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Simple Summary: Various cancer therapies are often ineffective for advanced metastatic liver disease. While immunotherapy can be effective in some cases, it does not provide significant benefits for metastatic cancer in the liver. CBL0137 is an experimental drug that helps form a special type of DNA called Z-DNA, which may help boost the body's immune response against tumors. We investigated how CBL0137 affects metastatic liver tumor models from colon (CT26) and breast (4T1) cancers focusing on how it triggers immune responses. The results showed that CBL0137 hepatic arterial infusion (HAI) enhanced anti-tumor effects by depleting immune-suppressing cells while preserving effector T cells. Combining CBL0137 HAI with conventional immunotherapy improved survival in 4T1 tumors but not in CT26 tumors, highlighting the importance of targeting specific immune cell populations for effective treatment. Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. Results: CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Conclusions: Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion pump (HAIP) treatment is a technique used to treat liver localized malignancy with intra-arterial chemotherapy. Methylene blue is generally administered to verify hepatic perfusion and exclude inadvertent extrahepatic perfusion. The use of indocyanine green dye (ICG) combined with near-infrared (NIR) fluorescence imaging during robot-assisted HAIP placement may be an attractive alternative by providing high contrast without blue discoloration of the operative field. Methods: Data was collected retrospectively from 2 centers in the Netherlands. Intraoperative perfusion of the liver segments and extrahepatic perfusion were assessed using ICG/NIR as well as methylene blue on video imaging and correlated to postoperative 99 m-Tc perfusion scintigraphy. Results: 13 patients underwent robot-assisted surgery for HAIP placement; median length of stay was 4 days, complications occurred in 4 patients. Hepatic perfusion showed identical patterns when ICG was compared with methylene blue. In 1 patient, additional extrahepatic perfusion was found using ICG, leading to further vessel ligation. Intraoperative ICG perfusion was concordant with 99 m-Tc perfusion scintigraphy. Discussion: Liver and extrahepatic perfusion determined by ICG fluorescence imaging is concordant with blue dye perfusion and 99 m-Tc perfusion scintigraphy. Therefore, ICG fluorescence imaging is deemed a safe and reliable technique for perfusion testing during robot-assisted HAIP placement. [ABSTRACT FROM AUTHOR]

Introduction: Intrahepatic cholangiocarcinoma (ICC) is the 2nd most common primary liver malignancy. For nonsurgical candidates, the primary treatment option is systemic chemotherapy, which can be combined with locoregional therapies to enhance local control. Common intra-arterial locoregional therapies include transarterial hepatic embolization, conventional transarterial chemoembolization, drug-eluting bead transarterial chemoembolization, transarterial radioembolization with Yttrium-90 microspheres, and hepatic artery infusion. This article aims to review the latest literature on intra-arterial locoregional therapies for treating ICC. Areas covered: A literature search was conducted on PubMed using keywords: intrahepatic cholangiocarcinoma, intra-arterial locoregional therapy, embolization, chemoembolization, radioembolization, hepatic artery infusion, and immunotherapy. Articles from 2008 to 2024 were reviewed. Survival data from retrospective and prospective studies, meta-analyses, and clinical trials were evaluated. Expert opinion: Although no level I evidence supports the superiority of any specific intra-arterial therapy, there has been a shift toward favoring radioembolization. In our expert opinion, radioembolization may offer superior outcomes when performed by skilled operators with meticulous planning and personalized dosimetry, particularly for radiation segmentectomy or treating lobar/bilobar disease in appropriate candidates. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the performance of a convolutional neural network (CNN) with preoperative MRI and clinical factors in predicting the treatment response of unresectable hepatocellular carcinoma (HCC) patients receiving hepatic arterial infusion chemotherapy (HAIC). A total of 191 patients with unresectable HCC who underwent HAIC in our hospital between May 2019 and March 2022 were retrospectively recruited. We selected InceptionV4 from three representative CNN models, AlexNet, ResNet, and InceptionV4, according to the cross-entropy loss (CEL). We subsequently developed InceptionV4 to fuse the information from qualified pretreatment MRI data and patient clinical factors. Radiomic information was evaluated based on several constant sequences, including enhanced T1-weighted sequences (with arterial, portal, and delayed phases), T2 FSE sequences, and dual-echo sequences. The performance of InceptionV4 was cross-validated in the training cohort (n = 127) and internally validated in an independent cohort (n = 64), with comparisons against single important clinical factors and radiologists in terms of receiver operating characteristic (ROC) curves. Class activation mapping was used to visualize the InceptionV4 model. The InceptionV4 model achieved an AUC of 0.871 (95% confidence interval [CI] 0.761–0.981) in the cross-validation cohort and an AUC of 0.826 (95% CI 0.682–0.970) in the internal validation cohort; these two models performed better than did the other methods (AUC ranges 0.783–0.873 and 0.708–0.806 for cross- and internal validations, respectively; P < 0.01). The present InceptionV4 model, which integrates radiomic information and clinical factors, helps predict the treatment response of unresectable HCC patients receiving HAIC treatment. [ABSTRACT FROM AUTHOR]

Background and objectives: STA-MCA bypass surgery is mainly used for Moyamoya disease, giant intracranial aneurysms, and resection of intracranial tumors requiring sacrifice of blood vessels. The intraoperative patency of the reconstructive vessels is critical to the efficacy of the procedure. This study aimed to evaluate the efficacy of intra-arterially infused tirofiban for the treatment of acute thrombosis during STA-MCA bypass surgery and countermeasures for acute thrombosis. Methods: This study involved 209 patients (272 hemispheres) who underwent STA-MCA surgery between November 2020 and December 2023. Intraoperative acute thrombosis occurred in eight patients (3.83%,8 hemispheres). We retrospectively reviewed the clinical and imaging data, surgical procedure, and follow-up outcomes of eight patients. We implemented the different thrombolytic methods to evaluate the optimal thrombosis management during the bypass surgery. After three months, we assessed neurological functions using the modified Rankin Scale (mRS) and conducted a literature review using PubMed. Results: Eight patients (four male patients and four female patients) developed acute thrombosis during the bypass surgery. Of the eight patients, two underwent re-anastomosis after thrombus removal, three received local injections of tirofiban into the anastomosis or the branches of the superficial temporal artery, and three underwent superselective intra-arterial tirofiban infusion using a microcatheter. Thrombosis were resolved, and arteries were recanalized in all patients. The mRS score was 0 in all patients. No major ischemic or hemorrhagic complications occurred. Conclusion: Our treatment methods were efficacious in the management of acute thrombosis. Intra-arterial tirofiban administration seems to be a simple and effective treatment option for acute thrombosis during STA-MCA bypass surgery. [ABSTRACT FROM AUTHOR]

Objectives: Currently, there remains debate regarding the optimal anesthesia approach for patients undergoing intra-arterial therapy for acute ischemic stroke. Therefore, we conducted a comparative analysis to assess the effects of general anesthesia versus non general anesthesia on patient outcomes. Methods: The research methodology entailed comprehensive searches of prominent databases such as the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. Data synthesis employed techniques like risk ratio or standardized mean difference, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024523079). Results: A total of 27 trials and 12,875 patients were included in this study. The findings indicated that opting for non-general anesthesia significantly decreased the risk of in-hospital mortality (RR, 1.98; 95% CI: 1.50 to 2.61; p<0.00001; I2 = 20%), as well as mortality within three months post-procedure (RR, 1.24; 95% CI: 1.15 to 1.34; p<0.00001; I2 = 26%), while also leading to a shorter hospitalization duration (SMD, 0.24; 95% CI: 0.15 to 0.33; p<0.00001; I2 = 44%). Conclusion: Ischemic stroke patients who undergo intra-arterial treatment without general anesthesia have a lower risk of postoperative adverse events and less short-term neurological damage. In routine and non-emergency situations, non-general anesthetic options may be more suitable for intra-arterial treatment, offering greater benefits to patients. In addition to this, the neuroprotective effects of anesthetic drugs should be considered more preoperatively and postoperatively. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, comprising 90% of liver cancer cases worldwide, with a five-year survival rate of less than 20%. Standard treatments for early-stage HCC include surgical resection and liver transplantation, but many patients are diagnosed at later stages and are ineligible for these interventions. For such patients, transarterial chemoembolization (TACE) is an alternative treatment that delivers chemotherapy directly to the tumor and blocks its blood supply. TACE can be used to help patients maintain eligibility for transplants, improve liver function, and alleviate symptoms. It is particularly effective for intermediate-stage HCC but also shows promise in the early and advanced stages when combined with other therapies. While generally safe, TACE can cause post-embolization syndrome (PES) and other complications in a minority of cases. The efficacy of TACE is continually being improved through advancements in techniques and the integration of novel systemic therapies and artificial intelligence for better patient selection and outcomes. Hepatocellular carcinoma (HCC) accounts for 90% of liver cancer cases worldwide and is currently the most quickly increasing cause of cancer-related deaths in the United States. The 5-year survival rate for primary liver cancer is estimated to be below 20%, and HCC mortality is expected to increase by 41% by 2040. Currently, surgical resection is the first-line approach to definitive treatment of early-stage HCC. However, the majority of patients present with late-stage, unresectable disease due to the asymptomatic nature of early HCC. For patients who present with unresectable HCC, locoregional therapies such as transarterial chemoembolization (TACE) represent an alternative approach to HCC treatment. TACE is a minimally invasive, catheter-based technique that allows for targeted delivery of chemotherapy to tumor sites while occluding tumor-feeding blood vessels. In appropriately selected patients, outcomes for TACE therapy have been shown to be more favorable than supportive care or conservative management. The increasing incidence and mortality of HCC, in addition to the late-stage presentation of most HCC patients, demonstrates the need to expand the role of locoregional therapies in the treatment of HCC. TACE represents an appealing approach to HCC management, including disease control, palliation, and potentially curative-intent strategies. In this review, we will describe the current utility of TACE in the treatment of HCC, characterize the outcomes of patients treated with TACE across different HCC stages, and outline future applications of TACE in the treatment paradigm. [ABSTRACT FROM AUTHOR]

Simple Summary: Discovering hypervascular incidentalomas (HVIs) during intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC) is a common condition, but guidelines lack precise management suggestions. This study examines whether to include HVIs in IAT for HCC patients awaiting liver transplantation. A retrospective study analyzed liver-transplanted HCC patients who received TACE or TARE before LT from 2014 to 2018. The study compared HCC detection rates between pre-interventional imaging and per-interventional CBCT and investigated correlations between HVIs and poor prognosis criteria. Results showed higher nodule detection with CBCT and no significant correlations between HVIs and poor prognosis criteria, tumor recurrence, or mortality. Kaplan–Meier analysis found no significant impact of HVIs on recurrence-free, recurrence-related, or overall survival. These data may indicate that the treatment plan during IAT should not be impacted or modified in response to HVI detection in patients awaiting LT. Background: Current guidelines do not indicate any comprehensive management of hepatic hypervascular incidentalomas (HVIs) discovered in hepatocellular carcinoma (HCC) patients during intra-arterial therapies (IATs). This study aims to evaluate the prognostic value of HVIs detected on per-interventional cone beam computed tomography (CBCT) during IAT for HCC in patients waiting for liver transplantation (LT). Material and methods: In this retrospective single-institutional study, all liver-transplanted HCC patients between January 2014 and December 2018 who received transarterial chemoembolization (TACE) or radioembolization (TARE) before LT were included. The number of ≥10 mm HCCs diagnosed on contrast-enhanced pre-interventional imaging (PII) was compared with that detected on per-interventional CBCT with a nonparametric Wilcoxon test. The correlation between the presence of an HVI and histopathological criteria associated with poor prognosis (HPP) on liver explants was investigated using the chi-square test. Tumor recurrence (TR) and TR-related mortality were investigated using the chi-square test. Recurrence-free survival (RFS), TR-related survival (TRRS), and overall survival (OS) were assessed according to the presence of HVI using Kaplan–Meier analysis. Results: Among 63 included patients (average age: 59 ± 7 years, H/F = 50/13), 36 presented HVIs on per-interventional CBCT. The overall nodule detection rate of per-interventional CBCT was superior to that of PII (median at 3 [Q1:2, Q3:5] vs. 2 [Q1:1, Q3:3], respectively, p < 0.001). No significant correlation was shown between the presence of HVI and HPP (p = 0.34), TR (p = 0.095), and TR-related mortality (0.22). Kaplan–Meier analysis did not show a significant impact of the presence of HVI on RFS (p = 0.07), TRRS (0.48), or OS (p = 0.14). Conclusions: These results may indicate that the treatment plan during IAT should not be impacted or modified in response to HVI detection. [ABSTRACT FROM AUTHOR]

Background In intra-arterial chemotherapy for retinoblastoma, a backflow from unreachable external carotid artery branches in the ophthalmic artery can be challenging. Objective To describe a new endovascular technique using Gelfoam pledgets to temporarily occlude distal branches of the external carotid artery to reverse the competitive backflow into the ophthalmic artery in order to perform intra-arterial chemotherapy via the ostium of the ophthalmic artery in selected cases. Methods We queried our prospectively collected database of 327 consecutive patients treated for retinoblastoma by intra-arterial chemotherapy and identified those employing Gelfoam pledgets. We describe this new technique with emphasis on feasibility and safety. Results We treated 11 eyes with 14 infusions of intra-arterial chemotherapy using Gelfoam pledgets to occlude the distal branches of the external carotid artery. We report no perioperative complications due to this occlusion technique. At the ophthalmologic follow-up 1 month after the injection of Gelfoam pledgets, all cases showed tumor regression or stable disease. Two injections into the same eye as the rescue intra-arterial chemotherapy infusion resulted in a transient exudative retinal detachment, and one injection in a heavily pretreated case was followed by iris neovascularization and retinal ischemia. None of the pledget injections led to irreversible vision-threatening intraocular complications. Conclusions Intra-arterial chemotherapy in retinoblastoma using Gelfoam to transiently occlude the distal branches of the external carotid artery and reverse the backflow into the ophthalmic artery seems feasible and safe. Larges series will help to confirm the effectiveness of this new technique. [ABSTRACT FROM AUTHOR]

Background Melphalan, which is poorly soluble at room temperature, is widely used for the treatment of retinoblastoma by selective ophthalmic artery infusion. Evomela, a propylene glycol-free formulation of melphalan with improved solubility and stability, has recently been used as an alternative. OBJECTIVE To compare the safety and efficacy of Evomela with standard-formulation melphalan (SFM) in the treatment of retinoblastoma by selective ophthalmic artery infusion. Methods We performed a retrospective case--control study of patients with retinoblastoma undergoing selective ophthalmic artery infusion with SFM or Evomela at a single institution. Cycle-specific percent tumor regression (CSPTR) was estimated by comparing photos obtained during pretreatment examination under anesthesia (EUA) with those obtained during post-treatment EUA 3--4 weeks later. CSPTR, ocular salvage rates, complication rates, operation times (unadjusted and adjusted for difficulty of ophthalmic artery catheterization), and intraprocedural dose expiration rates were compared between Evomela-and SFM-treated groups. Univariate and multivariate analyses were performed. Results Ninety-seven operations (melphalan: 45; Evomela: 52) for 23 patients with 27 retinoblastomas were studied. The ocular salvage rate was 79% in the SFM-treated group and 69% in the Evomela-treated group. Multivariate regression controlling for tumor grade, patient age, and treatment history revealed no significant differences in ocular salvage rate, CSPTR, complication rates, or operation times. Although the dose expiration rate was higher for the SFM-treated group, the difference was not statistically significant. Notably, there were no ocular or cerebral ischemic complications. Conclusion Evomela has non-inferior safety and efficacy relative to SFM when used for the treatment of retinoblastoma by selective ophthalmic artery infusion. [ABSTRACT FROM AUTHOR]

Background: Cerebral vasospasm (CV) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), leading to increased morbidity and mortality rates. Endovascular therapy, particularly intra-arterial vasodilator infusion (IAVI), has emerged as a potential alternative treatment for CV. Methods: A systematic review and meta-analysis were conducted to compare the efficacy of endovascular therapy with standard treatment in patients with CV following aSAH. The primary outcomes assessed were in-hospital mortality, discharge favorable outcome, and follow-up favorable outcome. Secondary outcomes included major infarction on CT, ICU stay duration, and total hospital stay. Results: Regarding our primary outcomes of interest, patients undergoing intervention exhibited a significantly lower in-hospital mortality compared to the standard treatment group, with the intervention group having only half the mortality risk (RR = 0.49, 95% CI [0.29, 0.83], p = 0.008). However, there were no significant differences between the two groups in terms of discharge favorable outcome (RR = 0.99, 95% CI [0.68, 1.45], p = 0.963) and follow-up favorable outcome (RR = 1.09, 95% CI [0.86, 1.39], p = 0.485). Additionally, there was no significant difference in major infarction rates (RR = 0.79, 95% CI [0.34, 1.84], p = 0.588). It is important to note that patients undergoing endovascular treatment experienced longer stays in the ICU (MD = 6.07, 95% CI [1.03, 11.12], p = 0.018) and extended hospitalization (MD = 5.6, 95% CI [3.63, 7.56], p < 0.001). Subgroup analyses based on the mode of endovascular treatment further supported the benefits of IAVI in lowering in-hospital mortality (RR = 0.5, 95% CI [0.27, 0.91], p = 0.023). Conclusion: Endovascular therapy, particularly IAVI, holds promising potential in reducing in-hospital mortality for patients with CV following aSAH. However, it did not show significant improvement in long-term prognosis and functional recovery. Further research with larger sample sizes and randomized controlled trials is necessary to validate these findings and optimize the treatment strategy for cerebral vasospasm in aSAH patients. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. Methods: Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. Results: Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102– 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102– 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. Conclusion: HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr. [ABSTRACT FROM AUTHOR]

Background Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival. Methods We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods. Results Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9). Conclusion IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and lenvatinib exhibits strong antitumor effects against advanced hepatocellular carcinoma (HCC). Higher antitumor activity is expected for the combination treatment. The aim of this trial was to evaluate the efficacy and safety of lenvatinib in combination with HAIC using cisplatin in patients with advanced HCC. Methods: In this multicenter, open-labeled, single-arm, phase II trial, patients with advanced HCC categorized as Child-Pugh class A with no prior history of systemic therapy were enrolled. Patients received lenvatinib plus HAIC with cisplatin (lenvatinib: 12 mg once daily for patients ≥60 kg, 8 mg once daily for patients <60 kg; HAIC with cisplatin: 65 mg/m2, day 1, every 4–6 weeks, maximum of six cycles). The primary endpoint was the objective response rate (ORR) assessed using modified RECIST by the Independent Review Committee. The secondary endpoints were the ORR assessed using RECIST v1.1, progression-free survival, overall survival, and frequency of adverse events associated with the treatment. Results: A total of 36 patients were enrolled between September 2018 and March 2020. In the 34 evaluable patients, the ORR assessed by the Independent Review Committee using modified RECIST and RECIST v1.1 were 64.7% (95% confidence interval [CI]: 46.5–80.3%) and 45.7% (95% CI: 28.8–63.4%), respectively. The median progression-free survival and overall survival were 6.3 months (95% CI: 5.1–7.9 months) and 17.2 months (95% CI: 10.9 – not available, months), respectively. The main grade 3–4 adverse events were increased aspartate aminotransferase (34%), leukopenia (22%), increased alanine aminotransferase (19%), and hypertension (11%). Conclusion: Lenvatinib plus HAIC with cisplatin yielded a favorable ORR and overall survival and was well tolerated in patients with advanced HCC. Further evaluation of this regimen in a phase III trial is warranted. [ABSTRACT FROM AUTHOR]

Peptide receptor radionuclide therapy (PRRT) confers significant progression-free survival advantage for patients with small bowel grade 1 and 2 well-differentiated neuroendocrine tumors (WD NET). PRRT may also be clinically beneficial for patients with NET of pancreatic, bronchial, and other sites of origin; patients with paragangliomas; as well as for patients with well-differentiated grade 3 NET. Direct intra-arterial (IA) administration of PRRT into the hepatic artery for patients with NET liver metastases may result in higher radiopharmaceutical dose and longer dwell time in the liver tumors while relatively sparing non-tumor liver tissue and other organs such as the kidneys and bone marrow when compared with intravenous (IV) administration. This review summarizes currently available data on IA and IV PRRT dose distribution, reports safety and efficacy of IA PRRT, and proposes future research questions. [ABSTRACT FROM AUTHOR]

Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open‐label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra‐arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8–3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra‐arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3–200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230–320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra‐arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: Identify risk factors for biliary toxicity in patients with colorectal liver metastases who received floxuridine (FUDR) via a surgically implanted hepatic artery infusion pump (HAIP). Describe the incidence of biliary toxicity and evaluate relevant patterns in the biliary toxicity cohort. Methods: A single center, retrospective, case-control study included adult colorectal cancer patients with liver metastases who received at least one cycle of FUDR via a surgically implanted HAIP from 1 January 2017, to 1 October 2021. Patients were excluded if they had incomplete records, cholangiocarcinoma diagnosis, or received concurrent mitomycin and FUDR. Biliary toxicity criteria derived from existing HAIP literature were utilized to determine whether patients experienced biliary toxicity. Multiple variables were compared by univariate statistical analysis between the biliary toxicity and non-biliary toxicity cohorts to identify potential risk factors for development of FUDR-induced biliary toxicity. Results: Out of 50 patients who had a HAIP implanted, 39 met the inclusion criteria. Five of the 39 patients (12.7%) included in the analysis met the pre-specified biliary toxicity criteria. No risk factors for biliary toxicity were identified. All five patients who developed biliary toxicity demonstrated elevations in alkaline phosphatase (ALP) prior to meeting the toxicity criteria. Conclusion: Biliary toxicity remains a significant and therapy-limiting consequence of FUDR administration. Rising ALP may be an early indicator of subsequent biliary toxicity. Future studies with more patients may identify risk factors that can facilitate risk mitigation strategies. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the effects of hepatic arterial infusion chemotherapy (HAIC) with or without systemic chemotherapy compared to systemic chemotherapy alone in patients with locally advanced hepatocellular carcinoma (HCC). Methods: Following a registered protocol (PROSPERO 2023 CRD42023386780 Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42023386780), a comprehensive search was performed using reputable databases and registries up to December 26, 2022, with no language, publication date, or status restrictions. Only randomized controlled trials (RCTs) investigating the effects of HAIC with or without systemic chemotherapy versus systemic therapy alone were included. The primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events. The secondary outcomes included the objective response rate (ORR) and disease control rate (DCR). A random-effects model was used, and the certainty of the evidence was rated using GRADE. Results: Seven RCTs involving 1,010 patients were included. All trials utilized sorafenib as the comparator. Five trials (690 patients) compared HAIC plus sorafenib to sorafenib alone, while two trials (320 patients) compared HAIC to sorafenib. The results indicate that HAIC, with or without sorafenib, may increase OS, PFS, and ORR compared with sorafenib alone. HAIC may enhance DCR, but the evidence is very uncertain. Adverse events were comparable between HAIC plus sorafenib and sorafenib alone. However, adverse events might be decreased in HAIC alone. Discussion: HAIC with or without systemic chemotherapy may improve survival outcomes and response rates of patients with HCC. Since the current body of evidence is moderate to very low, more robust randomized trials are needed to confirm the efficacy of HAIC. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of intrahepatic cholangiocarcinoma continues to rise, but survival remains dismal. Because malignancy often remains clinically indolent, treatment of the neoplasm becomes challenging. In advanced disease, locoregional therapies may be employed as a means of reducing toxicity and gaining disease control. A thorough understanding of these locoregional therapies will allow for optimal, individualized treatment. The intent of this review is to describethe role of intra-arterial therapies in the management of intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality. [ABSTRACT FROM AUTHOR]

Simple Summary: Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market, leading to a decrease in the number of patients eligible for this therapy. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. Fourteen patients underwent 15 modified procedures. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien–Dindo classification. Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices. Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. We retrospectively included patients who underwent a percutaneous placement of a hepatic intra-arterial port catheter in a single tertiary center from February 2021 to June 2022. We examined the patient baseline characteristics, technical features of the modified procedures, technical success rates, complications and oncological outcomes. Fourteen patients (median age: 60 years; q1 = 54; q3 = 70; range: 53–81 years) underwent 15 modified procedures. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien–Dindo classification. The median liver progression free survival was 6.1 months (q1 = 2.5; q3 = 7.2; range: 1.3–11.6). Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices. [ABSTRACT FROM AUTHOR]

Background: Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT). Methods: A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score. Results: A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1 year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04). Conclusion: This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases. [ABSTRACT FROM AUTHOR]

Aims: To mediate its pharmacodynamic effects, glyceryl trinitrate (GTN) requires bioactivation, by which it releases nitric oxide or a nitric oxide moiety. The exact mechanism of GTN bioactivation remains uncertain. Mitochondrial aldehyde dehydrogenase (ALDH‐2) has been proposed as the primary enzyme responsible for this bioactivation process. Evidence for the importance of ALDH‐2 in GTN bioactivation has been inconsistent, particularly in human models. An alternative hypothesis suggests that decreased ALDH‐2 activity leads to accumulation of reactive cytotoxic aldehydes, which either inhibit the vasoactive product(s) of GTN or impair other enzymatic pathways involved in the bioactivation of GTN. We investigated the effect of supplemental vitamin C on vascular responses to GTN in healthy volunteers of East Asian descent, of whom 12 with and 12 without the ALDH‐2 polymorphism participated. Methods: Subjects underwent 2 sequential brachial artery infusions of GTN at rates of 5, 11 and 22 nmol/min, separated by a 30‐min washout period. The GTN infusions were carried out in the presence and absence of vitamin C using a randomized, crossover design. Venous occlusion plethysmography was used to measure forearm blood flow responses to GTN. Results: Compared to subjects with functional ALDH‐2, the variant group exhibited blunted hemodynamic responses to intra‐arterial GTN infusions, although this reduction in response was not statically significant. Contrary to our hypothesis, vitamin C had an inhibitory effect on GTN mediated vasodilation as compared to GTN during saline in both groups. Conclusion: We conclude that vitamin C did not augment the acute vascular response to GTN in those with the ALDH‐2 polymorphism. [ABSTRACT FROM AUTHOR]

Insulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-treated hypertensives. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. During the follow-up [median: 117 months (range: 31–211)], we documented 223 new cases of HF (3.3 events/100 patient-years). We stratified the study population into progressors and non-progressors; progressors showed an older age and a higher prevalence of females, as well as higher mean values of baseline glucose, insulin, homeostasis model assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP), whereas the estimated glomerular filtration rate (e-GFR) and endothelium-dependent vasodilation were lower. In the multiple Cox regression analysis, serum hs-CRP (HR = 1.362, (95% CI = 1.208–1.536), HOMA (HR = 1.293, 95% CI = 1.142–1.465), maximal acetylcholine (Ach)-stimulated forearm blood flow (FBF) (100% increment, HR = 0.807, 95% CI = 0.697–0.934), and e-GFR (10 mL/min/1.73 m2 increment, HR = 0.552, 95% CI = 0.483–0.603) maintained an independent association with incident HF. HOMA and endothelial dysfunction interact between them in a competitive manner (HR = 6.548, 95% CI = 4.034–10.629), also showing a mutual effect modification. Our findings demonstrate that both endothelial dysfunction and HOMA are independent and strong predictors of incident HF in hypertensives, these two risk factors interact between them with a competitive mechanism. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) is a sophisticated structure whose full functionality is required for maintaining the executive functions of the central nervous system (CNS). Tight control of transport across the barrier means that most drugs, particularly large size, which includes powerful biologicals, cannot reach their targets in the brain. Notwithstanding the remarkable advances in characterizing the cellular nature of the BBB and consequences of BBB dysfunction in pathology (brain metastasis, neurological diseases), it remains challenging to deliver drugs to the CNS. Herein, we outline the basic architecture and key molecular constituents of the BBB. In addition, we review the current status of approaches that are being explored to temporarily open the BBB in order to allow accumulation of therapeutics in the CNS. Undoubtedly, the major concern in field is whether it is possible to open the BBB in a meaningful way without causing negative consequences. In this context, we have also listed few other important key considerations that can improve our understanding about the dynamics of the BBB. [ABSTRACT FROM AUTHOR]

Platinum-fluorouracil combination chemotherapy is the standard neoadjuvant treatment for locally advanced gastric cancer in China, but it does not improve the survival benefit of patients. In recent years, the application of immune checkpoint inhibitors and/or targeted drugs in neoadjuvant therapy for gastric cancer has achieved certain efficacy, but the survival benefit of patients is still not obvious. Intra-arterial infusion chemotherapy, as a method of regional therapy, has been widely used in the treatment of many advanced tumors and achieved remarkable curative effect. The role of arterial infusion chemotherapy in neoadjuvant therapy for gastric cancer is not clear. We describe two patients with locally advanced gastric cancer treated with continuous arterial infusion neoadjuvant chemotherapy. Two patients received continuous arterial infusion of chemotherapy drugs for 50 hours, the drugs were pumped into the main feeding artery of the tumor through the arterial catheter. A total of 4 cycles were followed, then undergone surgical resection. The postoperative pathological pCR of two patients was 100%, TRG was 0 grade, and no further anti-tumor therapy was required after operation, achieving clinical cure. During the treatment period, no serious adverse events occurred in either patient. These results suggest that continuous arterial infusion chemotherapy may be a new adjuvant therapy for locally advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: Inflammation-induced free radical release is important in the pathogenesis of several diseases, including atherosclerosis and sepsis. Heme oxygenase (HO) breaks down heme into carbon monoxide, iron, and biliverdin. Biliverdin IXα is directly converted to bilirubin by biliverdin reductase. Unconjugated bilirubin is a powerful antioxidant, and elevated levels have beneficial effects in preclinical models and human cardiovascular disease. However, its impact during acute inflammation in humans is unknown. In the present study, we investigated the impact of atazanavir-induced (unconjugated) hyperbilirubinemia on antioxidant capacity, inflammation, and vascular dysfunction in human experimental endotoxemia. Approach and results: Following double-blinded four-day treatment with atazanavir 2dd300 mg (or placebo), twenty healthy male volunteers received 2 ng/kg Escherichia coli lipopolysaccharide intravenously. Blood was drawn to determine the bilirubin levels, antioxidant capacity, and cytokine response. It was demonstrated that following atazanavir treatment, total bilirubin concentrations increased to maximum values of 4.67 (95%CI 3.91-5.59) compared to 0.82 (95%CI 0.64-1.07) mg/dL in the control group (p<0.01). Furthermore, the anti-oxidant capacity, as measured by the ferric-reducing ability of plasma (FRAP), was significantly increased with 36% in hyperbilirubinemia subjects (p<0.0001), and FRAP concentrations correlated strongly to bilirubin concentrations (R2 = 0.77, p<0.001). Hyperbilirubinemia attenuated the release of interleukin-10 from 377 (95%CI 233-609) to 219 (95%CI 152-318) pg/mL (p=0.01), whereas the release of pro-inflammatory cytokines remained unaltered. In vitro, in the absence of hyperbilirubinemia, atazanavir did not influence lipopolysaccharide-induced cytokine release in a whole blood assay. Vascular function was assessed using forearm venous occlusion plethysmography after intra-arterial infusion of acetylcholine and nitroglycerin. Hyperbilirubinemia completely prevented the LPS-associated blunted vascular response to acetylcholine and nitroglycerin. Conclusions: Atazanavir-induced hyperbilirubinemia increases antioxidant capacity, attenuates interleukin-10 release, and prevents vascular hyporesponsiveness during human systemic inflammation elicited by experimental endotoxemia. [ABSTRACT FROM AUTHOR]

An elderly woman with preinvasive breast cancer, atrial fibrillation, coronary artery-pulmonary artery fistula, pulmonary hypertension and Stage 4 diabetic nephropathy underwent a mastectomy and sentinel lymph node biopsy. Managing her perioperative fluid balance and anticoagulation treatment were challenging. Having a malignancy, atrial fibrillation plus underhydration will increase her risk of hypercoagulation. However, fluid overload will lead to pulmonary oedema which will decrease her oxygenation further in pulmonary hypertension. Cessation of anticoagulation also increased the risk of hypercoagulation. Anticoagulant therapy increases the risk of a perioperative wound haematoma, which may require another general anaesthesia for identification and arrest of the bleeding source and haematoma evacuation. A haematoma will also increase the risk of surgical site infection; especially as a diabetic. Her anticoagulant therapy (rivoroxaban) was stopped four days preoperatively. Her ejection fraction was 50%, with Grade II diastolic dysfunction and TAPSE 0.6 cm. Her CHA2DS2-VASc Score was 5. Perioperatively, intraarterial cannulation was connected to the FloTrac™ sensor and EV1000™ monitor. Her fluid management was monitored using goal directed (GD) fluid therapy. The patient underwent surgery successfully and her anticoagulant therapy was recommenced 14 days postoperatively. [ABSTRACT FROM AUTHOR]

Background. High-grade glioma is the commonest primary malignant brain tumour in adults. Intra-arterially selectively infused chemotherapeutic agents into the tumour bulk is being widely trialled recently with promising results. Methods. This is a prospective study designed between November 2015 and November 2019. Thirty patients were diagnosed with recurrent histo-pathologically proven GBM after one surgery at least and followed by standard radiotherapy and temodal. Patients aged between 37-76 years, 18 males and 12 females were subdivided into group A of 21 patients who underwent intra-arterial delivery of carboplatinand group B of 9 patients who underwent re-surgical resection and local application of carboplatin. Results. The mean age of the included cases was 55.4 years (range, 37-76 years). Selective intra-arterial injection was performed in 21 cases (70%), while the remaining 9 cases (30%) had local application of carboplatin in the tumour bed. Post-treatment vomiting was reported in 7 cases (23.3%). Significant and partial responses were achieved in 2 cases for each (6.7%). Time to tumour progression had a mean of 19.03 weeks (range, 3 - 30 weeks). After receiving carboplatin, the study cases had a mean survival of 26.5 weeks (range, 6 - 70 weeks). Intra-arterial injection had significantly better results compared to local tumour bed infiltration (p = 0.01). Conclusion. Although recurrent glioblastoma multiformis has poor survival, intraarterial delivery of carboplatin may have a slight positive impact on patient survival. The procedure however is relatively safe with manageable complications. [ABSTRACT FROM AUTHOR]

Background: The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas. Case presentation: A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer "T3", left tongue cancer "T2" and lower left lip cancer "T1", N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period. Conclusions: This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Superselective cisplatin (CDDP) infusion via the external carotid artery system and concomitant radiotherapy (RADPLAT) provides favorable oncological and functional outcomes in patients with maxillary sinus cancer. However, targeted lesions are occasionally fed by the branch of the internal carotid artery. Methods: In RADPLAT for maxillary sinus cancer partly fed by the ophthalmic artery, the ethmoid arteries were ligated in two patients without medial orbital wall involvement. In four patients with that, CDDP was administered via the ophthalmic artery. Results: A complete response was obtained in all six patients. Locoregional recurrence was not observed in any cases. However, visual acuity was lost in four patients who received the ophthalmic artery infusion. Conclusions: Ligation of the ethmoid arteries is recommended in RADPLAT for maxillary sinus cancer with lesions fed by the ophthalmic artery. CDDP administered via the ophthalmic artery may be considered if a patient accepts the possibility of visual loss. [ABSTRACT FROM AUTHOR]

Simple Summary: Unresectable biliary tract cancer has a poor prognosis, with insufficient response rates from the standard treatment. We developed a new combination therapy regimen of intra-arterial chemotherapy plus radiation therapy based on a retrospective study, and we found its high effectiveness in cases of some unresectable biliary tract cancers. Then, we conducted this prospective study, which demonstrated the benefits for some patients with unresectable biliary tract cancer, resulting in high clinical response and disease control rates of 71.4% and 100%, respectively. Furthermore, two patients converted to surgery, indicating its high potential as a preoperative therapeutic strategy to achieve a long-term prognosis. This treatment was considered tolerated due to the absence of treatment-related deaths. This prospective pilot study is an important step toward determining the usefulness and safety of intra-arterial chemotherapy plus radiation therapy, as well as its potential future utility. The standard treatment of unresectable biliary tract cancer (BTC) has shown an insufficient response rate (RR). Our retrospective setting revealed that a combination therapy consisting of intra-arterial chemotherapy plus radiation therapy (IAC + RT) provided a high RR and long-term survival benefits in unresectable BTC. This prospective study aimed to test the effectiveness and safety of IAC + RT as the first-line therapy. The regimen included one-shot IAC with cisplatin, 3–6 months of reservoir IAC (5-FU and cisplatin, q/week), and 50.4 Gy of external radiation. The primary endpoints include the RR, disease control rate, and adverse event rate. This study included seven patients with unresectable BTC without distant metastasis, with five cases classified as stage 4. RT was completed in all cases, and the median number of reservoir IAC sessions was 16. The RR was 57.1% for imaging and 71.4% for clinical assessment, and the disease control rate was 100%, indicating a high antitumor efficacy, which allowed two cases to be transferred to surgery. Five cases of leukopenia and neutropenia; four cases of thrombocytopenia; and two cases of hemoglobin depletion, pancreatic enzyme elevation, and cholangitis were observed, but with no treatment-related deaths. This study revealed a very high antitumor effect with IAC + RT for some unresectable BTC, and it could be useful for conversion therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Intrahepatic cholangiocarcinoma is an aggressive primary liver cancer originating in the intrahepatic bile ducts. While surgical resection is the only curative treatment, many patients present with locally advanced, unresectable, or metastatic disease, and few are candidates for curative-intent resection. In this review, we examine locoregional therapy approaches and summarize the current literature. Current locoregional therapies include thermal ablation, transarterial chemoembolization, transarterial radioembolization, external beam radiotherapy, stereotactic body radiotherapy, hepatic arterial infusion of chemotherapy, irreversible electroporation, and brachytherapy. These therapies are most often offered to patients with unresectable primary or recurrent intrahepatic cholangiocarcinoma, and studies on each modality have shown these locoregional approaches to be effective for prolonging overall survival. The findings of this review also further inform the need for future research regarding the efficacy of these treatments in comparison to each other due to the limited literature on optimal treatment strategies. Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, and surgical resection (SR) offers the only potential for cure. Unfortunately, only a small proportion of patients are eligible for resection due to locally advanced or metastatic disease. Locoregional therapies (LRT) are often used in unresectable liver-only or liver-dominant ICC. This review explores the role of these therapies in the treatment of ICC, including radiofrequency ablation (RFA), microwave ablation (MWA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), external beam radiotherapy (EBRT), stereotactic body radiotherapy (SBRT), hepatic arterial infusion (HAI) of chemotherapy, irreversible electroporation (IE), and brachytherapy. A search of the current literature was performed to examine types of LRT currently used in the treatment of ICC. We examined patient selection, technique, and outcomes of each type. Overall, LRTs are well-tolerated in the treatment of ICC and are effective in improving overall survival (OS) in this patient population. Further studies are needed to reduce bias from heterogenous patient populations and small sample sizes, as well as to determine whether certain LRTs are superior to others and to examine optimal treatment selection. [ABSTRACT FROM AUTHOR]

Simple Summary: Although reduced skeletal muscle mass affects therapeutic efficacy and adverse events in various therapies for hepatocellular carcinoma (HCC), there are no reports on skeletal muscle mass or its changes and prognostic indications in patients with advanced HCC undergoing hepatic arterial infusion chemotherapy (HAIC). This is the first study to show the association between the presence of a decreased skeletal muscle index (SMI) and clinical outcomes in HAIC, with novel evidence having a strong impact. A decrease in the SMI immediately after the start of HAIC was significantly associated with poor progression-free survival and overall survival in patients with advanced HCC, whereas the pre-treatment SMI was not a significant factor. Additionally, patients with a decreased SMI after treatment had worse nutritional status and liver function and poor therapeutic effects. It is effective to monitor the SMI and evaluate the therapeutic effects by using computed tomography to evaluate general conditions and predict clinical outcomes. Sarcopenia-related factors, including the skeletal muscle index (SMI), are reportedly associated with prognosis in patients with hepatocellular carcinoma (HCC) receiving various treatments. However, there is no evidence relating to hepatic arterial infusion chemotherapy (HAIC). In this study, we investigated whether a low SMI was associated with worse clinical outcomes of HAIC. Seventy patients with advanced HCC were included. Clinical outcomes were compared between the decreased SMI (n = 27) and non-decreased SMI (n = 43) groups, which were classified according to changes in the SMI after 3 weeks of treatment. In the prognostic analysis, patients in the decreased SMI group had significantly shorter progression-free and overall survival (OS) than those in the non-decreased SMI group. In addition, poor nutritional status and liver function were associated with an immediate decrease in the SMI after HAIC. The therapeutic effect was worse in the decreased SMI group than in the non-decreased SMI group, although the incidence of adverse events did not significantly differ. In multivariate analysis, a decreased SMI at 3 weeks after HAIC was identified as a significant independent factor associated with OS. A decreased SMI in patients with advanced HCC undergoing HAIC was associated with poor prognosis. It is effective to monitor the SMI to evaluate general conditions and predict clinical outcomes. [ABSTRACT FROM AUTHOR]

Despite the high success rate in reconstruction using free tissue transfer, flap failure is often caused by microvascular thrombosis. In a small percentage of cases with complete flap loss, a salvage procedure is performed. In the present study, the effectiveness of intra-arterial urokinase infusion through the free flap tissue was investigated to develop a protocol to prevent thrombotic failure. The retrospective study evaluated the medical records of patients who underwent salvage procedure with intra-arterial urokinase infusion after reconstruction with free flap transfer between January 2013 and July 2019. Thrombolysis with urokinase infusion was administered as salvage treatment for patients who experienced flap compromise more than 24 hours after free flap surgery. Because of an external venous drainage through the resected vein, 100,000 IU of urokinase was infused into the arterial pedicle only into the flap circulation. A total of 16 patients was included in the present study. The mean time to re-exploration was 45.4 hours (range: 24–88 hours), and the mean quantity of infused urokinase was 69,688 IU (range: 30,000–100,000 IU). 5 cases presented with both arterial and venous thrombosis, while 10 cases had only venous thrombosis and 1 case had only arterial thrombosis; in a study of 16 patients undergoing flap surgery, 11 flaps were found to have survived completely, while 2 flaps experienced transient partial necrosis and 3 were lost despite salvage efforts. In other word, 81.3% (13 of 16) of flaps survived. Systemic complications, including gastrointestinal bleeding, hematemesis, and hemorrhagic stroke, were not observed. The free flap can be effectively and safely salvaged without systemic hemorrhagic complications using high-dose intra-arterial urokinase infusion within a short period of time without systemic circulation, even in delayed salvage cases. Urokinase infusion results in successful salvage and low rate of fat necrosis. [ABSTRACT FROM AUTHOR]

Background: We aimed to verify the role of hENT1 as a prognostic predictor for patients with resectable pancreatic ductal adenocarcinoma (PDAC) who underwent radical resection followed by intra-arterial infusion of gemcitabine-based regimen. Methods: We collected surgical samples from 102 patients with resectable PDAC who received radical resection followed by intra-arterial infusion of gemcitabine-based regimen. The hENT1 expression with the help of immunohistochemistry was conducted using formalin-fixed and paraffin embedded tissues. The Kaplan–Meier analyses and Cox regression were used to evaluate the mortality hazard associated with the discrepancy between strong and weak of hENT1 expression. Patients' clinical and pathological characteristics were compared between the two groups, then the role of hENT1 as a prognostic predictor was further explored. Results: A total of 102 patients were included to assess the hENT1 expression. 50 patients were classified into high hENT1 expression group, the other 52 patients were attributed into low hENT1 expression group. High hENT1 expression was related to a significantly improved overall survival (OS) (p = 0.014) and disease-free survival (DFS) (p = 0.004). Both univariate (p = 0.001) and multivariate analyses (p < 0.001) indicated that high hENT1 expression was related to a decreased mortality. Conclusions: High expression of hENT1 is positive prognostic factor for adjuvant intra-arterial gemcitabine-based chemotherapy in resectable PDAC. [ABSTRACT FROM AUTHOR]

Introduction: Radiation and intra-arterial cisplatin infusion chemotherapy (RADPLAT) for advanced maxillary sinus cancer has accumulated evidence as a treatment with fewer complications and better 5-year survival rates. In this study, we report a case in which pterygoid muscle necrosis occurred 6 months following RADPLAT treatment for maxillary sinus cancer. Case Presentation: The 45-year-old woman had a long history of taking immunosuppressants against rheumatoid arthritis (RA) prior to treatment. Although achieving complete response (CR) to RADPLAT, the patient developed trismus (1 fingerbreadth or less) 6 months following treatment. Abscess formation and recurrence were suspected from the imaging findings; however, the biopsy with endoscopy indicated necrotic tissue. Currently, 18 months have passed without cancer recurrence. Although trismus temporarily improved with rehabilitation, the width of the mouth opening is currently a few millimeters, so the patient can only take liquid food. Conclusion: Pterygoid muscle necrosis should be recognized as a new major complication. [ABSTRACT FROM AUTHOR]

Objective: To preliminarily evaluate the efficacy and safety of pancreatic intra-arterial infusion chemotherapy (PAIC) with nab-paclitaxel in patients with advanced pancreatic carcinoma. Methods: Fifteen patients with advanced pancreatic carcinoma received monthly, inpatient, 3-h, continuous PAIC of nab-paclitaxel at 180 mg/m2, combined with 60 mg oral tegafur gimeracil oteracil potassium capsule for 2 weeks. The therapeutic courses were repeated every 4 weeks. All patients had a preliminary diagnosis based on clinical symptoms, imaging data (computed tomography or magnetic resonance imaging or positron emission tomography/computed tomography), and tumor markers. The adverse effects, clinical benefit response (CBR), objective response rate (ORR), median progression free survival (mPFS), and median overall survival (mOS) were monitored. Results: Fifteen patients with advanced pancreatic carcinoma were enrolled in this study, including 10 male and 5 female patients. The mean age at the time of treatment was 66.3 years (53–84 years). A total of 49 cycles of PAIC (mean = 3.27 cycles/patient) were performed. The most common treatment-related toxicities were alopecia, diarrhea, and nausea/vomiting. No procedure-related complications were observed. The longest overall survival observed was 22 months and the maximum number of treatments for the same patient was six cycles. PAIC contributed a high rate (13/15 [86.67%]) and fast (10/15 [66.67%]) easement of pain, with apparent symptom relief within 24 h, especially local pain symptom. The pain anesis rate was 13 (86.67%). CBR was achieved in 13 (86.67%) patients (95%CI [59.54,98.34]). ORR was achieved in four (26.67%) patients (95%CI [7.79,55.10]). Disease Control Rate was achieved in 14 (93.33%) patients. The mPFS was 5.22 months (interquartile range [IQR], 4.27–7.85 months). The mOS was 8.97 months (IQR, 5.65–13.70 months). Conclusions: In this study, the dose of the chemotherapeutics and the schedule of the transcatheter pancreatic arterial chemotherapy perfusion were shown to be safe, well-tolerated, and effective for the relief of clinical symptoms and CBR. These advantages can quickly establish the treatment belief and improve patient quality of life. This regimen requires further investigation in patients with advanced pancreatic carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery is the current standard for locally advanced tongue cancer. However, substantial impairment may occur even after treatment. Therefore, more effective and less toxic treatment strategies are needed to avoid a reduction in the patient's quality of life. This study aims to evaluate the efficacy and safety of a novel device that we have developed for retrograde intra-arterial chemotherapy (IACT) in patients with locally advanced tongue cancer. Our study demonstrates that the 3-year overall survival and progression-free survival were 81.6% and 74.2%, respectively. These results are not inferior to those of surgery, and no complications (e.g., cerebral infarction or catheter-related infection) have been associated with IACT were observed. We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control's 8th TNM stage III–IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil.Methods: This study included patients with a primary diagnosis of unresectable HCC. These patients received HAIC for 1 day or 2 days. The overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were compared. The propensity score matching (PSM) was used to reduce bias. Peripheral blood samples before the treatments were collected and used to measure the concentration of TYMS through enzyme-linked immunosorbent assay (ELISA). ELISA was performed according to the manufacturers' guidelines.Results: We included 368 patients for this study: 248 in the HAIC 1d group and 120 in the HAIC 2d group. There was no significant difference of OS between the two groups (14.5 for HAIC 1d vs 15.3 months for HAIC 2d, p=0.46). Compared with the HAIC 1d group, the HAIC 2d group did not prolong the PFS (7.3 vs 7.5 months, p=0.91) or elevate the tumor response (42.5% vs 39.1%, p=0.53) per RECIST 1.1. In the PSM cohort, the efficacy between the two groups was similar. The total frequencies of grade 3-4 events were higher with the HAIC 2d group than with the HAIC 1d group, especially in the PSM cohort (p=0.043). Additionally, patients with TYMS low level might benefit longer OS from the HAIC 2d group (18.7 vs 13.6 months, p=0.014).Conclusions: There was not much of a difference in efficacy between the two groups, but the HAIC for 1 day might be safer, which needed further research. The level of TYMS might be the predictive biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: New-FP is a regimen of hepatic arterial infusion chemotherapy for hepatocellular carcinoma (HCC). In the study, the regimen significantly prolonged the survival of patients with major portal vein tumor thrombus-HCC. Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy (HAIC) regimens New-FP and sorafenib for various tumor conditions in preserved liver function. Methods: We retrospectively collected the data of 1709 patients with HCC who were treated with New-FP or sorafenib. Survival was assessed after propensity score matching. Subgroup analyses were conducted: cohort 1 (no MVI or extrahepatic spread (EHS)), cohort 2 (MVI only), cohort 3 (EHS only), cohort 4 (MVI and EHS), and cohort 5 (major PVTT). Results: The New-FP group had a longer median survival time (MST) than the sorafenib in the whole analysis (18 vs. 9 months; p < 0.0001). New-FP demonstrated a longer MST compared with sorafenib in cohort 2 and cohort 4. In cohort 5, the MST of the New-FP group was 16 months, while that of sorafenib was 6 months (p < 0.0001). For major PVTT-HCC, the response rate of New-FP was 73.0%. The MST of patients who achieved complete response with New-FP was 59 months. Conclusions: HAIC using New-FP is promising for patients with MVI- and major PVTT-HCC in preserved liver function. [ABSTRACT FROM AUTHOR]

Objective: To provide a comprehensive review of intra-arterial cerebral infusions of chemotherapeutics in glioblastoma multiforme treatment and discuss potential research aims. We describe technical aspects of the intraarterial delivery, methods of blood-brain barrier disruption, the role of intraoperative imaging and clinical trials involving intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Method: 159 articles in English were reviewed and used as the foundation for this paper. The Medline/Pubmed, Cochrane databases, Google Scholar, Scielo and PEDro databases have been used to select the most relevant and influential papers on the intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Additionally, we have included some relevant clinical trials involving intra-arterial delivery of chemotherapeutics to other than GBM brain tumours. Conclusion: Considering that conventional treatments for glioblastoma multiforme fall short of providing a significant therapeutic benefit, with a majority of patients relapsing, the neuro-oncological community has considered intra-arterial administration of chemotherapeutics as an alternative to oral or intravenous administration. Numerous studies have proven the safety of IA delivery of chemotherapy and its ability to ensure higher drug concentrations in targeted areas, simultaneously limiting systemic toxicity. Nonetheless, the scarcity of phase III trials prevents any declaration of a therapeutic benefit. Given that the likelihood of a single therapeutic agent which will be effective for the treatment of glioblastoma multiforme is extremely low, it is paramount to establish an adequate multimodal therapy which will have a synergistic effect on the diverse pathogenesis of GBM. Precise quantitative and spatial monitoring is necessary to guarantee the accurate delivery of the therapeutic to the tumour. New and comprehensive pharmacokinetic models, a more elaborate understanding of glioblastoma biology and effective methods of diminishing treatment-related neurotoxicity are paramount for intra-arterial cerebral infusion of chemotherapeutics to become a mainstay treatment for glioblastoma multiforme. Additional use of other imaging methods like MRI guidance during the procedure could have an edge over X-ray alone and aid in selecting proper arteries as well as infusion parameters of chemotherapeutics making the procedure safer and more effective. [ABSTRACT FROM AUTHOR]

Background: Cerebral vasospasm (CVS) is a leading cause of morbidity and mortality in patients after aneurysmal subarachnoid hemorrhage (aSAH). Endovascular treatment, including intraarterial infusion of drugs with vasodilation effects, and balloon- and stentriever angioplasty, are helpful but may achieve only short-term effects. There is a clinical need for long-lasting treatment of refractory recurrent vasospasm. We report our experience in stent implantation as a treatment for recurrent severe post-SAH vasospasm.Methods: A retrospective analysis of our institutional database of 883 patients with SAH, managed between January 2010 and December 2021, was performed. Six patients were identified as having received intracranial stenting in the context of post-SAH cerebral vasospasm. All patients were initially treated with intra-arterial infusion of nimodipine and/or milrinone. Self-expanding intracranial stents were implanted during endovascular aneurysm treatment to enable access despite impaired perfusion (Group 1) or as a bail-out strategy after failed intraarterial drug infusion or mechanical treatment (Group 2). All stented patients received dual antiplatelet therapy (DAPT) for 6 months.Results: Nine vessels in six patients with severe post-SAH vasospasm were stented. The stents were deployed in 16 vessel segments. All attempted implantations were technically successful. All patients demonstrated radiographic and clinical improvement of the vessel narrowing. No recurrent vasospasm or permanent vessel occlusion of the stented vessels was encountered. A thrombus formation in a Group 1 patient resolved under 4 mg eptifibatide IA infusion. During long-term angiographic follow-up, neither in-stent stenosis nor stent occlusion was found.Conclusions: Endovascular implantation of self-expanding stents is a potential ultima ratio strategy for patients with severe refractory post-SAH cerebral vasospasm. Stents with reduced thrombogenicity (avoiding DAPT) and bioabsorbable self-expanding stents might further advance this concept. [ABSTRACT FROM AUTHOR]

Background Cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage (aSAH) is still a problem. Hypertension, hypervolemia, and hemodilution (triple-H) therapy and oral nimodipine only a modest effect on patients. Intra-arterial treatment, including nimodipine, has been studied, but only as retrospective and single-arm prospective studies. We compared the outcomes between CV patients who received an adjunct intra-arterial nimodipine infusion (IANI) and those who received the standard medical treatment alone in a prospective randomized controlled trial. Methods In this study, patients between the age of 18 and 80 years, who underwent angiography within 14 days after aneurysm obliteration, were recruited and randomized to receive adjunct IANI or not, if they were identified with angiographic vasospasm. All the angiographic and neurologic data were recorded and analyzed during their admission, at the discharge date, and during the 6-month follow-up period. Results From June 2016 to December 2018, we enrolled 68 patients who were randomized into two groups, 36 in the intervention group and 32 in the control group. The patients' characteristics, aneurysm data, and modalities of treatment were similar between the two groups. Within 24 hours after IANI, Glasgow Coma Scale (GCS) score and motor strength revealed a significant improvement of 33.33 and 38.89%, respectively, in the intervention group versus 12.5 and 9.38%, respectively, in the control group. At discharge, the intervention group still had significant motor improvement (58.33 vs. 21.88%; p = 0.002). Conclusion IANI could be considered an effective treatment for CV without significant complications. This is the first RCT demonstrating statistically significant motor strength improvement within 24 hours and at discharge. [ABSTRACT FROM AUTHOR]

Purpose: To report our thrombolytic technique, treatment strategy, and clinical outcomes for porto-mesenteric venous thrombosis (PMVT) in non-cirrhotic patients. Methods: Sixteen acute or chronic non-cirrhotic PMVT patients (mean age: 48.6 years) with imminent intestinal ischemia were enrolled from 2004 to 2020. Eight patients presented thrombus extension into the peripheral mesenteric vein, close to the venous arcade. Transhepatic catheter-directed thrombolysis (CDT) was performed by urokinase infusion (60,000–30,000 IU/h concomitant with heparin 300–400 IU/h), catheter aspiration, and/or balloon dilation/stent placement. Additional intra-arterial mesenteric infusion of urokinase (30,000 IU/h) was given in patients with the peripheral mesenteric venules involved. Transjugular intrahepatic porto-systemic shunt (TIPS) was created in patients with poor recanalization of the intrahepatic portal flow (PV). Results: The transhepatic route was adopted in all patients, with adjunct indirect mesenteric arterial thrombolytic infusion in eight patients. A total of up to 20.4 million IU urokinase was infused for 1–21 days' treatment duration. TIPS was created in three patients with recanalization failure of the intrahepatic PV. Technical success was achieved in 100% of patients with complete recanalization of 80% and partial recanalization of 20%. No major procedure-related complications were encountered. The 30-day mortality rate was 6.7%. The overall two-year primary patency was 84.6%. Conclusions: CDT can be performed as a primary salvage treatment once the diagnosis is made. CDT via the transhepatic route with tailored thrombolytic regimen is safe and effective for both acute and chronic PMVT. TIPS creation can be preserved in non-cirrhotic PMVT patients if intrahepatic PV recanalization fails. [ABSTRACT FROM AUTHOR]

Introduction: Systematic and quantitative descriptions of vein of Marshall (VOM)‐induced tissue ablation are lacking. We sought to characterize the distribution of low voltage observed in the left atrium (LA) after VOM ethanol infusion. Methods and Results: The distribution of ethanol‐induced low voltage was evaluated by comparing high‐density maps performed before and after VOM ethanol infusion in 114 patients referred for atrial fibrillation ablation. The two most frequently impacted segments were the inferior portion of the ridge (82.5%) and the first half of the mitral isthmus (pulmonary vein side) (92.1%). Low‐voltage absence in these typical areas resulted from inadvertent ethanol infusion in the left atrial appendage vein (n = 3), initial VOM dissection (n = 3), or a "no branches" VOM morphology (n = 1). Visible anastomosis of the VOM with roof or posterior veins more frequently resulted in low‐voltage extension beyond typical areas, toward the entire left antrum (19.0% vs. 1.9%, p =.0045) or the posterior LA (39.7% vs. 3.8%, p <.001) but with a limited positive predictive value ranging from 29.4% to 43.5%. Ethanol‐induced low voltage covered a median LA surface of 3.6% (1.9%–5.0%) and did not exceed 8% of the LA surface in 90% of patients. Conclusion: VOM ethanol infusion typically locates at the inferior ridge and the adjacent half of the mitral isthmus. Low‐voltage extensions can be anticipated but not guaranteed by the presence of visible anastomosis of the VOM with roof or posterior veins. [ABSTRACT FROM AUTHOR]

Besides visual assessment of the intra-vascular appearance, intravascular optical coherence tomography (IVOCT) enables precise diameter measurements within the coronary arteries. The current study presents an upgraded test setup allowing the investigation of the elastic properties of porcine coronary arteries ex vivounder pulsatile flow conditions. IV-OCT imaging was performed within the left circumflex artery of a porcine heart applying a normotensive and a hypertensive pressure regime at different pulse rates. Radial compliance was derived from the luminal diameter as well as intra-arterial pressure measurements. Test results show a significant reduction of radial compliance under pulsatile conditions, when compared to reference measurements under steady flow. The mean radial compliance decreased with increasing pulse rate, which can be attributed to the viscoelastic properties of the arterial wall. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Insulinoma presenting only with postprandial hypoglycemia is difficult to diagnose. Repeated episodes of hypoglycemia can lead to “hypoglycemia unawareness”, which can be even more dangerous and requires early detection and treatment. Case Report: We report the case of a 35-year-old man with an insulinoma presenting as postprandial hypoglycemia who was treated with diazoxide and monitored using a factory-calibrated continuous glucose monitoring (CGM) system until surgery. When the patient initially presented with hypoglycemia, relative hyperinsulinemia was present. There were no obvious abnormal findings on imaging examination. Hypoglycemia was not repeated on endocrinological examination, even while fasting. Four months later, asymptomatic postprandial hypoglycemia of 48 mg/dL was incidentally detected. Although none of the conventional 3 indicators of relative hyperinsulinemia were met, an insulinoma was suspected based on the results of a fasting test. Computed tomography and magnetic resonance imaging showed a mass in the pancreatic uncinate process, and selective intra-arterial calcium infusion revealed high insulin levels in the same area, leading to a diagnosis of insulinoma. The patient was treated medically with diazoxide, using a factory-calibrated CGM system until surgery. Subsequently, pancreatic mass enucleation was performed, and pathological examination confirmed the diagnosis. After surgery, the hypoglycemia resolved, and the blood glucose level remained within a range of 100 to 180 mg/dL, without the use of diazoxide. Conclusions: A factory-calibrated CGM system is useful for evaluating the course of medical treatment, monitoring hypoglycemic episodes during the diagnostic period, detecting unconscious hypoglycemia, monitoring the response to medical treatment, and treating insulinoma after surgery. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy.Methods: This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle.Results: Among 47 patients, 32 (68%) were males. The median age was 61 (29-75). With a median follow-up of 22.2 months (3.7-50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0-13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events.Conclusions: Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy. [ABSTRACT FROM AUTHOR]