Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial)

BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor

In den beginne... De 'schepping' in beeld, woord en klank

Geen enkel boek heeft zo intens onze cultuur beïnvloed als de bijbel. Talloze werken uit de West-Europese muziek, beeldende kunsten en literatuur zijn door de Bijbel geïnspireerd, hetzij rechtstreeks, hetzij via 'vertaling', parafrase en interpretatie. Ook nu nog blijft de Bijbel de hedendaagse kunstenaars intrigeren. Tegen de achtergrond van de herdenking van de tweehonderdste verjaardag van de geboorte van Charles Darwin en de tweehonderdste sterfdag van de componist Franz Haydn, kozen de organisatoren van de jaarlijkse lezingencyclus 'Bijbel en Cultuur' ervoor om, na de succesvolle lessenreeksen over Hooglied (2006), koning Salomo (2007) en Job (2008), in 2009 de Bijbelse scheppingsvoorstellingen en hun doorwerking in de Westerse cultuur te bestuderen. Immers, wars van elke vorm van creationisme, hebben de Bijbelse scheppingsverhalen nog altijd iets te vertellen. Die Bijbelse teksten teksten willen immers niet verklaren hoede wereld en de mens er zijn gekomen. Ze willen veeleer verkondigen dat het leven zin heeft en roepen tot het streven naar een wereld waarin het goed is om leven. En precies deze gedachte heeft kunstenaars van alle tijden ertoe aangezet de Bijbelse scheppingsmythen te verbeelden, te verwoorden en te verklanken

The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy

The revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown. We used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance. Among the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48). The reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NAC

Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer?: An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial

BACKGROUND: To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. METHODS: We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. FINDINGS: The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. INTERPRETATION: Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rates

Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial

To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rate