Management of Venous Access Ports with Varying Maintenance Intervals after Chemotherapy for Malignant Tumors

Summary

Here, we present a protocol evaluating extended port maintenance intervals (8-12 weeks) after chemotherapy, showing safety, cost-efficiency, and key risk factors.

Abstract

Totally implantable venous access ports (TIVAPs) are essential for chemotherapy in malignant tumor patients, but catheter blockage and infection remain concerns. The standard 4-week maintenance interval increases financial and logistical burdens, and its necessity in hypercoagulable patients is unclear. This retrospective study analyzed 303 patients with malignant tumors and TIVAPs treated between June 2021 and June 2023. Based on maintenance frequency, patients were categorized into Group A (4-week, n = 97), Group B (8-week, n = 101), and Group C (12-week, n = 105). Clinical outcomes and complication rates were compared, and patients were further divided into complication (n = 51) and non-complication (n = 252) groups to identify risk factors. Compared with the standard 4-week interval, extending maintenance to 8 or 12 weeks significantly reduced 48-week costs by 50.66% and 65.91%, respectively, without increasing thrombosis (Wells score: P = 0.723) or complication rates (P = 0.872). Follow-up compliance improved as maintenance frequency decreased (24-week compliance: Group C 28.9 ± 2.5 vs. Group A 22.3 ± 3.1, P < 0.001). No significant differences were observed among groups in thrombosis risk, catheter patency, quality of life, or overall complication rates (P > 0.05). Group A incurred the highest costs, Group C the lowest, and patient satisfaction peaked in Group B. Multivariate analysis identified older age (OR = 1.048, 95% CI 1.018-1.079), higher BMI (OR = 5.072, 95% CI 1.238-20.775), and chronic diseases (OR = 3.391, 95% CI 1.761-6.531) as independent risk factors for port-related complications. In conclusion, extending TIVAP maintenance intervals to 8-12 weeks after chemotherapy is safe, reduces costs, and enhances compliance. However, patients who are older, overweight, or have chronic conditions require closer monitoring during non-chemotherapy periods.

Introduction

Totally Implantable Venous Access Ports (TIVAP) are a closed intravenous infusion system that is completely implanted in the body. It was first reported to be used by Niederhuber JE in 1982¹. TIVAP can be used for the infusion of various high-concentration chemotherapy drugs, total parenteral nutrition solutions, as well as for blood collection and transfusion, etc. It reduces the irritation of drugs on patients' blood vessels and alleviates the pain caused by repeated venipuncture. Its daily management and maintenance are convenient, and it provides good comfort, making it one of the first choices for the venous access in the treatment of malignant tumor patients². However, due to the high cost of TIVAP and the fact that it is currently still at patients' own expense, most patients choose to keep TIVAP during the non-treatment period after completing the phased cycle of anti-tumor treatment in case of disease recurrence and the need for reuse³. Thiel K⁴ followed up 1005 tumor patients with implanted TIVAP and found that 11.94% (120/1005) of the patients had related complications. Although compared with previous infusion methods such as PICC and CVC, the incidence of complications is lower and the indwelling time is longer^5,6, related complications are still unavoidable. TIVAP complications include port-related bloodstream infections, catheter-related thrombosis, catheter blockage, pinch-off syndrome, port body flipping, catheter detachment, and other complications^7,8. The occurrence of complications will lead to the delay of patients' treatment. In severe cases, it will affect patients' psychology and disease prognosis, causing physical and mental harm to patients and their families, and an increase in medical expenses⁹. The maintenance of implantable venous access ports involves assessing the functional status of the port catheter, replacing non-coring needles and dressings, and performing timely flushing and sealing of the catheter¹⁰. To ensure the optimal performance of TIVAP in patients' bodies, regular maintenance is necessary to maintain the patency of the infusion path, ensure the device's normal operation, and help extend its service life, thereby preventing and reducing the occurrence of adverse events such as catheter blockage.

There is still controversy regarding the maintenance interval of TIVAP during the non-chemotherapy period. Clinical studies have shown^11,12 that the shorter the maintenance cycle of TIVAP during the non-treatment period is, the lower the risk of catheter blockage will be. At present, most studies recommend maintenance once every 4 weeks, mainly to prevent catheter blockage¹³. However, relevant studies reported in recent years¹⁴ showed that there is no direct relationship between the length of the maintenance interval and the blockage of the TIVAP catheter, but there are relatively few studies on malignant tumor patients. Due to the existence of cancer procoagulant in malignant tumor cells, which secrete mucin and tissue factor, resulting in an increase in blood viscosity, and combined with the fact that TIVAP needs to be indwelling in blood vessels for a long time, compared with other patients, it is extremely easy to form thrombosis at the top of the catheter. Compared with the conventional 4-week maintenance interval, extending the maintenance interval of Totally Implantable Venous Access Ports (TIVAPs) to 8-12 weeks can reduce the frequency of patients' hospital visits and alleviate their economic burden. However, cancer patients often present with a hypercoagulable state after chemotherapy, and there is still a lack of targeted verification regarding whether such an extended maintenance scheme is applicable to this specific population. The core of the current clinical controversy over TIVAP maintenance intervals during the non-chemotherapy period lies in the absence of clear definitions for the scheme's applicable scenarios, operational standards, and scope of limitations. Although existing studies have mentioned the feasibility of extended intervals, they have not clarified whether this approach is exclusively applicable to the non-treatment phase following chemotherapy completion. Meanwhile, the standardization level of maintenance operations has not been specified in conjunction with the interval schemes.

This study intends to address the aforementioned issues in a targeted manner. First, the research scenario is strictly limited to the non-treatment period of malignant tumor patients after chemotherapy, excluding patients who require frequent TIVAP use during chemotherapy. Second, the clinically routine 4-week interval is clearly set as the control group, while two experimental intervals (8 weeks and 12 weeks) are simultaneously included, and the core maintenance operation standards are unified. This study aims to compare the application value of TIVAP management schemes with different maintenance frequencies in patients with malignant tumors after completing chemotherapy, explore the factors associated with infusion-related complications, provide a scientific basis for clinical practice, and identify the most suitable TIVAP maintenance strategy for this patient population.

Protocol

This study has been approved by the Ethics Committee of The First Affiliated Hospital of Jinan University (Guangzhou Overseas Chinese Hospital; Approval No. SYJS2024-05-22-09). Before enrollment, all patients were informed of the study objectives, protocol, and potential risks by trained research nurses. After fully understanding the information, each patient signed the Informed Consent Form; for patients unable to sign independently, their legal guardians signed the Proxy Informed Consent Form on their behalf. The equipment and software used are listed in the Table of Materials.

1. Sample size estimation

The sample size was calculated using the formula for a multi-group equal design:

​where, k = number of groups; Z values are the standard normal deviates for type I error and power; s is the estimated standard deviation; and µ_i = and µ denote the mean outcome for group i and the overall mean, respectively.

For this study, k = 3, two-sided α = 0.05 (Z_1-α/2 = 1.96), and power = 0.90 (Z_1-β = 1.28). Based on pilot data, s = 0.15. Substituting these parameters yielded an estimated n = 95 per group, giving a minimum total sample size of 285. Allowing for a 10% dropout rate, at least 106 patients were required per group, with a final target enrollment of ≥318 patients. The study workflow is illustrated in Figure 1, which structures the research into 5 phases: Enrollment: 350 initial patients were screened, with exclusions detailed in the next module. A total of 303 patients were finally included and completed the follow-up. The discrepancy in sample size (15 cases less than the initial estimate) was attributed to the following reasons: 10 patients withdrew due to adjustments in their chemotherapy regimens after enrollment, and 5 patients were lost to follow-up. All withdrawals and losses to follow-up occurred within 12 weeks of enrollment, and the loss-to-follow-up rates were balanced across the three groups (Group A: 3.1%, Group B: 4.9%, Group C: 4.8%), with no selective bias observed. Grouping: Patients chose maintenance intervals (4-week/8-week/12-week) per preference, forming Groups A/B/C as shown. Intervention & Outcomes: Six key endpoints were compared, using: Wells score for thrombosis; SF-36 questionnaire for quality of life. Complication Analysis: Unifactor/multifactor models identified predictors as visualized. Targeted measures and study findings were derived, with all steps traceable to Figure 1.

2. General information

A total of 303 patients with malignant tumors who underwent implantation of a venous access port in our hospital between June 2021 and June 2023 were enrolled. Inclusion criteria were: (1) confirmed diagnosis of malignant tumor requiring chemotherapy; (2) successful implantation of a venous access port; and (3) ability to provide informed consent and comply with follow-up. Exclusion criteria were: (1) severe coagulation disorders; (2) active local or systemic infection at the time of implantation; (3) previous history of central venous catheter-related complications; or (4) refusal to participate.

Patients were allocated to three groups according to their preferred port management frequency: Group A (high-frequency maintenance, n = 97), Group B (medium-frequency maintenance, n = 101), and Group C (low-frequency maintenance, n = 105). Clinical outcomes among the three frequency-management strategies were compared over a 48-week follow-up period after port implantation. Maintenance was considered timely if the actual visit date differed from the scheduled interval by no more than 1 week.

For safety evaluation, complications were defined as catheter occlusion, infection, thrombosis, bleeding, or mechanical dysfunction occurring during the maintenance period. Patients were further categorized into a complication group and a non-complication group to identify risk factors for adverse events associated with venous access ports in chemotherapy-treated patients.

3. Management of implantable venous access ports

1. Contraindications for implantation
   All 303 patients included in this study were implanted with the same brand and model of totally implantable venous access port (TIVAP) system. Implantation was permitted if platelet count was ≥50 × 10⁹/L, international normalized ratio (INR) ≤1.8, and activated partial thromboplastin time (APTT) ≤1.3-fold of the normal value, without the need for pretreatment reversal. If the platelet count was <50 × 10⁹/L, INR >1.8, or APTT >1.3-fold of normal, coagulation dysfunction was corrected before surgery. Severe coagulation disorders not correctable by medical intervention were considered an absolute contraindication due to the risk of uncontrollable bleeding.
2. Preoperative preparations
   1. Informed consent
      Patients were informed of procedural risks, intraoperative precautions, postoperative care, potential complications, and associated costs. Written informed consent was obtained.
   2. Preoperative examinations
      Routine blood counts, liver and kidney function, coagulation profile, and electrolytes were assessed. Electrocardiography and ultrasound of the carotid vein and superior vena cava were performed to confirm vascular patency.
   3. Components of the totally implantable venous access port (TIVAP) system, ultrasound equipment, surgical instruments, sterile surgical drapes and dressings, anesthetic drugs, 100 IU/mL heparin sodium dilution, 0.9% sterile sodium chloride injection, and catheter tip positioning device.
3. Approaches for implantation
   ​The implantation standards for infusion ports refer to the Shanghai expert consensus on totally implantable access ports¹⁵. Two common approaches were used: arm ports and chest wall ports.
   1. Arm port implantation
      ​Patients were placed supine with the ipsilateral arm abducted. After disinfection and sterile draping, the basilic or axillary vein (upper third of the arm) was punctured under real-time ultrasound guidance. A guidewire was inserted, followed by advancement of the sheath and catheter. The catheter was guided across the sternoclavicular joint into the superior vena cava. Position was confirmed, and a subcutaneous pocket was created on the medial aspect of the upper arm. The port body was connected and secured in the pocket, and the incision was closed. The catheter was locked with 5 mL of heparinized saline (100 IU/mL).
   2. Chest wall port implantation
      Patients were placed supine, with landmarks identified on the chest wall. After local anesthesia, the internal jugular or subclavian vein was punctured under ultrasound guidance. The catheter was advanced along a guidewire, and a pocket was created in the subclavicular region. Using a tunneling device, the catheter was guided to the chest wall incision, connected to the port body, and secured. The incision was sutured, and the catheter was locked with 5-10 mL of heparinized saline (100 IU/mL).
      The three groups were assigned strictly in accordance with the access site stratification principle: specifically, within the 4-week, 8-week, and 12-week groups, the sample proportions of upper arm ports and chest wall ports showed no significant difference from the distribution in the total sample. This design aimed to avoid interference from uneven access site distribution in the evaluation of maintenance efficacy and complications.
4. Maintenance procedures
   Aseptic techniques were strictly followed by nurses. The skin around the TIVAP was cleaned and disinfected using 75% ethanol and 2% chlorhexidine gluconate. Blood was aspirated from the catheter to check for smooth blood return. A 20 mL volume of 0.9% sterile sodium chloride injection was used for pulsatile flushing. This volume of flushing solution creates intraluminal turbulence, enabling thorough removal of residual medication from the inner wall of the catheter¹⁶. Finally, 5 mL of 100 IU/mL heparin sodium dilution was used for positive-pressure capping: the 100 IU/mL concentration can maintain an anticoagulant effect in the catheter lumen for 7-14 days, and the total dose of 5 mL is far below the daily safe dose for adults (≤10,000 IU), with no increased risk of bleeding¹⁷.
   For patients who developed adverse complications during treatment, nurses provided targeted interventions and conducted patient education: (1) For patients with loose skin, when turning over or lifting the operative-side arm significantly, they were instructed to gently press the TIVAP reservoir with the contralateral hand to enhance fixation; (2) For patients with excessive chest wall mobility, education was provided to advise them to avoid strenuous movements in daily activities that might increase pressure on the skin over the TIVAP pocket; (3) For patients with excessive movement during sleep, nurses could consider using a restraint strap if necessary.
5. Patient education and management schemes
   The nursing staff distributed educational materials and explained key self-observation points. Patients were taught to recognize early symptoms of complications (local redness, swelling, pain, exudation, fever) and instructed to seek medical care for catheter breakage, detachment, or severe bleeding.
   ​Patients were scheduled for hospital-based maintenance at different intervals: every 4 weeks (Group A), every 8 weeks (Group B), or every 12 weeks (Group C). Patients were also guided to perform home self-monitoring for skin changes around the port.
6. Safety precautions and waste disposal
   1. Heparin handling
      Heparinized solutions were prepared in sterile conditions, with attention to dosage accuracy to prevent bleeding or thrombosis. Any signs of bleeding or thrombotic complications were monitored and documented.
   2. Restraint belt policy
      Use was restricted to patients with excessive movement, applied only with informed consent and continuous monitoring.
   3. Waste disposal
      Sharps (needles, guidewires) were discarded in puncture-proof containers. Blood-contaminated dressings and heparinized waste were disposed of as biohazard materials in accordance with institutional biosafety protocols.

4. Observation indicators

Patients' baseline data were collected at enrollment, including age, sex, body mass index (BMI), tumor type, metastatic status, comorbidities (chronic diseases were defined as long-term conditions such as hypertension, diabetes, coronary heart disease, and chronic obstructive pulmonary disease), and type of venous access port. Laboratory results at admission were also recorded, including platelet count, white blood cell count, neutrophil count, and serum albumin level. The observation period was 48 weeks after port implantation. Outcomes included thrombosis risk, catheter patency, complications, quality of life, management satisfaction, compliance, and cost of maintenance.

1. Thrombosis risk
   The Wells score for deep vein thrombosis (DVT) was applied¹⁸. Patients with a score ≤0 were classified as low-risk, those with scores of 1-2 as moderate-risk, and those with scores ≥3 as high-risk. If both lower limbs presented symptoms, the limb with the more severe manifestations was used for evaluation.
2. Catheter patency
   Patency was defined as visible blood reflux on aspiration and unobstructed flushing of the catheter. "Withdrawal obstruction" was defined as the absence of blood reflux, regardless of whether flushing was smooth.
3. The diagnosis of suspected complications was made by 2 vascular surgeons. After a patient developed suspected complications, the surgeons conducted a comprehensive assessment based on clinical symptoms, imaging examinations (ultrasound/CT angiography [CTA]), and laboratory results (complete blood count [CBC], secretion culture).
   1. Catheter pinch-off (Pinch-Off Syndrome, POS)
      ​Chest X-ray showed catheter compression and deformation in the costoclavicular space (with an angle of deflection >30°), accompanied by difficulty in blood aspiration or increased resistance to infusion.
   2. Puncture site infection
      ​The puncture site exhibited redness, swelling, heat, and pain, with purulent secretions; bacterial culture of the secretions was positive.
   3. Catheter-Related Thrombosis (CRT)
      ​Ultrasound/CT venography revealed thrombus formation within the catheter lumen or in the vein within 5 cm of the catheter tip, with or without clinical symptoms.
   4. Catheter occlusion:
      Complete occlusion: Inability to aspirate blood and significantly increased resistance to flushing with normal saline; (2) Partial occlusion: Difficulty in blood aspiration but ability to flush slowly with normal saline.

5. Assessment of complications, quality of life, satisfaction, and compliance

Complications included catheter occlusion, infection, thrombosis, bleeding, and mechanical dysfunction, which were assessed throughout the 48-week maintenance period. Patients' quality of life was evaluated at 48 weeks using the 36-item Short-Form Health Survey (SF-36)¹⁹, comprising 36 items across eight domains: general health, social function, physical role, bodily pain, physical function, vitality, mental health, and emotional role. Domain scores were standardized, weighted, and summed to yield a total score ranging from 0 to 100, with higher scores indicating better quality of life. At 48 weeks, patient satisfaction with venous access port management was assessed using a self-designed questionnaire containing 10 items, each rated on a 4-point Likert scale, resulting in a total score ranging from 0 to 40, where higher scores indicated greater satisfaction. Compliance with venous access port maintenance was evaluated at 24 and 48 weeks using another self-designed 10-item compliance questionnaire scored on a 4-point Likert scale, with total scores ranging from 0 to 32. Compliance levels were classified as follows: 28-32, indicating high compliance (strict adherence to requirements); 20-27, indicating moderate compliance; 12-19, indicating mild compliance; and 0-11, indicating poor compliance.

6. Statistical methods

The SPSS 27.0 statistical software was used to analyze the clinical values of the management schemes with different maintenance frequencies. Measurement data that conformed to the normal distribution were expressed as mean ± standard deviation, and the two independent samples t-test was adopted for comparison between groups. Count data were expressed as the number of cases (n) and percentage (%), and the χ² test was used for comparison between groups. Multivariate Logistic regression analysis was employed to analyze the influencing factors for the occurrence of complications in TIVAP. A p-value less than 0.05 was considered statistically significant for all analyses.

Results

Clinical data of patients
There were no significant differences in baseline data and laboratory indicators among the three groups, as analyzed by one-way ANOVA and chi-square test (all P > 0.05), as shown in Table 1.

Thrombosis risk and catheter patency of TIVAP
There was no significant difference in thrombosis risk assessment among the three groups of patients (P > 0.05). All the patients' infusion ports had good catheter patenc...

Discussion

The blood of patients with malignant tumors is in a hypercoagulable state, and they are more prone to catheter blockage than ordinary patients. Some patients are often accompanied by pleural effusion, ascites, bone metastasis, etc., resulting in forced postures. Long-term lateral or semi-recumbent positions can easily cause the catheter in the body to bend and kink, leading to catheter blockage²⁰. At the same time, the immunity decreases after chemotherapy, making it easier to catch a cold and exp...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
GraphPad Prism	GraphPad Software, LLC	10	Draw the comparison chart of maintenance costs (Figure 2) and the SF-36 score chart (Figure 3), including the error line and statistical annotations
Heparin Sodium Injection	Shanghai Pharmaceuticals Holding Co., LTD	100 IU/mL	Catheter sealing solution, use 5 mL each time at a concentration of 100 IU/mL
Self-designed review compliance questionnaire	Developed by this research team	NA	Evaluate the compliance of follow-up at 24/48 weeks using a 10-item 4-point scale
Self-designed satisfaction questionnaire	Developed by this research team	NA	Evaluate the satisfaction of maintenance management after 48 weeks, using a 10-item 4-point scale
SF-36 Health Survey Scale	The Medical Outcomes Study Group (MOS) of the United States	NA	Evaluate the quality of life for 48 weeks, with a total score ranging from 0 to 100 for the 8 dimensions
SPSS Statistics	IBM Corporation	27	One-way analysis of variance (ANOVA) was conducted to compare maintenance costs and SF-36 scores. The chi-square test was used to analyze the complication rate; Multivariate Logistic regression was used to screen risk factors
Ultrasound Probe	GE Healthcare	GE Logiq E9	7–12 MHz linear probe (model: Logiq E9); used for guiding TIVAP implantation and assessing complications (e.g., catheter-related thrombosis).
Venous Port Kit	B. Braun	Celsite PSU	Single-lumen design; features polysulfone body and titanium chamber, pressure resistance up to 325 PSI (22.4 bar); equipped with high-density silicone septum (for reliable puncture and extended service life) and 3 suture holes (for secure fixation). Radiopaque catheter marked from 5 cm for accurate implantation; round atraumatic tip with radiopaque connection ring and anti-kinking protection. MRI-compatible, latex/DEHP/PVC-free; implanted via surgical incision.
Wells Score Scale	NA	NA	DVT risk assessment version; used for evaluating the risk of deep vein thrombosis in patients with TIVAP.