Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial): design and rationale of a nationwide stepped-wedge cluster-randomized trial

BACKGROUND: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. METHODS: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide da

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1):a multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Surgical strategies in endocrine tumors

Endocrine surgery has become more custom-made throughout the years. Endocrine tumors can be sporadic or develop as part of familial syndromes. Several familial syndromes are known to cause endocrine tumors. The most common are multiple endocrine neoplasia (MEN) syndromes type 1, 2A and 2B. This thesis addresses the currently available surgical strategies in the management of endocrine tumors. The studies described in this thesis offer more insight in the prognostic implications of several factors in endocrine cancers and the surgical treatment of endocrine cancer. The following matters have been studied. For thyroid cancer we have studied the currently known diagnostic markers and prognostic factors and the expression on matrix metalloproteinases. In patients with recurrent papillary thyroid cancer we have studied the influence of fluorodeoxyglucose-positron emission tomography (PET) scan positive lesions on the prognosis and implications for surgical management. It appears that patients with recurrent papillary thyroid cancer that have PET positive lesions have a worse prognosis than those who have PET negative lesions. The surgical treatment for patients with recurrent papillary thyroid cancer that have PET positive lesions should be aggressive. For patients with Multiple Endocrine Neoplasia Type 2A we studied the factors that determine outcome after total thyroidectomy for medullary thyroid cancer. A higher age and type of codon (918 and 634) are the most important prognostic factors and are associated with persistent and recurrent medullary thyroid cancer. For the parathyroid glands, we determined the optimal surgical treatment of primary hyperparathyroidism in MEN 1 and MEN2A. For MEN 1 patients, a subtotal parathyroidectomy is recommended, whereas for MEN 2A patients, a minimally invasive parathyroidectomy is recommended, because the clinical presentation is less aggressive. For the pancreas a systematic review was conducted to determine the timing and best surgical strategy for pancreatic endocrine tumors in MEN 1 patients. Even after a systematic review it remains difficult to recommend a clear cut indications and type of surgical procedure for pancreatic endocrine tumors in MEN1. Adrenal gland surgery was also studied. A cost-effectiveness analysis was carried out for retroperitoneal endoscopic versus conventional open adrenalectomy followed by a large series of posterior retroperitoneal adrenalectomies, in which the procedure was shown to be safe and effective. Finally, the clinical spectrum in terms of hormone levels and clinical presentation of pheochromocytoma was studied. The size of pheochromocytoma correlate to the levels of cathecholamine production especially up to 4cm. The largest tumors produce the highest hormone ratios. From this thesis, it can be concluded that the management of patients who have an endocrine tumor is complex and individual. The treatment of these patients has become tailor-made more and more throughout the years. Patients with familial endocrine syndromes should be regarded as distinctly different from patients with sporadic endocrine disease and often require a different and more aggressive approach. These patients and their families are entitled to centralized care with a multidisciplinary team of endocrinologists and endocrine surgeons

Searching for predictors of surgical complications in critically ill surgery patients in the intensive care unit: a review

Contains fulltext : 153930.pdf (publisher's version ) (Closed access)We reviewed the use of the levels of C-reactive protein, lactate and procalcitonin and/or the Sequential Organ Failure Assessment score to determine their diagnostic accuracy for predicting surgical complications in critically ill general post-surgery patients. Included were all studies published in PubMed from inception to July 2013 that met the following inclusion criteria: evaluation of the above parameters, describing their diagnostic accuracy and the risk stratification for surgical complications in surgical patients admitted to an intensive care unit. No difference in the Sequential Organ Failure Assessment scores was seen between patients with or without complications. The D-lactate levels were significantly higher in those who developed colonic ischemic complications after a ruptured abdominal aortic aneurysm. After gastro-intestinal surgery, contradictory data were reported, with both positive and negative use of C-reactive protein and procalcitonin in the diagnosis of septic complications. However, in trauma patients, the C-reactive protein levels may help to discriminate between those with and without infectious causes. We conclude that the Sequential Organ Failure Assessment score, lactate concentration and C-reactive protein level have no significant predictive value for early postoperative complications in critically ill post-surgery patients. However, procalcitonin seems to be a useful parameter for diagnosing complications in specific patient populations after surgery and/or after trauma

Thyroid surgery and the usefulness of intraoperative neuromonitoring, a single center study

Item does not contain fulltextPurpose/Aim of study: To compare the use of intraoperative neuromonitoring (IONM) versus visualization of the recurrent laryngeal nerve (RLN) alone in thyroid surgery with regard to incidence in postoperative RLN injury and operation time. MATERIALS AND METHODS: This retrospective cohort study was performed in the Amphia Hospital, the Netherlands. All thyroid gland operations were collected from September 2009 to October 2012. For each case we recorded the patient characteristics, indication for surgery, intraoperative data, complications, results of pathological evaluation, and consultation of a ENT-surgeon. Research of current literature and statistical analysis was performed. RESULTS: In total, 147 patients were included and classified into an IONM and non-IONM group. Both groups were similar in demographical aspects and indications for surgery. In total, we had 170 nerves at risk (NAR). In both groups, there were 85 (50%) NAR. Overall injury to the RLN was 6%. A statistical significant decrease of permanent RLN injuries was noticed in the IONM group compared to the non-IONM group (n = 0 vs n = 6; p = .044). In transient RLN injury, no difference was noticed (n = 2 vs n = 2). Operation time with or without IONM was not significantly different for hemithyroidectomies, neither for total thyroidectomies. CONCLUSION: IONM is a useful tool as an adjunct in thyroid surgery to prevent RLN injury. A statistical significant decrease in permanent RLN injury with the use of IONM was found, but it did not significantly decrease time of operation

Neoadjuvant Chemotherapy for Locally Advanced T4 Colon Cancer: A Nationwide Propensity-Score Matched Cohort Analysis

Contains fulltext : 220811.pdf (Publisher’s version ) (Open Access

A Clinical Decision Tool for Selection of Patients With Symptomatic Cholelithiasis for Cholecystectomy Based on Reduction of Pain and a Pain-Free State Following Surgery

IMPORTANCE: There is currently no consensus on the indication for cholecystectomy in patients with uncomplicated gallstone disease. OBJECTIVE: To report on the development and validation of a multivariable prediction model to better select patients for surgery. DESIGN, SETTING, AND PARTICIPANTS: This study evaluates data from 2 multicenter prospective trials (the previously published Scrutinizing (In)efficient Use of Cholecystectomy: A Randomized Trial Concerning Variation in Practice [SECURE] and the Standardized Work-up for Symptomatic Cholecystolithiasis [Success] trial) collected from the outpatient clinics of 25 Dutch hospitals between April 2014 and June 2019 and including 1561 patients with symptomatic uncomplicated cholelithiasis, defined as gallstone disease without signs of complicated cholelithiasis (ie, biliary pancreatitis, cholangitis, common bile duct stones or cholecystitis). Data were analyzed from January 2020 to June 2020. EXPOSURES: Patient characteristics, comorbidity, surgical outcomes, pain, and symptoms measured at baseline and at 6 months' follow-up. MAIN OUTCOMES AND MEASURES: A multivariable regression model to predict a pain-free state or a clinically relevant reduction in pain after surgery. Model performance was evaluated using calibration and discrimination. RESULTS: A total of 1561 patients were included (494 patients in 7 hospitals in the development cohort and 1067 patients in 24 hospitals in the validation cohort; 6 hospitals included patients in both cohorts). In the development cohort, 395 patients (80.0%) underwent cholecystectomy. After surgery, 225 patients (57.0%) reported that they were pain free and 295 (74.7%) reported a clinically relevant reduction in pain. A multivariable prediction model showed that increased age, no history of abdominal surgery, increased visual analog scale pain score at baseline, pain radiation to the back, pain reduction with simple analgesics, nausea, and no heartburn were independent predictors of clinically relevant pain reduction after cholecystectomy. After internal validation, good discrimination was found (C statistic, 0.80; 95% CI, 0.74-0.84) between patients with and without clinically relevant pain reduction. The model had very good overall calibration and minimal underestimation of the probability. External validation indicated a good discrimination between patients with and without clinically relevant pain reduction (C statistic, 0.74; 95% CI, 0.70-0.78) and fair calibration with some overestimation of probability by the model. CONCLUSIONS AND RELEVANCE: The model validated in this study may help predict the probability of pain reduction after cholecystectomy and thus aid surgeons in deciding whether patients with uncomplicated cholelithiasis will benefit from cholecystectomy

The impact of cancer treatment on quality of life in patients with pancreatic and periampullary cancer: a propensity score matched analysis

Background: The impact of pancreatic and periampullary cancer treatment on health-related quality of life (HRQoL) is unclear.Methods: This study merged data from the Netherlands Cancer Registry with EORTC QLQ-C30 and-PAN26 questionnaires at baseline and three-months follow-up of pancreatic and periampullary cancer patients (2015-2018). Propensity score matching (1:3) of group without to group with treatment was performed. Linear mixed model regression analyses were performed to investigate the association between cancer treatment and HRQoL at follow-up.Results: After matching, 247 of 629 available patients remained (68 (27.5%) no treatment, 179 (72.5%) treatment). Treatment consisted of resection (n = 68 (27.5%)), chemotherapy only (n = 111 (44.9%)), or both (n = 40 (16.2%)). At follow-up, cancer treatment was associated with better global health status (Beta-coefficient 4.8, 95% confidence-interval 0.0-9.5) and less constipation (Beta-coefficient -7.6, 95% confidence-interval -13.8-1.4) compared to no cancer treatment. Median overall survival was longer for the cancer treatment group compared to the no treatment group (15.4 vs. 6.2 months, p < 0.001).Conclusion: Patients undergoing treatment for pancreatic and periampullary cancer reported slight improvement in global HRQoL and less constipation at three months-follow up compared to patients without cancer treatment, while overall survival was also improved.Experimentele farmacotherapi