The impact of diagnostic delay on the course of acute appendicitis

BACKGROUND: The diagnosis of acute appendicitis is often delayed, which may complicate the further course of the disease. AIMS: To review appendectomy cases in order to determine the incidence of diagnostic delay, the underlying factors, and impact on the course of the disease. METHODS: Records of all children who underwent appendectomy from 1994 to 1997 were reviewed. The 129 cases were divided into group A (diagnostic period within 48 hours) and group B (diagnostic period 48 hours or more). RESULTS: In the group with diagnostic delay, significantly more children had first been referred to a paediatrician rather than to a surgeon. In almost half of the cases in this group initial diagnosis was not appendicitis but gastroenteritis. The perforation rate in group A was 24%, and in group B, 71%. Children under 5 years of age all presented in the delayed group B and had a perforation rate of 82%. The delayed group showed a higher number of postoperative complications and a longer hospitalisation period. CONCLUSIONS: Appendicitis is hard to diagnose when, because of a progressing disease process, the classical clinical picture is absent. The major factor in diagnostic delay is suspected gastroenteritis. Early surgical consultation in a child with deteriorating gastroenteritis is advised. Ultrasonographs can be of major help if abdominal signs and symptoms are non-specific for appendicitis

Modulators of drug dependence phenomena : factors affecting morphine withdrawal syndrome and cocaine-intake in rodents

This thesis compiles the experimental studies on several drugs, which modulate drug dependence phenomena in rodents. The main part of the studies is related to the morphine withdrawal (chapters 3-7), while a minor part is dealing with cocaine psychic dependence (chapter 9)

Evolutions in rectal cancer MRI staging and risk stratification in The Netherlands

PURPOSE: To analyze how the MRI reporting of rectal cancer has evolved (following guideline updates) in The Netherlands.METHODS: Retrospective analysis of 712 patients (2011-2018) from 8 teaching hospitals in The Netherlands with available original radiological staging reports that were re-evaluated by a dedicated MR expert using updated guideline criteria. Original reports were classified as "free-text," "semi-structured," or "template" and completeness of reporting was documented. Patients were categorized as low versus high risk, first based on the original reports (high risk = cT3-4, cN+, and/or cMRF+) and then based on the expert re-evaluations (high risk = cT3cd-4, cN+, MRF+, and/or EMVI+). Evolutions over time were studied by splitting the inclusion period in 3 equal time periods.RESULTS: A significant increase in template reporting was observed (from 1.6 to 17.6-29.6%; p &lt; 0.001), along with a significant increase in the reporting of cT-substage, number of N+ and extramesorectal nodes, MRF invasion and tumor-MRF distance, EMVI, anal sphincter involvement, and tumor morphology and circumference. Expert re-evaluation changed the risk classification from high to low risk in 18.0% of cases and from low to high risk in 1.7% (total 19.7%). In the majority (17.9%) of these cases, the changed risk classification was likely (at least in part) related to use of updated guideline criteria, which mainly led to a reduction in high-risk cT-stage and nodal downstaging.CONCLUSION: Updated concepts of risk stratification have increasingly been adopted, accompanied by an increase in template reporting and improved completeness of reporting. Use of updated guideline criteria resulted in considerable downstaging (of mainly high-risk cT-stage and nodal stage).</p

Value of MRI and diffusion-weighted MRI for the diagnosis of locally recurrent rectal cancer

OBJECTIVES: To evaluate the accuracy of standard MRI, diffusion-weighted MRI (DWI) and fusion images for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. METHODS: Forty-two patients with a clinical suspicion of recurrence underwent 1.5-T MRI consisting of standard T2-weighted FSE (3 planes) and an axial DWI (b0,500,1000). Two readers (R1,R2) independently scored the likelihood of recurrence; [1] on standard MRI, [2] on standard MRI+DWI, and [3] on T2-weighted+DWI fusion images. RESULTS: 19/42 patients had a local recurrence. R1 achieved an area under the ROC-curve (AUC) of 0.99, sensitivity 100% and specificity 83% on standard MRI versus 0.98, 100% and 91% after addition of DWI (p = 0.78). For R2 these figures were 0.87, 84% and 74% on standard MRI and 0.91, 89% and 83% with DWI (p = 0.09). Fusion images did not significantly improve the performance. Interobserver agreement was kappa0.69 for standard MRI, kappa0.82 for standard MRI+DWI and kappa0.84 for the fusion images. CONCLUSIONS: MRI is accurate for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. Addition of DWI does not significantly improve its performance. However, with DWI specificity and interobserver agreement increase. Fusion images do not improve accuracy

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO):study protocol for an international multicentre prospective diagnostic accuracy study

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI.METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI.DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy.TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.</p

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO):study protocol for an international multicentre prospective diagnostic accuracy study

Abstract Background Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. Methods In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. Discussion The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. Trial registration The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019

Long-Term Outcome of Immediate Versus Postponed" Intervention in Patients With Infected Necrotizing Pancreatitis" (POINTER)" Multicenter Randomized Trial

Objective: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis. Background: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention. Methods: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications. Results: Out of 104 patients, 88 were re-evaluated with a median followup of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P=0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P=0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups (P=0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P=0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar. Conclusions: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach.</p

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION):Long-term Follow-up of a Randomized Trial

Background & Aims: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. Methods: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. Results: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65–1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08–0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09–0.99). Pancreatic insufficiency and quality of life did not differ between groups. Conclusions: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571