Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Effect of microwave ablation treatment of hepatic malignancies on serum cytokine levels.

BACKGROUND: Microwave ablation (MWA) is widely used to treat unresectable primary and secondary malignancies of the liver, and a limited number of studies indicate that ablation can cause not only necrosis at the in situ site but also an immunoreaction of the whole body. This study aimed to investigate the effects of MWA on cytokines in patients who underwent MWA for a hepatic malignancy. METHODS: Patients admitted to the Oncology Department in the First Affiliated Hospital of Soochow University between June 2015 and February 2019 were selected. Peripheral blood was collected from patients with a hepatic malignancy treated with MWA. The levels of cytokines (IL-2, IFN-γ, TNF-α, IL-12 p40, IL-12 p70, IL-4, IL-6, IL-8, IL-10, and vascular endothelial growth factor (VEGF)) were detected with a Milliplex® MAP Kit. The comparison times were as follows: before ablation, 24 h after ablation, 15 days after ablation, and 30 days after ablation. Data were analyzed using a paired sample t-tests and Spearman's correlation analysis. RESULTS: A total of 43 patients with hepatic malignancies were assessed. There were significant differences in IL-2, IL-12 p40, IL-12 p70, IL-1ß, IL-8, and TNF-α at 24 h after MWA. Significant increases (> 2-fold vs. before ablation) were observed in IL-2, IL-1ß, IL-6, IL-8, IL-10, and TNF-α after MWA. Elevated IL-2 and IL-6 levels after ablation were positively correlated with energy output during the MWA procedure. CONCLUSIONS: WA treatment for hepatic malignancies can alter the serum levels of several cytokines such as IL-2 and IL-6.

Microwave ablation of the liver in a live porcine model: the impact of power, time and total energy on ablation zone size and shape.

Objective: To explore various microwave (MW) time/power combinations to achieve maximum single-probe system performance in a live pig liver model.Methods: Fifty-one microwave ablations performed in 12 female pigs using the following time/power combinations: 65 W for 10 min (65W 10MIN), ramped from 20 to 65 W (RAMPED), 95 W pulses with cooling periods (95W PULSED), 40 W for 16 min 15 s (LOW POWER), 1 min 95 W pulse then 8 min 65 W then a second 1 min 95 W pulse (BOOKEND 95W) and 65 W for 15 min (65W 15MIN). Temperatures 1.5 cm from the antenna were measured. Livers were excised, and ablations were measured and compared.Results: At fixed overall energy, LOW POWER produced ablation zones with the smallest volume compared to 65W 10MIN, RAMPED and 95W PULSED. At a fixed time of 10-min, BOOKEND 95W protocol achieved wider and larger ablation zones than 65W 10MIN (p = 0.038, p = 0.008) and 95W PULSED (p = 0.049, p = 0.004). The 65W 15MIN combination had significantly larger diameters (p = 0.026), larger lengths (p = 0.014) and larger volumes (p = 0.005) versus 65W 10MIN. Maximum temperatures were highest with BOOKEND 95W (62.9 °C) and 65 W 15 MIN (63.0 °C) and lowest with LOW POWER (45.9 °C), p = 0.009.Conclusions: Low power ablations, even if controlled for total energy delivery, create small ablation zones. High peak powers are associated with larger ablation zones and high margin temperatures if cooling pauses are avoided. Ramping and pulsing protocols with interleaved cooling appear to be of no benefit versus continuous 65 W for creating large ablation zones.

Ex vivo liver resection coupled with associated liver partition and portal vein ligation: Combining existing techniques to achieve surgical resectability.

Incorporation of liver transplant techniques in hepatopancreaticobiliary surgery has created an opportunity for the resection of locally advanced hepatic tumors formerly considered unresectable. A 73-year-old woman presented with cholangiocarcinoma involving inferior vena cava, all three hepatic veins, and right anterior portal pedicle, initially deemed nonoperative. This case demonstrates the first combined application of associating liver partition and portal vein ligation for staged hepatectomy and ex vivo resection to perform an R0. For diseases dependent upon resection, surgical advances and innovations expand the spectrum of interventions through interdisciplinary techniques.

Semi-automated computed tomography Volumetry can predict hemihepatectomy specimens' volumes in patients with hepatic malignancy.

BACKGROUND: One of the major causes of perioperative mortality of patients undergoing major hepatic resections is post-hepatectomy liver failure (PHLF). For preoperative appraisal of the risk of PHLF it is important to accurately predict resectate volume and future liver remnant volume (FLRV). The objective of our study is to prospectively evaluate the accuracy of hemihepatectomy resectate volumes that are determined by computed tomography volumetry (CTV) when compared with intraoperatively measured volumes and weights as gold standard in patients undergoing hemihepatectomy. METHODS: Twenty four patients (13 women, 11 men) scheduled for hemihepatectomy due to histologically proven primary or secondary hepatic malignancies were included in our study. CTV was performed using a semi-automated module (S, hereinafter) (syngo.CT Liver Analysis VA30, Siemens Healthcare, Germany). Conversion factors between CT volumes on the one side and intraoperative volumes and weights on the other side were calculated using the method of least squares. Absolute and relative disagreements between CT volumes and intraoperative volumes were determined. RESULTS: A conversion factor of c = 0.906 most precisely predicted intraoperative volumes of exsanguinated hemihepatectomy specimens from CT volumes in all patients with mean absolute and relative disagreements between CT volumes and intraoperative volumes of 57 ml and 6.3%. The use of operation-specific conversion factors yielded even better results. CONCLUSIONS: CTV performed with S accurately predicts intraoperative volumes of hemihepatectomy specimens when applying conversion factors which compensate for exsanguination. This allows to precisely estimate the FLRV and thus minimize the risk of PHLF in patients undergoing major hepatic resections.

Metastatic cholangiocarcinoma in a patient with undiagnosed Wilson disease.

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. Although the frequency of malignancy is generally increased in chronic liver disease, CC rarely presents in Wilson disease (WD). The incidence of hepatic malignancy in WD is only 1.2%, with CC accounting for 0.5%. A 66 year old male with history of hypertension, diabetes, and compensated cryptogenic cirrhosis presented with acute onset dyspnea and pleuritic chest pain. He was incidentally found to have a sizeable mass in the right hepatic lobe. Ultimately, a liver biopsy revealed dense demoplasia and increased mucin production, consistent with diagnosis of CC. Biopsy also demonstrated increased copper deposition consistent with WD, explaining the patient's underlying cirrhosis. Unlike other forms of chronic liver disease where incidence of liver cancer is increased, the lower rate of malignancy seen in WD may be explained by a protective effect of copper in WD. Copper acts to both directly stabilize DNA and inhibit angiogenesis. In this case, it is possible that the degree of copper deposition in his liver was mild, causing cirrhosis and the chronic liver inflammation that caused his CC. However, it may not have been sufficient to "protect" against development of CC.

Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy.

The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. The most prominent finding was an immediate and significant (p < 0.05) decrease of lymphocyte proliferation and interferon-γ production directly after therapy which lasted until day 28 and was stronger upon stimulation with microbial antigens than with mitogens. Moreover, lymphopenia was revealed, affecting all lymphocyte subsets (CD3+, CD4+, CD8+ T cells, CD4+ CD8+ T cells, B cells and NK cells). SIRT led to a reduction in the percentage of activated HLA-DR+ monocytes and of CD45R0+ memory T cells. Higher radiation activity, the presence of liver cirrhosis, chronic kidney disease, diabetes mellitus and metastases were unfavorable factors for immunocompetence, while a better Eastern Cooperative Oncology Group performance status was associated with stronger immunological reactions. In conclusion, SIRT leads to severe impairment of cellular in vitro immune responses. Further studies are needed to assess a potential clinical impact.

Recurrence patterns following irreversible electroporation for hepatic malignancies.

BACKGROUND: Irreversible electroporation (IRE) has emerged as a novel, safe ablative therapy for peri-vascular lesions. However, there remains a paucity of data on long-term outcomes. METHODS: We identified patients who underwent open IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local ablation-zone recurrence (LR) was determined by cross-sectional imaging. Cumulative incidence (CumI) of LR was calculated and a competing risks regression assessed factors associated with LR. RESULTS: Forty patients had 77 lesions treated. The majority of lesions were of colorectal origin (74%). Median tumor size was 1.3 cm (range 0.5-6). Most patients (86%) had prior systemic therapy and 29% received systemic therapy following IRE. With a median follow-up of 25.7 months (range 4.5-58.8 months), 10 lesions in 9 patients recurred locally (CumI: 13.4%, 95%CI: 7.8-22.2%). Median estimated time to LR was not reached and no LR occurred after 19 months. Factors significantly associated with LR included ablation zone size (HR 1.58; 95%CI 1.12-2.23; P = 0.0093) and body mass index (HR 1.21 95%CI 1.10-1.34; P = 0.0001). CONCLUSION: IRE LR rates were low after the treatment of well selected, small tumors. This technique is useful for lesions in anatomic locations precluding resection or thermal ablation.

Surgical resection of a malignant liver lesion: what the surgeon wants the radiologist to know.

OBJECTIVE: Hepatic malignancy is a common and lethal disease, whether due to a primary tumor or metastasis. There are numerous treatment options available depending on the stage of the disease and medical condition of the patient, including systemic chemotherapy, transcatheter embolization, thermal ablation, and surgical resection. In a subset of patients with liver malignancy, surgical resection can offer the best chance of long-term survival and potentially even cure. This article reviews the major indications and contraindications for resection, basic surgical techniques and terminology, key clinical and imaging preoperative workup, and pertinent interventional oncology procedures in the management of hepatic malignancy. CONCLUSION: Diagnostic and interventional radiology plays an important role in the assessment and treatment of malignant hepatic lesions. Radiologists should be familiar with how surgeons select, work up, and treat candidates for liver resection to provide the most clinically valuable service.

Survival disparities among racial groups with hepatic malignant tumors.

BACKGROUND: Investigating the impact of race on the clinicopathologic characteristics and prognosis of hepatic malignant tumors represents a complex and significant area of research. Notably, distinct differences exist among various racial groups in terms of the clinical manifestations, pathologic features, and prognosis of hepatic malignant tumors. AIM: To explore the effect of race on clinicopathologic features and prognosis of hepatic malignancies. METHODS: Data from patients with hepatic malignancies diagnosed between 2000 and 2019 were collected from the Surveillance, Epidemiology, and End Results database and statistically analyzed. RESULTS: This study included 123558 patients with hepatic malignant tumors, among whom 21078 (17.06%) were Asian, 14810 (11.99%) were Black, and 87670 (70.95%) were white. The median survival times for patients with hepatic malignant tumors of different races were 12.56, 7.70, and 9.35 months for Asian patients, Black patients, and white patients, respectively. The 3-year survival rates for Asian, Black, and white patients were 29%, 19%, and 21%, respectively, and the 5-year survival rates were 22%, 13%, and 15%, respectively. The Kruskal-Wallis test indicated a significant difference in the survival time of patients with hepatic malignant tumors between different races (P < 0.001). Univariate analysis revealed gender disparities in the prognosis among different ethnic groups (Asian: P > 0.05; Black: P < 0.001; White: P < 0.05). Among Black patients, the prognosis was less affected by the degree of hepatic fibrosis than among Asian patients and white patients (Black patients: P < 0.05; Asian patients: P < 0.001; White patients: P < 0.001). Significant differences were observed in the median survival time among patients with hepatic neuroendocrine tumors and hepatoblastomas during pathologic staging between races. Tumor number was inversely related to the prognosis. Cox regression analyses revealed that T stage, M stage, surgery, chemotherapy, alpha-fetoprotein, and tumor size independently influenced prognosis. Age was a specific independent prognostic factor for white patients. Among the tumor stages, N stage is a self-reliant prognostic element specific to white patients. Conversely, radiotherapy and liver fibrosis were not self-reliant prognostic factors for Black patients. Income alone did not independently influence the prognosis of Asian patients. CONCLUSION: The prognosis of hepatic malignant tumors is better among Asian patients than among Black patients. The prognosis of hepatic malignant tumors among white patients is affected by multiple factors, including age and N stage.

The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.

Current updates on the molecular and genetic signals as diagnostic and therapeutic targets for hepatitis B virus-associated hepatic malignancy.

Liver cancer caused by the hepatitis B virus (HBV) is the third most common cancer-related cause of death worldwide. Early detection of HBV-caused hepatic tumors increases the likelihood of a successful cure. Molecular and genetic signals are becoming more and more recognized as possible indicators of HBV-associated hepatic malignancy and of how well a treatment is working. As a result, we have discussed the current literature on molecular and genetic sensors, including extracellular vesicle microRNAs (EV-miRNAs), long non-coding circulating RNAs (lncRNAs), extracellular vesicles (EVs), and cell free circulating DNA (cfDNA), for the diagnosis and forecasting of HBV-related hepatic cancer. Extracellular vesicle microRNAs such as miR-335-5p, miR-172-5p, miR-1285-5p, miR-497-5p, miR-636, miR-187-5p, miR-223-3p, miR-21, miR-324-3p, miR-210-3p, miR-718, miR-122, miR-522, miR-0308-3p, and miR-375 are essential for the posttranscriptional regulation of oncogenes in hepatic cells as well as the epigenetic modulation of many internal and external signaling pathways in HBV-induced hepatic carcinogenesis. LncRNAs like lnc01977, HULC (highly up-regulated in liver cancer), MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), and HOTAIR (hox transcript antisense intergenic RNA) have been demonstrated to control hepatic-tumors cell growth, relocation, encroachment, and cell death resiliency. They are also becoming more and more involved in immune tracking, hepatic shifting, vasculature oversight, and genomic destabilization. EVs are critical mediators involved in multiple aspects of liver-tumors like angiogenesis, immunology, tumor formation, and the dissemination of malignant hepatocytes. Furthermore, cfDNA contributes to signals associated with tumors, including mutations and abnormal epigenetic changes during HBV-related hepatic tumorigenesis.

Hepatic Radioembolization: A Multistep Theragnostic Procedure.

This article provides a thorough overview of the practice and multistep approach of hepatic radioembolization. The current literature on hepatic radioembolization in primary or metastatic liver tumors as well as future perspectives are discussed.

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data.

Purpose: Holmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry. Methods: Retrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients' health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma. Results: A total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries. Conclusion: This study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

Prospective comparison of positron emission tomography (PET)/magnetic resonance and PET/computed tomography dosimetry in hepatic malignant neoplastic disease after 90Y radioembolization treatment.

Background: 90Y radioembolization is an established treatment modality for hepatic malignancies. Successful radioembolization requires optimal dose delivery to tumors while minimizing dosages to parenchyma. Post-treatment positron emission tomography (PET)/computed tomography (CT) dosimetry is the established benchmark, whereas PET/magnetic resonance (MR) is an emerging modality. The goal of this study was to assess the intermodality agreement between PET/MR and PET/CT 90Y dosimetry. Methods: In this single-institution study, 18 patients (20 treatment sessions) with a primary or metastatic hepatic malignancy underwent both PET/MR and PET/CT after 90Y radioembolization. Patients were randomized to undergo one modality first, followed by the other. The region of interest was delineated using MR images and tumor and liver dosimetry was calculated. Intermodality agreement was assessed using the Bland-Altman method. A generalized linear model was used to assess the effect of baseline variables on intermodality dose differences. Results: PET/MR underestimated tumor and liver absorbed doses when compared to PET/CT by -3.7% (P=0.042) and -5.8% (P=0.029), respectively. A coverage probability plot demonstrated that 80% and 90% of tumor dose measurements fell within intermodality differences of 11% and 18%, respectively. PET/MR underestimated tumor dose at both low (<1 GBq) and high (>3 GBq) injected activity levels (P<0.001) by -22.3 [standard deviation (SD) =13.5] and -24.3 (SD =18.7), respectively. Conclusions: Although PET/MR significantly underestimated the absorbed dose when compared to PET/CT, the intermodality agreement was high and the degree of underestimation was better than previously reported. Intermodality differences were more pronounced at low and high injected doses. Additional studies are required to assess the clinical implications of these findings.

Risk Factors for Abscess Development Following Percutaneous Microwave Ablation Therapy of Hepatic Tumors.

PURPOSE: To investigate risk factors associated with post-microwave ablation (MWA) abscess development. MATERIALS AND METHODS: A retrospective case-control analysis was conducted to identify hepatic MWA performed at a single tertiary medical center between January 2010 and January 2022. Case and control patients were defined as those who did or did not develop intrahepatic abscess within 3 months following MWA, respectively. Correlations between risk factors and post-MWA abscess development were assessed by Fisher's exact test. RESULTS: Between 2010 and 2022, 253 patients underwent 376 MWA sessions with post-ablation abscess complication rate of 1.1% (4/376). Complications associated with intrahepatic abscess included bacteremia, empyema, pleural abscess, subcutaneous abscess, cholangitis, bile leak, biliocutaneous and arterio-biliary fistulae, and pseudoaneurysm. One patient expired from septic shock 5 days post-ablation. All abscesses were treated by percutaneous drainage and antibiotics. One patient required concomitant placement of a biliary stent and embolization of a biliocutaneous tract. History of Sphincter of Oddi manipulation (p < 0.01), cholangiocarcinoma (p < 0.05), transarterial radioembolization (TARE) to the index lesion (p < 0.05), and abnormal serum alkaline phosphatase levels (p < 0.05) were significantly correlated with post-MWA abscess. The risk of developing post-MWA abscesses for patients with a history of cholangiocarcinoma or a history of Sphincter of Oddi manipulation were 20.0% and 27.2%, respectively. CONCLUSION: Patients with prior Sphincter of Oddi manipulation, cholangiocarcinoma, or TARE are at greater risk of developing post-MWA abscess.

The Evolving Role of Intra-arterial Chemotherapy in Adult and Pediatric Cancers: A Comprehensive Review.

The development of intra-arterial chemotherapy (IAC) was driven by an ambition to mitigate systemic side effects, enhance the bioavailability of drugs, and optimize the efficacy of chemotherapeutic agents. While the initial research on IAC primarily examined its effectiveness in treating various liver malignancies, the application of this treatment has undergone significant advancements since its introduction. The primary objective of this article is to examine the current range of utilization of IAC, both with and without radiotherapy, while also evaluating the results of relevant clinical trials. Furthermore, this article explores potential future advancements and opportunities in this field. From the scoping review of available articles, it can be concluded that IAC is an effective treatment alternative and, sometimes, a better first-line option, but there is a need for more evidence to make IAC a regular treatment option available for patients.

Pediatric living donor liver transplantation for biliary embryonal rhabdomyosarcoma: a case report of a case showing disease-free survival over 2 years.

Biliary rhabdomyosarcoma is a rare tumor, but it is still the most common tumor of the biliary tract in children. We report a case of a 6-year-old boy with biliary embryonal rhabdomyosarcoma and liver metastasis, which were treated with neoadjuvant and adjuvant chemotherapy combined with living donor liver transplantation (LDLT). Initial imaging studies showed a low-attenuation intraductal mass from the left hepatic duct to the intrapancreatic common bile duct with diffuse upstream dilatation of the intrahepatic duct and liver metastasis. Endoscopic biopsy revealed embryonal rhabdomyosarcoma. After tumor size reduction through neoadjuvant chemotherapy, LDLT was planned to remove the tumor completely. A left lateral section graft weighing 330 g was harvested from his 38-year-old mother and the graft-to-recipient weight ratio was 1.94%. Routine pediatric LDLT operation was performed with deep excavation of intrapancreatic distal bile duct. The explant liver showed minimal residual embryonal rhabdomyosarcoma with no lymph node metastasis. The patient recovered uneventfully from LDLT operation. Scheduled adjuvant chemotherapy was performed for 6 months. The patient is doing well without any evidence of tumor recurrence for 26 months after LDLT. In conclusion, liver transplantation could be an effective treatment for unresectable biliary rhabdomyosarcoma in children according to the location of tumor.

Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.