Thromboembolic and bleeding complications in patients with oesophageal cancer.
ABSTRACT: BACKGROUND:In patients who undergo curative treatment for oesophageal cancer, risk estimates of venous thromboembolism (VTE), arterial thromboembolism and bleeding are needed to guide decisions about thromboprophylaxis. METHODS:This was a single-centre, retrospective cohort study of patients with stage I-III oesophageal cancer who received neoadjuvant chemoradiation followed by oesophagectomy. The outcomes VTE, arterial thromboembolism, major bleeding, clinically relevant non-major bleeding and mortality were analysed for four consecutive cancer treatment stages (from diagnosis to neoadjuvant chemoradiotherapy, during neoadjuvant treatment, 30-day postoperative period, and up to 6?months after postoperative period). RESULTS:Some 511 patients were included. The 2-year survival rate was 67·3 (95 per cent c.i. 63·2 to 71·7) per cent. During the 2-year follow-up, 50 patients (9·8 per cent) developed VTE, 20 (3·9 per cent) arterial thromboembolism, 21 (4·1 per cent) major bleeding and 30 (5·9 per cent) clinically relevant non-major bleeding. The risk of these events was substantial at all treatment stages. Despite 30-day postoperative thromboprophylaxis, 17 patients (3·3 per cent) developed VTE after surgery. Patients with VTE had worse survival (time-varying hazard ratio 1·81, 95 per cent c.i. 1·25 to 2·64). Most bleeding events occurred around the time of medical intervention, and approximately one-half during concomitant use of prophylactic or therapeutic anticoagulation. CONCLUSION:Patients with oesophageal cancer undergoing neoadjuvant chemoradiotherapy and surgery are at substantial risk of thromboembolic and bleeding events throughout all stages of treatment. Survival is worse in patients with thromboembolic events during follow-up.
Project description:BACKGROUND:Risk assessment is relevant to predict postoperative outcomes in patients with gastro-oesophageal cancer. This cohort study aimed to assess body composition changes during neoadjuvant chemotherapy and investigate their association with postoperative complications. METHODS:Consecutive patients with gastro-oesophageal cancer undergoing neoadjuvant chemotherapy and surgery with curative intent between 2016 and 2019 were identified from a specific database and included in the study. CT images before and after neoadjuvant chemotherapy were used to assess the skeletal muscle index, sarcopenia, and subcutaneous and visceral fat index. RESULTS:In a cohort of 199 patients, the mean skeletal muscle index decreased during neoadjuvant therapy (from 51·187 to 49·19?cm2 /m2 ; P?<?0·001) and the rate of sarcopenia increased (from 42·2 to 54·3 per cent; P?<?0·001). A skeletal muscle index decrease greater than 5 per cent was not associated with an increased risk of total postoperative complications (odds ratio 0·91, 95 per cent c.i. 0·52 to 1·59; P = 0·736) or severe complications (odds ratio 0·66, 0·29 to 1·53; P = 0·329). CONCLUSION:Skeletal muscle index decreased during neoadjuvant therapy but was not associated with postoperative complications.
Project description:Venous thromboembolism (VTE) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Many guidelines advise on the ideal pharmacological thromboprophylaxis strategy; however, despite its use, approximately 1.5% of patients still develop symptomatic VTE. Considering the large number of THAs and TKAs performed worldwide (2.5 million in total), the impact of VTE following these interventions is enormous. This paper discusses a concept how to further lower rates of VTE and bleeding complications following surgery. By stratifying patients according to their risk, we can optimize the balance between VTE and bleeding for each individual. This way, low-risk patients may be safely withheld from treatment (and avoid unnecessary bleeding complications and costs), whereas high-risk patients should receive adequate therapy (for instance, an increased thromboprophylaxis dosage and duration). An individualized strategy requires a well-functioning VTE prediction model following THA and TKA to help physicians to decide on optimal thromboprophylaxis therapy.
Project description:The Caprini and Padua venous thromboembolism (VTE) risk assessment models (RAMs) are used to assess VTE risk in surgical and in medical patients respectively. This study aims to compare the proportion of medical inpatients eligible for VTE prophylaxis using the hospital Caprini-based RAM to using the Caprini and Padua RAMs and to assess the associated clinical outcomes. In a prospective observational study, we assessed 297 adult medical inpatients for whom VTE thromboprophylaxis was initiated according to the hospital Caprini-based RAM, referred to as the Lebanese American University Medical Center RAM (LAUMC-RAM). The Padua, Caprini and IMPROVE bleeding risk scores were also assessed for all patients. Bleeding and thromboembolism were evaluated at 14 and 30 days post VTE risk assessment. Pharmacologic thromboprophylaxis was warranted in 97.6%, 99.7%, and 52.9% of patients using the Caprini-based, Caprini, and Padua RAMs respectively. The Caprini-based and Caprini RAMs were highly correlated (r?=?0.873 p?<?0.001) and were significantly less correlated with the Padua RAM. Major and overall bleeding occurred in 1.4% and 9.2% respectively. VTE was reported in 0.4% with no VTE related mortality. In hospitalized medical patients, the Caprini-based RAM can accurately distinguish low and high VTE risk without resulting in increased risk of bleeding.
Project description:This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma.A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging.TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P?<?0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P?=?0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P?<?0·001).A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.
Project description:Venous thromboembolism (VTE) is a common complication among hospitalized patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for VTE prevention. As trials on thromboprophylaxis in medical patients have proven the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH), all acutely medical ill patients should be considered for pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk of associated VTE attributable to surgery is well recognized, and where widespread use of pharmacological thromboprophylaxis and early mobilization has resulted in significant reductions in the risk of VTE, appropriate VTE prophylaxis is under-used in medical patients. Many reasons for this under-use have been identified, including low perceived risk of VTE in medical patients, absence of optimal tools for risk assessment, heterogeneity of patients and their diseases, and fear of bleeding complications. A consistent group among hospitalized medical patients is composed of elderly patients with impaired renal function, a condition potentially associated with bleeding. How these patients should be managed is discussed in this review. Particular attention is devoted to LMWHs and fondaparinux and to measures to improve the safety and the efficacy of their use.
Project description:Venous thromboembolism (VTE) is a frequent complication among acutely ill medical patients hospitalized for congestive heart failure, acute respiratory insufficiency, rheumatologic disorders, and acute infectious and/or inflammatory diseases. Based on robust data from randomized controlled studies and meta-analyses showing a reduced incidence of VTE by 40% to about 60% with pharmacologic thromboprophylaxis, prevention of VTE with low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is currently recommended in all at-risk hospitalized acutely ill medical patients. In patients who are bleeding or are at high risk for major bleeding, mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression may be suggested. Thromboprophylaxis is generally continued for 6 to 14 days or for the duration of hospitalization. Selected cases could benefit from extended thromboprophylaxis beyond this period, although the risk of major bleeding remains a concern, and additional studies are needed to identify patients who may benefit from prolonged prophylaxis. For hospitalized acutely ill medical patients with renal insufficiency, a low dose (1.5 mg once daily) of fondaparinux or prophylactic LMWH subcutaneously appears to have a safe profile, although proper evaluation in randomized studies is lacking. The evidence on the use of prophylaxis for VTE in this latter group of patients, as well as in those at higher risk of bleeding complications, such as patients with thrombocytopenia, remains scarce. For critically ill patients hospitalized in intensive care units with no contraindications, LMWH or UFH are recommended, with frequent and careful assessment of the risk of bleeding. In this review, we discuss the evidence for use of thromboprophylaxis for VTE in acutely ill hospitalized medical patients, with a focus on (low-dose) fondaparinux.
Project description:Background:Benchmarking on an international level might lead to improved outcomes at a national level. The aim of this study was to compare treatment and surgical outcome data from the Swedish National Register for Oesophageal and Gastric Cancer (NREV) and the Dutch Upper Gastrointestinal Cancer Audit (DUCA). Methods:All patients with primary oesophageal or gastric cancer who underwent a resection and were registered in NREV or DUCA between 2012 and 2014 were included. Differences in 30-day mortality were analysed using case mix-adjusted multivariable logistic regression. Results:In total, 4439 patients underwent oesophagectomy (2509 patients) or gastrectomy (1930 patients). Estimated resection rates were comparable. Swedish patients were older but had less advanced disease and less co-morbidity than Dutch patients. Neoadjuvant treatment rates were lower in Sweden than in the Netherlands, both for patients who underwent oesophagectomy (68·6 versus 90·0 per cent respectively; P?<?0·001) and for those having gastrectomy (38·3 versus 56·6 per cent; P?<?0·001). In Sweden, transthoracic oesophagectomy was performed in 94·7 per cent of patients, whereas in the Netherlands, a transhiatal approach was undertaken in 35·8 per cent. Higher annual procedural volumes per hospital were observed in the Netherlands. Adjusted 30-day and/or in-hospital mortality after gastrectomy was statistically significantly lower in Sweden than in the Netherlands (odds ratio 0·53, 95 per cent c.i. 0·29 to 0·95). Conclusion:For oesophageal and gastric cancer, there are differences in patient, tumour and treatment characteristics between Sweden and the Netherlands. Postoperative mortality in patients with gastric cancer was lower in Sweden.
Project description:Venous thromboembolism (VTE) is a common complication for critically ill patients. Intermittent pneumatic compression (IPC) is recommended for patients with high risk of bleeding. We aim to evaluate the effectiveness of IPC for thromboprophylaxis in critically ill patients. We searched PubMed, Embase, and ClinicalTrials for randomized controlled trials (RCTs) and observational studies that evaluated IPC in critically ill patients. RevMan 5.3 software was used for the meta-analysis. A total of 10 studies were included. The IPC group significantly reduced the VTE incidence compared with no thromboprophylaxis group (risk ratio [RR]: 0.35, confidence interval [CI]: 0.18-0.68, P = .002) and the IPC group also showed lower VTE incidence than the graduated compression stockings (GCS) group (RR: 0.47, CI: 0.24-0.91, P = .03). There were no significant differences between using IPC and low-molecular-weight heparin (LMWH) for VTE incidence (RR: 1.26, CI: 0.72-2.22, P = .41), but LMWH showed significantly more bleeding events. Intermittent pneumatic compression as an adjunctive treatment did not further reduce VTE incidence (RR: 0.55, CI: 0.24-1.27, P = .16). Intermittent pneumatic compression can reduce the incidence of VTE for critically ill patients, which is better than GCS and similar to LMWH, but it has no significant advantage as an adjunct therapy for thromboprophylaxis.
Project description:Background:Thrombosis is a common complication in patients with cancer. Whether thromboprophylaxis could benefit patients with cancer is unclear. The aim of this systematic review was to determine the efficacy and safety of thromboprophylaxis in patients with cancer undergoing surgery or chemotherapy. Methods:We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2018 to investigate whether thromboprophylaxis measures were more effective than a placebo in patients with cancer. Results:In total, 33 trials with 11,942 patients with cancer were identified. In patients with cancer undergoing surgery, the administration of thromboprophylaxis was associated with decreasing trends in venous thromboembolism (VTE) [relative risk (RR) 0.51, 95% confidence interval (CI) 0.32-0.81] and DVT (RR 0.53, 95% CI 0.33-0.87). In patients with cancer undergoing chemotherapy, the administration of thromboprophylaxis reduced the incidences of VTE, DVT, and pulmonary embolism compared with no thromboprophylaxis (RR 0.54, 95% CI 0.40-0.73; RR 0.47, 95% CI 0.31-0.73; RR 0.51, 95% CI 0.32-0.81, respectively). The pooled results regarding major bleeding showed no significant difference between prophylaxis and no prophylaxis in either the surgical or the chemotherapy groups (RR 2.35, 95% CI 0.74-7.52, p?=?0.1482, I2?=?0%; RR 1.30, 95% CI 0.93-1.83, p?=?0.1274, I2?=?0%, respectively). Conclusion:Thromboprophylaxis did not increase major bleeding events or the incidence of thrombocytopenia. All-cause mortality was not significantly different between those who received thromboprophylaxis and those who did not. This meta-analysis provides evidence that thromboprophylaxis can reduce the number of VTE and DVT events, with no apparent increase in the incidence of major bleeding in patients with cancer.
Project description:Guidelines suggest thromboprophylaxis for ambulatory cancer patients starting chemotherapy with an intermediate to high risk of venous thromboembolism (VTE) according to Khorana score. Data on thromboprophylaxis efficacy in different Khorana score risk groups remain ambiguous. We sought to evaluate thromboprophylaxis in patients with an intermediate- to high-risk (?2 points) Khorana score and an intermediate-risk score (2 points) or high-risk score (?3 points) separately. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials (RCTs) comparing thromboprophylaxis with placebo or standard care in ambulatory cancer patients. Outcomes were VTE, major bleeding, and all-cause mortality. Relative risks (RRs) were calculated in a profile-likelihood random-effects model. Six RCTs were identified, involving 4626 cancer patients. Thromboprophylaxis with direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH) significantly reduced VTE risk in intermediate- to high-risk (RR, 0.51; 95% confidence interval [CI], 0.34-0.67), intermediate-risk (RR, 0.58; 95% CI, 0.36-0.83), and high-risk patients (RR, 0.45; 95% CI, 0.28-0.67); the numbers needed to treat (NNTs) were 25 (intermediate to high risk), 34 (intermediate risk), and 17 (high risk), respectively. There was no significant difference in major bleeding (RR, 1.06; 95% CI, 0.69-1.67) or all-cause mortality (RR, 0.90; 95% CI, 0.82-1.01). The numbers needed to harm (NNHs) for major bleeding in intermediate- to high-risk, intermediate-risk, and high-risk patients were 1000, -500, and 334, respectively. The overall NNH was lower in DOAC studies (100) versus LMWH studies (-500). These findings indicate thromboprophylaxis effectively reduces the risk of VTE in patients with an intermediate- to high-risk Khorana score, although the NNT is twice as high for intermediate-risk patients compared with high-risk patients.