Minimally invasive versus open distal pancreatectomy (LEOPARD): Study protocol for a randomized controlled trial

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. Methods: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. Discussion: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Trial registration: Dutch Trial Register, NTR5188. Registered on 9 April 201

Locally advanced pancreatic cancer: Work-up, staging, and local intervention strategies

Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence

Similarity, modularity, and commonality analysis of navigation locks in the Netherlands

\u3cp\u3eIn the coming decades, Rijkswaterstaat (RWS), the executive branch of the Dutch Ministry of Infrastructure and the Environment, has to replace or thoroughly renovate more than fifty navigation locks. Given the substantial number of locks that needs to be renewed in a relatively short time frame, Rijkswaterstaat is exploring the development of a lock family platform from which future locks can be designed and realized. This study aims to find basic lock component modules, optional lock component modules, and their interfaces, together shaping the platform. Its aim is to identify modules and components that are candidates for standardization. For this purpose, 127 locks in the Netherlands are analyzed using a similarity matrix to find lock variants. Dependency structure matrices (DSM) are built to find commonalities among the variants. By projecting impact scores upon the DSM, component modules are sought that are candidates for (partial) standardization. The results provide clear insight in how to design the lock family platform.\u3c/p\u3

Generation of a function-component-parameter multi-domain matrix from structured textual function specifications

\u3cp\u3eThis study introduces a method to build a multi-domain matrix (MDM), visualizing the intended architecture of a system within the component, function, and parameter domains. The MDM is generated from textual function specifications that are subject to a specific grammatical structure and vocabulary based upon the functional basis and interaction basis as presented in the literature. Two types of functions are distinguished: functions specifying what functionality a particular component provides to another component, and functions specifying the internal working (transformation of flow) of a particular component. The fixed grammar for the specification of the two types of functions allows for the automated derivation of dependencies between components, between functions of components, and between system parameters. A case study on a navigation lock demonstrates that the system architecture generated from function specifications matches the architecture of the real lock system fairly well. As such the method can be used in the early design phase to reveal the product architecture that is embodied in the function specifications of system components. The method may also support modeling of high-definition DSMs of existing engineering systems.\u3c/p\u3

Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report

Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternativel

Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy

Determining the resectability of locally advanced pancreatic cancer (LAPC) after induction chemotherapy is complex since CT-imaging cannot accurately portray tumor response. We hypothesized that CA19-9 response adds to RECIST-staging in predicting resectability of LAPC. Post-hoc analysis within a prospective study on LAPC (>90° arterial or >270° venous involvement). CA19-9 response was determined after induction chemotherapy. Surgical exploration was performed in RECIST-stable or -regressive disease. The relation between CA19-9 response, resectability and survival was assessed. Restaging in 54 patients with LAPC after induction chemotherapy (mostly FOLFIRINOX) identified 6 RECIST-regressive, 32 RECIST-stable, and 16 patients with RECIST-progressive disease. The resection rate was 20.3% (11/54 patients). Sensitivity and specificity of RECIST-regression for resection were 40% and 87% whereas the positive predictive value (PPV) and negative predictive value (NPV) were 67% and 68%. Using a 30% decrease of CA19-9 as cut-off, 9/10 patients were correctly classified as resectable (90% sensitivity, PPV 43%) and 3/15 as unresectable (20% specificity, NPV 75%). In the total cohort, a CA19-9 decrease ≥30% was associated with improved survival (22.4 vs. 12.7 months, p = 0.02). Adding CA19-9 response after induction chemotherapy seems useful in determining which patients with RECIST non-progressive LAPC should undergo exploratory surger

Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer

FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC. The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate. Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity. Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resectio

Time-Dependent Impact of Irreversible Electroporation on Pathology and Ablation Size in the Porcine Liver: A 24-Hour Experimental Study

Irreversible electroporation causes cell death through low frequency, high voltage electrical pulses and is increasingly used to treat non-resectable cancers. A recent systematic review revealed that tissue damage through irreversible electroporation is time-dependent, but the impact of time on the ablation zone size remains unknown. Irreversible electroporation ablations were performed hourly during 24 consecutive hours in the peripheral liver of 2 anaesthetized domestic pigs using clinical treatment settings. Immediately after the 24th ablation, the livers were harvested and examined for tissue response in time based on macroscopic and microscopic pathology. The impact of time on these outcomes was assessed with Spearman rank correlation test. Ablation zones were sharply demarcated as early as 1 hour after treatment. During 24 hours, the ablation zones showed a significant increase in diameter (rs = 0.493, P = .014) and total surface (rs = 0.499, P = .013), whereas the impact of time on the homogeneous ablated area was not significant (rs = 0.172, P = .421). Therefore, the increase in size could mainly be attributed to an increase in the transition zone. Microscopically, the ablation zones showed progression in cell death and inflammation. This study assessed the dynamics of irreversible electroporation on the porcine liver during 24 consecutive hours and found that the pathological response (ie, cell death/inflammation), and ablation size continue to develop for at least 24 hours. Consequently, future studies on irreversible electroporation should prolong their observation period