Peripheral Bile Duct Research Articles

Efficacy of a Novel Dual-Layer Plastic Stents for Malignant Biliary Obstruction

Objectives: In hepatopancreatic diseases, stenting is widely employed to manage cholangitis and obstructive jaundice. Stent materials are primarily categorized as plastic or metal. Plastic stents have notable advantages, such as reduced likelihood of peripheral bile duct obstruction, a lower cost, and the ease of replacement compared to metallic stents. However, their patency period is shorter due to narrower diameters. Plastic stents are typically composed of materials like polyurethane or polyethylene. To improve patency, new dual-layer stents combine polyurethane with polytetrafluoroethylene (PTFE). PTFE, used in the inner layer, is expected to prevent biofilm formation. This study aimed to assess the clinical efficacy of this dual-layer stent. Methods: A retrospective analysis was performed on 48 cases (Group R) using REGULUS® from November 2022 to November 2023 and 30 cases (Group IS) using inside-type plastic stents from January 2020 to November 2023 for malignant hilar and intrahepatic bile duct obstructions. Stent patency and clinical outcomes were compared between the groups. Results: There was no significant difference in the recurrent biliary obstruction (RBO) rate between the groups (p = 0.644). The time to recurrent biliary obstruction (TRBO) was 74 days in Group R and 118 days in Group IS, with no significant difference (p = 0.219). Conclusions: The dual-layer stent placed across the papilla demonstrated comparable clinical outcomes to inside-type stents. The PTFE inner layer likely reduces biofilm formation, enhancing patency. Across-the-papilla placement may facilitate reinterventions in challenging cases, broadening stent options.

Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review

Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous bile duct adenocarcinoma with a rising global incidence and a poor prognosis. This review aims to present a comprehensive overview of the most recent radiological research on iCCA, focusing on its histopathologic subclassification and the use of imaging findings to predict prognosis and inform treatment decisions. Histologically, iCCA is subclassified into small duct (SD-iCCA) and large duct (LD-iCCA) types. SD-iCCA typically arises in the peripheral small bile ducts and is often associated with chronic hepatitis or cirrhosis. It presents as a mass-forming lesion with a relatively favorable prognosis. LD-iCCA originates near the hepatic hilum, is linked to chronic bile duct diseases, and exhibits more aggressive behavior and poorer outcomes. Imaging is essential for differentiating these subtypes and assessing prognostic factors like tumor size, multiplicity, vascular invasion, lymph node metastasis, enhancement patterns, and intratumoral fibrosis. Imaging-based prognostic models have demonstrated predictive accuracy comparable to traditional pathological staging systems. Furthermore, imaging findings are instrumental in guiding treatment decisions, including those regarding surgical planning, lymphadenectomy, neoadjuvant therapy, and the selection of targeted therapies based on molecular profiling. Advancements in radiological research have improved our understanding of iCCA heterogeneity, facilitating prognosis prediction and treatment personalization. Imaging findings assist in subclassifying iCCA, predicting outcomes, and informing treatment decisions, thus optimizing patient management. Incorporating imaging-based approaches into clinical practice is crucial for advancing personalized medicine in the treatment of iCCA. However, further high-level evidence from international multicenter prospective studies is required to validate these findings and increase their clinical applicability.

Kinase library screening identifies IGF-1R as an oncogenic vulnerability in intrahepatic cholangiocarcinoma stem-like cells

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer of the peripheral bile ducts and is recognized by the abundance of cancer stem-like cells (CSCs) within the tumor mass. While CSC markers in iCCA are well-defined, the molecular vulnerabilities of this subpopulation remain elusive. The 96-well, three dimensional (3D) tumorsphere culture was adapted from a well-established CSC model, validated for CSC markers through gene expression analysis. Kinase library screening was then conducted to reveal potential oncogenic vulnerable pathways. RNA interference was utilized to stably silence the candidate gene in three iCCA cell lines and its impact on iCCA cell proliferation and tumorsphere formation efficiency (TFE) was evaluated. Kinase inhibitor library screening identified the top 50 kinase inhibitors crucial for tumorsphere viability, with 11 inhibitors targeting the IGF-1R/PI3K/AKT axis. Further dose-dependent analysis of the top 'hit' inhibitors confirmed IGF-1R as the candidate molecule. Upon stably silencing of IGF-1R, all three iCCA cell lines exhibited decreased AKT activation, impeded proliferation and reduced TFE, indicating a decline in CSC subpopulations. IGF-1R plays a critical role in maintaining iCCA-stem like cell populations. Our data highlight the potential utility of IGF-1R as a prognostic marker of iCCA and a therapeutic target for eliminating its CSC subpopulation.

Parenchyma Sparing Anatomic Liver Resections (Bi- and Uni-Segmentectomies) for Liver Tumours in Children-A Single-Centre Experience.

This study included 23 patients that underwent (bi)segmentectomy. There were 15 malignant tumours (hepatoblastoma-13 patients), 7 benign tumours, and 1 calcifying nested stromal epithelial tumour. The median tumour diameter was 52 mm (range 15-170 mm). Bisegmentectomy 2-3 was most frequently performed (seven patients), followed by bisegmentectomy 5-6 (four patients). The median operative time was 225 min (range 95-643 min). Intraoperative complications occurred in two patients-small bowel perforation in one and an injury of the small peripheral bile duct resulting in biloma in the other. The median resection margin in patients with hepatoblastoma was 3 mm (range 1-15 mm). Microscopically negative margin status was achieved in 12 out of 13 patients. There were two recurrences. After a median follow-up time of 38 months (range 12-144 months), all 13 patients with HB were alive with no evidence of disease. Two relapsed patients were alive with no evidence of disease. From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in carefully selected paediatric patients and is sufficient to achieve a cure. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome should be conducted with a larger dataset.

Association of Cholangiocarcinoma among People with Periductal Fibrosis.

Cholangiocarcinoma (CCA) is a highly fatal tumor, and the most favorable chance for long-term survival lies in curative resection. Periductal fibrosis (PDF), a precancerous condition associated with chronic inflammation of the bile ducts, can serve as a screening marker for CCA using hepatobiliary ultrasonography (US). However, limited studies have explored the relationship between PDF and CCA. This study aimed to investigate the association between PDF and CCA in a population at risk in Northeast Thailand. The study included participants enrolled in the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 and 2021 who underwent US. Histological evaluations were conducted following the standard protocol of the tertiary hospital at Khon Kaen University, Thailand. PDF was defined as the presence of fibrosis in the peripheral (PDF1), segmental (PDF2), or main bile duct (PDF3), diagnosed by well-trained general practitioners or radiologists. The association between PDF and CCA was assessed using multiple logistic regression, calculating adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Out of 751,061 participants, the overall prevalence of PDF was 115,267 (15.35%), with an overall CCA rate of 0.11%. The rates of CCA were 0.1%, 0.15%, and 0.27% in participants with PDF1, PDF2, and PDF3, respectively. After adjusting for gender, age at enrollment, education levels, history of O. viverrini infection, smoking, and alcohol consumption, the AORs for CCA were 0.94 (95% CI: 0.74 - 1.20), 1.4 (95% CI: 1.03 - 1.91), and 2.52 (95% CI: 1.38 - 4.58) for participants with PDF1, PDF2, and PDF3, respectively. Our findings demonstrate a significant association between fibrosis of the segmental and main bile ducts (PDF2 and PDF3) and CCA, with the strongest association observed in participants with PDF3. Hepatobiliary US screening could serve as a valuable tool for early detection of CCA, enabling timely curative treatment.

Spatially segregated defects and IGF1-responsiveness of hilar and peripheral biliary organoids from a model of Alagille syndrome.

Alagille syndrome (ALGS) manifests with peripheral intrahepatic bile duct (IHBD) paucity, which can spontaneously resolve. In a model for ALGS, Jag1Ndr/Ndr mice, this occurs with distinct architectural mechanisms in hilar and peripheral IHBDs. Here, we investigated region-specific IHBD characteristics and addressed whether IGF1, a cholangiocyte mitogen that is downregulated in ALGS and in Jag1Ndr/Ndr mice, can improve biliary outcomes. Intrahepatic cholangiocyte organoids (ICOs) were derived from hilar and peripheral adult Jag1+/+ and Jag1Ndr/Ndr livers (hICOs and pICOs, respectively). ICOs were grown in Matrigel or microwell arrays, and characterized using bulk RNA sequencing, immunofluorescence, and high throughput analyses of nuclear sizes. ICOs were treated with IGF1, followed by analyses of growth, proliferation, and death. CellProfiler and Python scripts were custom written for image analyses. Key results were validated invivo by immunostaining. Cell growth assays and transcriptomics demonstrated that Jag1Ndr/Ndr ICOs were less proliferative than Jag1+/+ ICOs. IGF1 specifically rescued survival and growth of Jag1Ndr/Ndr pICOs. Jag1Ndr/Ndr hICOs were the least proliferative, with lower Notch signalling and an enrichment of hepatocyte signatures and IGF uptake/transport pathways. Invitro (Jag1Ndr/Ndr hICOs) and invivo (Jag1Ndr/Ndr hilar portal tracts) analyses revealed ectopic HNF4a+ hepatocytes. Hilar and peripheral Jag1Ndr/Ndr ICOs exhibit differences in Notch signalling status, proliferation, and cholangiocyte commitment which may result in cholangiocyte-to-hepatocyte transdifferentiation. While Jag1Ndr/Ndr pICOs can be rescued by IGF1, hICOs are unresponsive, perhaps due to their hepatocyte-like state and/or expression of IGF transport components. IGF1 represents a potential therapeutic for peripheral bile ducts.

Nightmare of straight-type plastic stent migration into the peripheral bile duct: what is my savior?

Nightmare of straight-type plastic stent migration into the peripheral bile duct: what is my savior?

Endoscopic retrieval of a sheared guidewire remnant with microbiopsy forceps from a peripheral intrahepatic bile duct.

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Changing survival of intrahepatic cholangiocarcinoma based on Surveillance, Epidemiology, and End Results Database (2000–2018).

e16182 Background: Intrahepatic cholangiocarcinoma (iCCA) is a primary hepatic malignancy arising from peripheral intrahepatic bile ducts with poor survival and increasing incidence. Treatment regimen has changed in the last two decades, whereas new molecular targeted therapies have emerged. The present study aims to characterize changes in treatment outcomes of iCCA using a national representative database. Methods: Data were retrieved from the Surveillance, Epidemiology and End Results (SEER) 18 Research Plus Database. Overall survival (OS) was analyzed based on age, gender, race, histological grade, stage, and treatment. Predictors of OS were evaluated by Cox regression models. Statistical analysis was performed with Stata 15.1 (STATA Corp., College Station, TX, USA). Results: The overall observed OS from 2000 to 2018 at 12, 36, and 60 months were 42.6%, 16.4%, and 10.2%, respectively. The median survival time (MST) increased from 6 to 11 months from 2000-2004 time period to 2015-2018 (p < 0.0001). Such an improved trend was observed in all stage groups (p < 0.0001). Among patients diagnosed after 2015, the 12, 24, and 36 month OS were 45.9%, 26.4% and 17.4 %, respectively; the MST were 25, 13, and 6 months for patients with localized (12-month OS: 72.7%; 36-month OS: 37.5% ), regional (12-month OS: 51.4%; 36-month OS: 18.9%), and distant diseases(12-month OS: 28.2%; 36-month OS: 4.5%), respectively (p < 0.0001). On multivariable analysis, older age, female, grade, stage, whether surgery, chemotherapy or radiotherapy was performed were statistically significant predictors of OS (p < 0.001). Conclusions: Survival outcomes of iCCA improved in the last twenty years in all cancer stages. Age, gender, grade, stage, and whether interventions were performed were prognostic factors.

Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need.

Cholangiocarcinoma is a highly aggressive cancer of the biliary tract epithelium. This form of cancer is prevalent in Asia, and recent reports show that its incidence is relatively rare but increasing in the United States. Although risk factors for cholangiocarcinoma have yet to be elucidated, a growing body of literature suggests chronic infection of genetically susceptible individuals with the food-borne zoonotic trematodes Clonorchis sinensis (C sinensis) and Opisthorchis viverrini (O viverrini) may play a role. Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for almost 30 years. During this period, the trematodes' feeding activities and their excretory-secretory products may damage the bile duct epithelium and promote local inflammation. These pathological processes could then provoke epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to the initiation and progression of cholangiocarcinoma in genetically susceptible people. The International Agency for Research on Cancer has determined that there is sufficient evidence in humans for the carcinogenicity of chronic infections with C sinensis and O viverrini. Timely serodiagnosis of indolent C sinensis and O viverrini infections is important as these parasites may be a risk factor for cholangiocarcinoma in veterans who served in Vietnam. About 774,000 living Americans served in Vietnam and there is an urgent need to develop sensitive and specific serologic assays to detect both acute and indolent infections. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival.

Abstract 5806: Kinase library screening identifies IGF-1R/PI3K/AKT axis as a crucial pathway for survival of intrahepatic cholangiocarcinoma cells with stemness characteristics

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a subtype of biliary malignancy that arises along the peripheral bile duct epithelium. Given its limited and inefficacious treatment options, the mortality rate of iCCA remains high and thus a novel therapeutic strategy is urgently needed. The concept of cancer stem cells (CSCs) explains a subpopulation of cancer cells that possesses self-renewal and differentiation capacities. These CSCs become the culprit for cancer metastasis, cancer recurrence and chemotherapeutic resistance, making them promising targets for cancer treatment. The propose of this study is to identify the signaling pathways crucial for the survival of iCCA with stemness characteristics. Gene expression analysis on a dataset of Thai iCCA patients (n=91) showed that iCCA tumors are enriched in the Adult Stem Cell (ASC) signature which are the shared characteristics among the epithelial-derived cancer with stemness characteristics. Although iCCA cells exhibit some degree of enrichment in stem cells markers when compared with cholangiocyte cells, further upregulation of stem cell-related genes, e.g. Nanog, Oct3/4, Sox2, and Sox9, were found in iCCA cells grown as 3D tumorspheres. A kinase inhibitor screening library was then performed on iCCA tumorspheres. Our initial screening demonstrated that 11 out of the top 50 kinase inhibitors that effectively decrease viability of iCCA tumorspheres belongs to the insulin-like growth factor-1 receptor (IGF-1R)/phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB/AKT) axis. Additionally, these inhibitors increase cell apoptosis, judged by the caspase 3/7 activity, within iCCA tumorspheres. Conversely, IGF-1 treatment which is sufficient to induce activation of IGF-1R and AKT also enhances cell viability and decrease cell apoptosis in iCCA. Taken together, our data demonstrate that IGF-1R/PI3K/AKT axis is crucial for survival of iCCA cells with stemness characteristics and this pathway could be a potential therapeutic target in iCCA. Citation Format: Chotirat Rattanasinchai, Chidchanok Chornkrathok, Donlaporn Sriphan, Panida Navasumrit, Mathuros Ruchirawat. Kinase library screening identifies IGF-1R/PI3K/AKT axis as a crucial pathway for survival of intrahepatic cholangiocarcinoma cells with stemness characteristics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5806.

Tips and Techniques for Traversing the Impassable Biliary Stricture

AbstractBiliary obstruction is a common indication for referral to interventional radiology, particularly when endoscopic retrograde cholangiopancreatography has failed or is not possible due to postsurgical anatomy. The standard approach to percutaneous transhepatic biliary drainage involves gaining needle access to a peripheral bile duct, followed by advancement of a guidewire and drainage catheter across the obstruction and into bowel to allow internal drainage. While most cases of biliary obstruction are managed successfully with this conventional approach, in some situations it is not possible to traverse the occlusion with a guidewire and catheter, and thus advanced techniques may be required. This article has reviewed the available strategies for managing the impassable biliary obstruction.

Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I—integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer.

Outcomes and management of delayed complication after severe blunt liver injury

BackgroundThe treatment of delayed complications after liver trauma such as bile leakage (BL) and hepatic artery pseudoaneurysms (HAPs) is difficult. The purpose of this study is to investigate the outcomes and management of post-traumatic BL and HAPs.MethodsWe retrospectively evaluated patients diagnosed with blunt liver injury, graded by the American Association for the Surgery of Trauma Liver Injury Scale, who were admitted to our hospital between April 2010 and December 2019. Patient characteristics and treatments were analyzed.ResultsA total of 176 patients with blunt liver injury were evaluated. Patients were diagnosed with grade I–II liver injury (n = 127) and with grade III-V injury (n = 49). BL was not observed in patients with grade I–II injury. Eight patients with grade III-V injury developed BL: surgical intervention was not needed for six patients with peripheral bile duct injury, but hepaticojejunostomy was needed for two patients with central bile duct injury. Out of 10 patients with HAPs, only three with grade I–II injury and one with grade III–V were treated conservatively; the rest six with grade III-V injury required transcatheter arterial embolization (TAE). All pseudoaneurysms disappeared.ConclusionsSevere blunt liver injury causing peripheral bile duct injury can be treated conservatively. In contrast, the central bile duct injury requires surgical treatment. HAPs with grade I–II injury might disappear spontaneously. HAPs with grade III–V injury should be considered TAE.

Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats.

We revealed the therapy effect of the stable gastric pentadecapeptide BPC 157 (10 μg/kg, 10 ng/kg ig or po) with specific activation of the collateral rescuing pathways, the azygos vein, on bile duct ligation in particular, and acute pancreatitis as local disturbances (i.e., improved gross and microscopy presentation, decreased amylase level). Additionally, we revealed the therapy’s effect on the acute pancreatitis as vascular failure and multiorgan failure, both peripherally and centrally following “occlusion-like” syndrome, major intoxication (alcohol, lithium), maintained severe intra-abdominal hypertension, and myocardial infarction, or occlusion syndrome, and major vessel occlusion. The application-sacrifice periods were ligation times of 0–30 min, 0–5 h, 0–24 h (cured periods, early regimen) and 4.30 h–5 h, 5 h–24 h (cured periods, delayed regimen). Otherwise, bile duct-ligated rats commonly presented intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, gross brain swelling, hemorrhage and lesions, heart dysfunction, lung lesions, liver and kidney failure, gastrointestinal lesions, and severe arterial and venous thrombosis, peripherally and centrally. Unless antagonized with the key effect of BPC 157 regimens, reversal of the inferior caval and superior mesenteric vein congestion and reversal of the failed azygos vein activated azygos vein-recruited direct delivery to rescue the inferior-superior caval vein pathway; these were all antecedent to acute pancreatitis major lesions (i.e., acinar, fat necrosis, hemorrhage). These lesions appeared in the later period, but were markedly attenuated/eliminated (i.e., hemorrhage) in BPC 157-treated rats. To summarize, while the innate vicious cycle may be peripheral (bile duct ligation), or central (rapidly developed brain disturbances), or peripheral and central, BPC 157 resolved acute pancreatitis and its adjacent syndrome.

The "zipline" technique for double-balloon enteroscopy-assisted removal of a migrated stent in a peripheral bile duct.

The "zipline" technique for double-balloon enteroscopy-assisted removal of a migrated stent in a peripheral bile duct.

The Auxiliary Diagnosis and Imaging Characteristics of MRI Combined with CT in Patients with Cholangiocarcinoma.

Background Patients with cholangiocarcinoma (CCA) have poor prognosis and high mortality. Therefore, early detection and early diagnosis are extremely important to control the development of CCA. This study aims to explore the diagnostic effect in patients with CCA and imaging characteristics of MRI combined with CT. Methods 109 patients with suspected CCA underwent CT and MRI before diagnosis. The examination results were compared with the “gold standard.” ROC curve was drawn to analyze the diagnostic efficacy of MRI combined with CT for CCA patients. Results The diagnosis rate of suspected CCA patients was 95.41%. The diagnostic coincidence rate of CT and MRI examination was 89.42% and 92.31%, respectively. The diagnostic coincidence rate of MRI combined with CT examination was 100.00%. The number of CT delayed enhancement, peripheral bile duct dilatation, and hepatic capsular depression were more than those of MRI. The number of circular enhancement cases in the CT group was less than that in the MRI group. ROC curve results showed that the sensitivity and specificity of MRI combined with CT for the diagnosis of CCA patients were higher than those of MRI or CT alone. Conclusion MRI combined with CT has high diagnostic sensitivity and specificity and can provide imaging evidence for the clinical diagnosis and treatment of CCA.

Percutaneous Transhepatic Treatment for Obstructing Retained Surgical Biliary Stents After Pediatric Liver Transplantation Without Placement of Biliary Drain

Percutaneous Transhepatic Treatment for Obstructing Retained Surgical Biliary Stents After Pediatric Liver Transplantation Without Placement of Biliary Drain

DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome.

Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.

Two elder cases of hepatocellular carcinoma adjacent to intrahepatic vessels successfully treated by carbon ion radiotherapy

The treatment for hepatocellular carcinoma (HCC) adjacent to the portal vein and/or bile duct requires considerable caution to avoid the complications, such as hepatic infarction and obstructive jaundice. Carbon ion radiotherapy (CIRT) has been attempted for HCC and has become accepted as a promising modality for minimizing hepatic damage with good local tumor control. We experienced two elder cases of HCC adjacent to intrahepatic vessels successfully treated by CIRT. Case 1, a 75-year-old man, was treated by CIRT for a 2-cm HCC near the porta hepatis adjacent to the right first portal branch. The treatment was sufficiently effective, and no vascular damage was demonstrated after CIRT. The liver function transiently deteriorated after CIRT, but recovered quickly. Alpha-fetoprotein transiently increased after the treatment and decreased thereafter. Tumor stain persisted for 3 months after CIRT, so a liver tumor biopsy was performed. However, no viable carcinoma cells were detected. There was no local recurrence or complications for 17months. Case 2, 76-year-old male HCC patient, showed dilation of the peripheral bile duct in the left lobe, suggesting tumor invasion to the duct. The tumor was hypovascular and was found to be well-differentiated HCC by a tumor biopsy. He was treated with CIRT, because he had a history of cerebral infarction and was being administered an antiplatelet agent daily. He achieved complete remission, and no adverse events were observed after the treatment for 3 years.