Totally implantable venous access ports (TIVAPs) can be used long-term for safe administration of intravenous drugs. TIVAP complications include catheter-related infections, venous thrombosis, extravasation, TIVAP migration, and pain. The relationship between the timing of the first chemotherapy administration after port implantation and complications is controversial. This study aimed to investigate the safety of immediate use of TIVAPs and the associated risk factors for complications.
Between January 2016 and December 2018, 305 patients (median age, 53 years; 256 women) who underwent TIVAP placement at our institution were included. Chemotherapy was administered within 2 days of implantation. A retrospective analysis of patients’ clinical data was performed to investigate catheter days and complications of TIVAPs.
Overall, 305 patients were evaluated over 57,324 catheter days (median, 168 catheter days; interquartile range, 105). The median interval between placement and first use of TIVAPs was 0.98 days. The overall morbidity rate was 2.95%. Nine complications occurred in nine patients, including TIVAP-related infection (4), pain (2), port occlusion (1), thrombosis (1), and scar disunion (1), of which five required port removal (1.64%). The median number of catheter days before complications occurred was 61 (range, 10–457 days; interquartile range, 51). No complications occurred within 7 days of implantation. Body mass index was an independent risk factor for TIVAP-related complications in the Cox proportional hazards model (multivariable analysis: hazard ratio, 1.221; 95% confidence interval, 1.054–1.414; P=0.008).
This study suggests the safe long-term use of TIVAPs following their immediate chemotherapy administration within 2 days of implantation.
Since their first use in the early 1980s, totally implantable venous access ports (TIVAPs) have been safely used in patients with cancers to administer long-term chemotherapy [
Several studies have reported the relationship between the timing of the first chemotherapy administration after port insertion and complications [
Between January 2016 and December 2018, 305 patients (median age, 53 years; interquartile range [IQR], 13; 256 women) who underwent insertion of TIVAPs for adjuvant or neoadjuvant chemotherapy in Soonchunhyang University Bucheon Hospital, South Korea were included. A retrospective analysis was performed on the clinical data of the patients to investigate patient characteristics, catheter days, and complications of TIVAPs. We conducted this study in compliance with the principles of the Declaration of Helsinki. The study’s protocol was reviewed and approved by the Institutional Review Board of Soonchunhyang University Bucheon Hospital (IRB No. 2021-07-033-001). Informed consent was waived.
All TIVAPs were implanted by an experienced general surgeon at our institution. The implantations were performed in an operating room using local anesthesia and ultrasound-guided internal jugular vein puncture. Only polyurethane chemoports were used. Heparin was administered to prevent intraluminal thrombosis and the operation was terminated after checking the patency of the port by drawing blood and flushing with saline. After implantation, chest radiography was performed to confirm the appropriate position of the chemoport. No prophylactic antibiotics were administered. All patients received chemotherapy at our institution. The surgical wound was removed in 7 days after implantation, except in cases of wound-related complications.
The lifespans of TIVAPs, as catheter days, were defined as the number of days from the day of implantation to the day when the catheter was removed or the last follow-up date, whichever came first. The interval days were defined as the number of days from the day of implantation to the day when the port was first used for chemotherapy.
TIVAP-related complications in this study included catheter-related infections, pain, thrombosis, and occlusion, and etc. The definitions for each are as follows.
TIVAP-related infection was defined according to the Infectious Diseases Society of America guidelines [
Pain as a complication was defined as follows: (1) chronic and persistent moderate to severe pain; (2) pain that occurs during intravenous infusion via chemoport; thus, the chemotherapeutic agent was administered via peripheral intravenous line; or (3) acute pain that occurred from the time of port insertion to the first postoperative day with a score of 4 points on the numeral rating scale (NRS) was excluded.
Catheter-related thrombosis was diagnosed using imaging tests, such as neck ultrasonography or computed tomography (CT).
Catheter occlusion was defined as failure of catheter regurgitation and saline flushing which was caused by adherent collagen and fibrin covering the tip of the catheter and not by catheter malposition or thrombosis.
Complications were defined as early and late complications when they occurred within 7 days of implantation and 7 days after the procedure, respectively.
Continuous data were presented as medians (range, IQR) and categorical data were presented as numbers (proportions). The Cox proportional hazards model was used to assess the influence of each variable on the TIVAP-related complication rate. All statistical analyses were performed using SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). A two-tailed P-value <0.05 was considered statistically significant.
Overall, 305 patients were evaluated over 57,324 catheter days (median catheter days, 168 days; IQR, 105). The median interval between insertion and first use of the TIVAPs was 0.98 days. The characteristics of the study population are summarized in
TIVAP-related complications and clinical characteristics of patients in this study are described in
TIVAP-related infections occurred in four patients, due to which the chemoports had to be removed in all four patients. Bacteria identified in the blood culture were Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis in each of the three patients, respectively. After sensitivity testing, the infections were controlled with antibiotics following the removal of the chemoports. In the other patient, no bacteria were detected in the blood culture, and the infection symptoms improved after port removal.
TIVAP-related pain was reported in two patients. Both patients complained of chronic pain with an NRS score of 5 for at least 1 month after TIVAP insertion. Chemotherapy was continued as planned for these patients because no abnormal findings were noted on radiography and the chemoports were functional. The pain was managed with intravenous and oral analgesics.
Port occlusion occurred on day 131 after chemoport insertion in one patient. Hence, chemotherapy was performed through the peripheral line and the port was removed after completion of the scheduled chemotherapy.
Thrombosis was reported in one patient. A 42-year-old woman with no specific medical history complained of neck pain and shoulder swelling 55 days after chemoport insertion. Ultrasound imaging of the neck revealed thrombotic obstruction of the right internal jugular vein. The chemoport was removed and oral rivaroxaban (20 mg) was administered once daily for 6 months. A follow-up neck CT scan performed after treatment showed no remaining thrombus.
In one patient with scar disunion, the wound was opened 10 days after implantation due to skin necrosis at the chemoport insertion site; thus, wound revision was performed. Subsequently, the port continued to be used without any further complications.
The results of the univariate and multivariate Cox regression models are summarized in
This study suggests the safe long-term use of TIVAPs following their immediate chemotherapy administration within 2 days of implantation. Administration of chemotherapy drugs through the peripheral vein begun in the early 1980s and have been reported to cause various complications, such as vascular toxicity, extravasation, and irritability. TIVAPs have been used for chemotherapy worldwide more recently [
We carried out a retrospective, single-center study that included 305 TIVAPs over 57,324 catheter days. The overall incidence of complications was 2.95%, which is significantly lower than that reported by Narducci et al. (16.1%) [
In our institution, the first administration of chemotherapy is performed 1 day after TIVAP implantation after confirming the function of the port. This protocol reduces the patient’s discomfort in having to visit the hospital for a second time to receive chemotherapy. In addition, as patients are admitted as inpatients after the procedure, postoperative complications such as hematoma, pneumothorax, or hemothorax can be detected and treated in the hospital more immediately and efficiently. Lastly, immediate administration of chemotherapy following TIVAP implantation reduces the patient’s hospital stay.
In our study, nine patients had TIVAP-related complications, of whom five needed removal of the chemoports. Among the complications, TIVAP-related infection and pain were the most common, followed by occlusion, thrombosis, and scar disunion; however, there were no major acute complications, such as hemothorax, pneumothorax, or acute thrombosis. Infection is one of the most frequent TIVAP-related complications. According to recent studies, infection rates range from 0.018 events/1,000 catheter days to 0.35 events/1,000 catheter days in adult cancer patients [
Thrombosis has been the second major long-term complication of catheter use in cancer patients after infection [
In this study, when analyzing the risk factors for complications, there was no difference in the incidence of complications based on age, primary tumor site, and port insertion location. Whereas, patients with TIVAP-related complications had higher BMI. Obesity has been reported to be associated with TIVAP-related complications in other studies [
This study has several limitations. First, most participants had breast cancer and were receiving adjuvant chemotherapy. The low overall complication rate reported in our study may be due to the lower incidence of infectious complications in solid tumors compared to hematologic tumors and the predominance of young to middle-aged women with no underlying disease in our study population [
In conclusion, our results show that the immediate administration of chemotherapy following TIVAP implantation is potentially safe for long-term use and may not increase complications.
This research was supported by Soonchunhyang University Research.
No potential conflict of interest relevant to this article was reported.
Clinical characteristics of the patients
Characteristics | All patients (n=305) | No complications (n=296) | Complications (n=9) | P-value |
---|---|---|---|---|
Age (yr), median (interquartile range) | 53.0 (13) | 53.2 (13) | 55.4 (14) | 0.491 |
| ||||
Sex | 0.183 | |||
Male | 49 (16.1) | 49 (16.6) | 0 | |
Female | 256 (83.9) | 247 (83.4) | 9 (100) | |
| ||||
Body mass index (kg/m2), median (interquartile range) | 23.7 (4.8) | 23.6 (4.8) | 29.6 (6.2) | 0.008 |
| ||||
Tumor sites | 0.295 | |||
Breast | 225 (73.8) | 217 (73.3) | 8 (88.9) | |
Gastrointestinal tract | 74 (24.3) | 73 (24.7) | 1 (11.1) | |
Other tumors | 6 (1.9) | 6 (2.0) | 0 | |
| ||||
Indication for chemotherapy | 0.879 | |||
Adjuvant chemotherapy | 266 (87.2) | 258 (87.2) | 8 (88.9) | |
Neoadjuvant chemotherapy | 39 (12.8) | 38 (12.8) | 1 (11.1) | |
| ||||
Anticoagulant therapy | 31 (10.2) | 28 (9.5) | 3 (33.3) | 0.020 |
Antiplatelets | 27 (8.9) | 25 (8.5) | 2 (22.2) | |
New oral anticoagulants | 4 (1.3) | 3 (1.0) | 1 (11.1) |
Values are presented as number (%) unless otherwise indicated.
Characteristics of patients with totally implantable venous access port-related complications
No. | Complication | Age (yr) | Sex | BMI (kg/m2) | Comorbidity | Tumor site | Chemotherapy | Anticoagulation therapy | Port insertion site | Interval-day | Catheter-day | Event catheter-day | Reason for removal |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Infection | 64 | F | 30.4 | CAD, HL | Breast | Adjuvant | Antiplatelet | RIJV | 1 | 94 | 94 | Infection |
2 | Infection | 59 | F | 29.9 | None | Breast | Adjuvant | None | RIJV | 1 | 35 | 22 | Infection |
3 | Infection | 55 | F | 25.7 | None | Breast | Adjuvant | None | RIJV | 1 | 61 | 61 | Infection |
4 | Infection | 47 | F | 31.2 | HTN | Breast | Neoadjuvant | None | LIJV | 1 | 457 | 457 | Infection |
5 | Pain | 61 | F | 24.2 | None | Breast | Adjuvant | None | LIJV | 1 | 195 | 43 | End of treatment |
6 | Pain | 42 | F | 29.6 | HTN, DM, HL | Breast | Adjuvant | None | LIJV | 1 | 177 | 63 | End of treatment |
7 | Port occlusion | 71 | F | 35.0 | HTN, CAD | GI tract | Adjuvant | Antiplatelet | RIJV | 2 | 161 | 131 | End of treatment |
8 | Thrombosis | 42 | F | 23.5 | None | Breast | Adjuvant | NOAC | RIJV | 1 | 55 | 55 | Venous thrombosis |
9 | Scar disunion | 58 | F | 22.3 | None | Breast | Adjuvant | None | LIJV | 1 | 77 | 10 | End of treatment |
BMI, body mass index; F, female; CAD, coronary artery disease; HL, hyperlipidemia; HTN, hypertension; DM, diabetes mellitus; GI, gastrointestinal; NOAC, new oral anticoagulant; RIJV, right internal jugular vein; LIJV, left internal jugular vein.
Results of univariable and multivariable Cox regression analyses
Factor | Univariable analysis | Multivariable analysis | ||||
---|---|---|---|---|---|---|
|
| |||||
HR | 95% CI | P-value | HR | 95% CI | P-value | |
Age | 1.023 | 0.958–1.092 | 0.500 | |||
| ||||||
BMI | 1.234 | 1.070–1.423 | 0.004 | 1.221 | 1.054–1.414 | 0.008 |
| ||||||
Hypertension | 1.265 | 0.316–5.057 | 0.740 | |||
| ||||||
Diabetes mellitus | 0.903 | 0.113–7.218 | 0.923 | |||
| ||||||
Coronary artery disease | 0.076 | 0.016–0.364 | 0.001 | |||
| ||||||
Hyperlipidemia | 3.239 | 0.672–15.604 | 0.143 | |||
| ||||||
Right side | 0.362 | 0.097–1.350 | 0.130 | |||
| ||||||
Breast primary | 3.193 | 0.398–25.619 | 0.275 | |||
| ||||||
Anticoagulation therapy | 0.214 | 0.054–0.857 | 0.029 | 0.284 | 0.070–1.146 | 0.077 |
| ||||||
Hemoglobin | 1.081 | 0.604–1.934 | 0.793 | |||
| ||||||
WBC | 1.060 | 0.729–1.543 | 0.760 |
HR, hazard ratio; CI, confidence interval; BMI, body mass index; WBC, white blood cell.