Identification of reversed portal flow on 4DCT and of factors contributing to reversed portal flow in patients with liver cirrhosis and portosystemic shunt before interventional radiology procedures.

AIM: Patients with liver cirrhosis and portosystemic shunt occasionally develop reversed portal flow in the portal venous system. The factors contributing to reversed portal flow in these patients remain unclear. The aim of this study was to identify factors contributing to reversed portal flow in patients with portosystemic shunts based on four-dimensional computed tomography (4DCT), which visualized flow dynamics in the portal venous system. METHODS: Data from 34 consecutive patients with portosystemic shunts who had undergone 4DCT before interventional radiology procedures were retrospectively investigated in this study. Uni- and multivariate analyses were performed to identify factors contributing to reversed portal flow. RESULTS: Flow dynamics could be visualized on 4DCT in 32 of the 34 patients. Fifteen patients had forward portal flow; 17 had reversed portal flow. The main portal, splenic, and superior mesenteric veins displayed reversed portal flow in five, 12, and five vessels, respectively. Portosystemic shunt originating from splenic and superior mesenteric veins, worse albumin-bilirubin score, and small main portal vein diameter were significant factors contributing to reversed portal flow in both univariate (p = 0.049, p = 0.027, and p = 0.002) and multivariate (odds ratio [OR] 6.345, p = 0.012; OR 4.279, p = 0.039; and OR 5.516, p = 0.019) analyses. CONCLUSIONS: The reversed portal flow was visualized on 4DCT. Portosystemic shunt originating distant to the liver, worse albumin-bilirubin score, and small diameter of the main portal vein were factors contributing to reversed flow in the portal venous system.

Maskless 2-Dimensional Digital Subtraction Angiography Generation Model for Abdominal Vasculature using Deep Learning.

PURPOSE: To develop a deep learning (DL) model to generate synthetic, 2-dimensional subtraction angiograms free of artifacts from native abdominal angiograms. MATERIALS AND METHODS: In this retrospective study, 2-dimensional digital subtraction angiography (2D-DSA) images and native angiograms were consecutively collected from July 2019 to March 2020. Images were divided into motion-free (training, validation, and motion-free test datasets) and motion-artifact (motion-artifact test dataset) sets. A total of 3,185, 393, 383, and 345 images from 87 patients (mean age, 71 years ± 10; 64 men and 23 women) were included in the training, validation, motion-free, and motion-artifact test datasets, respectively. Native angiograms and 2D-DSA image pairs were used to train and validate an image-to-image translation model to generate synthetic DL-based subtraction angiography (DLSA) images. DLSA images were quantitatively evaluated by the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) using the motion-free dataset and were qualitatively evaluated via visual assessments by radiologists with a numerical rating scale using the motion-artifact dataset. RESULTS: The DLSA images showed a mean PSNR (± standard deviation) of 43.05 dB ± 3.65 and mean SSIM of 0.98 ± 0.01, indicating high agreement with the original 2D-DSA images in the motion-free dataset. Qualitative visual evaluation by radiologists of the motion-artifact dataset showed that DLSA images contained fewer motion artifacts than 2D-DSA images. Additionally, DLSA images scored similar to or higher than 2D-DSA images for vascular visualization and clinical usefulness. CONCLUSIONS: The developed DL model generated synthetic, motion-free subtraction images from abdominal angiograms with similar imaging characteristics to 2D-DSA images.

Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas.

INTRODUCTION: Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated. METHODS: This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020. RESULTS: Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; p = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; p < 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; p < 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was >90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed. DISCUSSION/CONCLUSION: It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.

[Diffuse large B-cell lymphoma with markedly improved chylothorax by lymphangiography].

Chylothorax is a rare clinical sign in patients with diffuse large B-cell lymphoma (DLBCL), which is often challenging to manage and has a poor prognosis. We report the case of a 59-year-old woman who presented with right pleural effusion at the time of DLBCL diagnosis. Lymphadenopathy rapidly improved in response to chemotherapy. However, the pleural effusion progressed and was identified as chylothorax by thoracentesis. Because attempts to manage the condition with fasting and central venous nutrition were unsuccessful, we performed ultrasound-guided intranodal lipiodol lymphangiography from the inguinal lymph node. Although leak sites were not detected, the pleural effusion markedly improved on the day after the examination and resolved after 2 months. Lymphangiography is a minimally invasive examination with few complications. It contributes not only to the identification of leak sites but also to the improvement and resolution of chylothorax. Therefore, lymphangiography should be considered for refractory chylothorax that is unresponsive to chemotherapy or nutritional management.

Establishment of an orthotopic patient-derived xenograft mouse model using uveal melanoma hepatic metastasis.

BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment. To overcome these limitations, we developed a new method to directly transplant biopsy specimens to the liver of immunocompromised mice. RESULTS: By using two metastatic uveal melanoma cell lines, we demonstrated that the liver provides a more suitable microenvironment for tumor growth compared to subcutaneous sites and that surgical orthotopic implantation (SOI) of tumor pieces allows the creation of a liver tumor in immunocompromised mice. Subsequently, 10 of 12 hepatic metastasis specimens from patients were successfully xenografted into the immunocompromised mice (83.3% success rate) using SOI, including 8 of 10 needle biopsy specimens (80%). Additionally, four cryopreserved PDX tumors were re-implanted to new mice and re-establishment of PDX tumors was confirmed in all four mice. The serially passaged xenograft tumors as well as the re-implanted tumors after cryopreservation were similar to the original patient tumors in histologic, genomic, and proteomic expression profiles. CT imaging was effective for detecting and monitoring PDX tumors in the liver of living mice. The expression of Ki67 in original patient tumors was a predictive factor for implanted tumor growth and the success of serial passages in PDX mice. CONCLUSIONS: Surgical orthotopic implantation of hepatic metastasis from uveal melanoma is highly successful in the establishment of orthotopic PDX models, enhancing their practical utility for research applications. By using CT scan, tumor growth can be monitored, which is beneficial to evaluate treatment effects in interventional studies.

Establishment and Characterization of Orthotopic Mouse Models for Human Uveal Melanoma Hepatic Colonization.

Uveal melanoma (UM) is a rare type of melanoma, although it is the most common primary ocular malignant tumor in adults. Nearly one-half the patients with primary UM subsequently develop systemic metastasis, preferentially to the liver. Currently, no treatment is effective for UM hepatic metastasis, and the prognosis is universally poor. The main challenge in designing a treatment strategy for UM hepatic metastasis is the lack of suitable animal models. We developed two orthotopic mouse models for human UM hepatic metastases: direct hepatic implantation model (intrahepatic dissemination model) and splenic-implantation model (hematogenous dissemination model) and investigated the tumorgenesis in the liver. A human UM cell line, established from a hepatic metastasis and nonobese diabetic severe combined immunodeficient γ mice, were used for development of in vivo tumor models. In the direct hepatic implantation model, a localized tumor developed in the liver in all cases and intrahepatic dissemination was subsequently seen in about one-half of cases. However, in the splenic implantation model, multiple hepatic metastases were observed after splenic implantation. Hepatic tumors subsequently seeded intra-abdominal metastasis; however, lung metastases were not seen. These findings are consistent with those observed in human UM hepatic metastases. These orthotopic mouse models offer useful tools to investigate the biological behavior of human UM cells in the liver.

Prediction for Improvement of Liver Function after Balloon-Occluded Retrograde Transvenous Obliteration for Gastric Varices to Manage Portosystemic Shunt Syndrome.

PURPOSE: To investigate predictive factors and cutoff value of transient elastography (TE) measurements for assessing improvement in liver function after balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GV). MATERIALS AND METHODS: Retrospective analysis was performed of 50 consecutive patients followed for > 3 months after BRTO, who had undergone TE before BRTO between January 2011 and February 2015. The correlation between change in liver function (total bilirubin, albumin, and prothrombin time) and baseline liver function values and liver stiffness measurement (LSM) by TE was evaluated by Pearson correlation test. Receiver operating characteristic curves were used to determine cutoff values for discriminating between patients who had improved liver function and patients who did not. The time interval from BRTO to aggravation of esophageal varices (EV) (worsening morphology, development of new varices, or variceal rupture) grouped by cutoff values was also analyzed. RESULTS: Serum albumin was significantly improved at 3 months after BRTO (3.57 g/dL vs 3.74 g/dL, P < .001). There was a significant negative correlation between change in albumin and baseline LSM (r = -0.50, P < .001). The best cutoff point for LSM was ≤ 22.9 kPa, with sensitivity and specificity of 78.4% and 69.2%, respectively, for predicting which patients would have improved albumin after BRTO. Among 33 patients, 29 (88%) patients had improved albumin. The 1-year progression rate of EV after BRTO was 13.6% in patients with LSM ≤ 22.9 kPa. CONCLUSIONS: The predictive factor for improvement in albumin after BRTO was lower LSM (≤ 22.9 kPa) using TE.

Combination radiofrequency ablation and local injection of the immunostimulant bacillus Calmette-Guérin induces antitumor immunity in the lung and at a distant VX2 tumor in a rabbit model.

PURPOSE: To evaluate whether the combination of radiofrequency (RF) ablation and local injection of the immunostimulant Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces systemic antitumor immunity. MATERIALS AND METHODS: Japanese White rabbits with lung and auricle VX2 tumors were randomized into three groups: control (n = 8; no treatment), RF ablation only (n = 8; RF ablation to the lung tumor), and RF ablation with local BCG injection into the lung tumor (n = 8). Treatments were performed 1 week after tumor implantation. Survival was evaluated with Kaplan-Meier method and log-rank test. Weekly mean volume and specific growth rate (SGR) of auricle tumors were calculated, and comparisons were made by Mann-Whitney test. RESULTS: Median survival of control, RF-only, and RF/BCG groups were 23, 41.5, and 103.5 days, respectively. Survival was significantly prolonged in the RF-only and RF/BCG groups compared with the control group (P = .034 and P =.003, respectively), but no significant difference was found between the RF-only and RF/BCG groups (P = .279). Only in the RF/BCG group was mean auricle tumor volume decreased 5 weeks after implantation. No significant difference in SGR was found between the control and RF-only groups (P = .959), but SGR in the RF/BCG group was significantly lower than in the control group (P = .005). CONCLUSIONS: The combination of RF ablation and local injection of BCG resulted in distant tumor suppression compared with the control group, whereas RF ablation alone did not produce this effect. Therefore, the combination of RF ablation and local injection of BCG may induce systemic antitumor immunity.

Injectable cell scaffold restores impaired cell-based therapeutic angiogenesis in diabetic mice with hindlimb ischemia.

The clinical success of cell-based therapeutic angiogenesis has been limited in diabetic patients with critical limb ischemia. We previously reported that an injectable cell scaffold (ICS), which is a nano-scaled hydroxyapatite (HAp)-coated polymer microsphere, enhances therapeutic angiogenesis. Subsequently, we developed a modified ICS for clinical use, measuring 50 µm in diameter using poly(l-lactide-co-ε-caprolactone) as a biodegradable polymer, which achieved appropriately accelerated absorption in vivo. The aim of the present study was to evaluate the effectiveness of this practical ICS in diabetic hindlimb ischemia. Bone-marrow mononuclear cells (BMNCs) were intramuscularly injected, without or with a practical ICS, into the ischemic hindlimbs of mice (BMNCs or ICS+BMNCs group, respectively). Kaplan-Meier analysis demonstrated that the beneficial effects of BMNC transplantation for limb salvage after ischemic surgery were almost entirely abrogated in streptozotocin-induced diabetic mice. In contrast, injection of ICS+BMNCs revealed significant limb salvage in diabetic mice to a similar extent as in non-diabetic mice. The number of apoptotic transplanted BMNCs was 1.8-fold higher in diabetic mice 10 days after transplantation compared to non-diabetic mice, while that in the ICS+BMNCs group was markedly lower (8.3% of that in the BMNCs group) even in diabetic mice. The proangiogenic factors VEGF and FGF2, also known as antiapoptotic factors, mostly co-localized with transplanted GFP-positive BMNCs that were closely aggregated around the ICS in ischemic tissue. In conclusion, the practical ICS significantly augmented cell-based therapeutic angiogenesis even in diabetic animals, through local accumulation of proangiogenic factors and antiapoptotic effects in transplanted cells.

Usefulness of CT volumetry for gastric varix before balloon-occluded retrograde transvenous obliteration.

BACKGROUND/AIMS: To evaluate the feasibility of gastric variceal (GV) volumetry using computed tomography (CT) images taken before balloon-occluded retrograde transvenous obliteration (B-RTO) and to assess its correlation with the actual amount of 5% ethanolamine oleate and iodinated contrast medium (EOI) injected in B-RTO. METHODOLOGY: Forty-seven consecutive patients with GV underwent B-RTO of the gastrorenal shunt. GV volume was measured with preoperative CT images by three radiologists. Statistical significance was examined by intraclass correlation coefficient (ICC) for concordance among three radiologists and by Pearson correlation test for correlation between GV volume and the amount of 5% EOI injected. RESULTS: GV volumes measured by three radiologists significantly correlated with each other (ICC=0.959). Combining all patients and all measurements, the mean GV volume and the mean amount of 5% EOI were 27.02±16.67cm3 and 28.72±17.72mL, respectively. There was a significant correlation between GV volume, calculated as a mean of the three values measured by the three radiologists, and the amount of EOI (r2=0.706, p<0.001). CONCLUSIONS: GV volume measured on CT showed a significant correlation with the amount of 5% EOI injected. CT volumetry of GV has the potential to determine an amount of the sclerosing agent to be injected in B-RTO.

CT-guided transperineal biopsy for prostate cancer in the absence of rectal access.

This case report presents CT-guided transperineal biopsy as an alternative method for diagnosis of prostate cancer in a patient with anorectal stenosis. A 69-year-old male had a history of anorectal surgeries. Conventional transrectal biopsy was unfeasible due to anorectal stenosis. The CT-guided transperineal biopsy was successfully performed using a cranio-caudal puncture technique, revealing adenocarcinoma. After the biopsy, the patient received appropriate hormone therapy and radiation therapy. This case report highlights the feasibility and safety of CT-guided transperineal biopsy for the patients with anorectal complications.

A case of percutaneous deep pelvic abscess drainage using CT fluoroscopic guided cranio-caudal puncture technique.

A 52-year-old male patient presented with complaints of abdominal and back pain. CT revealed a deep pelvic abscess extending into the anterior sacral space. Since puncture via the conventional transgluteal approach cannot reach a deep abscess, percutaneous pelvic abscess drainage was performed under CT fluoroscopy using the cranio-caudal puncture technique. The cranio-caudal puncture requires needle insertion perpendicular to the CT cross-section. This method advances the CT gantry deeper than the needle tip and follows the CT cross-section with the needle tip. This series of images and movements continues until the needle reaches the target. The procedure was successful without complications, the abscess was reduced in size, and blood test data improved. The cranio-caudal puncture technique provides an alternative for the drainage of deep pelvic abscesses that avoids the complications associated with gluteal muscle puncture. Percutaneous drainage of pelvic abscesses under CT fluoroscopy-guided cranio-caudal puncture offers a safe option as a puncture route for deep pelvic abscesses.

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.

Embolization with or without portal vein stenting for bleeding ectopic jejunal varices in hepatopetal portal collaterals due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery.

PURPOSE: To evaluate the efficacy and safety of embolization with or without portal vein stenting for bleeding ectopic jejunal varices in the hepatopetal portal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery. MATERIALS AND METHODS: This study included consecutive patients who underwent embolization for bleeding ectopic jejunal varices in the hepatopetal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery between September 2012 and December 2020. The safety, technical and clinical success rates (no re-bleeding within 1 month) and re-bleeding-free survival after the first therapy and overall survival were assessed. RESULTS: Fourteen sessions in 11 patients were included. Four patients (7 sessions) underwent variceal embolization only, and the remaining seven patients (7 sessions) underwent portal vein stenting and variceal embolization. Technical success was achieved in all 14 sessions (100%). Clinical success was achieved in 13 of 14 sessions (92.9%). No treatment-related serious complications including liver failure were observed. One-year and 2-year re-bleeding-free survival rate after the first endovascular therapy in all 11 patients was 90.9 and 60.6%, respectively. Two patients who experienced re-bleeding had repeat embolization treatment. There was no significant difference in re-bleeding-free survival after endovascular therapy between the combination with stenting and embolization group and the embolization-only group (p = 0.13). CONCLUSION: Embolization with or without portal vein stenting of bleeding ectopic jejunal varices in the hepatopetal portal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery can be considered a safe, effective, and repeatable therapy for long-term hemostasis of uncontrollable bleeding.

Transparaumbilical Intravariceal Sclerotherapy for Duodenal Varices Using Outflow Embolization.

A 55-year-old patient was admitted for variceal treatment, a complication of chronic portal hypertension and liver cirrhosis. Imaging studies revealed prominent duodenal varices, the pancreaticoduodenal vein as its afferent pathway, a drainer vessel into the inferior vena cava, and a paraumbilical vein. We successfully performed complete obliteration of the varix, including its afferent and efferent vessels, via the paraumbilical vein approach.

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 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.