infectious port complications are more frequent in younger ...for long-term use in the 1970s [2] ....

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University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2008 Infectious Port Complications Are More Frequent in Younger Patients with Hematologic Malignancies than in Solid Tumor Patients Samaras, P; Dold, S; Braun, J; Kestenholz, P; Breitenstein, S; Imhof, A; Renner , C; Stenner-Liewen, F; Pestalozzi, B C Samaras, P; Dold, S; Braun, J; Kestenholz, P; Breitenstein, S; Imhof, A; Renner , C; Stenner-Liewen, F; Pestalozzi, B C (2008). Infectious Port Complications Are More Frequent in Younger Patients with Hematologic Malignancies than in Solid Tumor Patients. Oncology, 74(3-4):237-244. Postprint available at: http://www.zora.uzh.ch Posted at the Zurich Open Repository and Archive, University of Zurich. http://www.zora.uzh.ch Originally published at: Oncology 2008, 74(3-4):237-244.

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Page 1: Infectious Port Complications Are More Frequent in Younger ...for long-term use in the 1970s [2] . Implantable port de-vices have numerous advantages over conventional cen-tral venous

University of ZurichZurich Open Repository and Archive

Winterthurerstr. 190

CH-8057 Zurich

http://www.zora.uzh.ch

Year: 2008

Infectious Port Complications Are More Frequent in YoungerPatients with Hematologic Malignancies than in Solid Tumor

Patients

Samaras, P; Dold, S; Braun, J; Kestenholz, P; Breitenstein, S; Imhof, A; Renner , C;Stenner-Liewen, F; Pestalozzi, B C

Samaras, P; Dold, S; Braun, J; Kestenholz, P; Breitenstein, S; Imhof, A; Renner , C; Stenner-Liewen, F; Pestalozzi,B C (2008). Infectious Port Complications Are More Frequent in Younger Patients with Hematologic Malignanciesthan in Solid Tumor Patients. Oncology, 74(3-4):237-244.Postprint available at:http://www.zora.uzh.ch

Posted at the Zurich Open Repository and Archive, University of Zurich.http://www.zora.uzh.ch

Originally published at:Oncology 2008, 74(3-4):237-244.

Samaras, P; Dold, S; Braun, J; Kestenholz, P; Breitenstein, S; Imhof, A; Renner , C; Stenner-Liewen, F; Pestalozzi,B C (2008). Infectious Port Complications Are More Frequent in Younger Patients with Hematologic Malignanciesthan in Solid Tumor Patients. Oncology, 74(3-4):237-244.Postprint available at:http://www.zora.uzh.ch

Posted at the Zurich Open Repository and Archive, University of Zurich.http://www.zora.uzh.ch

Originally published at:Oncology 2008, 74(3-4):237-244.

Page 2: Infectious Port Complications Are More Frequent in Younger ...for long-term use in the 1970s [2] . Implantable port de-vices have numerous advantages over conventional cen-tral venous

Infectious Port Complications Are More Frequent in YoungerPatients with Hematologic Malignancies than in Solid Tumor

Patients

Abstract

Background: We assessed longevity and complications of totally implantable venous access devices inoncology patients. Methods: 197 patients received a total of 201 port devices via the subclavian vein fordelivery of chemotherapy between January 1, 2005, and December 31, 2006. We reviewed the patientcharts for port-related complications and risk factors until July 31, 2007. Results:A total of 47,781catheter days were analyzed (median, 175 days; range, 1-831). Forty-six different complicationsoccurred (0.96 complications/1,000 catheter days). The only risk factor significantly associated with ahigher complication rate was younger age. Older patients had a lower risk for developing complicationswith a risk reduction of 2.4% for each year. There were no differences regarding underlying tumor,gender, access side, method of placement (subclavian/cephalic vein) or implanting team (thoracic versusvisceral surgery). A trend was seen for shorter port longevity in hematologic patients compared tooncologic patients (p = 0.059). The former developed significantly more port-associated infections thansolid tumor patients [11/53 cases (21%) versus 2/148 cases (1.4%); p < 0.0001]. Conclusions:Port-associated infections were mostly observed in younger patients with hematologic neoplasms.Prospective trials should be performed to evaluate the benefit of a prophylactic antimicrobial lock inthese selected patients.

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Fax +41 61 306 12 34E-Mail [email protected]

Clinical Study

Oncology 2008;74:237–244 DOI: 10.1159/000151393

Infectious Port Complications Are More Frequent in Younger Patients with Hematologic Malignancies than in Solid Tumor Patients

Panagiotis Samaras a Stefan Dold a Julia Braun b Peter Kestenholz c

Stefan Breitenstein d Alexander Imhof a Christoph Renner a

Frank Stenner-Liewen a Bernhard C. Pestalozzi a

a Department of Oncology, b Biostatistics Unit, Institute of Social and Preventive Medicine, c Department of Thoracic Surgery, d Department of Visceral and Transplantation Surgery, University Hospital Zürich, Zürich , Switzerland

0.0001]. Conclusions: Port-associated infections were most-ly observed in younger patients with hematologic neo-plasms. Prospective trials should be performed to evaluate the benefit of a prophylactic antimicrobial lock in these se-lected patients. Copyright © 2008 S. Karger AG, Basel

Introduction

Totally implantable port systems have been widely used in the last two decades for delivery of long-term medical therapy like antibiotics, parenteral nutrition or anticancer drugs in oncology patients [1] . They succeed-ed the subcutaneously tunneled catheter systems like Hickman or Groshong lines, which had been developed for long-term use in the 1970s [2] . Implantable port de-vices have numerous advantages over conventional cen-tral venous catheters (CVCs). They can be used over long periods of time after one-time implantation thus avoid-ing repeated insertions of a CVC. They can be implanted in local anesthesia in an outpatient setting. Patient com-pliance is excellent since peripheral venipunctures can be

Key Words

Port system � Central venous access � Central venous catheter infection

Abstract

Background: We assessed longevity and complications of totally implantable venous access devices in oncology pa-tients. Methods: 197 patients received a total of 201 port de-vices via the subclavian vein for delivery of chemotherapy between January 1, 2005, and December 31, 2006. We re-viewed the patient charts for port-related complications and risk factors until July 31, 2007. Results: A total of 47,781 cath-eter days were analyzed (median, 175 days; range, 1–831). Forty-six different complications occurred (0.96 complica-tions/1,000 catheter days). The only risk factor significantly associated with a higher complication rate was younger age. Older patients had a lower risk for developing complications with a risk reduction of 2.4% for each year. There were no dif-ferences regarding underlying tumor, gender, access side, method of placement (subclavian/cephalic vein) or implant-ing team (thoracic versus visceral surgery). A trend was seen for shorter port longevity in hematologic patients compared to oncologic patients (p = 0.059). The former developed sig-nificantly more port-associated infections than solid tumor patients [11/53 cases (21%) versus 2/148 cases (1.4%); p !

Received: February 1, 2008 Accepted after revision: April 1, 2008 Published online: August 21, 2008

Oncology

Panagiotis Samaras Department of Oncology, Rämistrasse 100 CH–8091 Zürich (Switzerland) Tel. +41 44 255 2214, Fax +41 44 255 4548 E-Mail [email protected]

© 2008 S. Karger AG, Basel0030–2414/08/0744–0237$24.50/0

Accessible online at:www.karger.com/ocl

F.S.-L. and B.C.P. contributed equally to this article.

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Samaras et al.

Oncology 2008;74:237–244238

avoided and quality of life is not impaired [3] . The high purchase and insertion costs are redeemed by low main-tenance costs [4] .

Generally, implantation of a port system is considered when a medical therapy is planned to exceed 2 months or if peripheral vascular access is difficult to achieve.

Different studies have evaluated the usefulness and re-liability of totally implantable catheter devices with par-ticular interest for the most common complications oc-curring during or after implantation [5–11] . As a measure of quality control at our center, we performed a retrospec-tive analysis to identify complications in our patients with implanted port systems.

Patients and Methods

We performed a retrospective analysis of 197 oncology pa-tients who received a total of 201 port systems for delivery of che-motherapy between January 1, 2005, and December 31, 2006. The study was approved by the ethics committee, and patients gave written informed consent for the scientific analysis of their data. A single type of port system (BardPort TM implantable titanium device with a self-sealing rubber septum and an open-ended sili-cone catheter; Bard Access Systems, Salt Lake City, Utah, USA) was used. Patients who received intra-abdominal port systems for regional hepatic chemotherapy or other types of central venous access devices like Shaldon’s catheters for stem cell apheresis were excluded from the present study. The ports were placed by the team of either the department of thoracic surgery (n = 153) or of the department of visceral and transplantation surgery (n = 48) in the operating room under general or local anesthesia. Peri-in-sertional antibiotics were given in selected patients only. In 59 of the 201 cases (29%) either � -lactam antibiotics or quinolones were applied as prophylaxis. The port system was implanted in the right (n = 160) or left (n = 41) pectoralis fascia after formation of

a subcutaneous pocket in the infraclavicular area. Two techniques were used for venous access: direct puncture of the subclavian vein (n = 62; 31%) or surgical cut-down to the cephalic vein (n = 139; 69%), depending on the patient’s anatomy. When the surgeon could not access the subclavian vein by advancing the guide wire through the cephalic vein, the procedure was changed to a direct puncture of the subclavian vein. The correct catheter position in the superior vena cava was checked perioperatively by fluoros-copy and postoperatively by chest radiography. Immediate use of the system was permitted after radiological control of the catheter position. Patients were treated in an outpatient and/or inpatient setting by specially trained oncology nursing staff. The same team took care of the ports according to the recommendations of the manufacturer. Lock with heparin solution was performed af-ter every access and every 4–12 weeks if the system was not in use. Patients did not routinely receive oral anticoagulants or heparin for prevention of thrombosis.

Ninety (47%) patients were female and 107 (53%) male. The median patient age was 58 years (range, 18–86).

In 148 cases, the underlying disease was a solid tumor, and in 53 cases a hematologic malignancy. Underlying diagnoses are shown in figure 1 . We analyzed the electronic patient charts of our digital clinical information system (KISIM version 4.813, CISTEC AG, Zurich, Switzerland) and the patient charts of the oncology department to determine the incidence of port-related complications up to July 31, 2007, and evaluated possible risk fac-tors. An event leading to censoring of the data was defined as the occurrence of either a complication, death of any cause, end of analysis or port removal. All complications that occurred in the observation period were considered for analysis if they were pre-sumably associated with the port system. Early postoperative complications like pneumothorax or hematoma were also includ-ed. Deep venous thrombosis was defined as occlusion of the large veins as seen with Doppler ultrasound, phlebography or CT scan. Occlusions of the catheter by a fibrin sleeve without radiographic proof of thrombosis were defined as thrombotic complication only if flushing with urokinase did not result in patency of the system. Infections of the catheter or needle insertion site, pocket infections and catheter-related blood stream infections (CRBSI) were defined as port-associated infections. Fever of unknown or-igin (FUO) was defined as port related if persistent symptoms under antibiotic therapy necessitated port removal.

Neutropenia was defined as less than 1,000 neutrophils per cubic millimeter of blood.

Statistical calculations were performed with the Statistical Analysis Software SPSS 13 for Mac OS X (SPSS Inc., Chicago, Ill., USA). The log rank test was used to compare two groups in regard to the time to port-related complications. In order to determine risk factors for complications, a Cox regression analysis was per-formed. The significance of an association between two variables was assessed by Fisher’s exact test or Student’s t test. p values ! 0.05 were considered statistically significant.

Results

One hundred and ninety-seven patients received a to-tal of 201 port systems. A total of 47,781 catheter days were documented (median, 175 days; range, 1–831). For-

Lower GI tract: 33 (16.4%)

Upper GI tract: 18 (9%)

Liver: 3 (1.5%)

Hodgkin: 8 (4%)

Head/neck: 9 (4.5%)

Urogenital: 11 (5.5%)

ALL: 6 (3%)

Lung: 26 (12.9%)Myeloma: 12 (6%)

Breast: 17 (8.5%)

NHL: 27 (13.4%)

Other: 10 (5%)

Sarcoma: 4 (2%)

Pancreas: 17 (8.5%)

Fig. 1. Primary diagnoses in the patient population. ALL = Acute lymphoblastic leukemia; GI = gastrointestinal; NHL = non-Hodg-kin’s lymphoma.

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Port Complications in Oncology Patients Oncology 2008;74:237–244 239

ty-six (23%) complications occurred until the cut-off date of July 31, 2007 (0.96 complications/1,000 port days). The complications and actions taken are listed in table 1 . The most common complications were thrombosis (n = 12; 6%; 0.25 complications/1,000 port days), port-associated infection (n = 13; 6.5%; 0.27) and catheter malposition(n = 9; 4.5%; 0.19). Other complications were hematoma (n = 5; 2.5%; 0.1), pneumothorax (n = 4; 2%; 0.08), arte-rial puncture (n = 1; 0.5%; 0.02), FUO (n = 1; 0.5%; 0.02) and unsuccessful port placement (n = 1; 0.5%; 0.02). Nine-teen complications required port removal and one im-plantation failed (n = 20; 10%; 0.42). In 22 of the 46 cases with documented complications, port function was pre-served and the system remained in use. Four port systems remained in situ without further use. After detection of a deep venous thrombosis, the port system remained functional in 7 of 12 cases, two ports had to be removed, and three remained in situ without further use. Port-as-sociated infections consisted of four catheter or port nee-dle insertion site infections, two pocket infections and seven CRBSI. Infections and one case of FUO resulted in removal of 12 of the 14 devices. In two cases of insertion

site infection, the systems could be rescued by systemic antibiotics and vancomycin lock. Identified pathogens were coagulase-negative Staphylococcus (n = 4), Staphylo-coccus aureus (n = 2), Escherichia coli (n = 1), Pseudomo-nas aeruginosa (n = 1) and Corynebacterium amycolatum (n = 1). The underlying diagnoses in patients with infec-tious complications were aggressive non-Hodgkin’s lym-phomas (n = 6), acute lymphocytic leukemia (n = 2), Hodgkin’s lymphoma (n = 2), multiple myeloma (n = 1), nonseminomatous germ cell tumor (n = 1), small cell lung cancer (n = 1) and colorectal cancer (n = 1). These patients received the following treatments: Hyper-CVAD (cyclo-phosphamide, vincristine, doxorubicin, dexamethasone, cytarabine, methotrexate) with (n = 1) or without (n = 2) rituximab, EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone; n = 2), ICE (ifosfamide, carboplatin, etoposide) with rituximab (n = 1), CHOP (cyclophosphamide, doxorubicin, vincristine, predni-sone) with rituximab (n = 1), cytarabine/etoposide (n = 1), Mini-BEAM (carmustine, etoposide, cytarabine, mel-phalan; n = 1), docetaxel/ifosfamide (n = 1), topotecan monotherapy (n = 1) and dose-intense chemotherapy (cy-

Table 1. Complications

All cases(n = 201)

Events/1,000port days

Solid(n = 148)

Hem(n = 53)

Actions taken

Unsuccessful placement 1 (0.5) 0.02 0 1 (2) –Hematoma 5 (2.5) 0.1 3 (2) 2 (4) hematoma excision (n = 2)

port functional, left in situ (n = 5)Arterial puncture 1 (0.5) 0.02 1 (1) 0 port removalPneumothorax 4 (2) 0.08 4 (3) 0 chest tube (n = 3)

port functional, left in situ (n = 4)Port-associated infection 13 (6.5) 0.27 2 (1) 11 (21) port removal (n = 11)

antibiotic lock, rescue (n = 1)systemic antibiotics, rescue (n = 1)

Port-associated bacteremia 1 (0.5) 0.02 1 (1) 0 port removalDeep venous thrombosis 12 (6) 0.25 9 (6) 3 (6) port removal (n = 2)

port nonfunctional, left in situ,anticoagulation (n = 3)port functional, left in situ,anticoagulation (n = 7)

Malposition 9 (4.5) 0.19 6 (4) 3 (6) port removal (n = 4)port not used, left in situ (n = 1)port functional, left in situ (n = 2)port revision (n = 2)

Total 46 (23) 0.96 26 (18) 20 (38) –

Figures in parentheses indicate percentages. Solid = Patients with solid tumors; Hem = patients with hematologic neoplasms.

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Oncology 2008;74:237–244240

clophosphamide/total body irradiation and high-dose melphalan, respectively) with autologous stem cell trans-plantation (n = 2). At the time of infection, 6 patients were neutropenic and 4 patients had just recovered from neu-tropenia. The median duration of neutropenia in patients with an infection was 5 days (range, 0–25 days).

The median port survival time was not reached at the end of the study, exceeding 831 days. The risk of an event was highest in the first month due to inclusion of periop-erative and early postoperative complications in the anal-ysis and leveled off thereafter ( fig. 2 a). The only signifi-cant risk factor associated with a higher complication rate in the Cox regression analysis was younger age (multipli-

cative effect on the hazard ratio per year, 0.976; 95% CI, 0.957–0.996; p = 0.019). Older patients had a lower risk for developing port complications with a calculated risk re-duction of 2.4% for each year. While the median age of the whole patient population was 58 years (range, 18–86), patients with port-related infections had a median age of 45 years (range, 18–74), whereas patients with thrombo-ses were 52 years (range, 22–65) and patients with cath-eter malpositions 64 years (range, 31–74) old.

There were no significant differences regarding the underlying tumor, gender, placement side (left versus right), access method (subclavian versus cephalic vein) or implanting team (from the department of thoracic sur-gery versus the department of visceral surgery). When the patients were divided into two groups, i.e. as having hematologic neoplasms or solid tumors, a trend was seen for shorter event-free port longevity in patients with he-matologic malignancies compared with solid tumor pa-tients (p = 0.059 in the log rank test). The hazard ratio for an event was 0.572 in favor of solid tumor patients (95% CI, 0.318–1.03; p = 0.063; fig. 2 b). Patients with hemato-logic malignancies were significantly younger than solid tumor patients (mean 47.3 8 15.2 years versus 58.6 8 12.2 years; p ! 0.001 in the Student’s t test; 95% CI for the difference in age, 7.17–15.39 years; fig. 3 ).

When analyzed in reference to port-associated infec-tions, patients with hematologic diseases developed sig-nificantly more complications compared to patients who had solid tumors [11/53 cases (21%) versus 2/148 cases (1.4%); p ! 0.0001 in the Fisher’s exact test].

00 200 400

Time from implantation (days)a

600 800

0.2

0.4

0.6

0.8

1.0

+Survival functionCensored

Port

frac

tion

in p

lace

20

30

40

50

60

70

80

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e(y

ea

rs)

Solid Nonsolid

00 200 400

Time from implantation (days)b

600 800

0.2

0.4

0.6

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1.0

+Nonsolid tumorsCensored

Solid tumorsPort

frac

tion

in p

lace

Fig. 3. Boxplot showing the difference in age between patients with solid tumors (solid) and patients with hematologic malig-nancies (nonsolid).

Fig. 2. a Kaplan-Meier analysis of the event-free port longevity measured from the day of placement. b Event-free port longevity in patients with solid tumors compared to patients with hemato-logic neoplasms. Marks represent censored data, i.e. day of port removal, patient’s death, end of study period or occurrence of complication. Perioperative complications (pneumothorax and hematoma) were included in the analysis.

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Port Complications in Oncology Patients Oncology 2008;74:237–244 241

Discussion

Totally implantable venous access devices have proved to be less susceptible to complications than tunneled catheter systems [10, 12, 13] . The reported event rate ranged from 0.45 to 1.16 events/1,000 port days [5–11] . Our study showed comparable results with 0.96 overall events/1,000 port days. The main complications observed were port-associated thrombosis (0.25 events), port-as-sociated infection (0.27 events) and catheter malposition (0.19 events). A comparison of the published literature and our data is presented in table 2 showing similar re-sults. Rare complications were puncture of the artery, port placement failure and hematoma in the early post-operative period. Four cases of pneumothorax occurred after puncture of the subclavian vein. This complication could be avoided by using the surgical cut-down tech-nique to the cephalic vein. An option to reduce the rate of complications and to improve the success rate with the percutaneous approach may be the use of two-dimen-sional ultrasound for guidance of the cannulation [14, 15] .

Six percent of our patients developed catheter-related thrombosis. No predisposing risk factors were observed in our study. Other trials have identified significant vari-ables for the development of arm vein thrombosis: cath-eter tip position, side of catheter insertion (right versus left), platelet count, female gender and underlying lung cancer [11, 16–18] . One study tested treatment with low molecular weight heparin (LMH) for prevention of cath-eter-related thrombosis after port placement and found a significant reduction in the incidence of thrombotic com-plications. However, this study had a very high thrombo-sis rate in the untreated arm (62% of the patients) [19] . High rates of thrombotic complications were also ob-served in two other trials with indwelling CVCs using

LMH or low dose warfarin for prophylaxis [20, 21] . The main reason for these high rates reported may be the sys-tematic search for thromboses by using phlebography in all study patients. We performed phlebography only in case of suspected thrombosis based on clinical symp-toms. But even if only the symptomatic patients who re-ceived a prophylaxis were considered for comparison, we found a low rate of thrombosis without any anticoagula-tion (6%). In more recent trials, the thrombosis rate was in the range of our study, ranging from 3.5 to 18%, and no significant reduction of the thrombosis incidence was seen with LMH or warfarin administration compared with placebo [22–25] . Apparently, thorough system care by flushing the port system at regular intervals with a heparin solution may be sufficient for maintaining these low rates of thrombotic complications. Therefore, the use of LMH or oral anticoagulants for prevention of port-re-lated thrombosis is not generally recommended.

Twenty-nine percent of the patients received peri-in-sertional antibiotics. In our series, only 4 of the docu-mented 14 infectious complications occurred within the first month with the earliest occurring at day 15 after im-plantation. One of these 4 patients had received prophy-lactic antibiotic treatment. We suggest that the applied prophylaxis with � -lactam antibiotics or quinolones did not have a relevant impact on the infection rate.

Patients with hematologic malignancies developed significantly more infectious complications than patients with solid tumors. Coagulase-negative Staphylococcus was the main pathogen isolated. This observation has been made in previous studies as well [11] . The difference in the incidence of infections may be attributable to more intense chemotherapy, resulting in prolonged neutrope-nia, and also to a direct impairment of the immune sys-tem by the disease itself. Lack of immunocompetence is a main risk factor for infections, as seen in patients with

Table 2. Literature comparison

Study Cases Days insitu

Events/1,000 port days

Infections/1,000 port days

Thrombosis/1,000 port days

Biffi et al., 1997 [5] 178 180 0.65 0.16 0.06Brown et al., 1997 [6] 158 270 0.62 0.35 0.14Kock et al., 1998 [7] 1,500 284 0.45 0.17 0.11Lyon et al., 1999 [8] 205 169 1.16 0.21 0.27Wolosker et al., 2004 [9] 519 353 0.5 0.23 0.07Caers et al., 2005 [11] 448 366 0.85 0.19 0.35Present study 201 238 0.96 0.27 0.25

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Oncology 2008;74:237–244242

HIV, who develop significantly more port infections than cancer patients (1.5 vs. 0.96 infections/1,000 port days) [26] . The pathogens described in the literature are pre-dominantly Gram-positive cocci with coagulase-nega-tive Staphylococcus accounting for 50% of all cases [13, 26–28] . Our treatment usually comprised the removal of the colonized port system. However, while pocket infec-tions are always an indication for device removal, a com-bined local and systemic antibiotic therapy may be con-sidered to preserve the port in CRBSI if risk factors for treatment failure like heart valve prosthesis or concur-rent thrombosis are absent, according to guidelines for the treatment of catheter-related infections [29, 30] . The strategy is also dependent on the isolated pathogen. Re-moval is always necessary in infections with S. aureus and Candida spp., while a preservation of the system may be successful with coagulase-negative Staphylococcus , Corynebacterium jeikeium and P. aeruginosa [31] . Byapplying antibiotics intraluminally in high concentra-tions – the so called antibiotic lock technique – 80% of the colonized catheter lines may be rescued [32, 33] . The antibiotic-lock technique was superior to systemic treat-ment alone with regard to preservation of infected ports in immunocompromised patients [34, 35] . Numerous an-tibiotics were tested for the lock technique, but the agent most extensively studied is vancomycin [36] . The use of vancomycin has various advantages: it targets Gram-pos-itive pathogens, it is compatible with heparin in effective concentrations, and it remains chemically stable and bio-logically active for at least 25 days in vivo [37–39] . Since hematologic patients are at high risk for developing in-fectious complications, prophylaxis with a vancomycin-heparin lock was studied to reduce the incidence of port-associated infections. A prophylactic vancomycin-hepa-rin lock was tested in pediatric populations and proved effective in reducing CRBSI [40, 41] . In one study of 117 adult hematology patients, local application of vancomy-cin and heparin led to significantly less colonization of the catheter system with Gram-positive bacteria and also significantly less bacteremias [42] . Despite good results in a few prospective trials with this approach, the wide-spread use of a vancomycin-heparin lock for prevention of CRBSI is not generally recommended because of con-cerns regarding the emergence of vancomycin-resistant pathogens [31, 43] . As of today, the appearance of antibi-otic resistance has not been described after a vancomycin lock. This may be related to the fact that the solution does not reach the circulation if applied properly. We think that prophylaxis with a vancomycin-heparin lock could be considered an option in selected hematologic patients

who are at high risk for developing CRBSI. Another promising approach to circumvent this problem may be the prophylactic application of ethylenediaminetetraace-tic acid (EDTA), a chelating, nonantibiotic agent to re-main in the port system. More recent studies have dem-onstrated its efficacy in reducing CRBSI due to its anti-microbial properties against various pathogens, either alone or combined with other agents [44, 45] . In addition, EDTA prevents coagulation by binding calcium and is therefore an adequate agent to preserve patency of the catheter system.

The only patient-related risk factors for the develop-ment of port-related complications identified in the Cox regression analysis were younger age and underlying he-matologic malignancy. These two factors are related to each other, since patients with hematologic neoplasms were significantly younger than solid tumor patients (mean, 47.3 8 15.2 years vs. 58.6 8 12.2 years). Here, in-fections were the main type of complication. This is most likely attributable to the more intense chemotherapy causing prolonged neutropenia. We observed that 10 of the 14 patients who developed infectious complications were neutropenic or had recovered from neutropenia shortly before the complication occurred. A direct cor-relation between the degree of neutropenia and infec-tious complications was demonstrated 40 years ago [46] . The risk for a patient to develop catheter-related infec-tions is elevated during neutropenic periods compared to nonneutropenic periods [47, 48] . Patients who receive dose-intensive chemotherapy might therefore be treated with granulocyte colony-stimulating factor to reduce the length of neutropenia and the incidence of infectious complications [49] .

In conclusion, in our series of 201 port placements, thrombotic complications were observed rarely. Patients with hematologic malignancies were younger and had a higher risk of developing port-associated infections than solid tumor patients, resulting in a trend to shorter event-free port longevity.

Therefore, we suggest that trials be performed to eval-uate the benefit of a catheter lock with antimicrobial agents at regular intervals in younger patients with hema-tologic malignancies.

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Port Complications in Oncology Patients Oncology 2008;74:237–244 243

References

1 Gyves JW, Ensminger WD, Niederhuber JE, et al: A totally implanted injection port sys-tem for blood sampling and chemotherapy administration. JAMA 1984; 251: 2538–2541.

2 Hickman RO, Buckner CD, Clift RA, et al: A modified right atrial catheter for access to the venous system in marrow transplant re-cipients. Surg Gynecol Obstet 1979; 148: 871–875.

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