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1.
Support Care Cancer ; 30(11): 9635-9646, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36197513

ABSTRACT

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.


Subject(s)
Colonic Neoplasms , Mental Disorders , Neuroendocrine Tumors , Adult , Humans , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/diagnosis , Incidence , Retrospective Studies , Serotonin , Mental Disorders/epidemiology
3.
J Natl Compr Canc Netw ; 18(3): 297-303, 2020 03.
Article in English | MEDLINE | ID: mdl-32135510

ABSTRACT

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.


Subject(s)
Adenocarcinoma/therapy , Medical Oncology/methods , Pancreatic Neoplasms/therapy , Female , Humans , Male , Treatment Outcome
4.
Oncologist ; 24(10): 1384-1394, 2019 10.
Article in English | MEDLINE | ID: mdl-31270268

ABSTRACT

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.


Subject(s)
Neuroendocrine Tumors/diagnosis , Patient Reported Outcome Measures , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/pathology , Prospective Studies , Retrospective Studies , Young Adult
5.
Ann Surg Oncol ; 26(9): 2711-2721, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31147993

ABSTRACT

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.


Subject(s)
Neuroendocrine Tumors/complications , Patient Reported Outcome Measures , Quality of Life , Severity of Illness Index , Symptom Assessment/mortality , Terminal Care/statistics & numerical data , Adult , Aged , Aged, 80 and over , Anxiety/diagnosis , Anxiety/etiology , Fatigue/diagnosis , Fatigue/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nausea/diagnosis , Nausea/etiology , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/therapy , Ontario/epidemiology , Pain/diagnosis , Pain/etiology , Palliative Care , Prevalence , Prognosis , Prospective Studies , Retrospective Studies , Survival Rate , Young Adult
6.
Cancer Cell ; 35(2): 267-282.e7, 2019 02 11.
Article in English | MEDLINE | ID: mdl-30686769

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Pancreatic Ductal/genetics , Cell Cycle/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Mutation , Pancreatic Neoplasms/genetics , Transcription, Genetic , Animals , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/secondary , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Genetic Predisposition to Disease , Humans , Israel , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Mice , Neoplasm Invasiveness , North America , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Phenotype , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptome , Tumor Hypoxia
7.
HPB (Oxford) ; 21(1): 96-106, 2019 01.
Article in English | MEDLINE | ID: mdl-30297304

ABSTRACT

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.


Subject(s)
Centralized Hospital Services , Digestive System Neoplasms/diagnostic imaging , Digestive System Neoplasms/surgery , Magnetic Resonance Imaging , Medical Record Linkage , Radiology Information Systems , Tomography, X-Ray Computed , Unnecessary Procedures , Aged , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Referral and Consultation , Retrospective Studies , Time Factors , Time-to-Treatment , Treatment Outcome
8.
Ann Surg Oncol ; 25(13): 3943-3949, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30298321

ABSTRACT

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.


Subject(s)
Gastrectomy/adverse effects , Postoperative Complications/etiology , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Aged , Databases, Factual , Female , Humans , Length of Stay , Male , Middle Aged , Mortality , Neoplasm Metastasis , Palliative Care , Retrospective Studies
9.
Ann Surg Oncol ; 25(6): 1768-1774, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29560571

ABSTRACT

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.


Subject(s)
Cytoreduction Surgical Procedures , Intestinal Neoplasms/pathology , Intestinal Neoplasms/surgery , Liver Neoplasms/surgery , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/pathology , Peritoneal Neoplasms/surgery , Retroperitoneal Neoplasms/surgery , Aged , Cytoreduction Surgical Procedures/adverse effects , Embolization, Therapeutic , Female , Hepatectomy , Humans , Hydroxyindoleacetic Acid/urine , Intestinal Neoplasms/secondary , Length of Stay , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Lymphatic Metastasis , Male , Mesentery , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/secondary , Peritoneal Neoplasms/secondary , Progression-Free Survival , Retroperitoneal Neoplasms/secondary , Retrospective Studies , Survival Rate
10.
HPB (Oxford) ; 20(7): 669-675, 2018 07.
Article in English | MEDLINE | ID: mdl-29459001

ABSTRACT

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.


Subject(s)
Blood Loss, Surgical/prevention & control , Decision Support Techniques , Erythrocyte Transfusion , Hepatectomy/adverse effects , Aged , Clinical Decision-Making , Databases, Factual , Erythrocyte Transfusion/adverse effects , Female , Humans , Male , Middle Aged , North America , Predictive Value of Tests , Registries , Reproducibility of Results , Risk Assessment , Risk Factors , Treatment Outcome
11.
Gastric Cancer ; 21(4): 710-719, 2018 07.
Article in English | MEDLINE | ID: mdl-29230588

ABSTRACT

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.


Subject(s)
Gastrectomy/mortality , Stomach Neoplasms/surgery , Age Factors , Aged , Aged, 80 and over , Cohort Studies , Female , Gastrectomy/adverse effects , Humans , Male , Middle Aged , Morbidity , North America/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Stomach Neoplasms/mortality , Treatment Outcome
12.
World J Surg ; 41(12): 3180-3188, 2017 12.
Article in English | MEDLINE | ID: mdl-28717907

ABSTRACT

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.


Subject(s)
Hepatectomy/adverse effects , Lactic Acid/blood , Postoperative Complications/blood , Postoperative Complications/etiology , Aged , Blood Loss, Surgical , Female , Hepatectomy/mortality , Humans , Length of Stay , Male , Middle Aged , Operative Time , Postoperative Period
13.
HPB (Oxford) ; 18(12): 991-999, 2016 12.
Article in English | MEDLINE | ID: mdl-27765582

ABSTRACT

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.


Subject(s)
Antifibrinolytic Agents/administration & dosage , Blood Loss, Surgical/prevention & control , Fibrinolysis/drug effects , Hepatectomy/adverse effects , Laparoscopy/adverse effects , Tranexamic Acid/administration & dosage , Aged , Antifibrinolytic Agents/adverse effects , Antifibrinolytic Agents/blood , Biomarkers/blood , Drug Monitoring/methods , Female , Hepatectomy/methods , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Ontario , Predictive Value of Tests , Prospective Studies , Thrombelastography , Time Factors , Tranexamic Acid/adverse effects , Tranexamic Acid/blood , Treatment Outcome
14.
J Gastrointest Surg ; 20(12): 1986-1996, 2016 12.
Article in English | MEDLINE | ID: mdl-27688212

ABSTRACT

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.


Subject(s)
Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Liver Neoplasms/surgery , Pancreatic Neoplasms/surgery , Patient Compliance , Postoperative Complications/prevention & control , Venous Thromboembolism/prevention & control , Aged , Anticoagulants/administration & dosage , Female , Health Knowledge, Attitudes, Practice , Heparin, Low-Molecular-Weight/administration & dosage , Hepatectomy/adverse effects , Humans , Male , Medication Adherence , Middle Aged , Pancreatectomy/adverse effects
15.
Can J Surg ; 59(5): 322-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27668330

ABSTRACT

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.


Subject(s)
Erythrocyte Transfusion/statistics & numerical data , Gastrectomy/statistics & numerical data , Outcome and Process Assessment, Health Care/statistics & numerical data , Perioperative Care/statistics & numerical data , Stomach Neoplasms/surgery , Adult , Aged , Cohort Studies , Databases, Factual/statistics & numerical data , Erythrocyte Transfusion/mortality , Female , Gastrectomy/mortality , Humans , Male , Middle Aged , Perioperative Care/mortality , Quality Improvement/statistics & numerical data , Societies, Medical/statistics & numerical data
16.
Hepatobiliary Surg Nutr ; 5(3): 217-24, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27275463

ABSTRACT

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.

17.
Surgery ; 159(6): 1591-1599, 2016 06.
Article in English | MEDLINE | ID: mdl-26817962

ABSTRACT

BACKGROUND: Perioperative red blood cell transfusions (RBCTs) are common in patients undergoing partial hepatectomy. We sought to explore the relationship between RBCTs and posthepatectomy perioperative outcomes in the contemporary surgical era. METHODS: We reviewed all patients undergoing partial hepatectomy from 2003 to 2012. Primary outcome was 30-day major morbidity (MM). We compared patients who did and received perioperative RBCT (defined as from time of operation until 30 days postoperatively. Multivariate analysis was performed to identify factors associated with MM and duration of stay, using logistic and negative binomial regression. RESULTS: Among 712 patients, 16.8% experienced MM, of whom 53.3% received RBCT. Patients who received RBCT experienced MM more commonly (30.8% vs 11.1%; P < .001). On multivariate analysis, the only factors associated with MM were age (relative risk [RR], 1.03; 95% CI, 1.00-1.06), greater operative time (RR, 1.29; 95% CI, 1.11-1.50), and RBCT (RR, 3.57; 95% CI, 1.81-7.04). RBCT was associated independently with a greater duration of stay (RR, 1.47; 95% CI, 1.13-1.91). CONCLUSION: Receipt of RBCT is associated independently with perioperative MM and prolonged hospitalization after partial hepatectomy. These findings further the rationale supporting the need for a strategy of blood management to decrease the use of RBCT after hepatectomy.


Subject(s)
Erythrocyte Transfusion , Hepatectomy/adverse effects , Intraoperative Complications/epidemiology , Liver Diseases/surgery , Perioperative Care , Postoperative Complications/epidemiology , Age Factors , Aged , Female , Humans , Length of Stay , Liver Diseases/mortality , Liver Diseases/pathology , Male , Middle Aged , Operative Time , Retrospective Studies , Risk Factors , Treatment Outcome
18.
J Surg Res ; 200(1): 139-46, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26342837

ABSTRACT

BACKGROUND: Perioperative red blood cell transfusion (RBCT) remains common after liver resection and carries risk of increased morbidity and worse oncologic outcomes. We sought to assess the factors associated with perioperative RBCT after hepatectomy with a focus on intraoperative hemodynamics. METHODS: We performed a retrospective review of our prospective hepatectomy database, supplemented by a review of anesthetic records of all patients undergoing hepatectomy with hemodynamic monitoring (arterial and central venous pressures [CVP]) from 2003-2012. Primary outcome was perioperative RBCT (during and within 30 d after surgery). After descriptive and univariate comparisons, multivariate analysis was conducted to identify factors associated with RBCT. RESULTS: Of 851 hepatectomies, 530 had complete hemodynamic data and 30.2% (161 of 530) received RBCT. Among transfused patients, female gender (P = 0.01), preoperative anemia (P < 0.001), and major liver resection (P = 0.02) were more common. Mean estimated blood loss was 1.1 L higher (2.0 versus 0.9 L; P < 0.001) and operating time was 1.1 h longer (5.8 versus 4.7 h; P < 0.001) in transfused patients. Trends in intraoperative CVP differed significantly based on transfusion status (P = 0.007). Independent factors associated with RBCT included female gender (odds ratio [OR], 2.27; P = 0.01), preoperative anemia (OR, 2.38; P = 0.03), longer operative time (OR, 1.19 per hour; P = 0.03), and higher intraoperative CVP at 1 h during surgery (OR, 1.10 per mm Hg; P = 0.005). CONCLUSIONS: Likelihood of RBCT is independently associated with female gender, preoperative anemia, longer operative time, and higher intraoperative CVP. Focus on management of preoperative anemia, operative efficiency, and low intraoperative CVP is needed to minimize the need for RBCTs.


Subject(s)
Blood Loss, Surgical/statistics & numerical data , Central Venous Pressure , Erythrocyte Transfusion/statistics & numerical data , Hepatectomy , Intraoperative Care/statistics & numerical data , Monitoring, Intraoperative/methods , Postoperative Care/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical/prevention & control , Blood Pressure Determination , Databases, Factual , Female , Humans , Intraoperative Period , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
19.
HPB (Oxford) ; 17(11): 975-82, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26301741

ABSTRACT

BACKGROUND: Peri-operative red blood cell transfusions (RBCT) may induce transfusion-related immunomodulation and impact post-operative recovery. This study examined the association between RBCT and post-pancreatectomy morbidity. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry, patients undergoing an elective pancreatectomy (2007-2012) were identified. Patients with missing data on key variables were excluded. Primary outcomes were 30-day post-operative major morbidity, mortality, and length of stay (LOS). Unadjusted and adjusted relative risks (RR) with a 95% confidence interval (95%CI) were computed using modified Poisson, logistic, or negative binomial regression, to estimate the association between RBCT and outcomes. RESULTS: The database included 21 132 patients who had a pancreatectomy during the study period. Seventeen thousand five hundred and twenty-three patients were included, and 4672 (26.7%) received RBCT. After adjustment for baseline and clinical characteristics, including comorbidities, malignant diagnosis, procedure and operative time, RBCT was independently associated with increased major morbidity (RR 1.49; 95% CI: 1.39-1.60), mortality (RR 2.19; 95%CI: 1.76-2.73) and LOS (RR 1.27; 95%CI 1.24-1.29). CONCLUSION: Peri-operative RBCT for a pancreatectomy was independently associated with worse short-term outcomes and prolonged LOS. Future studies should focus on the impact of interventions to minimize the use of RBCT after an elective pancreatectomy.


Subject(s)
Blood Transfusion/methods , Pancreatectomy/standards , Perioperative Care/methods , Postoperative Complications/prevention & control , Quality Improvement , Risk Assessment/methods , Societies, Medical , Follow-Up Studies , Humans , Length of Stay/trends , Morbidity/trends , Postoperative Complications/epidemiology , Prognosis , Prospective Studies , Registries , Risk Factors , Survival Rate/trends , Time Factors , United States/epidemiology
20.
HPB (Oxford) ; 17(9): 796-803, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26278322

ABSTRACT

INTRODUCTION: Portal pedicle clamping (PPC) may impact micro-metastases' growth. This study examined the association between PPC and survival after a hepatectomy for colorectal liver metastases (CRLM). METHODS: A matched cohort study was conducted on hepatectomies for CRLM at a single institution (2003-2012). Cohorts were selected based on PPC use, with 1:1 matching for age, time period and the Clinical Risk Score. Outcomes were overall and recurrence-free survival (OS and RFS). Cox regression was performed to assess the association between PPC and survival. RESULTS: Of 481 hepatectomies, 26.9% used PPC. One hundred and ten pairs of patients were matched in the cohorts. There was no significant difference in OS [hazard ratio (HR) 1.18; 95% confidence interval (CI): 0.76-1.83], with a 5-year OS of 57.8% (95%CI: 52.4-63.2%) with PPC versus 62.3% (95%CI: 57.1-67.5%) without. Five-year RFS did not differ (HR 0.98; 95%CI: 0.71-1.35) with 29.7% (95%CI: 24.9-34.5%) with PPC versus 28.0% (95%CI: 23.2-32.8%) without. When adjusting for extent of resection, transfusion, operative time and surgeon, there was no difference in OS (HR 0.91; 95%CI: 0.52-1.60) or RFS (HR: 0.86; 95%CI: 0.57-1.30). CONCLUSIONS: PPC was not associated with a significant difference in OS or RFS in a hepatectomy for CRLM. PPC remains a safe technique during hepatectomy.


Subject(s)
Blood Loss, Surgical/prevention & control , Colorectal Neoplasms/pathology , Hepatectomy/methods , Liver Neoplasms/surgery , Aged , Colorectal Neoplasms/mortality , Constriction , Disease-Free Survival , Female , Follow-Up Studies , Humans , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Ontario/epidemiology , Portal Vein , Retrospective Studies , Survival Rate/trends
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