Percutaneous Ethanol Injection Therapy Research Articles

Ethanol ablation of thyroid cysts in the young with a focus on efficacy and quality of life.

Ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) is used in patients with recurrent symptomatic thyroid cysts as a credible alternative to surgery. Young patients commonly do not wish to undergo surgery and prefer ethanol ablation, if available. The effect of this approach on quality of life is an essential factor in deciding on the treatment options, especially in the young with a long life expectancy and no comorbidity. We performed US-PEIT in a cohort of young patients, 15-30 years, from 2015 to 2020. The patients' general quality of life (QoL), self-reported compression symptoms and neck appearance were evaluated. The cohort comprised 59 patients with 63 cysts, more women than men, with a mean age of 23.8 years. About 1.5 mL of injected alcohol were needed to reach a 90.7% mean cyst volume reduction ratio in 12 months. The method did not fail in any of the patients; a single US-PEIT session was undertaken in 46% of them. The procedure significantly improved each of the patients' symptoms with a significant total score difference (P < 0.001). The total symptom score correlated with the initial cyst volume (P = 0.002; r = 0.395). The mean QoL score by SF-36 6 months after the last US-PEIT was significantly different for physical component summary 56.5 (P < 0.001) but not different for mental component summary 47.7 (P = 0.125), compared to age-corresponding norms. US-PEIT is a safe and effective method for the young, leading to improvements in cosmetic and subjective complaints, and should also be considered as first-line treatment in the young.

Vertebral hemangioma - the current radiation therapy perspective.

Vertebral hemangiomas are benign tumors of the spine, most often detected incidentally and on other instances, when signs and symptoms of the disease arise. About 10% of the population are affected worldwide with a female to male ratio of 2:1. The majority of these cases are asymptomatic and no intervention is generally required. Less often, back pain and neurological deficit may occur. Such hemangiomas are termed aggressive by the Enneking staging and warrant treatment. In this review, staging and diagnostics are discussed in detail followed by treatment options. Treatment options entail Surgical intervention, Percutaneous ethanol injection, radiofrequency ablation and Radiation Therapy. There are no set guidelines on preference or order of the treatment options. Further, in this review, studies favouring Radiation therapy regimes and their outcomes are elaborated.

Diagnosis and treatment of trigeminal neuralgia

Background: Trigeminal neuralgia is a sudden and painful facial condition that is triggered by activities of daily living. The pain is debilitating and patients are often unable to perform routine daily tasks such as washing their face, shaving, and brushing their teeth, which in turn has an impact on their social life and mental well-being as they are often anxious and fearful of not knowing when the pain may occur.Current Concepts: Treatment for trigeminal neuralgia involves local nerve destruction surgeries, including neuroblocking, percutaneous ethanol injection therapy, percutaneous radio-frequency rhizotomy, and gamma knife surgery. Although these types of surgeries reduce pain, the side effects are unpleasant and include decreased facial sensation, which originates from the damage to the trigeminal nerve. Furthermore, these surgeries provide insufficient long-term outcomes and symptoms often recur. Microvascular decompression is a radical surgical approach that separates the blood vessels that cause pain from the nerves. In a large-scale study, microvascular decompression significantly reduced the pain in 80–96% of the patients who underwent initial treatment. Of these, 85% experienced significant pain reduction 38 months post-surgery, and 72–85% reported that they were able to manage their pain 5 years post-surgery. Currently, microvascular decompression is the most appropriate surgical approach to control pain in patients with trigeminal neuralgia, as it exhibits the highest rate of pain control and lowest rate of recurrence.Discussion and Conclusion: The accurate diagnosis of trigeminal neuralgia, through clinical symptoms and imaging, is important to obtain good treatment outcomes. Microvascular decompression should be considered when a patient responds poorly to initial treatment approaches, cannot receive surgical treatment due to side effects, or experiences pain recurrence following local nerve destruction.

Percutaneous implantation of ethanol fueled catalytic hydrogel suppresses tumor growth by triggering ferroptosis

Percutaneous ethanol injection therapy (PEIT) is a nonthermal locoregional treatment modality widely used in the treatment of solid tumors such as small hepatocellular carcinoma (HCC). Restricted by the inhomogeneous diffusion and unwanted leakage of injected ethanol, PEIT that usually requires multiple injections is often associated with a high local recurrence rate and potential severe complications. Herein, we propose an alternative locoregional treatment strategy to effectively ablate tumors by utilizing the reactive oxygen species generated from the percutaneously implanted catalytic couple fueled by orally administrated ethanol. It is shown that the catalytic couple of alcohol oxidase and iron catalyst hemin conjugated chitosan can sequentially convert ethanol to cytotoxic hydrogen peroxides and then hydroxyl radials, thereby result in efficient cancer cell killing by triggering ferroptosis. Upon being fixed inside tumors with in-situ formed alginate hydrogels, such catalytic couple together with multiple ethanol gavages shows great inhibitory effect on murine H22 liver and 4T1 breast tumors, comparable to those treated by PEIT. The efficient therapeutic potency of the combination treatment is further confirmed in a rat orthotopic N1S1 HCC model. This work highlights that our ‘alcohol drinking’ anti-tumor strategy is of great effectiveness, operation convenience, and high safety.

Temulence Therapy to Orthotopic Colorectal Tumor via Oral Administration of Fungi-Based Acetaldehyde Generator.

Taking inspiration from percutaneous ethanol injection (PEI) for tumor ablation, an acetaldehyde generator (SC@ZIF@ADH) is constructed for tumor treatment by modifying a metal-organic framework nanocarrier (ZIF), which is loaded with alcohol dehydrogenase (ADH), onto the surface of Saccharomyces cerevisiae (SC). Oral administration of SC@ZIF@ADH can target tumor via mannose-mediated targeting to tumor associated macrophages (TAMs) and generate ethanol at the hypoxic tumor areas. Ethanol is subsequently catalyzed to toxic acetaldehyde by ADH, inducing tumor cells apoptosis and polarizing TAMs toward the anti-tumor phenotype. In vivo animal results show that this acetaldehyde generator can cause a temulence-like reaction in the tumor, significantly inhibiting tumor progression, and might provide an intelligent and nonsurgical substitute for PEI therapy.

Autonomously functioning thyroid nodule: a patient-based review

Autonomously Functioning Thyroid Nodule (AFTN) is a rare cause of hyperthyroidism. AFTN, first described by Emil Goetsch in 1918, is the presence of a single hyperfunctioning thyroid nodule, which is not under the control of the pituitary/thyroid axis. The current theory on the development of hyperfunctioning nodules is the constitutive activation of Thyroid Stimulating Hormone Receptor (TSHR) due to a somatic point mutation and mutations of Gsa. The reported incidence of AFTN is about 1% on the investigation of thyroid nodules. Only about 10% - 30% become hyperfunction. Due to the rarity and lack of understanding of its characteristic clinical behaviour, AFTNs are often overlooked and undertreated. The ensuing review is based on a 36-year-old female who underwent left hemithyroidectomy for an AFTN and is well to date. There are two main issues in the diagnosis and management of AFTN. The first is that the diagnosis is not always made as most patients with AFTNs are functionally euthyroid. The other is the paucity of data in the literature to offer evidencebased individualized management for patients. As there are no tissue diagnostic criteria for AFTN; clinical, biochemical and radiological assessments to establish TSH independent nodular hyperfunction will clinch the diagnosis.Surgery and Radioiodine ablation remain the main forms of treatment for AFTN. Other methods such as percutaneous ethanol injection therapy (PEIT), laser ablation (LA), radiofrequency ablation (RFA) have a limited role in the management of an AFTN. The newer methods alluded to above will need further evaluation and a better definition of exact roles in the management of an AFTN.

Sklerotizace krčních cyst alkoholem pod ultrasonografickou kontrolou jako alternativa operačního řešení

Summary Introduction: Some extrathyroidal cervical cystic lesions can be treated in selected situations by minimally invasive, low-risk method – ultrasound--guided percutaneous ethanol injection therapy (US-PEIT). Here we present 6 cases of neck cysts of various origins – ranula, thyroglossal duct cyst, branchial cleft cyst, midline neck cyst of the pyramidal lobe and dermoid cyst. Method and material: The cohort consisted of 6 patients (mean age 58 ± 13.3 years), who were followed for recurrent cervical cysts located outside the thyroid gland. The cysts were visible, palpable, aesthetically unpleasant and also mechanically compressing the surrounding tissue. After repeated evacuations, they filled in again. The patients repeatedly refused the recommended surgery and demanded an alternative solution. US-PEIT of thyroid cysts is used worldwide as a full-fledged alternative to surgical treatment. We used the same procedure for the treatment of presented neck cysts. Results: The initial volume of cysts was 2–35 mL (mean 17.7 mL); the patients underwent 1–6 sclerotization sessions (mean 3.6). The patients were followed for 12 months; the final volume of solid residue was 0.1–2 mL (mean 1 mL) representing volume reduction by 80–99% (mean 92%). Therapeutic success (volume reduction &gt; 50%) was achieved in all patients. Conclusion: US-PEIT of cervical cysts as an alternative to surgery can be used especially in elderly patients with increased surgical risk or in patients refusing surgery. In middle-aged and older adults, the possibility of a necrotic metastatic lymph node should always be considered. Therefore, a benign cytological examination and an unsuspecting ultrasonographic and CT finding are the basic conditions before performing the ethanol ablation. Key words neck cysts – ultrasound-guided percutaneous ethanol injection therapy

Percutaneous ethanol injection therapy as the first line of treatment of symptomatic thyroid cysts

BackgroundOur aim was to evaluate the efficacy and security of ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) for the treatment of recurrent symptomatic thyroid cysts in two high-resolution consultations of thyroid nodule in the Valencian Community. Patients and methodsThe study comprised thirty-three consecutive patients (51 ± 12 years, 76% women) with symptomatic benign thyroid cysts relapsed after drainage and benign cytology prior to treatment. Through ultrasound, maximum cyst diameter and volume were determined, and the content of the cyst was drained. We then instilled between 2 and 4 ml of ethanol (according to initial volume). We followed up with ultrasound at one, 3, 6 and 12 months and we calculated the total volume and the Volume Reduction Rate (VRR). We evaluated the perceived pain using a visual analog scale. ResultsThe initial median cyst volume was 11.6 ml (8.5–16.5) A single session of US-PEIT was required in 22 patients (67%), two in 8 (24%) and three in 3 (9%). During PEIT, 49% of the patients experienced virtually no pain, 39% mild pain and 12% moderate pain. There were no complications. After 6 months of follow up the median VRR was 93% (84–98). All the patients achieved a volume reduction of more than 50%, 94% of more than 70% and 56% of more than 90%. Twenty-four patients completed a year of follow-up, achieving a VRR of 97% (93–98). ConclusionsIn our experience US-PEIT has proven to be an effective, safe treatment of symptomatic thyroid cysts. For this reason it can be considered as the first line of treatment and included in the portfolio of services of a high-resolution consultation.

Long-term survival of 11\xa0years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report

We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd–Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.

Inclusión de la inyección percutánea de etanol como primera línea de tratamiento de los quistes tiroideos sintomáticos

BackgroundOur aim was to evaluate the efficacy and security of ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) for the treatment of recurrent symptomatic thyroid cysts in two high-resolution consultations of thyroid nodule in the Valencian Community. Patients and methodsThe study comprised thirty-three consecutive patients (51±12 years, 76% women) with symptomatic benign thyroid cysts relapsed after drainage and benign cytology prior to treatment. Through ultrasound, maximum cyst diameter and volume were determined, and the content of the cyst was drained. We then instilled between 2 and 4mL of ethanol (according to initial volume). We followed up with ultrasound at one, 3, 6 and 12 months and we calculated the total volume and the Volume Reduction Rate (VRR). We evaluated the perceived pain using a visual analog scale. ResultsThe initial median cyst volume was 11.6mL (8.5-16.5) A single session of US-PEIT was required in 22 patients (67%), two in 8 (24%) and three in 3 (9%). During PEIT, 49% of the patients experienced virtually no pain, 39% mild pain and 12% moderate pain. There were no complications. After 6 months of follow up the median VRR was 93% (84-98). All the patients achieved a volume reduction of more than 50%, 94% of more than 70% and 56% of more than 90%. Twenty-four patients completed a year of follow-up, achieving a VRR of 97% (93-98). ConclusionsIn our experience US-PEIT has proven to be an effective, safe treatment of symptomatic thyroid cysts. For this reason it can be considered as the first line of treatment and included in the portfolio of services of a high-resolution consultation.

Effect of Chinese herbal medicine for patients with benign thyroid nodules in adults: A protocol for systematic review and meta-analysis.

Background:Thyroid nodules (TN) are discrete lesions within the thyroid gland and are a common clinical problem detected in 19% to 68% of people. TN are more common as age increases and occur more frequently in women. TN can cause pressure symptoms, cosmetic complaints, and thyroid dysfunction. Treatment for benign thyroid nodules includes thyroid hormone therapy, surgery, radioiodine treatment, percutaneous ethanol injection therapy, and laser or radiofrequency treatment to shrink nodules. In China and many other countries, doctors use Chinese herbal medicines (CHM) to treat TN. However, systematic review and meta-analysis has not been found to assess the effects and safety of CHM in curing TN at present. Hence, the systematic review is conducted to scientifically and methodically evaluate the value of its effectiveness and safety of CHM on TN.Methods:Literatures related to CHM for TN from the establishment of the database to November 2020 will be retrieved from the following databases: PubMed, Excerpta Medica Database (EMBASE), MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform (ICTRP), Wanfang Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP). There are no language restrictions for retrieving literatures. Case reports, animal studies, editorials, expert opinions, reviews without original data, and studies on pediatric population were excluded. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in TN patients will be put in the study including nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data.Result:This study will provide high-quality available evidence for the treatment of TN with CHM based on nodule volume reduction ≥50%, pressure symptoms, cosmetic complaints, quality of life, and adverse events.Conclusion:The systematic review will to evaluate the efficacy of CHM in treating benign thyroid nodules in adults and provide evidence for clinicians.INPLASY registration number:INPLASY2020120093.

Efficacy of Radiofrequency ablation versus Percutaneous Ethanol Injection in Treating Small HCC Among Cirrhotic/bilharzial Patients

Background and study aim: The incidence of hepatocellular carcinoma (HCC) is rising worldwide being the fifth most common cancer and the third cause of cancer-related mortality. Early detection of HCC is associated with a better outcome. In Egypt and over the last decades, a remarkable rise of HCC was observed in the proportion of chronic liver disease patients. The aim of this study is to compare between Radiofrequency ablation (RF) & Percutaneous Ethanol Injection (PEI) in treating small HCC in cirrhotic /bilharzial patients. Patients and Methods: We divided patients into two groups; Group 1: (n=24) were HCC patients with small focal lesions treated by ethanol injection therapy using 99% sterile alcohol delivered in the lesion through a 21-gauge needle, amount of alcohol not exceeding 10ml every session. Group II: (n=24) were HCC patients with small focal lesions treated by radiofrequency ablation using Leveen Needle Electrode.patients were followed up at 1 and 3 months by abdominal ultrasoungraphy& triphasic CT to assess ablation status. Results: The 2 groups are comparable regarding their baseline. The incidence of HCC ablation by PEI is 87.5% while it was to 91.7% in the radiofrequency ablation group with no relapse after 3 months follow up. In both groups, this difference was not statistically significant. Conclusion: The Efficacy of PEI therapy is not inferior to percutaneous RF ablation in the treatment of small HCC lesions up to 2.5 cm in patients with mixed cirrhosis/bilharzial hepatic fibrosis.

Hepatocellular carcinoma recurrence with portal vein thrombosis and bile duct thrombosis 6 years after percutaneous ethanol injection therapy: A case report

Hepatocellular carcinoma recurrence with portal vein thrombosis and bile duct thrombosis 6 years after percutaneous ethanol injection therapy: A case report

Safe and effective percutaneous ethanol injection therapy of 200 thyroid cysts.

Ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) is a minimally invasive procedure that may be performed as an alternative to surgery for the treatment of recurrent symptomatic thyroid cysts for which simple aspiration failed. The present study aimed at assessing US-PEIT in a large cohort of patients, identifying factors influencing treatment outcome. Retrospective analysis of 193 patients with 200 thyroid cysts who underwent US-PEIT in 2004-2018. The initial median cyst volume was 8.5 mL [5.5-16.0]; median final volume at 12 months after the completion of therapy was 0.5 mL [0.2-1.3]. A Volume Reduction Rate (VRR) of 95.0% [86.7-98.0] was achieved. For successful US-PEIT, relatively small total amount of ethanol was needed, on average corresponding to 20.0% [16.7-28.6] of the initial cyst volume. VRR positively correlated with the initial cyst volume and negatively with the presence of complex cyst. Multiple regression analysis showed the presence of complex cyst as an independent predictor of treatment efficacy. US-PEIT of thyroid cysts of all sizes was very successful with using total amounts of ethanol, corresponding to ≈20% of the initial cyst volume.

Effectiveness of Percutaneous Ethanol Injection Therapy Compared to Parathyroidectomy in the Management of Secondary and Tertiary Hyperparathyroidism

Background: Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are a common complication of chronic renal failure. Percutaneous ethanol injection therapy (PEIT) has been used as alternative to surgery, but its effectiveness is inconsistent. Objectives: The objective of the study is to evaluate the effectiveness of PEIT in the management of patients with SHPT and THPT. Materials and Methods: Ninety-one patients with chronic renal failure and SHPT or THPT were treated with PEIT (n = 55) and surgery (n = 36) between January 2006 and July 2015. The medical records, imaging studies, and ablation techniques were reviewed to assess the efficacy of each treatment modality and complications. Results: Parathyroid hormone (PTH) level after treatment &lt;160 pg/mL was used to indicate success of treatment. PEIT showed lower effectiveness compared to surgery (1.8% vs. 61.1%). There was no complication in PEIT group. Symptomatic hypocalcemia was found 11.1% in surgery group. Conclusion: PEIT in treatment of secondary and THPT was much less effective than surgery due to large nodule sizes, high levels of PTH, and multiple parathyroid nodules.

Image-guided, minimally invasive surgery and other local therapeutic procedures for primary liver tumors

The incidence of primary liver tumors is rising. Modern minimally invasive, image-guided procedures offer apotentially curative therapy option. The aim of this study was to evaluate the multitude of image-guided minimally invasive procedures concerning their evidence-based effect on local tumor control and overall survival. Asystematic search of MEDLINE focused on hepatocellular cancer, minimally invasive treatment, local ablative therapy, therapeutic stratification and comparative studies was performed. The level of evidence varied greatly depending on the procedure used. The highest quality evidence including prospective randomized studies was found for radiofrequency ablation (RFA) of hepatocellular cancer. The RFA is superior with respect to local tumor control and overall survival in comparison to other ablative procedures. Prospective randomized studies comparing surgery and RFA showed diverging and contradictory results. Microwave ablation and robotic stereotactic irradiation showed sufficient potential in retrospective studies in comparison to RFA and surgery in order to confirm the techniques in randomized studies. There is only anecdotal evidence concerning high intensity focused ultrasound (HIFU) and irreversible electroporation. Percutaneous ethanol injection(PEI), cryoablation and laser-induced thermal therapy (LITT) were inferior techniques to RFA in most studies. Minimally invasive resection and local ablative therapies based on structured imaging and image reporting can improve the prognosis of patients with hepatocellular cancer even in patients that exceed the BCLC0/A stage.

Simultánní sklerotizace dvou cyst štítné žlázy absolutním alkoholem

Simultánní sklerotizace dvou cyst štítné žlázy absolutním alkoholem

Effective combination therapy of percutaneous ethanol injection and chemotherapy based on injectable low molecular weight gels

Percutaneous ethanol injection (PEI) therapy was used in liver cancer treatment, however, the therapeutic ethanol in PEI easily flew away from injected solid tumours and hinder the treatment effect. In this paper, injectable supramolecular gels formed by self-assembly of low molecular weight gelators (LMWGs) based on glycylglycine modified phenylboronic acid were prepared to localize ethanol and load chemotherapeutic drug for in situ synergistic therapy. The mechanism, morphology and rheological property of supramolecular gels were characterized by NMR, UV, SEM, etc. The rheological study revealed that the gels were formed in situ rapidly and recovered promptly once damaged. The gels were non-toxicity to both normal 3T3 fibroblasts cells and 4T1 breast cancer cells. Doxorubicin (DOX) hydrochloride and ethanol were encapsulated in the gels for the combination of chemotherapy and PEI therapy. The in vivo anticancer activity of the DOX-loaded gels was carried out in tumour bearing mice. The injected gels were coated around tumour tissues to lock ethanol, and DOX was released sustainingly from the gels to maintain effective concentration to induce the apoptosis of tumour cells. DOX-loaded gels and the ethanol exhibited excellent therapeutic efficacy and low side effects in local cancer therapy.

Long-term outcomes of ethanol injection therapy for locally recurrent papillary thyroid cancer.

The standard treatment regimen for locally recurrent lesions is total thyroidectomy, or complete removal of the recurrent thyroid lesion within the thyroid bed. However, reoperation increases the risk of complications and patients have to undergo general anesthesia. Percutaneous ethanol injection therapy represents a far less invasive procedure without general anesthesia and with lower risk of complications. Thirty-four patients who received PEIT at Yonsei University Medical Center between October 2002 and August 2009 for recurrent cervical nodal metastases of differentiated papillary thyroid cancer were included in this retrospective study. During a minimum follow-up of 60months, treatment outcomes were determined by measuring the lesion size prior to the first injection and 3months after the last injection. A total of 46 recurrent lesions were detected in 34 patients. Five patients underwent surgery and PEIT was administered to the remaining 19 and 22 lesions in the central compartment and lateral neck lymph nodes, respectively. Size increases were observed in seven (17.1%) lesions, whereas no changes in size and decreases were detected in 10 (24.4%) and 24 (58.5%) lesions. Patients with increased lymph nodes were significantly older (65.3±14.4 vs. 48.2±16.3years; p=0.02) and had smaller sizes (9.3±1.0 vs. 12.3±6.4mm; p=0.012). Although reoperation remains the first-line treatment for recurrent thyroid cancer, PEIT may be considered as a treatment option in selected patients with lesions larger than 1cm who are ineligible for surgery or have refused reoperation.

Proton Beam Therapy for Hepatocellular Carcinoma: A Review of the University of Tsukuba Experience.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Many treatment modalities were developed for HCC, including surgical resection, percutaneous ethanol injection, radiofrequency ablation, transarterial chemoembolization, liver transplantation, and sorafenib therapy. Our institution has shown that proton beam therapy (PBT) is also a safe, effective, and feasible treatment modality for HCC. The University of Tsukuba began to use PBT for HCC in 1983, and we have reported many findings during the past 3 decades. In this review, we will describe the history of PBT, our experience of using PBT for HCC, and its application based on tumor location, thrombosis, tumor size, and liver function.