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.

Trends in Early and Late Mortality in Patients With Severe Acute Pancreatitis Admitted to ICUs: A Nationwide Cohort Study.

OBJECTIVES: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality. DESIGN: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality. SETTING: Not applicable. PATIENTS: Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010. CONCLUSIONS: Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP.

Elderly Patients Strongly Benefit from Centralization of Pancreatic Cancer Surgery: A Population-Based Study.

BACKGROUND: Series from expert centers suggest that pancreas cancer surgery is safe for elderly patients but nationwide data, taking hospital volume into account, are lacking. METHODS: From the Netherlands Cancer Registry, all 3420 patients who underwent pancreatoduodenectomy (PD) for primary pancreatic or periampullary carcinoma in 2005-2013 were selected. Associations between age (<75, ≥75 years), hospital volume (tertiles), and postoperative mortality (30, 90 day) were evaluated by χ (2) tests and logistic regression analyses. Overall survival was investigated by means of Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: The proportion of elderly patients (≥75 years) undergoing PD increased from 15 % in 2005-2007 to 20 % in 2011-2013 (p = 0.009). In low (<15 per year), medium (15-28 per year), and high (>28 per year) hospital volume tertiles, the proportion of elderly patients was 16, 20, and 17 %, respectively (p = 0.10). With increasing hospital volume, 30-day postoperative mortality was 6.0-4.5-2.9 % (p = 0.002) and 90-day mortality 9.3-8.0-5.3 % (p = 0.001), respectively. Within each volume tertile, adjusted 30- and 90-day mortality of elderly patients was 1.6-2.5 times higher compared to outcomes of younger patients. Adjusted 30-day mortality in elderly patients was higher in low-volume hospitals (odds ratio = 2.87, 95 % confidence interval 1.15-7.17) compared to high-volume hospitals. Similarly, elderly patients had a worse overall survival in low-volume hospitals (hazard ratio = 1.28, 95 % confidence interval 1.01-1.63). Postoperative mortality of elderly patients in high-volume hospitals was similar to mortality of younger patients in low- and medium-volume hospitals. CONCLUSIONS: Elderly patients benefit from centralization by undergoing PD in high-volume hospitals, both with respect to postoperative mortality and survival. It would seem reasonable to place elderly patients into a high-risk category; they should only undergo surgery in the highest-tertile-volume hospitals.

Fluxomics reveals cellular and molecular basis of increased renal ammoniagenesis.

The kidney plays a critical role in excreting ammonia during metabolic acidosis and liver failure. The mechanisms behind this process have been poorly explored. The present study combines results of in vivo experiments of increased total ammoniagenesis with systems biology modeling, in which eight rats were fed an amino acid-rich diet (HD group) and eight a normal chow diet (AL group). We developed a method based on elementary mode analysis to study changes in amino acid flux occurring across the kidney in increased ammoniagenesis. Elementary modes represent minimal feasible metabolic paths in steady state. The model was used to predict amino acid fluxes in healthy and pre-hyperammonemic conditions, which were compared to experimental fluxes in rats. First, we found that total renal ammoniagenesis increased from 264 ± 68 to 612 ± 87 nmol (100 g body weight)-1 min-1 in the HD group (P = 0.021) and a concomitated upregulation of NKCC2 ammonia and other transporters in the kidney. In the kidney metabolic model, the best predictions were obtained with ammonia transport as an objective. Other objectives resulting in a fair correlation with the measured fluxes (correlation coefficient >0.5) were growth, protein uptake, urea excretion, and lysine and phenylalanine transport. These predictions were improved when specific gene expression data were considered in HD conditions, suggesting a role for the mitochondrial glycine pathway. Further studies are needed to determine if regulation through the mitochondrial glycine pathway and ammonia transporters can be modulated and how to use the kidney as a therapeutic target in hyperammonemia.

A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study).

BACKGROUND: The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS) recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? METHOD/DESIGN: The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation) and the indirect non medical costs (friction method). Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor) of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05), a group size of 3 x 40 = 120 patients is calculated. DISCUSSION: The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. TRIAL REGISTRATION: ISRCTN44649165.

To pee or not to pee: ammonia hypothesis of hepatic encephalopathy revisited.

Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure. Its aetiology has been debated for the past 100 years. Nevertheless, elevated ammonia levels are still believed to play a central role in its pathogenesis. After intestinal production, ammonia is detoxified by the liver. In liver failure, skeletal muscle and brain have been proposed to be alternative, although temporary, ammonia detoxifying organs. However, there is an increasing body of evidence that the kidney, in addition to the gut, is a pivotal organ determining systemic ammonia levels. In the last 20 years, it has been shown that the kidney can switch from an organ of systemic net ammonia production to a net ammonia excretion organ. The kidney plays a central role in the determination of ammonia levels. It is at least as important as the gut and could therefore serve as a target for new treatments for hepatic encephalopathy.

Fixation methods for electron microscopy of human and other liver.

For an electron microscopic study of the liver, expertise and complicated, time-consuming processing of hepatic tissues and cells is needed. The interpretation of electron microscopy (EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation, embedding, sectioning, contrast staining and microscopic imaging. Hence, the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue, for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects.

Sacral neuromodulation in patients with fecal incontinence: a single-center study.

PURPOSE: Fecal incontinence is a psychologically devastating and socially incapacitating condition. Conventional treatment is likely to improve continence in many patients; however, there remains a group with persisting symptoms who are not amenable for a simple surgical repair. We evaluated the effect of sacral neuromodulation in patients with structurally intact sphincters after failure of conventional treatment. METHODS: Patients aged 18 to 75 years were evaluated. Incontinence was defined as involuntary loss of stool at least once per week, which was objectified by completion of a three-week bowel-habits diary during ambulatory electrode stimulation at the S3 or S4 foramen. Patients were qualified for permanent stimulation when showing a reduction of at least 50 percent in incontinence episodes or days. RESULTS: Seventy-five patients (66 females; mean age, 52 (range, 26-75) years) were treated. Three patients had partial spinal cord injury, two patients a previous low-anterior resection, and nine patients had a previous sphincter repair. Evaluation after trial screening showed that 62 patients (83 percent) had improved continence. Median incontinence episodes per week decreased from 7.5 to 0.67 (P < 0.01), median incontinence days per week from 4 to 0.5 (P < 0.01). The symptomatic response stayed unchanged after implantation of a permanent electrode and pacemaker in 50 patients. After a median follow-up of 12 months, this effect could be sustained in 48 patients. Anal manometry during stimulation showed no increase of sphincter pressures. CONCLUSIONS: Sacral neuromodulation is a feasible treatment option for fecal incontinence in patients with structurally intact sphincters.