Health-Related Quality of Life Following Simultaneous Resection for Synchronous Colorectal Cancer Liver Metastases.

INTRODUCTION: Up to 25% of colorectal cancer patients present with synchronous liver metastases that can be treated with two operations or a single 'simultaneous' operation. Morbidity and mortality appear similar between approaches, however changes in health-related quality-of-life following simultaneous resection are not well reported. METHODS: A prospective, feasibility trial for simultaneous resection of synchronous colorectal liver metastases was conducted. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 at baseline (preoperatively), and 4 and 12 weeks postoperatively. Week 4 and 12 scores were compared with baseline using t-tests. Minimally important clinical differences were considered as a 10-point difference from baseline. RESULTS: C30 and QLQ-LMC21 were completed at baseline, 4 weeks, and 12 weeks by 39 (95%), 35 (85%) and 34 (83%) patients, and 39 (95%), 33 (80%) and 33 (80%) patients, respectively; 79% and 75% had at least one MICD according to QLQ-C30 at 4 and 12 weeks. At 4 weeks, physical functioning (mean difference (MD) - 11.9%, p = 0.002), role functioning (MD - 23.6, p = 0.007), and pain (MD + 19.7, p = 0.017) had significant worsening from baseline. At 12 weeks postoperatively, role functioning (MD - 19.7, p = 0.011) and fatigue (MD + 14.3, p = 0.03) were the only domains that remained significantly worse. By 12 weeks, pain and physical functioning had returned to baseline. There were no major demographic differences among those with and without an MICD at 12 weeks. CONCLUSIONS: Simultaneous resection of colorectal liver metastases led to clinically significant worsening fatigue and role functioning that persisted at 12 weeks post-surgery.

Regional Therapies for Colorectal Liver Metastases: Systematic Review and Clinical Practice Guideline.

BACKGROUND: Resection is the foundation for cure for colorectal cancer (CRC) liver metastases; however, only 20% of patients are suitable for surgery. Those suitable would be considered for resection or local therapies before being considered for regional therapies. Noncurative treatment is usually systemic chemotherapy. For patients with liver-only or liver-predominant metastases that are unresectable, regional therapies [conventional transarterial chemoembolization (cTACE), drug-eluting bead transarterial chemoembolization (DEB-TACE), and transarterial radioembolization (TARE)] may be considered. We review the current evidence for regional therapies for CRC liver metastases. PATIENTS AND METHODS: Literature searches (January 2000 to March 2019 or January 2010 to March 2019 depending on the specific systematic review question) were conducted, including Medline, Embase, Cochrane Library, and 2018 American Society of Clinical Oncology (ASCO) abstracts. RESULTS: A total of 4100 articles were identified; 15 studies were included in the review. There were no comparative data regarding the resectable population. There was either insufficient evidence (cTACE or DEB-TACE) or evidence against (TARE) the addition of regional therapies to systemic therapy in the first line in the unresectable population. There was either no evidence (cTACE) or weak evidence (DEB-TACE or TARE) for the addition of regional therapies with or without systemic therapy in the second line or later in the unresectable population. CONCLUSION: Limited evidence supports the delivery of percutaneous regional therapies in patients with unresectable CRC liver metastases. There are strong data demonstrating positive effects of TARE within the liver, but they do not translate to a benefit in patient-important outcomes. DEB-TACE appears to offer a survival benefit in the second-line setting, although the evidence is limited by small sample size and larger trials are needed.

Early operative management in patients with adhesive small bowel obstruction: population-based cost analysis.

BACKGROUND: Adhesive small bowel obstruction (aSBO) is a potentially recurrent disease. Although non-operative management is often successful, it is associated with greater risk of recurrence than operative intervention, and may have greater downstream morbidity and costs. This study aimed to compare the current standard of care, trial of non-operative management (TNOM), and early operative management (EOM) for aSBO. METHODS: Patients admitted to hospital between 2005 and 2014 in Ontario, Canada, with their first episode of aSBO were identified and propensity-matched on their likelihood to receive EOM for a cost-utility analysis using population-based administrative data. Patients were followed for 5 years to determine survival, recurrences, adverse events and inpatient costs to the healthcare system. Utility scores were attributed to aSBO-related events. Cost-utility was presented as the incremental cost-effectiveness ratio (ICER), expressed as Canadian dollars per quality-adjusted life-year (QALY). RESULTS: Some 25 150 patients were admitted for aSBO and 3174 (12·6 per cent) were managed by EOM. Patients managed by TNOM were more likely to experience recurrence of aSBO (20·9 per cent versus 13·2 per cent for EOM; P < 0·001). The lower recurrence rate associated with EOM contributed to an overall net effectiveness in terms of QALYs. The mean accumulated costs for patients managed with EOM exceeded those of TNOM ($17 951 versus $11 594 (€12 288 versus €7936) respectively; P < 0·001), but the ICER for EOM versus TNOM was $29 881 (€20 454) per QALY, suggesting cost-effectiveness. CONCLUSION: This retrospective study, based on administrative data, documented that EOM may be a cost-effective approach for patients with aSBO in terms of QALYs. Future guidelines on the management of aSBO may also consider the long-term outcomes and costs.

ANTECEDENTES: La oclusión de intestino delgado por adherencias (adhesive small bowel obstruction, aSBO) es una enfermedad potencialmente recidivante. Aunque el tratamiento no quirúrgico es a menudo eficaz, se asocia con un mayor riesgo de recidiva que la intervención quirúrgica, y puede provocar más adelante morbilidad y costes. El objetivo de este estudio fue comparar un Ensayo de Tratamiento No Quirúrgico (Trial of Non-operative Management, TNOM, el estándar actual de tratamiento) con Tratamiento Operatorio Precoz (Early Operative Management, EOM) para el tratamiento de aSBO. MÉTODOS: Pacientes ingresados en el hospital entre 2005-2014 en Ontario, Canadá con un primer episodio de aSBO fueron identificados y emparejados por puntaje de propensión respecto a la probabilidad de recibir EOM para un análisis de coste-utilidad utilizando datos administrativos de base poblacional. Los pacientes fueron seguidos durante 5 años para determinar la supervivencia, recidivas, eventos adversos, y costes de la hospitalización para el sistema de salud. Las puntuaciones de utilidad se atribuyeron a los eventos relacionados con la aSBO. El coste-utilidad se presentó como la razón costo efectividad incremental (incremental cost-effectiveness ratio, ICER) expresada como dólares por año de vida ajustado por calidad (quality-adjusted life-year, QALY). RESULTADOS: Un total de 25.150 pacientes fueron ingresados por aSBO y 3.174 (12,6%) fueron tratados con EOM. Los pacientes tratados mediante TNOM tenían más probabilidades de presentar una recidiva de la aSBO (20,9% versus 13,2%, P < 0,0001). La menor incidencia de recidivas asociada con EOM contribuyó a una eficacia neta global en términos de QALYs. Mientras que los costes medios acumulados para los pacientes tratados con EOM superaron a los de TNOM ($17,951 versus $11,594, P < 0,0001), el ICER de EOM versus TNOM fue $29,881/QALY, lo que sugiere un coste-eficacia de esta estrategia. CONCLUSIÓN: Este estudio retrospectivo basado en datos administrativos evidenció que EOM puede representar un abordaje coste-efectivo para pacientes con aSBO en términos de QALYs. Las futuras guías clínicas para el tratamiento de la aSBO pueden también considerar los resultados a largo plazo y los costes.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2018.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer.

Population-based study of the impact of small bowel obstruction due to adhesions on short- and medium-term mortality.

BACKGROUND: Small bowel obstruction due to adhesions (aSBO) is a common indication for admission to a surgical unit. Despite the prevalence of this condition, the short- and medium-term survival of this patient population has not been well described. The purpose of this study was to measure the short- and medium-term survival of patients admitted to hospital with aSBO. METHODS: Linked administrative data were used to identify patients admitted to hospital in Ontario, Canada, for aSBO between 2005 and 2011. Patients were divided into two groups: those aged less than 65 years (younger group) and those aged 65 years and older (older group). Thirty-day, 90-day and 1-year mortality rates were estimated. One-year mortality was compared with that in the general population, adjusting for age and sex. The timing of deaths in relation to admission was assessed, as well as the proportion of patients discharged before experiencing short-term mortality. RESULTS: There were 22 197 patients admitted to hospital for aSBO for the first time in the study interval. Mean age was 64·5 years and 52·2 per cent of the patients were women. Overall, the 30-day, 90-day and 1-year mortality rates for the cohort were 5·7 (95 per cent c.i. 5·4 to 6·0), 8·7 (8·3 to 9·0) and 13·9 (13·4 to 14·3) per cent respectively. For both groups, the 1-year risk of death was significantly greater than that of the age-matched general population. The majority of deaths (62·5 per cent) occurred within 90 days of admission, with 36·4 per cent occurring after discharge from the aSBO admission. CONCLUSION: Patients admitted with aSBO have a high short-term mortality rate. Increased monitoring of patients in the early period after admission is advisable.

ANTECEDENTES: La obstrucción del intestino delgado por adherencias (adhesive small bowel obstruction, aSBO) es una indicación frecuente de ingreso en una unidad quirúrgica. A pesar de la prevalencia de esta patología, la supervivencia de estos pacientes a corto y a medio plazo no ha sido bien descrita. El objetivo de este estudio fue determinar la supervivencia a corto y a medio plazo de pacientes con aSBO ingresados en el hospital. MÉTODOS: Utilizando el enlace de datos administrativos se identificaron a los pacientes ingresados por aSBO en Ontario, Canadá, entre 2005-2011. Los pacientes se dividieron en dos subgrupos: los menores de 65 años de edad (subgrupo joven) y los de 65 años o más (subgrupo mayor). Se estimó la mortalidad a los 30 días, 90 días y a 1 año. La mortalidad a 1 año se comparó con la de la población general, ajustando por edad y sexo. Se evaluó el momento del fallecimiento respecto al ingreso, así como la proporción de pacientes que fueron dados de alta antes de fallecer a los 30 días. RESULTADOS: Durante el periodo de estudio se ingresaron en el hospital 22.197 pacientes con aSBO por primera vez. La edad media de los pacientes era de 65 años y un 52% eran mujeres. La mortalidad global de la cohorte a los 30 días, a los 90 días y a 1 año fue del 5,7% (i.c. del 95%: 5,4-6,0%), 8,3% (i.c. del 95%: 8,3-9,0%) y 13% (i.c. del 95%: 12,9-15,0%), respectivamente. Para ambos subgrupos, el riesgo de mortalidad a 1 año fue significativamente mayor que en la población general emparejada por edad. La mayoría de los fallecimientos (59%) ocurrieron durante los 90 días del ingreso, con un 36% tras el alta después del ingreso por aSBO. CONCLUSIÓN: Los pacientes ingresados por aSBO presentan una alta mortalidad a corto plazo. Se recomienda incrementar la vigilancia de estos pacientes en el periodo temprano tras el alta hospitalaria.

Predictors of Post-operative Pain and Opioid Consumption in Patients Undergoing Liver Surgery.

BACKGROUND: Post-operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post-operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post-operative pain and opioid consumption in patients undergoing liver resection. METHODS: This is a multi-institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents-OME) and on pain scores (NRS-11), we used generalized linear models and multivariable linear regression model, respectively. RESULTS: One hundred and fifty-three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post-operative period (16.7 OME/10 years, p < 0.001). Patient factors that were significantly associated with increased NRS-11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p < 0.01 and p = 0.07, respectively). CONCLUSION: Younger patients and those with a history of analgesic use are more likely to report higher post-operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

Changes in preoperative endoscopic and percutaneous bile drainage in patients with periampullary cancer undergoing pancreaticoduodenectomy in Ontario: effect on clinical practice of a randomized trial.

Background: In 2010, a multicentre randomized controlled trial reported increased postoperative complications in pancreaticoduodenectomy (pde) patients undergoing preoperative biliary decompression (pbd). We evaluated the effect of that publication on rates of pbd at the population level. Methods: This retrospective observational cohort study identified patients undergoing pde for malignancy, 2005-2013, linking them with administrative health care databases covering medical services for a population of 13.5 million. Patients undergoing pbd within 6 weeks before their surgery were identified using physician billing codes and were divided into those undergoing pde before and after article publication, with a 6-month washout period. Chi-square tests were used to compare rates of pbd. Results: Of 1997 pde patients identified, 963 underwent surgery before article publication, and 911, after (123 during the washout period). The rate of pbd was 47.5% before publication, and 41.6% after (p = 0.01). The lowest pbd rates occurred immediately after publication, in 2010 and 2011. Similar results were observed when the cohort was restricted to patients seen preoperatively by a gastroenterologist (n = 1412). Conclusions: Rates of pbd have declined a small, but significant, amount after randomized trial publication. Persistence of pbd might relate to suboptimal knowledge translation, the role of pbd in diagnosis of periampullary malignancy, and treatment of complications (cholangitis, severe hyperbilirubinemia) or anticipation of delay from diagnosis to surgery. The nadir in pbd rates after article publication and the subsequent rise suggest an element of transience in the effect of article publication on clinical practice. Further investigation into the reasons for persistent pbd is needed.

Oxygen therapy for acutely ill medical patients: a clinical practice guideline

What is the best way to use oxygen therapy for patients with an acute medical illness? A systematic review published in the Lancet in April 2018 found that supplemental oxygen in inpatients with normal oxygen saturation increases mortality.1 Its authors concluded that oxygen should be administered conservatively, but they did not make specific recommendations on how to do it. An international expert panel used that review to inform this guideline. It aims to promptly and transparently translate potentially practice-changing evidence to usable recommendations for clinicians and patients.2 The panel used the GRADE framework and following standards for trustworthy guidelines.3

Three-point transfusion risk score in hepatectomy.

BACKGROUND: Perioperative red blood cell transfusions are required in up to 23 per cent of patients undergoing hepatectomy. Previous research has developed three transfusion risk scores to assess risk of perioperative red blood cell transfusion. Here, the performance of these transfusion risk scores was evaluated in a multicentre cohort of patients who underwent hepatectomy and compared with that of a simplified transfusion risk score. METHODS: A database of patients undergoing hepatectomy at four specialized centres between 2008 and 2012 was developed. External validity was assessed by discrimination and calibration. Discrimination was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Calibration was evaluated by the degree of agreement between predicted and actual red blood cell transfusion probabilities. A simplified transfusion risk score using variables common to the three models was created, and discrimination and calibration were evaluated. RESULTS: There were 1287 patients included in this study, with 341 (26·5 per cent) receiving a red blood cell transfusion. Discriminative ability was similar between the three transfusion risk scores, with AUCs of 0·66-0·68 and good calibration. A new three-point risk score was developed based on factors present in all models: haemoglobin 12·5 g/dl or less, primary liver malignancy and major resection (at least 4 segments). Discriminative ability and calibration of the three-point model were similar to those of the three existing models, with an AUC of 0·66. CONCLUSION: The three-point transfusion risk score simplifies assessment of perioperative transfusion risk in hepatectomy without sacrificing predictive ability.

Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial.

BACKGROUND: Decreased plasma fibrinogen concentration shortly after injury is associated with higher blood transfusion needs and mortality. In North America and the UK, cryoprecipitate transfusion is the standard-of-care for fibrinogen supplementation during acute haemorrhage, which often occurs late during trauma resuscitation. Alternatively, fibrinogen concentrate (FC) can be beneficial in trauma resuscitation. However, the feasibility of its early infusion, efficacy and safety remain undetermined. The objective of this trial was to evaluate the feasibility, effect on clinical and laboratory outcomes and complications of early infusion of FC in trauma. METHODS: Fifty hypotensive (systolic arterial pressure ≤100 mm Hg) adult patients requiring blood transfusion were randomly assigned to either 6 g of FC or placebo, between Oct 2014 and Nov 2015 at a tertiary trauma centre. The primary outcome, feasibility, was assessed by the proportion of patients receiving the intervention (FC or placebo) within one h of hospital arrival. Plasma fibrinogen concentration was measured, and 28-day mortality and incidence of thromboembolic events were assessed. RESULTS: Overall, 96% (43/45) [95% CI 86-99%] of patients received the intervention within one h; 95% and 96% in the FC and placebo groups, respectively (P=1.00). Plasma fibrinogen concentrations remained higher in the FC group up to 12 h after admission with the largest difference at three h (2.9 mg dL - 1 vs. 1.8 mg dL - 1; P<0.01). The 28-day mortality and thromboembolic complications were similar between groups. CONCLUSIONS: Early infusion of FC is feasible and increases plasma fibrinogen concentration during trauma resuscitation. Larger trials are justified.

Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era.

Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy. In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.

Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement.

Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

Co-morbidities in elderly patients with hip fracture: recommendations of the ISFR-IOF hip fracture outcomes working group.

INTRODUCTION: Hip fractures are the second leading cause of hospitalization in the aged and by 2041, epidemiologists forecast an increase in economic cost to $2.4 billion. The hip patient population often presents with comorbidities causing these patients to receive less aggressive medical treatment and have a low quality of life. We believe that physical function is a patient-important outcome for many medical and surgical interventions. The functional co-morbidity index (FCI), unlike prior co-morbidity indices, was developed with physical function as an outcome instead of being designed for administrative purposes or to predict mortality. Our objective was to evaluate the perceptions of practitioners in hip fracture care about the impact of comorbidities on physical function as primary outcome. METHODS: We piloted and then distributed a self-administered survey to members of the International Society for Fracture Repair hip fracture outcomes working group. For each of the 18 diagnoses included in the FCI index, we asked in our survey whether the presence of the co-morbidity and whether the severity of the co-morbidity was perceived to impact physical function in patients following a hip fracture. RESULTS: Seventeen out of 20 respondents completed the questionnaire. The presence and severity of arthritis was 'strongly' believed to predict physical function in those with hip fracture (69 and 85.7 %, respectively). Respondents 'agreed' (range 53-73 %) that 10/18 diagnoses would predict changes in physical function following hip fracture treatment. Whereas, 63 % of the practitioners'strongly disagreed' that diabetes types I and II would change physical function scores. Furthermore, dementia was listed as an additional diagnosis that would affect physical function. CONCLUSION: The FCI may provide a useful instrument to predict functional outcome after hip fracture; however, the index may need to be modified for this specific population.

Population-based trend analysis of 2813 patients undergoing laparoscopic sigmoid resection.

BACKGROUND: The use of laparoscopic sigmoid resection for diverticular disease has become increasingly popular. The objective of this trend analysis was to assess whether clinical outcomes following laparoscopic sigmoid resection for diverticular disease have improved over the past 10 years. METHODS: The analysis was based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery. Some 2813 patients undergoing elective laparoscopic sigmoid resection for diverticular disease from 1995 to 2006 were included. Unadjusted and risk-adjusted analyses were performed. RESULTS: Over time, there was a significant reduction in the conversion rate (from 27.3 to 8.6 per cent; P(trend) < 0.001), local postoperative complication rate (23.6 to 6.2 per cent; P(trend) = 0.004), general postoperative complication rate (14.6 to 4.9 per cent; P(trend) = 0.024) and reoperation rate (5.5 to 0.6 per cent; P(trend) = 0.015). Postoperative median length of hospital stay significantly decreased from 11 to 7 days (P(trend) < 0.001). CONCLUSION: This first trend analysis in the literature of clinical outcomes after laparoscopic sigmoid resection, based on almost 3000 patients, has provided compelling evidence that rates of postoperative complications, conversion and reoperation, and length of hospital stay have decreased significantly over the past 10 years.