more often than those with NP (90.9% vs. 65.0%; P=0.03). CONCLUSIONS: In patients who experience post-hepatectomy ILI, HP is associated with improved recovery, potentially indicating more efficient liver regeneration. Further studies should explore the usefulness of post-hepatectomy HP as an early prognostic factor of recovery from ILI.