Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy.

Contains fulltext : 109239.pdf (publisher's version ) (Open Access)BACKGROUND: Lynch syndrome is a disorder caused by mismatch repair gene mutations. Mutation carriers have a high risk of developing colorectal cancer. In patients with Lynch syndrome in whom colon cancer has been diagnosed, in general, subtotal colectomy instead of partial colectomy is recommended because of the substantial risk of metachronous colorectal cancer. However, the effect of more extensive surgery on quality of life and functional outcome is unknown. OBJECTIVE: The aim of this study was to investigate quality of life and functional outcome in patients with Lynch syndrome after partial colectomy and subtotal colectomy. DESIGN: This is a nationwide cross-sectional study in the Netherlands. SETTINGS: Two quality-of-life questionnaires (Short Form-36 and The European Organization for Research and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire Module) and a functional outcome questionnaire (Colorectal Functional Outcome) were used. PATIENTS: Patients with Lynch syndrome who underwent surgery for colon cancer were included. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and functional outcome. RESULTS: Questionnaires were sent to 192 patients with Lynch syndrome who underwent surgery for colorectal cancer. A total of 136 patients returned the questionnaire (response rate, 71%). Eighteen patients with rectal cancer, 9 patients with a permanent ileostomy, and 5 patients with an IPAA were excluded. Fifty-one patients underwent partial colectomy, and 53 underwent subtotal colectomy. None of the scales of the Short Form-36 survey showed a significant difference. Analysis of the Colorectal Functional Outcome questionnaire revealed that, after subtotal colectomy, patients have a significantly higher stool frequency (p </= 0.01) and a significantly higher score on stool-related aspects (p = 0.06) and social impact (p = 0.03). The European Organization for Research and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire Module presented more problems with defecation after subtotal colectomy (p </= 0.01). LIMITATIONS: Certain selection bias cannot be ruled out. CONCLUSIONS: Although functional outcome is worse after subtotal colectomy than after partial colectomy, generic quality of life does not differ after the 2 types of surgery in Lynch syndrome. When discussing the options for surgery with the patient, all advantages and disadvantages of both surgical procedures, including quality of life and functional outcome, should be discussed.01 juni 201

Reduction of ephrin-A5 aggravates disease progression in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the brainstem, spinal cord and motor cortex. ALS is characterized by genetic and clinical heterogeneity, suggesting the existence of genetic factors that modify the phenotypic expression of the disease. We previously identified the axonal guidance EphA4 receptor, member of the Eph-ephrin system, as an ALS disease-modifying factor. EphA4 genetic inhibition rescued the motor neuron phenotype in zebrafish and a rodent model of ALS. Preventing ligands from binding to the EphA4 receptor also successfully improved disease, suggesting a role for EphA4 ligands in ALS. One particular ligand, ephrin-A5, is upregulated in reactive astrocytes after acute neuronal injury and inhibits axonal regeneration. Moreover, it plays a role during development in the correct pathfinding of motor axons towards their target limb muscles. We hypothesized that a constitutive reduction of ephrin-A5 signalling would benefit disease progression in a rodent model for ALS. We discovered that in the spinal cord of control and symptomatic ALS mice ephrin-A5 was predominantly expressed in neurons. Surprisingly, reduction of ephrin-A5 levels in SOD1G93A mice accelerated disease progression and reduced survival without affecting disease onset, motor neuron numbers or innervated neuromuscular junctions in symptomatic mice. These findings suggest ephrin-A5 as a modifier of disease progression that might play a role in the later stages of the disease. Similarly, we identified a more aggressive disease progression in patients with lower ephrin-A5 protein levels in the cerebrospinal fluid without modifying disease onset. In summary, we identified reduced expression of ephrin-A5 to accelerate disease progression in a mouse model of ALS as well as in humans. Combined with our previous findings on the role of EphA4 in ALS our current data suggests different contribution for various members of the Eph-ephrin system in the pathophysiology of a motor neuron disease.status: publishe

Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial

Background: Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection. Methods: We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low–medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671. Findings: From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0·48, 95% CI 0·38–0·61; p<0·0001). Among patients treated according to the algorithm, compared with patients who received usual care there was a decrease in bleeding that required intervention (47 [5%] patients vs 51 [6%] patients; RR 0·65, 0·42–0·99; p=0·046), organ failure (39 [5%] patients vs 92 [10%] patients; 0·35, 0·20–0·60; p=0·0001), and 90-day mortality (23 [3%] patients vs 44 [5%] patients; 0·42, 0·19–0·92; p=0·029). Interpretation: The algorithm for the early recognition and minimally invasive management of complications after pancreatic resection considerably improved clinical outcomes compared with usual care. This difference included an approximate 50% reduction in mortality at 90 days. Funding: The Dutch Cancer Society and UMC Utrecht

The risk of not receiving adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: a nationwide analysis

Background: The relation between type of postoperative complication and not receiving chemotherapy after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim was to investigate which patient factors and postoperative complications were associated with not receiving adjuvant chemotherapy. Methods: Patients who underwent resection (2014–2017) for PDAC were identified from the nationwide mandatory Dutch Pancreatic Cancer Audit. The association between patient-, tumor-, center-, treatment characteristics, and the risk of not receiving adjuvant chemotherapy was analyzed with multivariable logistic regression. Results: Overall, of 1306 patients, 24% (n = 312) developed postoperative Clavien Dindo ≥3 complications. In-hospital mortality was 3.5% (n = 46). Some 433 patients (33%) did not receive adjuvant chemotherapy. Independent predictors (all p < 0.050) for not receiving adjuvant chemotherapy were older age (odds ratio (OR) 0.96), higher ECOG performance status (OR 0.57), postoperative complications (OR 0.32), especially grade B/C pancreatic fistula (OR 0.51) and post-pancreatectomy hemorrhage (OR 0.36), poor tumor differentiation grade (OR 0.62), and annual center volume of <40 pancreatoduodenectomies (OR 0.51). Conclusions: This study demonstrated that a third of patients do not receive chemotherapy after resection of PDAC. Next to higher age, worse performance status and lower annual surgical volume, this is mostly related to surgical complications, especially postoperative pancreatic fistula and post-pancreatectomy hemorrhage

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

BACKGROUND: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment.METHODS: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio &gt;1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes.RESULTS: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). CONCLUSIONS: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.</p

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

Background: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. Methods: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. Results: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). Conclusions: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome