Percutaneous Acetic Acid Injection Research Articles

The double intervention clinical value and application research of TACE with PAI on massive hepatocellular carcinoma

Objective To study the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous acetic acid injection (PAI) on massive hepatocellular carcinoma (MHCC).

Survival impact of delayed treatment in patients with hepatocellular carcinoma undergoing locoregional therapy: Is there a lead-time bias?

Objective. Many reports indicate the importance of active treatment for hepatocellular carcinoma (HCC), but there are few studies available that address the impact of delayed therapy on survival or take the lead-time bias into account. The objective of this study was to investigate whether patients with delayed locoregional therapy for HCC truly have a shortened survival from the time of diagnosis. Material and methods. Survival rates were compared between 48 HCC patients with treatment delay and 96 age- and gender-matched controls without delay. All patients underwent transarterial chemoembolization or percutaneous ethanol or acetic acid injection for HCC. Treatment delay was defined as a >2 months’ time interval between diagnosis and treatment. Results. Baseline comparison showed that patients with treatment delay had higher scores in the model for endstage liver disease compared with those of patients without delay (12.3±1.8 versus 11.1±2.5, p=0.01). In the Cox multivariate model, advanced cancer stage (relative risk (RR): 2.66, p=0.001), Child-Turcotte-Pugh class B (RR: 3.81, p<0.001), tumor size >5 cm (RR: 2.02, p=0.011) and treatment delay (RR: 2.91, p=0.001) were independent poor prognostic predictors. Among patients with treatment delay, disease progression was registered in 30 (63%) patients. Patients with prolonged treatment delay (>3 months) were more likely to have tumor progression (p=0.013). In the Cox model, a treatment delay of >3 months independently predicted a poor rate of survival (RR: 3.67, p=0.002). Conclusions. Delayed HCC treatment is linked with shortened overall survival unrelated to the lead-time bias in patients undergoing locoregional therapy. Prolonged treatment delay of more than 3 months in these patients may worsen the long-term outcome.

Fever and Infectious Complications After Percutaneous Acetic Acid Injection Therapy for Hepatocellular Carcinoma: Incidence and Risk Factor Analysis

Ultrasound-guided percutaneous acetic acid injection (PAI) therapy is effective for hepatocellular carcinoma (HCC). Posttreatment fever (>37.5 degrees C) may occur owing to acetic acid-induced tumor necrosis, but its incidence and clinical significance are not clear. A total of 402 treatment sessions in 127 consecutive patients undergoing PAI for HCC were prospectively studied. The incidence and risk factors associated with post-PAI fever were analyzed. There were 37 (9.2%) episodes of fever occurring in 29 HCC patients after PAI. Patients who developed fever more often had large-sized (3.5+/-1.3 cm vs. 2.7+/-1.2 cm, P=0.0002) tumor and a higher injection volume (2.6+/-0.1 mL vs. 2.2+/-0.1 mL, P=0.001) of acetic acid compared with those without fever. Multivariate logistic regression analysis showed that tumor size >3 cm was the only significant predictor associated with occurrence of posttreatment fever (odds ratio: 4.4, 95% confidence interval: 2.2-8.9, P<0.001). Three patients, all of whom had HCC diameter >3 cm, had 4 episodes of bacteremia after treatment; one of them developed liver abscess that required percutaneous drainage. Fever after PAI is not an uncommon event. Patients with tumor size >3 cm have a higher risk of posttreatment fever. Bacteremia and significant infectious complication could occur in a minority of patients. Prophylactic antibiotics before treatment may be necessary for high-risk patients.

Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.

Radiofrequency Ablation Therapy

Radiofrequency ablation (RFA) has emerged as the most popular and versatile of the local ablative therapies—techniques that treat tumors using thermal or chemical means. (Other techniques included in this category are cryoablation, laser therapy, microwave therapy, and percutaneous ethanol or acetic acid injection.) Radiofrequency ablation initially was used primarily for treatment of hepatic malignancies; however, in recent years, it has been used to treat tumors in many other organs. Radiofrequency ablation is seen as an alternative or adjunct to surgery, chemotherapy, or radiation therapy. It has been shown to be both safe and effective, with minimal mortality and morbidity, while achieving complete to near-complete tumor necrosis and acceptable local recurrence rates. This article reviews the mechanism of, indications for, efficacy of, and complications of RFA based on both the reported literature and our own experience.

Computed Tomography-Guided Percutaneous Acetic Acid Injection Therapy for Functioning Adrenocortical Adenoma

Computed Tomography-Guided Percutaneous Acetic Acid Injection Therapy for Functioning Adrenocortical Adenoma

Induction of complete tumor necrosis may reduce intrahepatic metastasis and prolong survival in patients with hepatocellular carcinoma undergoing locoregional therapy: a prospective study

BackgroundTransarterial chemoembolization (TACE) and percutaneous acetic acid injection (PAI) are effective locoregional therapies for hepatocellular carcinoma (HCC). This study aimed to investigate whether HCC patients who had initial complete response to these treatments had a subsequent lower risk of intrahepatic metastasis. Patients and methodsA total of 152 patients who underwent locoregional therapy (94 received PAI and58 received both TACE and PAI) for HCC (tumor size ≤5 cm) were prospectively evaluated. ResultsIn all, 60 (39%) patients had a complete tumor necrosis after treatment. The cumulative incidence of the development of intrahepatic metastasis was lower for patients with complete remission (P = 0.005) and for patients with smaller (≤3 cm) tumor size (P = 0.083). Cox multivariate survival analysis showed that absence of complete remission [relative risk (RR) 2.7; 95% confidence interval (CI) 1.4–5.3; P = 0.003] was the only independent factor that predicted the occurrence of intrahepatic metastasis. Patients with complete remission had a significantly better long-term survival than those without (P = 0.002), and the occurrence of intrahepatic metastasis over time independently predicted a decreased survival (RR 3.2; 95% CI 2.0–6.1; P = 0.019). ConclusionsInduction of complete tumor necrosis in HCC patients undergoing locoregional therapy may decrease the risk of intrahepatic metastasis and improve survival.

Image-guided tumour ablation - a new opportunity

It is less than 20 years since the very first papers on ultrasound (US)-guided ablation of liver tumours were published. Initially ablation centred on US-guided percutaneous ethanol injection (PEI) in small, non-resectable hepatocellular carcinoma (HCC) and neodymium yttrium aluminium garnet (NdYAG) laser heating techniques in liver metastases. Since then radiofrequency ablation (RFA), microwave, percutaneous cryotherapy, percutaneous acetic acid injection, photodynamic therapy and high intensity focussed US have all been used. Technological development has seen increased power application, water-cooling and the development of an array of different applicators. Currently the majority of centres use radiofrequency, a heating technique whereby alternating current produces ionic agitation and frictional heating in the tissue immediately around the electrode. US guidance remains the optimal, quickest technique for applicator placement but monitoring has become more sophisticated with micro-bubble contrast-enhanced US, multi-planar, multi-slice or preferably co-registered 3D computed tomography or magnetic resonance (MR). Initial hopes for MR temperature monitoring have not yet been realised. Changes in T1 and proton resonance frequency can provide temperature information but require subtraction imaging and work well in areas where image co-registration is easy. This does not apply to the liver which remains the commonest site of tumour ablation.

Persistent retention of acetic acid is associated with complete tumour necrosis in patients with hepatocellular carcinoma undergoing percutaneous acetic acid injection

Background: Ultrasound (US)‐guided percutaneous acetic acid injection therapy (PAIT) is effective for patients with hepatocellular carcinoma (HCC). This study aimed to determine the occurrence and predictive value of persistent intra‐tumoral retention of acetic acid after PAIT. Methods: We prospectively studied 60 (52 M, mean age 68 ± 10 years) patients with 72 HCC nodules (45 ≤ 3 cm) treated with PAIT. The presence of post‐treatment persistent retention of acetic acid, defined as a homogeneous and highly hyperechoid mass in US appearance 3 days after completion of the treatment, was correlated with the treatment response. Results: The mean size of the treated tumour was 2.9 ± 1.0 cm (range 1.5–5 cm). Thirty (42%) HCC nodules showed complete tumour necrosis demonstrated by contrast‐enhanced dynamic CT. Complete response was found in 22 (69%) of 32 nodules showing persistent intra‐tumoral retention of acetic acid (P < 0.001). Small (≤3 cm) tumour size was also significantly associated with complete tumour necrosis (P = 0.001). There were no significant differences of the injection volume and treatment sessions between those with and without complete tumour necrosis in either small or large (>3 cm) HCC (P > 0.1). Multivariate logistic regression analysis showed that persistent retention of acetic acid (odds ratio (OR) 10.4, 95% confidence interval (CI) 3.1–34.7; P < 0.001) and tumour size ≤3 cm (OR 6.8, 95%, CI 1.8–25.8; P = 0.002) were independent factors predicting complete tumour necrosis. Conclusions: The presence of persistent retention of acetic acid is associated with a favourable response and may predict complete tumour necrosis after PAIT.

Computed Tomography-Guided Percutaneous Acetic Acid Injection Therapy for Functioning Adrenocortical Adenoma

We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40-50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing's or subclinical Cushing's syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5-69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adrenocortical adenomas.

Combined treatment of radiofrequency ablation and acetic acid injection: an in vivo feasibility study in rabbit liver.

The aim of this study was to compare the effects of percutaneous radiofrequency ablation (RFA) combined with percutaneous acetic acid injection (PAI) and either therapy alone for their effects on in vivo rabbit liver tissue. Thirty New Zealand white rabbits were included in this study and were allocated to three groups: group A, conventional RFA (n = 10); group B, PAI (n = 10); and group C, combined RFA and PAI (n = 10). Under US guidance, 1 ml of 50% acetic acid was injected into the target area of the liver parenchyma through a 21-G Chiba needle before performing RFA. The RFA was then performed using a 17-G internally cooled electrode with 1-cm active tip, and RF energy (30 W) was applied for 3 min with or without acetic acid injection. After RFA or PAI, contrast-enhanced CT and CT pathologic correlation were performed. The maximum diameters of the thermal lesions in each group were compared. All procedures were technically successful, and a total of 30 lesions (10 lesions for each group) were produced. The mean maximum diameter of the coagulation necrosis in the rabbits of group C (25+/-9 mm) was significantly larger than the diameters of the other groups: 12.2 +/- 1 mm (group A) and 14.3 +/- 3 mm (group B; p = 0.001). On contrast-enhanced CT scanning, the lesions of group B (7 of 10, 70%) appeared frequently irregular compared with those of groups A (2 of 10, 20%) and C (4 of 10, 40%; p = 0.08). There were seven complications (23.3%): a localized hematoma in a group-A rabbit; two hematomas and one chemical peritonitis in group-B rabbits; and a hematoma, a chemical peritonitis, and a burn injury to the stomach in group-C rabbits. Compared with the group-A rabbits (1 of 10, 10%), the group-B (3 of 10, 30%) and group-C rabbits (3 of 10, 30%) showed a tendency toward complications, but the difference was not significant (p = 0.48). Under the present experimental condition, combined RFA and PAI was able to increase the diameter of coagulation necrosis up to 2.5 cm without significantly increasing complications.

Sequential transarterial chemoembolization and percutaneous acetic acid injection therapy versus repeated percutaneous acetic acid injection for unresectable hepatocellular carcinoma: a prospective study

BackgroundTransarterial chemoembolization (TACE) and percutaneous acetic acid injection (PAI) are effective treatments for hepatocellular carcinoma (HCC). We have conducted a prospective study to compare the efficacy of sequential TACE and PAI (TACE-PAI) versus repeated PAI therapy for HCC. Patients and methodsA total of 108 HCC patients with tumor size ≤5 cm were enrolled. Fifty-three patients were treated with TACE–PAI and 55 patients were treated with PAI alone. ResultsObjective responses were achieved in 72 of 80 nodules (90%) in the TACE–PAI group compared with 51 of 62 nodules (82%) in the PAI group (P = 0.217) during 24 ± 10 months of follow-up. Patients in the TACE–PAI group had a significantly lower cumulative tumor recurrence rate from the treated nodule (P = 0.004) or newly developed tumor elsewhere in liver (P = 0.010). Complete tumor necrosis in large (3–5 cm) HCCs was more frequently encountered in the TACE–PAI group (64% versus 37%; P = 0.034). There was no significant survival difference between the two groups with small (≤3 cm) HCC (P = 0.569), whereas PAI therapy was an independent poor prognostic predictor [relative risk 3.0 (95% confidence interval 1.2–7.6); P = 0.017] in the large HCC group. ConclusionsSequential therapy with TACE and PAI is superior to repeated PAI alone for patients with large HCC.

The role of real-time ultrasound in evaluating the effect of pure ethanol injection therapy and acetic acid injection therapy in treating small hepatocellular carcinoma

Objective: This study is to evaluate the role of real-time ultrasound (US) in monitoring percutaneous pure ethanol injection (PEI) and percutaneous acetic acid injection (PAI) in the treatment of small hepatocellular carcinoma (HCC).

Comparison of Percutaneous Acetic Acid Injection and Percutaneous Ethanol Injection for Hepatocellular Carcinoma in Cirrhotic Patients: A Prospective Study

Background: Ultrasound-guided percutaneous ethanol injection (PEI) and percutaneous acetic acid injection (PAI) are effective in the treatment of hepatocellular carcinoma (HCC). We conducted a prospective study to compare the therapeutic efficacy of both these methods. Methods: Sixty-three patients were treated by PAI using 50% acetic acid and 62 by PEI using pure ethanol. There were no significant baseline differences in age, sex, Child-Pugh class, tumour size and number, or other clinico-biochemical parameters between the two groups. Results: During a follow-up period of 24 ± 9 (range 6-38) months, 19 (30%) of the PAI group and 21 (34%) of the PEI group died ( P r = r 0.704). The 1- and 3-year survival rates were 84% and 51% for the PAI group and 81% and 46% for the PEI group ( P r = r 0.651). The corresponding tumour recurrence rates were 51% and 74% for the PAI group, and 54% and 64% for the PEI group ( P r = r 0.787). The treatment sessions were 3.9 ± 1.6 and 6.2 ± 2.3 for the PAI and PEI groups, respectively, in each treatment cycle ( P r = r 0.008). A multivariate analysis using the Cox regression model revealed that ascites (relative risk (RR) 3.1, 95% confidence interval (CI) 1.5-6.3, P r = r 0.002), large (>3 r cm) or multinodular HCCs (RR 2.4, 95% CI 1.1-5.4, P r = r 0.04), and development of tumour recurrence (RR 7.0, 95% CI 3.1-16.0, P r < r 0.001) were independent, poor prognostic factors in both groups. Conclusions: PAI and PEI are equally effective in the treatment of HCC. PAI has the advantage of fewer treatment sessions in each treatment course. Careful pretreatment patient selection may improve survival.

Percutaneous acetic acid injection for hepatocellular carcinoma: using CT fluoroscopy to evaluate distribution of acetic acid mixed with an iodinated contrast agent.

The purpose of our study is to evaluate the distribution of acetic acid mixed with iodinated contrast agent during percutaneous acetic acid injection on CT fluoroscopy for hepatocellular carcinoma. Monitoring acetic acid distribution on CT fluoroscopy can detect extratumoral diffusion and may optimize the distribution of acetic acid in hepatocellular carcinoma.

Percutaneous injection of a low-concentration alkaline solution targeting hepatocellular carcinoma.

We developed a percutaneous low-concentration alkali injection therapy (PLAIT) targeting hepatocellular carcinoma (HCC), and compared the necrotic areas in the livers of rats that had received PLAIT [an alkaline solution of sodium hydroxide (NaOH)] with those that had received percutaneous ethanol injection therapy (PEIT) and percutaneous acetic acid injection therapy (PAIT). The necrotic area increased with increasing concentrations of NaOH solution. The survival rate of rats was 100% up to a concentration of 4 N; however, the rate dropped below 80% with concentrations over 5 N. Also, at a concentration of 2 N, the necrotic area increased with increasing quantities from 0.01 ml to 0.1 ml. PLAIT using 0.05 ml of 2 N NaOH was 1.56 times more effective than PEIT using 0.05 ml of 99.5% ethanol, and 63.33% less effective than PAIT using 0.05 ml of 50% acetic acid. However, the survival rate after PAIT was 50%, while that after PLAIT was 100%. Histopathological observation of normal rat livers after injection of 2 N NaOH at a volume of 0.05 ml showed that the tissue necrosis spread radially from the site immediately after injection by PLAIT, but necroses were not found in other organs. We conclude that PLAIT has promise as a new form of local therapy for HCC.

Small hepatocellular carcinoma: safety and efficacy of single high-dose percutaneous acetic acid injection for treatment.

To evaluate the safety and efficacy of single high-dose percutaneous acetic acid injection (PAI) for treatment of small (<3-cm-diameter) hepatocellular carcinoma (HCC). Eighteen patients with HCC (22 nodules; diameter range, 1.5-3.0 cm) underwent single PAI. With ultrasonographic or computed tomographic (CT) guidance, 4-11 mL of 50% acetic acid was slowly injected into the center of the nodule through a skinny multiple-side-hole needle. Follow-up was performed with helical contrast material-enhanced CT. Complications of high-dose PAI were recorded. Seventeen nodules showed no local recurrence (follow-up, 6-29 months) after single PAI. At a mean follow-up of 15.6 months, mean tumor diameter was 2.1 cm and mean injected volume was 6.4 mL. Four nodules showed residual tumor (mean tumor diameter, 2.6 cm; mean injected volume, 5.8 mL). The mean ratio of injected to estimated volume of acetic acid was 1.21 in cases of successful single PAI and 0.72 in cases of local recurrence (P < .001). One patient with preexistent right portal venous thrombosis died of hepatic failure 37 days after PAI. Other complications included severe pain (11%), high fever (4%), and segmental wedge infarction (4%). Single high-dose PAI is safe and effective for treatment of small HCC.

Cytologic Changes in Hepatocellular Carcinoma After Percutaneous Acetic Acid Injection

To illustrate the cytologic features of hepatocellular carcinoma (HCC) after percutaneous acetic acid injection (PAI) and to correlate the cytologic findings with helical computed tomography (CT) findings. The study included 30 patients with 37 HCC who had undergone PAI. Baseline cytomorphology of HCC was evaluated by needle aspiration in all cases. PAI under ultrasound guidance was done every three to seven days. Upon completion of PAI, fine needle aspiration cytology was performed and followed by helical CT within two weeks. The degeneration of HCC after PAI was classified into two grades. Grade 1 showed incomplete degeneration (99% of nuclear area); grade 2 showed complete degeneration or severe degeneration with cell debris or amorphous material only. The specimens were stained with Riu's method (Romanowsky system). The cytologic changes after PAI included decreased cell number, reduced cellular aggregation, degeneration of cytoplasm and nucleus, and eosinophilic or basophilic background in all tumors. In all the 37 tumors without enhancement on helical CT, grade 2 degeneration was detected. Our results reveal that grade 2 degeneration alone, demonstrated cytologically, could indicate almost complete necrosis of HCC after PAI, probably implying no need for booster PAI.

Small functional adrenal cortical adenoma: treatment with CT-guided percutaneous acetic acid injection--report of three cases.

Two patients with Conn syndrome and one patient with Cushing syndrome underwent computed tomography (CT)-guided tumor ablation with a total of 5-11 mL of 50% acetic acid injected into their adrenal nodule (1.3-3.3 cm in diameter). No major complications were encountered during or after the procedure. All patients were symptom free with normal laboratory test results for at least 1-year follow-up. CT images showed complete cystic change with tumor size regression. Our preliminary results suggest that percutaneous acetic acid injection is a safe and effective alternative for treatment of small functional adrenal cortical adenoma.

Prospective randomized controlled trial comparing percutaneous acetic acid injection and percutaneous ethanol injection for small hepatocellular carcinoma

To assess whether ultrasound-guided percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small hepatocellular carcinoma (HCC), 60 patients with one to four HCCs smaller than 3 cm were entered onto a randomized controlled trial. Thirty-one and 29 patients, respectively, were treated by percutaneous acetic acid injection using 50% acetic acid or by percutaneous ethanol injection using absolute ethanol. There were no significant differences in age, sex ratio, Child-Pugh class, size of tumors, or number of tumors between the two groups. When there was no evidence of viable HCC from biopsy, plain and helical dynamic computed tomography, or angiography, the treatment was considered successful and was discontinued. All original tumors were treated successfully by either therapy. However, 8% of 38 tumors treated with percutaneous acetic acid injection and 37% of 35 tumors treated with percutaneous ethanol injection developed a local recurrence (P < .001) during the follow-up periods of 29 +/- 8 months and 23 +/- 10 months, respectively. The 1- and 2-year survival rates were 100% and 92% in percutaneous acetic acid injection and 83% and 63% in percutaneous ethanol injection (P = .0017). A multivariate analysis of prognostic factors revealed that treatment was an independent predictor of survival. The risk ratio of percutaneous acetic acid injection versus percutaneous ethanol injection was 0.120 (range, 0.027-0.528; P = .0050). In conclusion, percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small HCC.