Methods
Study Design
The study was performed according to the second principles of the Declaration of Helsinki. The study was retrospectively reviewed and approved by the Ethical Committee of the Veneto Institute of Oncology (protocol number 0001897; Internal code: 2014/13/NOTIFICA; date of approval 24th February 2014). This study is a retrospective review of a prospectively collected database created in 2006 by the authors including 796 consecutive totally implantable venous access devices (TIVAD) applied from November 2006 to November 2011 in the Surgical Oncology Unit of the Veneto Institute of Oncology (IOV-IRCCS). Follow up continued until the device was removed, patient died or the study was closed (30.11.2011). Patients gave their informed consent to have their data collected in a database and to have them anonymously used for scientific purposes. The devices were implanted in adult patients affected by several different neoplastic diseases requiring chemotherapy. All patients had the same type of TIVAD implanted: an M.R.I. Implantable Port with open end 8 French polyurethane single lumen venous catheter (C. R. Bard, Inc. Murray Hill, New Jersey, USA). The main tumor types were gastrointestinal, breast, head and neck, ovarian and sarcoma.
Preoperative evaluation included medical history and physical examination, focusing on possible anatomic pitfalls (cervical or mediastinal adenopathy, chest wall tumours, previous neck or thoracic surgery), body habitus, previous vascular access placements and complications. Laboratory studies consisted in full blood count and coagulation. Exclusion criteria were platelet count < 80.000/mm, INR > 1.5, neutrophil count <1000/mm, fever or sepsis. During the pre-treatment visit patients were informed on the procedure, risks, benefits, data management and follow up, and written informed consent for the inclusion in this study was obtained.
Data Collection and Follow-up
A score of procedural difficulty was assigned to each TIVAD implantation, ranging from 1 (easy) to 4 (extremely difficult). Patient characteristics, which included diagnosis, indication for catheter placement, age, height, weight, results of laboratory test parameters and current medications were recorded. Device type, site of venous access, surgeon and anaesthesiologist performing the procedures and placement complications were documented. Data from hospital admissions and telephone follow-up were recorded at regular intervals and prospectively collected in a database. All device-associated complications were recorded during follow up. Complications were classified into two main categories: early (intraoperative and post-implantation period to first use) and late complications (occurring after the first chemotherapy course administered through the device).
Criteria for the diagnosis of device-related bacteraemia were defined as follows: a over 10-fold increase in colony-forming units (CFU) of bacteria per ml of blood obtained through the device in comparison to peripheral blood cultures; over 1000 CFU of bacteria obtained through the device, in the absence of peripheral blood cultures; or positive catheter tip culture upon removal in the appropriate clinical setting. Port pocket infection was defined by induration, erythema and tenderness around the port with culture-positive material aspirated from the port pocket. Cutaneous site infection was defined by induration, erythema, or tenderness and exudate at the port surface needle access site. Thrombosis was detected with ultrasound and/or venography when clinically suggested by progressive arm or facial swelling.
The following assumptions were used as the basis for determining the cost-effectiveness of each strategy. Operative room hourly costs were based on current estimates of standard charges in an Italian setting (2013), including salaries for a surgeon, a anesthesiologist and two nurses (650 euro per hour). We calculated the overall cost for our institution.
Implantation Techniques
Devices were implanted in the operating room, using maximal sterile-barrier precautions, under local anaesthesia, administering a mixture of Lidocaine 1% and Ropivacaine 0.5% and employing fluoroscopic control. Premedication with midazolam 0.01–0.035 mg/kg (1–3 mg) was provided in case of patient anxiety. A single dose of Cefazoline 2 g was administered intravenously before the procedure. In beta-lactam allergic patients, Vancomycin 15 mg/kg was used. In order to prevent clot formation and catheter blockage, TIVAD were flushed with 20 ml saline and then filled with 5 ml of a solution containing 50 U/ml heparin. Standard protocol was to flush all the devices with heparinized saline solution after use and on a monthly outpatient basis.
Three different techniques were used for implantation. From November 2006 until January 2008 devices were placed using either a cephalic vein cut-down or a blind percutaneous approach based on anatomic landmarks. The choice of insertion technique was at the discretion of the surgeon. Since January 2008 the percutaneous approach was improved using ultrasound guidance.
Cut-down Approach
A single incision was made in the upper anterior chest wall along the delto-pectoral groove as first described by Heimbach and Ivey. The cephalic vein was identified and isolated between 2 vessel loops. The catheter was then directly inserted into the cephalic vein through a transverse venotomy. The distal cephalic vein was tied off. The reservoir was inserted superficially into a subcutaneous pocket, with the device located just inferior to the skin incision. Fluoroscopy was used to confirm positioning of the tip of the catheter at the cavo-atrial junction. No additional postoperative radiographs were performed.
"Blind" Percutaneous Technique
The preferred access site was the subclavian vein (SV). The internal jugular vein (IJV) was chosen when SV cannulation was contraindicated for anatomic pitfalls. A Seldinger technique was used to access the vein with dilators and peel away sheaths for the insertion. In case of subclavian vein cannulation, the site of puncture was at the inferior border of the clavicle, between the middle and the lateral third of it, directed toward the fingertip pressed firmly into the suprasternal notch. The needle passed beneath the inferior margin of the clavicle in a horizontal plane and directed toward the anterior margin of the trachea at the level of the suprasternal notch. The internal jugular vein was cannulated at the top of the triangle between the sternal and clavicular head of the sternocleidomastoid muscle, advancing the needle through the skin at a 45° angle in the direction of the omolateral nipple. Fluoroscopy confirmed the position of the catheter at the cavo-atrial junction, and a completion upright chest radiograph was performed before leaving the surgical ward to assess for the presence of pneumothorax. Usually 2 incisions were necessary: a small incision at the catheter exit site from the skin and a second larger incision for location of the implantable access device. A subcutaneous tunnel was made to pass the catheter from 1 incision to the other.
Ultrasound Guided Percutaneous Technique
A 7–12 MHz linear-array ultrasound probe connected to a real-time ultrasound unit (General Electric Logiq® P5, GE Healthcare Clinical Systems SrL,), and focused at 2–4 cm depth, was covered with ultrasonic gel and wrapped in a sterile plastic sheath. Standard ultrasound two-dimensional (2D) imaging was used to measure the depth and calibre of the IJV or SV, evaluate its patency and compressibility. In cases of pre-existing thrombus formation and/or failure to gain access due to trauma or other anatomical anomalies, the IJV or SV on the controlateral side was catheterised. Catheterisation was performed under continuous dynamic observation of real-time 2D images. The in-plane approach was used to achieve a long-axis view of the needle, allowing full visualization of the shaft and tip of the needle. The low lateral approach, as described by Jernigan and modified by Pittiruti, was used to obtain cannulation of the distal IJV, or whenever possible, of the brachiocephalic vein. The individuation of the brachiocephalic vein was obtained giving to the ultrasound probe a caudal direction, placing it with an inclination of 20–30 degrees with the neck and the clavicle. The ultrasound-guided subclavian vein catheterisation was performed positioning the probe below the clavicle, usually in the lateral third, to obtain a long axis of the vein. Using an in plane approach, the SV was cannulated just medially to the junction of cephalic vein to the axillary vein. An 18-gauge, 7-cm needle was advanced through the skin under ultrasound guidance into the vein. A guidewire was then placed through the needle into the vein, and the needle was removed. Fluoroscopy confirmed the position of the catheter at the cavo-atrial junction, considering an optimal position when the catheter tip was located within a range of 2 cm at the lower border of the right main bronchus. Also in this case, 2 incisions were necessary: 1 small incision at the wire exit site from the skin and a second larger incision for location of the implantable access device. A subcutaneous tunnel was made to pass the catheter from 1 incision to the other. No additional postoperative radiographs were performed except in case of repeated attempts or procedural complications.
Statistical Analysis
Statistical analysis was performed using both Microsoft Excel and STATISTICA 7.1 software (Statsoft, Tulsa, OK, USA). Continuous data are expressed as medians and interquartile ranges, while dichotomic data are expressed as frequencies and proportions. Continuous data were compared with two tailed Mann-Whiteny U test or Kruskall-Wallis ANOVA where appropriate, while frequencies were compared with Fisher's exact test or Chi square analysis. Odds ratios were calculated to assess the risk of complication. Only predictors resulting significant at univariate analysis were included in multivariate models. Life table analyses were created to assess risk rate of TIVAD removal. Two-tailed p-values <0.05 were considered significant.