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.

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.

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.

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 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.

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.

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.

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.

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.

Is central venous pressure still relevant in the contemporary era of liver resection?

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.

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.

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.

Rural-urban disparities in incidence and outcomes of neuroendocrine tumors: A population-based analysis of 6271 cases.

BACKGROUND: Despite their rising incidence, neuroendocrine tumors (NETs) remain a poorly understood disease. Living in a rural area (RA) affects the incidence and outcomes of other types of cancer. This study compared the incidence and outcomes of NETs for patients in RAs and patients in urban areas (UAs). METHODS: A population-based cohort study of patients with NETs in Ontario, Canada from 1994 to 2011 was conducted. An RA was defined as any community with a population < 10,000 and outside the commuting zone of a metropolitan area. Incidence, advanced stage at presentation, distant recurrence-free survival (dRFS), and overall survival (OS) were compared between patients who lived in RAs and patients who lived in UAs with univariate and multivariate regression analyses. RESULTS: The cohort included 6271 patients diagnosed with NETs, of whom 13.5% (n = 846) resided in RAs. The incidence of NETs was higher in RAs at 3.01 per 100,000 per year versus UAs at 2.82 per 100,000 per year (relative rate, 1.10; P = .04). RA living was not associated with an advanced stage at presentation (odds ratio, 1.15; 95% confidence interval, 0.96-1.38). Patients who lived in RAs had worse 10-year dRFS (62.8% vs 65.9%, P = .03) and OS (44.6% vs 48.8%, P = .004). RAs were independently associated with decreased OS (hazard ratio, 1.16; 95% confidence interval, 1.04-1.30). CONCLUSIONS: Patients are more commonly diagnosed with NETs in RAs, but they do not present at more advanced stages in comparison with patients diagnosed in UAs. Patients living in RAs experience worse cancer recurrence and OS, and this is possibly related to variations in socioeconomic status, rural environmental factors, and access to specialized health care.

The Impact of Perioperative Red Blood Cell Transfusions on Long-Term Outcomes after Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Red blood cell transfusions (RBCTs) are associated with cancer recurrence following resection of colorectal cancer. Their impact after colorectal liver metastases (CRLM) resection remains debated. We sought to explore the association between perioperative RBCT and oncologic outcomes following resection of CRLM. METHODS: We reviewed patients undergoing partial hepatectomy for CRLM from 2003 to 2012 at a single institution. Date of death was abstracted from a validated population-based cancer registry. Primary outcome was overall survival (OS). Secondary outcome was recurrence-free survival (RFS). Survivals were estimated using Kaplan-Meier methods and compared with log-rank test based on transfusion status. Cox regression analysis examined the association of RBCT with OS and RFS, while adjusting for age, preoperative chemotherapy, Clinical Risk Score, and period of treatment (2003-2007 vs. 2008-2012). RESULTS: Among 483 patients, 27.5 % received RBCT. Ninety-day postoperative mortality was 4.8 %. At median follow-up of 33 (interquartile range 20.1-54.8) months, 5-year OS was inferior in transfused patients (45.9 vs. 61.0 %; p < 0.0001). Five-year RFS was decreased with RBCT (15.5 vs. 31.6 %; p < 0.0001). The difference persisted when considering only 90-day survivors for 5-year OS (53.1 vs. 61.9 %, p = 0.023) and RFS (15.6 vs. 31.6 %; p < 0.0001). After adjustment for prognostic factors, RBCT was independently associated with decreased OS (hazard ratio 2.24; 95 % confidence interval 1.60-3.15) and RFS (hazard ratio 1.71; 95 % confidence interval 1.28-2.28). CONCLUSIONS: Perioperative RBCT is independently associated with decreased OS and RFS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted to mitigate this detrimental effect on long-term outcomes.

Lateral approach in laparoscopic distal pancreatectomy is safe and potentially beneficial compared to the traditional medial approach.

INTRODUCTION: Laparoscopic distal pancreatectomy has become widely accepted for the treatment of left-sided pancreatic lesions. Traditionally, a medial laparoscopic distal pancreatectomy (MDLP) has been employed, with division of the gland followed by medial to lateral mobilization. Recent technical reports of lateral laparoscopic distal pancreatectomy (LLDP) suggest that it offers easier access and more precise dissection. Data on this technique remain sparse and inconclusive, with no formal comparison with MLDP. We sought to compare outcomes of LLDP to MLDP. METHODS: We reviewed the charts of patients undergoing laparoscopic distal pancreatectomy at two academic institutions, from July 2009 to June 2013. Primary outcomes were operating time and estimated blood loss. Secondary outcomes included success of spleen-preserving procedures, length of sacrificed pancreas parenchyma, margins status, 30-day major morbidity (Clavien grade 3-5 complications), and length of stay. We reported data as proportions and medians. We performed comparative analysis using Chi square test or Fisher's exact test for categorical variables, and Mann-Whitney U test for continuous variables. RESULTS: We retrieved 43 cases (19 LLDP, 24 MLDP). Median operative time was shorter (166 vs 190 min; p = 0.03) and estimated blood loss lower (50 vs 250 mL; p < 0.01) with LLDP. No margin was positive with LLDP compared to 2 (8.3%) with MLDP. Major morbidity did not differ (LLDP 21.0% vs MLDP 25.0%; p = 0.76). Trends toward lower conversion rate (16.7 vs 5.3%; p = 0.36) and shorter length of stay (5 vs 4 days; p = 0.35) were not significant. CONCLUSION: LLDP is a feasible and safe approach for distal lesions of the pancreatic tail, associated with shorter operative time and decreased blood loss compared to traditional MLDP. Potential of decreased conversion rate and length of stay exists. These hypotheses need to be confirmed in larger prospective studies.

The impact of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction on pancreatic fistula after pancreaticoduodenectomy: meta-analysis of randomized controlled trials.

BACKGROUND: Pancreatic fistula (PF) remains a common source of morbidity following pancreaticoduodenectomy (PD). Despite numerous studies, the optimal method of pancreatic remnant reconstruction is controversial. This study examines the hypothesis that pancreaticogastrostomy (PG) is associated with a lower risk for PF after PD compared with pancreaticojejunostomy (PJ). METHODS: Five electronic databases and the grey literature were searched for randomized controlled trials (RCTs) comparing PJ and PG after PD. Two reviewers independently selected studies, extracted data and assessed methodology. The primary outcome was the occurrence of PF of International Study Group on Pancreatic Fistula (ISGPF) Grade B or C. RESULTS: Four RCTs including 676 patients were included. Pancreaticogastrostomy reduced the risk for PF [relative risk (RR) 0.41, 95% confidence interval (CI) 0.21-0.62] without any difference between high- and low-risk patients. Absolute risk reduction for PF was 4% (95% CI 2.4-5.6) in low-risk patients compared with 10% (95% CI 6.5-14.8) in high-risk patients undergoing PG rather than PJ. The strength of evidence for PF outcome was moderate according to the GRADE classification. CONCLUSIONS: Reconstruction by PG decreases the rate of PF in comparison with PJ. Surgeons should consider reconstructing the pancreatic remnant following PD with PG, particularly in patients at high risk for PF.

The impact of peri-operative blood transfusions on post-pancreatectomy short-term outcomes: an analysis from the American College of Surgeons National Surgical Quality Improvement Program.

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.

The impact of portal pedicle clamping on survival from colorectal liver metastases in the contemporary era of liver resection: a matched cohort study.

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.

Optimal management of colorectal liver metastases in older patients: a decision analysis.

BACKGROUND: Comparative trials evaluating management strategies for colorectal cancer liver metastases (CLM) are lacking, especially for older patients. This study developed a decision-analytic model to quantify outcomes associated with treatment strategies for CLM in older patients. METHODS: A Markov-decision model was built to examine the effect on life expectancy (LE) and quality-adjusted life expectancy (QALE) for best supportive care (BSC), systemic chemotherapy (SC), radiofrequency ablation (RFA) and hepatic resection (HR). The baseline patient cohort assumptions included healthy 70-year-old CLM patients after a primary cancer resection. Event and transition probabilities and utilities were derived from a literature review. Deterministic and probabilistic sensitivity analyses were performed on all study parameters. RESULTS: In base case analysis, BSC, SC, RFA and HR yielded LEs of 11.9, 23.1, 34.8 and 37.0 months, and QALEs of 7.8, 13.2, 22.0 and 25.0 months, respectively. Model results were sensitive to age, comorbidity, length of model simulation and utility after HR. Probabilistic sensitivity analysis showed increasing preference for RFA over HR with increasing patient age. CONCLUSIONS: HR may be optimal for healthy 70-year-old patients with CLM. In older patients with comorbidities, RFA may provide better LE and QALE. Treatment decisions in older cancer patients should account for patient age, comorbidities, local expertise and individual values.