Analysis of N- and K-Ras Mutations in the Distinctive Tumor Progression Phases of Melanoma

Mutations in the ras genes are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in cutaneous melanoma. To investigate whether these mutations occur in early or late tumor progression phases, we searched for point mutations in the N- and K-ras genes in 69 primary cutaneous melanoma, 35 metastases, and seven nevocellular nevi in association with cutaneous melanoma. Lesions were microdissected in order to procure pure tumor samples from the distinctive growth phases of the cutaneous melanoma; the very sensitive denaturing gradient gel electrophoresis technique was used to visualize the mutations, and was followed by sequencing. Point mutations in the N-ras gene but not in the K-ras gene were detected on denaturing gradient gel electrophoresis. Twenty-three primary (33%) and nine metastatic (26%) melanomas showed bandshifts for N-ras. In the majority of cases, mutations occurring in early growth phases (i.e., the “intraepidermal” radial growth phase), were preserved in later growth phases (i.e., the invasive radial growth phase, vertical growth phase, and metastatic phase), which proves the clonal relationship between the successive growth phases. In three cases, however, the mutations differed between the distinctive growth phases within the same cutaneous melanoma, due to the occurrence of an additional mutation (especially in codon 61) in a later tumor progression phase. Our approach also permitted us to analyze the mutational status of nevi, associated with cutaneous melanoma. Six out of seven associated nevi carried the same sequence (mutated or wild-type) as the primary cutaneous melanoma, whereas in one case the sequence for N-ras differed between the primary melanoma and the associated nevus. In conclusion, this approach allowed us to demonstrate the clonal relationship between subsequent growth phases of melanoma and associated nevi; our results suggest that N-ras exon 1 mutations preferentially occur during early stages of tumor progression and hence may be involved in melanoma initiation, whereas those in N-ras exon 2 are found preferentially during later stages and hence are more probably involved in metastatic spread of cutaneous melanoma

Management of venous access devices by Advanced Practice Nursing teams: More research needed

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Management of functional complications of totally implantable venous access devices by an advanced practice nursing team: 5 Years of clinical experience

PURPOSE: Our aim is to describe the number and distribution of requests addressed to an Advanced Practice Nursing team for functional problems of totally implantable venous access devices (TIVADs) and to describe, in detail, the malfunction management by the type and number of additional investigations and treatment modalities. METHOD: The Advanced Practice Nursing team recorded data about all requests for support as part of the standard care. A specific protocol, the Leuven Malfunction Management Protocol was used for troubleshooting. In this descriptive, retrospective study, data of 3950 consecutive requests for TIVAD-related functional problems in 2019 patients were analyzed. Data collection included (1) demographic information, (2) device-related details, and (3) malfunction and follow-up details. RESULTS: 'Easy injection, impossible aspiration' was the most frequently documented functional problem (66.9%) for all requests for help. Of all malfunctions, catheter tip was in an optimal position in 73.4%, thrombolytics were administered in 59.0%, and a linogram was performed in 4.9%. TIVAD removal/exchange was advised in 4.4% of the requests. CONCLUSIONS: TIVAD malfunction-defined operationally in terms of injection and/or aspiration problems-reflect all functional complications encountered in practice. Adherence to the Leuven Malfunction Management Protocol can ensure that, in most cases, catheter patency can be fully restored without removing or replacing the TIVAD. The Advanced Practice Nursing team coordinates the following treatments, investigations, and procedures: radiological catheter tip verification; thrombolytic agent administration and, if necessary, subsequent injection of solutions to dissolve drug precipitates or lipid deposits; linogram; percutaneous sleeve stripping; and TIVAD removal/replacement.status: publishe

Rare cause of cerebrovascular event

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Access of a fully rotated implantable port leads to extravasation

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Systematic review: Malfunction of totally implantable venous access devices in cancer patients

PURPOSE: Malfunction of totally implantable venous access devices is a common complication. The purpose was to identify definitions used to describe malfunction and to investigate the incidence of malfunction in different types of port and catheter designs. METHODS: Relevant studies were identified in PubMed that were published between January 1993 and February 2011. Empirical studies reporting functional outcomes in adults and where, at least 95% of the studied population consisted of onco-hematology patients with a newly inserted chest or arm port, were selected. The following data were extracted: patient and totally implantable venous access devices (TIVAD) characteristics, study design, definitions of malfunction, and functional outcomes. Two independent reviewers assessed the methodological quality of the series. RESULTS: Of the 4,886 potentially relevant articles, 57 were selected, involving 14,311 TIVADs. Twenty-nine percent of the studies explicitly defined malfunction. Malfunction incidence rates were expressed in six different ways, including the proportion of affected devices per inserted devices (incidence 0-47%); the number of affected devices per 1,000 catheter days (incidence 0-2.24 per 1,000 catheter days); and the number of malfunctions over the total number of accessing attempts (incidence 0-26%). CONCLUSIONS: Heterogeneity in the definitions used to describe device malfunction was evident. A broad range in the reported incidence of malfunction and in the kind of calculation and reporting methods was also found. Methodological quality of the studies was often poor. Standardization of definitions and accurate outcome measurement is needed. Calculation and report of malfunction incidence should be based on prospective data collected at the moment of an accession attempt.status: publishe

Occlusion in totally implantable vascular access devices: what is its incidence and what actions do nurses take to restore patency?

Background: Totally implantable vascular access devices (TIVAD) are considered safe and reliable for the administration of intravenous therapies, including chemotherapy and blood sampling. They provide direct vascular access through a simple percutaneous puncture. However, in order to avoid paravenous injection, it is mandatory to check for blood withdrawal before administering medication: this simple procedure confirms both the system’s patency, correct needle position in the chamber and the catheter tip’s intravascular location. This study’s objective was to evaluate the incidence of partial and total blood withdrawal impairment in TIVADs directly after accessing the port system. Material and Methods: From November 2003 to March 2004, nurses from 20 hospitals in Flanders (Belgium) agreed to take part in a prospective cohort study and collect data on TIVAD access procedures in cancer patients. In case of blood withdrawal problems or device occlusion, they recorded all actions needed for diagnosing the cause of the problem and restoring patency. In each hospital, TIVAD maintenance and solutions for troubleshooting were performed according to individual institutional protocols. Results: The data included 8685 accesses in 2853 patients. The incidence of blood withdrawal occlusion and total occlusion were 11.11% and 0.24% respectively. Overall incidence varied between hospitals from 3.05% to 28.37%. Nurses restored full device patency in 53.25% of cases, mostly by changing patients’ position or intrathoracic pressure, additional flushing and repositioning of the Huber needle in the port septum. In 83.51% of persistent occlusions, no further investigation into the cause of the functional impairment was undertaken. Thirty-one events of occlusion (3.14%) were treated by thrombolytics or device replacement. Altogether, blood aspiration was regained in 55.17%. Conclusions: Withdrawal and total occlusion problems occurred in 11.35% of TIVAD access and were resolved by nurses’ interventions in 53.25% of cases. The incidence expressed in function of the number of punctures reflects accurately the impact of this problem in daily practice. The differences between hospitals revealed that prevention of occlusion and established protocols for maintenance or troubleshooting solutions are important factors to maintain optimal TIVAD patency and deserves further analyses.status: publishe

Functional evaluation of conventional 'Celsite(R)' venous ports versus 'Vortex(R)' ports with a tangential outlet: a prospective randomised pilot study

GOAL OF WORK: Totally implantable venous access ports are widely accepted in cancer patient treatment, but withdrawal occlusion (WO) can hamper the use of the device. A newly designed Vortex(R) VX port, with a tangential outlet, should allow better clearance of the chamber, thereby reducing occlusion of the device. The present study compared the Vortex(R) port to the classically shaped Celsite(R) port with regards to functional complications. MATERIALS AND METHODS: Two hundred cancer patients were included in a prospective, randomised controlled trial and randomly assigned to the implantation of a Vortex(R) or a Celsite(R) port. Insertion details such as used vein, catheter tip position and infusion or aspiration abilities were recorded. Data were collected concerning ease of access, and functional evaluation was performed each time the port was accessed, regarding the ability to infuse fluids with a syringe and to withdraw blood by measuring the filling time of a Vacutainer(R) blood tube. MAIN RESULTS: Ninety-nine patients received a Celsite(R) port, and 101 had a Vortex(R) port. Demographic variables and insertion details were comparable in both groups. All functional complications, including WO, total occlusion, sluggish inflow and sluggish withdrawal, were higher in the Celsite(R) group (16.12%) than in the Vortex(R) group (11.36%). This difference was not statistically significant. CONCLUSIONS: This study revealed that functional problems occurred less frequently in Vortex(R) compared to Celsite(R) ports. Differences were small and not significant, which indicates that functional problems may be related to other factors.status: publishe

“The Catheter is Occluded?” The Catheter Injection and Aspiration (CINAS) Classification Answers Your Question Accurately!

Background A well-functioning intravenous catheter allows both easy injection and blood aspiration. Malfunction occurs when these procedures are difficult and/or impossible. Since malfunction is often vaguely described, misunderstandings may arise between healthcare providers. Consequently, the real problem remains uncertain and this may lead to erroneous prescription of thrombolytic drugs and to inadequate reports on functional outcomes. Purpose The heterogeneity in catheter function description led to the development of the CINAS classification tool. The CINAS is the first tool able to describe completely the catheter function based on assessment of both injection and aspiration abilities. It consists of nine scoring options combining three categories of functional outcome (1=easy; 2=difficult; 3=impossible). Project description We tested the validity and accuracy of the CINAS. First, all functional problems (n=3950) in all types of catheters for which an Advanced Practice Nursing team was consulted in our hospital over a five year period were classified along the CINAS. In a second phase, 111 nurses who were briefly informed about this classification, assessed implantable ports function of 150 patients during their daily practice. Their scoring results were compared to those of a reference standard to assess the accuracy. Results In 35 among 3950 malfunction events (1%), catheter function could not be classified. Therefore we added a fourth category “unspecified” to the CINAS. Nurses were able to use the CINAS for 150 port catheter function assessments. They scored in 99% correctly a well-functioning catheter and in 80% a malfunction into the correct malfunction class. Implications The CINAS is able to describe completely every catheter function assessment in clinical practice and for research purposes. In electronic patient records, malfunction management protocols may be linked to the different CINAS classes. Conclusions The CINAS classification is simple, clear, cheap and helps healthcare workers to document accurately the catheter function.status: publishe