A Dutch prediction tool to assess the risk of incidental gallbladder cancers after cholecystectomies for benign gallstone disease.

BACKGROUND: Despite the increasing implementation of selective histopathologic policies for post-cholecystectomy evaluation of gallbladder specimens in low-incidence countries, the fear of missing incidental gallbladder cancer (GBC) persists. This study aimed to develop a diagnostic prediction model for selecting gallbladders that require additional histopathological examination after cholecystectomy. METHODS: A registration-based retrospective cohort study of nine Dutch hospitals was conducted between January 2004 and December 2014. Data were collected using a secure linkage of three patient databases, and potential clinical predictors of gallbladder cancer were selected. The prediction model was validated internally by using bootstrapping. Its discriminative capacity and accuracy were tested by assessing the area under the receiver operating characteristic curve (AUC), Nagelkerke's pseudo-R2, and Brier score. RESULTS: Using a cohort of 22,025 gallbladders, including 75 GBC cases, a prediction model with the following variables was developed: age, sex, urgency, type of surgery, and indication for surgery. After correction for optimism, Nagelkerke's R2 and Brier score were 0.32 and 88%, respectively, indicating a moderate model fit. The AUC was 90.3% (95% confidence interval, 86.2%-94.4%), indicating good discriminative ability. CONCLUSION: We developed a good clinical prediction model for selecting gallbladder specimens for histopathologic examination after cholecystectomy to rule out GBC.

The Role of Expert Opinion in Projecting Long-Term Survival Outcomes Beyond the Horizon of a Clinical Trial.

INTRODUCTION: Clinical trials often have short follow-ups, and long-term outcomes such as survival must be extrapolated. Current extrapolation methods often produce a wide range of survival values. To minimize uncertainty in projections, we developed a novel method that incorporates formally elicited expert opinion in a Bayesian analysis and used it to extrapolate survival in the placebo arm of DAPA-CKD, a phase 3 trial of dapagliflozin in patients with chronic kidney disease (NCT03036150). METHODS: A summary of mortality data from 13 studies that included DAPA-CKD-like populations and training on elicitation were provided to six experts. An elicitation survey was used to gather the experts' 10- and 20-year survival estimates for patients in the placebo arm of DAPA-CKD. These estimates were combined with DAPA-CKD mortality and general population mortality (GPM) data in a Bayesian analysis to extrapolate long-term survival using seven parametric distributions. Results were compared with those from standard frequentist approaches (with and without GPM data) that do not incorporate expert opinion. RESULTS: The group expert-elicited estimate for 20-year survival was 31% (lower estimate, 10%; upper estimate, 40%). In the Bayesian analysis, the 20-year extrapolated survival across the seven distributions was 14.9-39.1%, a range that was 2.4- and 1.6-fold smaller than those produced by the frequentist methods (0.0-56.9% without and 0.0-39.2% with GPM data). CONCLUSIONS: Using expert opinion in a Bayesian analysis provided a robust method for extrapolating long-term survival in the placebo arm of DAPA-CKD. The method could be applied to other populations with limited survival data.

Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study.

OBJECTIVE: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy. BACKGROUND: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking. METHODS: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis. The surgeon's opinion on additional value of histopathological examination was reported before sending all specimens to the pathologist. Main outcomes were the number of hypothetically missed appendiceal neoplasms with clinical consequences benefiting the patient (upper limit two-sided 95% confidence interval below 3:1000 considered oncologically safe) and potential cost savings after selective histopathological examination. RESULTS: Seven thousand three hundred thirty-nine patients were included. After a selective policy, 4966/7339 (67.7%) specimens would have been refrained from histopathological examination. Appendiceal neoplasms with clinical consequences would have been missed in 22/4966 patients. In 5/22, residual disease was completely resected during additional surgery. Hence, an appendiceal neoplasm with clinical consequences benefiting the patient would have been missed in 1.01:1000 patients (upper limit 95% confidence interval 1.61:1000). In contrast, twice as many patients (10/22) would not have been exposed to potential harm due to re-resections without clear benefit, whereas consequences were neither beneficial nor harmful in the remaining seven. Estimated cost savings established by replacing routine for selective histopathological examination were €725,400 per 10,000 patients. CONCLUSIONS: Selective histopathological examination after appendectomy for suspected appendicitis is oncologically safe and will likely result in a reduction of pathologists' workload, less costs, and fewer re-resections without clear benefit.

Safety and economic analysis of selective histopathology following cholecystectomy: multicentre, prospective, cross-sectional FANCY study.

BACKGROUND: There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking. METHODS: In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy. Before sending all specimens to the pathologist, the surgeon judged whether histopathological examination was indicated. The main outcomes were the number of patients with hypothetically missed malignancy with clinical consequences (upper limit two-sided 95 per cent c.i. below 3:1000 considered oncologically safe) and potential cost savings of selective histopathological examination. RESULTS: Twenty-two (2.19:1000) of 10 041 specimens exhibited malignancy with clinical consequences. In case of a selective policy, surgeons would have held back 7846 of 10041 (78.1 per cent) gallbladders from histopathological examination. Malignancy with clinical consequences would have been missed in seven of 7846 patients (0.89:1000, upper limit 95% c.i. 1.40:1000). No patient benefitted from the clinical consequences, while two were harmed (futile additional surgery). Of 15 patients in whom malignancy with clinical consequences would have been diagnosed, one benefitted (residual disease radically removed), two potentially benefitted (palliative systemic therapy), and four experienced harm (futile additional surgery). Estimated cost savings established by replacing routine for selective histopathological examination were €703 500 per 10 000 patients. CONCLUSION: Selective histopathological examination following cholecystectomy is oncologically safe and could reduce pathology workload, costs, and futile re-resections.

Association between healthcare practitioners' beliefs about statins and patients' beliefs and adherence.

AIMS: Adherence to statins ranges from 32% to 79%. Patients' beliefs about medication are associated with adherence. There is lack of insight into the possible association between beliefs of healthcare practitioners (HCPs) about statins and patients' beliefs and adherence. This study aims to examine whether HCPs' beliefs about statins are associated with patients' beliefs and adherence about/to statins. METHODS: Cross-sectional study in 48 pharmacies and affiliated physicians' practices between 3 September 2014 and 20 March 2015. HCPs' (prescribers and pharmacy staff) and patients' beliefs about statins were assessed with the Beliefs about Medicine Questionnaire (BMQ) specific. Adherence to statins was assessed with the MARS-5 questionnaire. Multilevel regression analysis was performed to assess the association between HCPs' beliefs and patients' beliefs and adherence. RESULTS: 1504 patients (mean age 66.8 [s.d. ± 9.9] years, 46.5% female) and 734 HCPs (209 physicians, 118 pharmacists and 366 pharmacy technicians) participated in this study. Patients have higher BMQ necessity (16.9 [s.d. ± 4.3]) and BMQ concern (12.3 [s.d. ± 3.9]) scores than HCPs (15.0 [s.d. ± 3.0] and 11.5 [s.d. ± 2.9], P < 0.001). No associations were found between any of the HCPs' BMQ and patients' BMQ scores and adherence to statins. Patients' BMQ necessity, concern and necessity-concerns (NC)-differential scores were associated with patients' adherence (MARS-5) scores. B (95% CI) coefficients were 0.057 (0.035-0.079), -0.040 (-0.064 to -0.016) and.061 (0.043-0.079). CONCLUSIONS: Patients have stronger beliefs about medication compared to HCPs. No associations were found between HCPs' BMQ scores on the one hand and patients' BMQ scores and adherence to statins on the other hand.

Method for adequate macroscopic gallbladder examination after cholecystectomy.

BACKGROUND AND AIMS: There is no clear guideline nor protocol for macroscopic examination of the gallbladder, leaving surgeons extemporaneous in regard of gallbladder examination in selective histopathologic policy. The purpose of this article is to describe a surgical approach for adequate macroscopic inspection of the gallbladder. MATERIALS AND METHODS: The described practical method was developed in collaboration between surgeons and pathologists. This method was introduced in 2011 and implemented in 2012. We retrospectively reviewed the number of cholecystectomies and number of histopathologic examinations between 2006 and 2017, using our own patient database. We used the Netherlands Cancer Registry (NCR) to examine the incidence of gallbladder cancer patients before and after implementation of the selective policy in our hospital. In addition to the method, we depict several frequent macroscopic abnormalities in order to provide some examples for surgical colleagues. RESULTS: Since implementation of the selective policy, 2271 surgical macroscopic gallbladder examinations were performed. As a result, we observed a significant decrease from 83% in 2012 to 38% in 2017, in histopathologic examination of the gallbladder following cholecystectomy. We observed a stable trend of gallbladder carcinoma in the same period (0.17%, n = 4 during 2006-2011 and 0.26%, n = 6 during 2012-2017). CONCLUSION: A simple, valid and easy method is described for future macroscopic analysis by the surgeon following a cholecystectomy.

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression.

BACKGROUND: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. RESEARCH QUESTION: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? METHOD: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. RESULTS: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. CONCLUSION: "Standard" 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

Paraganglion, a pitfall in diagnosis after regular cholecystectomy.

INTRODUCTION: Neuroendocrine neoplasm of the gallbladder is an extremely uncommon diagnosis. We present a case of a benign gallbladder paraganglion that was initially incorrectly diagnosed as a neuroendocrine tumour (NET). PRESENTATION OF CASE: A 27-year-old female with symptomatic gallstone disease underwent an uncomplicated laparoscopic cholecystectomy. Routine histopathologic examination suggested the presence of a small adventitial NET. However, histopathological revision was performed by our pathologist because of regional gallbladder carcinoma (GBC) treatment evaluation. The revision demonstrated the presence of a normal paraganglion, a preexistent structure that is only rarely encountered during routine histopathologic examination of the gallbladder. DISCUSSION: Neuroendocrine neoplasms of the gallbladder are extremely rare. Treatment varies from a simple cholecystectomy to extensive surgical resections. Chemotherapy is usually reserved for metastatic disease. In contrast, a gallbladder paraganglion is a benign entity not requiring additional treatment. CONCLUSION: A neuroendocrine neoplasm of the gallbladder may closely resemble a benign paraganglion. If a NET is suspected, the clinician should be aware of the histopathologic mimicry of a paraganglion prior to initiating additional treatments.

Is there a difference in laparoscopic cholecystectomy performed in a teaching hospital or a general hospital in The Netherlands?

Introduction: Laparoscopic cholecystectomy may have a complicated course with severe complications such as bile duct injury. Studies in other countries than the Netherlands report ambivalent results regarding the influence of a residency program on patient safety, efficacy and financial consequences. This study aims to determine whether there is a difference between laparoscopic cholecystectomy performed in a teaching hospital or a non-teaching general hospital in Dutch clinics. Materials and methods: A prospective cohort study was performed to examine the safety of laparoscopic cholecystectomies in a teaching hospital with a residency program and a general hospital without surgical residents. All consecutive cholecystectomies in these two hospitals between September 2014 and March 2015 were included. Patient characteristics, operative procedure, level of experience, operation time, per- and postoperative complications, mortality, length of hospital stay, re-admittance and conversions to laparotomy were analyzed. Results: A total of 294 consecutive cholecystectomies were performed in both hospitals. Cholecystectomies performed in the teaching hospital took an average of 25 min longer to complete compared with a non-residency setting. Both the number of conversions and the number of re-admissions were not significantly different between both clinics. The residency program showed smaller peroperative liver lesions along with more postoperative complications, with most complications in patients that required a conversion. Discussion: Current practice where residents perform supervised cholecystectomies should not be discouraged. We believe that is safe and lead to an acceptable increase in operation time.

Postoperative drug-induced priapism.

We presented a case of a postoperative patient with low-flow priapism, possibly initiated by propofol-based anaesthesia or epidural anaesthesia. The delay in diagnosing priapism resulted in emergency interventions with a partially successful effect and eventually permanent erectile dysfunction. Due to the delay in treatment, erectile dysfunction ensued and was manageable with medication; hence, the patient decided against a penile prosthesis.

Traumatic herniation of the lung.

We present a relatively rare clinical presentation of herniation of lung parenchyma. In our case, the patient suffered multiple rib fractures, with an intercostal herniation of lung tissue after a trauma. We opted for a conservative treatment, given the clinical presentation, and the absence of incarceration or strangulation of the pulmonary tissue. In the absence of clear guidelines for this rare presentation, current treatment can be conservative or surgical, depending on the clinical presentation.

Rapid Naming and Phonemic Awareness in Children With Reading Disabilities and/or Specific Language Impairment: Differentiating Processes?

PURPOSE: The objective of this study was to assess and compare the predictive values of group membership for rapid automatized naming (RAN) and phonemic awareness (PA) in Dutch school children with and without reading disabilities (RD) or specific language impairment (SLI). METHOD: A composite word reading index and a formal SLI diagnosis were used to classify a total of 1,267 children aged 8 to 13 years old either as RD-only (n = 126), SLI-only (n = 21), comorbid (RD+SLI; n = 30), or typically developing (n = 1,090). RAN and PA were assessed with 4 standardized subtests. The clinical subgroups were compared to each other and contrasted with the control group. RESULTS: For each subgroup, results indicate substantial effect sizes of RAN and PA. However, the RD-only group seems to be more affected by poor RAN than the SLI-only group, whereas the 2 groups perform equally poorly on PA. The comorbid group was revealed as most severely impaired on all measurements. CONCLUSIONS: In studying RD and SLI, this research indicates that it is important to distinguish between RD-only, SLI-only, and comorbid groups. The comorbid group shows additive effects of both disorders.