A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma.

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

Percutaneous transhepatic sclerotherapy for ascending colonic varices due to left-sided portal hypertension.

Left-sided portal hypertension (LSPH) causes varices and splenomegaly due to splenic vein issues. Colonic varices are rare and lack standardized treatment. We report the successful treatment of colonic varices caused by LSPH, by addressing both the afferent and efferent veins. A 70-year-old man with distal cholangiocarcinoma had surgery without splenic vein resection, leading to proximal splenic vein stenosis and varices at multiple locations. Percutaneous transhepatic splenic venography revealed that collateral veins flowed into the ascending colonic varices and returned to the portal vein. Complete thrombosis of the varices was achieved by injecting sclerosants and placing coils in both the afferent and efferent veins. The procedure was safe and effective, with no variceal recurrence. This approach provides a minimally invasive option for treating colonic varices associated with LSPH.

A case of recurrent laryngeal nerve paralysis caused by radiofrequency ablation for mediastinal recurrence of lung cancer.

Radiofrequency ablation (RFA) has emerged as a potent therapeutic modality for tumor treatment, and offers benefits such as reduced recovery time and minimal damage to nearby tissues. However, RFA is not devoid of complications, notably nerve damage during intrathoracic lesion treatments, which can significantly impact patients' quality of life. This report describes the unique case of a 71-year-old male who experienced hoarseness attributed to injury to the recurrent nerve after RFA for a locally recurrent lung cancer lesion in the mediastinum near the aortic arch. Although RFA has the advantages of a minimally invasive nature and positive outcomes, its risk of nerve injury, specifically in the thoracic region, highlights the need for improved techniques and preventive measures.

Transcatheter Arterial Chemoembolization for Treatment-Naive Hepatocellular Carcinoma Has Different Treatment Effects Depending on Central or Peripheral Tumor Location.

Introduction: The purpose of this study was to evaluate the treatment efficacy of transcatheter arterial chemoembolization (TACE) for treatment-naive hepatocellular carcinoma (HCC) according to tumor location and burden. Methods: Between 2010 and 2019, consecutive patients who underwent TACE as the first treatment were enrolled. Tumors were classified into two categories based on their location, as central or peripheral tumors. Tumors in the central zone, which is within 1 cm of the main trunk or the first branch of the portal vein, were classified as central tumors, while those located in the peripheral zone were classified as peripheral tumors. Patients were grouped according to the HCC location and up-to-7 criteria. Patients with central tumors were classified into the central arm and those with only peripheral tumors were classified into the peripheral arm. Patients within and beyond the up-to-7 criteria were classified into the up-to-7 in and up-to-7 out-groups, respectively. Local recurrence-free survival (LRFS) and progression-free survival (PFS) were compared per nodule (central tumor vs. peripheral tumor) and per patient (central arm vs. peripheral arm), respectively. The prognostic factors of LRFS and PFS were analyzed by univariate and multivariate analyses. Results: A total of 174 treatment-naive patients with 352 HCCs were retrospectively enrolled. Ninety-six patients and 130 lesions were selected by propensity score matching. Median LRFS was longer for peripheral tumors than central tumors (not reached vs. 3.3 months, p < 0.001). Median PFS was 17.1 months (8.3-24.9) in the peripheral arm and up-to-7 in, 7.0 months (3.3-12.7) in the peripheral arm and up-to-7 out, 8.4 months (4.0-12.6) in the central arm and up-to-7 in, and 3.0 months (1.2-4.9) in the central arm and up-to-7 out-groups. The peripheral arm and up-to-7 in-groups had significantly longer PFS than the other three groups (p = 0.013, p = 0.015, p < 0.001, respectively). Multivariate analysis confirmed that the central zone and central arm were associated with high adjusted hazard ratios for tumor recurrence or death (2.87, p < 0.001; 2.89, p < 0.001, respectively). Conclusion: Treatment-naive HCCs in the peripheral zone had a longer LRFS and PFS following TACE compared to those in the central zone.

Atezolizumab plus bevacizumab-induced intratumoral hemorrhage in a patient with rib metastasis from unresectable hepatocellular carcinoma.

Recently, combination therapy with atezolizumab, a humanized monoclonal antiprogrammed death ligand-1 antibody, and bevacizumab, has become available for treatment of unresectable hepatocellular carcinoma (HCC). We herein report a 73-year-old man with advanced stage HCC who developed fatigue during treatment with atezolizumab-bevacizumab combination therapy. Computed tomography identified intratumoral hemorrhage within the HCC metastasis to the right fifth rib metastasis of HCC, which was confirmed on emergency angiography of the right 4th and 5th intercostal arteries and some branches of the subclavian artery confirmed intratumoral hemorrhage, following which transcatheter arterial embolization (TAE) was performed to achieve hemostasis. He continued to receive atezolizumab-bevacizumab combination therapy after TAE, and no rebleeding was seen. Although uncommon, rupture and intratumoral hemorrhage in the HCC metastasis to the ribs can cause life-threatening hemothorax. However, to our knowledge, no previous cases of intratumoral hemorrhage in HCC during atezolizumab-bevacizumab combination therapy have been reported. This is the first report of intratumoral hemorrhage with the combination therapy of atezolizumab and bevacizumab, which was successfully controlled by TAE. Patients receiving this combination therapy should be observed for intratumoral hemorrhage, which can be managed by TAE if it does occur.

Safety and Feasibility of Contrast-Enhanced Computed Tomography with a Nanoparticle Contrast Agent for Evaluation of Diethylnitrosamine-Induced Liver Tumors in a Rat Model.

RATIONALE AND OBJECTIVES: Safety and feasibility of contrast-enhanced computed tomography (CECT) with a nanoparticulate contrast agent, ExiTron nano 12000, was evaluated in a rat liver tumor model. MATERIALS AND METHODS: This study employed eighteen 8-week-old male F344 rats. Six rats given tap water for 8 weeks further divided into two: Control group and Normal Liver with CECT group. Six rats each were given tap water containing diethylnitrosamine (DEN) at 100 ppm for 8 or 14 weeks; Adenoma group and Hepatocellular carcinoma (HCC) group, respectively. Biochemical marker values and adverse events were evaluated after CT imaging. ExiTron nano 12000 was evaluated for the hepatic contrast enhancement, and the detection and measurement of liver nodules by CECT after 8- and 14-weeks administration of DEN. Post-mortem liver specimens were evaluated by hematoxylin-eosin (HE) staining, and the number and size of liver nodules were measured. The HCC group was evaluated for diagnostic concordance between HE-stained and CECT-detected nodules. RESULTS: The contrast agent enhanced liver and was tolerated after CECT in 15 rats. Biochemical parameter values did not differ significantly between the Control and Normal Liver groups. The numbers of CECT-detected nodules in the Adenoma and HCC groups were 14.8 ± 5.1, and 32.4 ± 8.1, respectively. The HCC group had 3.6 ± 2.7 of pathological HCCs, which were identified by CECT. The size of CECT-detected HCCs correlated significantly with that of pathological HCCs (r = 0.966, p < 0.0001). CONCLUSION: CECT with ExiTron nano 12000 is a safe and feasible method to measure tumors in a rat liver tumor model.

Efficacy of rechallenge transcatheter arterial chemoembolization after lenvatinib treatment for advanced hepatocellular carcinoma.

Background and Aim: We evaluated the efficacy of rechallenge transcatheter arterial chemoembolization (TACE) after lenvatinib (LEN) treatment in patients with previous TACE failure/refractoriness. Methods: We enrolled 63 consecutive patients with a history of TACE failure/refractoriness prior to LEN treatment as a first-line systemic therapy. We reviewed the clinical backgrounds and courses of the patients. Results: In total, 25 patients underwent rechallenge TACE after LEN due to LEN-refractoriness (17 cases) or intolerance (8 cases). A complete or partial response was obtained for 13 (65.0%) of the 20 patients whose therapeutic effects were determined. The survival rate of patients who underwent rechallenge TACE was significantly higher than that of patients who did not undergo rechallenge TACE (median survival time, not reached vs 403 days, P = 0.015). Rechallenge TACE significantly reduced the risk of death in univariate (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.08-0.69, P = 0.008) and multivariate analyses (HR 0.26, 95% CI 0.08-0.80, P = 0.019). If complete or partial response was obtained by rechallenge TACE, the median survival time of these patients was significantly longer than those of the progressive disease (PD) group (P = 0.05), and the median survival time of the PD group after rechallenge TACE was not different from that of the group who did not undergo rechallenge TACE (P = 0.36). We did not observe a decrease in the ALBI score after TACE. Conclusion: Rechallenge TACE after LEN is an effective treatment that may result in a favorable prognosis.

Visual and quantitative evaluation of microcalcifications in mammograms with deep learning-based super-resolution.

PURPOSE: To evaluate visually and quantitatively the performance of a deep-learning-based super-resolution (SR) model for microcalcifications in digital mammography. METHOD: Mammograms were consecutively collected from 5080 patients who underwent breast cancer screening from January 2015 to March 2017. Of these, 93 patients (136 breasts, mean age, 50 ± 7 years) had microcalcifications in their breasts on mammograms. We applied an artificial intelligence model known as a fast SR convolutional neural network to the mammograms. SR and original mammograms were visually evaluated by four breast radiologists using a 5-point scale (1: original mammograms are strongly preferred, 5: SR mammograms are strongly preferred) for the detection, diagnostic quality, contrast, sharpness, and noise of microcalcifications. Mammograms were quantitatively evaluated using a perception-based image-quality evaluator (PIQE). RESULTS: All radiologists rated the SR mammograms better than the original ones in terms of detection, diagnostic quality, contrast, and sharpness of microcalcifications. These ratings were significantly different according to the Wilcoxon signed-rank test (p <.001), while the noise score of the three radiologists was significantly lower (p <.001). According to PIQE, SR mammograms were rated better than the original mammograms, showing a significant difference by paired t-test (p <.001). CONCLUSION: An SR model based on deep learning can improve the visibility of microcalcifications in mammography and help detect and diagnose them in mammograms.

The Albumin-bilirubin Score Detects Changes in the Liver Function during Treatment for Budd-Chiari Syndrome: A Retrospective Observational Study.

Objective Mapping the long-term prognosis of Budd-Chiari syndrome (BCS) is difficult, as the prognosis is associated with changes in the liver function. The present study evaluated the time course changes in the liver function in a treatment group with percutaneous old balloon angioplasty (POBA) and a non-treatment group using the albumin-bilirubin score (ALBI) and Child-Pugh score during long-term follow-up. Methods In this retrospective study, 13 consecutive patients diagnosed with BCS at our hospital between 2007 and 2020 were categorized into a treatment group (n=8), which received POBA, and a non-treatment group (n=5). Differences in the liver function in the ALBI and Child-Pugh scores between the initial visit and one- and three-year follow-up were calculated and statistically evaluated. We investigated the changes in the liver function during the long-term follow-up, including events such as re-stenosis and re-treatment. Results While the Child-Pugh scores in the treatment group did not differ significantly between the initial visit and 1- or 3-year follow-up, the ALBI scores in this group improved significantly between the initial visit and the 1- or 3-year follow-up visit (p=0.0078 and 0.0156, respectively). The liver function according to the ALBI score in the treatment group showed gradual improvement from the initial value but gradual worsening in the non-treatment group. The ALBI scores also revealed that the liver function varies according to re-stenosis and re-POBA in BCS patients. Conclusion Unlike the Child-Pugh score, the ALBI score was able to capture changes in the liver function of BCS patients during the long-term course of BCS.

Platelet count and abdominal dynamic CT are useful in predicting and screening for gastroesophageal varices after Fontan surgery.

OBJECTIVE: Patients who undergo Fontan surgery for complex cardiac anomalies are prone to developing liver and gastrointestinal complications. In particular, gastroesophageal varices (GEVs) can occur, but their prevalence is unknown. We aimed to elucidate the occurrence of GEVs and the predicting parameters of GEVs in these patients. MATERIALS AND METHODS: Twenty-seven patients (median age, 14.8 years; median time since surgery, 12.9 years) who had undergone the Fontan surgery and were examined by abdominal dynamic computed tomography (CT) for the routine follow-up were included in the study. Radiological findings including GEVs and extraintestinal complications were retrospectively evaluated by experienced radiologists in a blinded manner. Relationships between blood-biochemical and demographic parameters and the presence of GEVs were statistically analyzed. RESULTS: Dynamic CT revealed gastric varices (n = 3, 11.1%), esophageal varices (n = 1, 3.7%), and gastrorenal shunts (n = 5, 18.5%). All patients with gastric varices had gastrorenal shunts. All gastric varices were endoscopically confirmed as being isolated and enlarged, with indications for preventive interventional therapy. A platelet count lower than 119 × 109 /L was identified as a predictor of GEV (area under the receiver operating curve, 0.946; sensitivity, 100%; and specificity, 87%). CONCLUSIONS: GEVs are important complications that should not be ignored in patients who have undergone a Fontan procedure. Platelet counts lower than 119 × 109 /L may help to prompt patient screening by using abdominal dynamic CT to identify GEVs and their draining collateral veins in these patients.

Observation of Intramural Fibroid Expulsion on MRI after Uterine Artery Embolization.

Uterine artery embolization (UAE) is a type of noninvasive treatment for symptomatic uterine fibroids. One of the complications of UAE is fibroid expulsion. Here, we report a case of a 45-year-old woman who underwent UAE for an intramural fibroid, which resulted in fibroid expulsion. To the best of our knowledge, there are only few reports of expulsion of intramural fibroids. The process of fibroid protrusion from the myometrium into the uterine cavity was depicted on magnetic resonance imaging (MRI) in this case. We discuss the risk factors and mechanisms of fibroid expulsion after UAE.

Assessing liver stiffness with conventional cut-off values overestimates liver fibrosis staging in patients who received the Fontan procedure.

AIM: Patients who undergo the Fontan procedure for complex congenital heart disease are prone to liver cirrhosis. Liver stiffness (LS) reflects liver fibrosis stage in patients with chronic viral hepatitis; however, its accuracy in predicting liver fibrosis stage in Fontan patients is controversial. We aimed to clarify the correlation between LS and liver fibrosis stage in Fontan patients. METHODS: Fifty-eight Fontan patients were prospectively measured for LS with transient elastography. We undertook liver biopsy, cardiac catheterization, and laboratory tests in 22 of these patients (median age, 14.7 years; range, 9.9-32.1 years) with LS > 11.0 kPa (median, 19.2 kPa; range, 12.2-39.8 kPa); these elevated LS values suggest liver cirrhosis. RESULTS: Histologically, all patients showed mild-to-severe portal and sinusoidal fibrosis but no cirrhosis. Statistically, LS did not predict histological liver fibrosis scores (p = 0.175). Liver stiffness was not correlated with central venous pressure (p = 0.456) or with the hepatic venous pressure gradient (HVPG; p = 0.062), although the p value for HVPG was only slightly above the threshold for significance. CONCLUSIONS: Fontan patients are prone to developing both portal and sinusoidal fibrosis. Liver stiffness could be influenced by HVPG, and using the conventional cut-off values for LS overestimates and overtreats liver fibrosis in these patients.

Survival Benefit of Radiofrequency Ablation with Intratumoral Cisplatin Administration in a Rabbit VX2 Lung Tumor Model.

PURPOSE: This study evaluated the survival benefit of a combination therapy with radiofrequency ablation (RFA) and intratumoral cisplatin (ITC) administration for lung tumors by using a rabbit VX2 tumor model. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. VX2 tumor suspension was injected into the lungs of Japanese white rabbits under CT guidance to create a lung tumor model. Thirty-two rabbits bearing a transplanted VX2 lung tumor were randomly assigned to four groups of eight: control (untreated); RFA alone; ITC alone; and RFA with ITC. All treatments were performed one week after tumor transplantation. Kaplan-Meier survival curves were compared by the log-rank test. RESULTS: The median survival time was 24.5 days (range 17-33 days) in the control group, 40 days (30-80 days) in the RFA alone group, 31.0 days (24-80 days) in the ITC alone group, and not reached (53-80 days) in the RFA with ITC group. The median survival was significantly longer with the RFA/ITC combination compared to the control group (P < 0.001), RFA alone (P = 0.034), and ITC alone (P = 0.004). The survival time after RFA alone was also significantly longer than that of the control group (P < 0.001). There was no significant difference in tumor size or the rate of pneumothorax between each group. CONCLUSION: RFA prolonged the survival of rabbits with lung VX2 tumors when combined with ITC.

Risk factors for local recurrence of hepatocellular carcinoma after transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE).

PURPOSE: To identify the risk factors for local recurrence in hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE). MATERIALS AND METHODS: In this retrospective study, 35 patients (27 males, 8 females; median age 73 years) with 116 tumors (median size 14 mm) treated with DEB-TACE from May 2014 to September 2018 were evaluated. Age, sex, etiology, Child-Pugh class, alpha-fetoprotein, des-gamma-carboxyprothrombin, previous conventional TACE, tumor location, tumor size, tumor number, contact with the liver surface, level of embolization, corona enhancement on CT during hepatic arteriography, vascular lakes, additional embolization with gelatin sponge particles, and supplying vessels on digital subtraction angiography (DSA) after embolization were analyzed. RESULTS: Univariate analysis showed that advanced age, female, large tumor, contact with the liver surface, and residual supplying vessels were significant risk factors for local recurrence (p = 0.012, 0.0013, 0.0023, 0.025, and < 0.001, respectively). On multivariate logistic analysis, large tumor, contact with the liver surface, and residual supplying vessels on DSA were significant risk factors for local recurrence (p = 0.0026, 0.038, and < 0.001, respectively). CONCLUSION: Large tumor size, contact with the liver surface, and residual supplying vessels on DSA were significant risk factors associated with local recurrence after DEB-TACE for HCC.

Three-dimensional conformal radiotherapy for locally advanced hepatocellular carcinoma with portal vein tumour thrombosis: evaluating effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification.

OBJECTIVE: The purpose of this study was to retrospectively evaluate the effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification in patients who received three-dimensional conformal radiotherapy (3D CRT) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) by analyzing toxicity and prognostic factors. METHODS: 56 consecutive patients who had locally advanced HCC with PVTT treated by 3D CRT between September 2007 and April 2013 were retrospectively reviewed. RESULTS: The median survival time of all patients was 6.4 months. Receiver-operating characteristic (ROC) analysis identified MELD score = 7.5 [area under the curve (AUC) 0.81] and Child-Pugh score = 6.5 (AUC 0.86) as the best cut-off values for predicting the incidence of complications over Common Terminology Criteria for Adverse Events grade 2. There was no significant difference in the discrimination power between the MELD score and the Child-Pugh score on comparison of the two ROC curves (p = 0.17). On multivariate analysis, age, MELD score and radiotherapy dose were significant prognostic factors for overall survival (p = 0.021, 0.038 and 0.006, respectively). In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis. CONCLUSION: This study showed that the best MELD score cut-off value is 7.5 and that the MELD score is a better prognostic factor than the Child-Pugh classification in 3D CRT for HCC with PVTT. ADVANCES IN KNOWLEDGE: The MELD score is useful for predicting the risk of severe toxicities and the prognosis of patients treated with 3D CRT for PVTT.