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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]

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]

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]

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]

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]

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]

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]

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]

Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer has a very poor prognosis. The few available therapeutic options are characterized by low efficacy and high toxicity due to the intrinsic chemoresistance of this tumor type. To improve clinical results, some clinical trials have evaluated regional chemotherapy as a treatment option for PC. The pancreatic arterial infusion of chemotherapeutics has the aim of obtaining higher local concentrations of drugs and, at the same time, of limiting systemic toxicity. This therapeutic approach has already been successfully evaluated for the treatment of several types of tumors. Regarding advanced pancreatic cancers, only a few clinical studies have investigated the safety and efficacy of this treatment, with very promising results. Therefore, in this review, we summarize literature data on the clinical approaches to pancreatic arterial drug administration for the treatment of advanced PC to deepen knowledge on this topic. Advanced pancreatic cancer (PC) has a very poor prognosis due to its chemoresistant nature. Nowadays, only a few therapeutic options are available for PC, and the most effective ones are characterized by low response rates (RRs), short progression-free survival and overall survival, and severe toxicity. To improve clinical results, small series studies have evaluated loco-regional chemotherapy as a treatment option for PC, demonstrating its dose-dependent sensitivity towards the tumor. In fact, pancreatic arterial infusion (PAI) chemotherapy allows higher local concentrations of chemotherapeutic agents, sparing healthy tissues with a lower rate of adverse events compared to systemic chemotherapy. This therapeutic approach has already been evaluated in different types of tumors, especially in primary and metastatic liver cancers, with favourable results. With regard to advanced PC, a few clinical studies have investigated the safety and efficacy of PAI with promising results, especially in terms of RRs compared to systemic chemotherapy. However, clear evidence about its efficacy has not been established yet nor have the underlying mechanisms leading to its success. In this review, we aim to summarize the literature data on the clinical approaches to pancreatic arterial drug administration in terms of techniques, drug pharmacokinetics, and clinical outcomes for advanced PC. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer is one of the leading causes of cancer-related deaths worldwide and balloon-occluded transarterial chemoembolization (B-TACE) has emerged as a safe and effective treatment for liver cancer. However, the hemodynamic alterations that are responsible for the successfulness of the treatment and are produced by the microballoon catheter used during the treatment are not yet well understood. In this study, we developed an in vitro model (IVM) that can simulate B-TACE. We designed clinically relevant experiments, and we obtained clinically realistic results. We conclude that the IVM allows for a visual understanding of a complex phenomenon (i.e., the blood flow redistribution after balloon occlusion) and it could be used as a base for future sophisticated and even patient-specific IVMs; in addition, it could be used to conduct IVM-based research on B-TACE. Background: Balloon-occluded transarterial chemoembolization (B-TACE) has emerged as a safe and effective procedure for patients with liver cancer, which is one of the deadliest types of cancer worldwide. B-TACE consist of the transcatheter intraarterial infusion of chemotherapeutic agents, followed by embolizing particles, and it is performed with a microballoon catheter that temporarily occludes a hepatic artery. B-TACE relies on the blood flow redistribution promoted by the balloon-occlusion. However, flow redistribution phenomenon is not yet well understood. Methods: This study aims to present a simple in vitro model (IVM) where B-TACE can be simulated. Results: By visually analyzing the results of various clinically-realistic experiments, the IVM allows for the understanding of balloon-occlusion-related hemodynamic changes and the importance of the occlusion site. Conclusion: The IVM can be used as an educational tool to help clinicians better understand B-TACE treatments. This IVM could also serve as a base for a more sophisticated IVM to be used as a research tool. [ABSTRACT FROM AUTHOR]

Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted. [ABSTRACT FROM AUTHOR]

Anticoagulant use, such as heparin, is usually contraindicated in acute stroke patients. We present a study of patients, who were treated with intravenous heparin after a stroke that were also found to have an intraluminal thrombus. Prior studies imply that recanalization is achieved with heparin; however heparin should only prevent thrombus propagation. Therefore it is unclear whether and how IV heparin can achieve recanalization of intraluminal thrombi in acute stroke patients. A retrospective review of all acute stroke patients from a single stroke center who received a therapeutic IV heparin infusion from 5/2006 to 9/2011 were included in the study. We compared patients who had complete/partial recanalization and/or improved flow versus those that did not, with both these groups on a standard intravenous heparin infusion protocol. Demographic data was compared between the groups. Average partial thromboplastin time (PTT) during heparin infusion, time between computed tomography angiographies (CTAs), time from stroke onset to receiving IV heparin, and vessel occluded were also compared between groups. Forty-one patients (19 female, 22 male) were included in the study with a total of 55 vessels (either carotid, middle cerebral artery, anterior cerebral artery, posterior cerebral artery/posterior circulation) having intraluminal thrombi; 31 patients had 41 vessels with either partial or complete recanalization of effected vessels, while 10 patients had 14 vessels that did not have at least one vessel recanalize while on heparin. Using t-test we noted that the average PTT between the vessels that had partial/complete recanalization group (61.74) and nonrecanalization group (66.30) was not statistical significantly different (P=0.37).The average time in days on heparin between vascular imaging studies (CTA/conventional angiogram) in the group of vessels with partial/complete recanalization (7.12 days) and the ones with no change (6.11 days) was not significantly different between the two groups (P=0.59). Patient's vessels receiving heparin for <24 hours versus those >24 hours did not significantly differ either (P=0.17). This study compares patient characteristics associated with recanalization of intraluminal thrombi in acute stroke patients on heparin. Recanalization of intraluminal thrombi are not associated with average PTT or duration on heparin. [ABSTRACT FROM AUTHOR]

Simple Summary: Although various molecular targeted agents have been approved, the therapeutic outcomes in hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) are still unsatisfactory. Locoregional treatment using hepatic arterial infusion chemotherapy is a promising treatment for MVI-HCC. In the study, we aimed to compare the therapeutic effects of low-dose cisplatin plus 5-fluorouracil (LFP), a conventional HAIC regimen, and New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) for MVI-HCC with preserved liver function. New FP was significantly superior to LFP in all therapeutic outcomes. New FP is a recommended HAIC regimen for the treatment of patients with MVI-HCC. Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) and low dose FP (LFP/cisplatin plus 5-fluorouracil) in the treatment of MVI-HCC patients with Child–Pugh class A. New FP is a regimen that consists of a fine-powder cisplatin suspended with lipiodol and 5-fluorouracil. Fifty-one patients were treated with LFP, and 99 patients were New FP. We compared the therapeutic effects of LFP and New FP and assessed factors that associated with the therapeutic effects. The median survival and progression-free survival times of LFP and New FP were 16.1/24.7 and 5.4/8.8 months, respectively (p < 0.05, p < 0.05). The complete response (29%) and objective response rate (76%) of New FP were significantly higher than those of LFP (p < 0.001, p < 0.01). Factors associated with better therapeutic response were better ALBI-grade and New FP treatment choice. New FP is a more powerful regimen than LFP in HAIC for MVI-HCC. New FP represents a recommended HAIC regimen for the treatment of patients with MVI-HCC. [ABSTRACT FROM AUTHOR]

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in "in vivo" animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver functional failure is one of the leading causes of cancer-related death. Systemic chemotherapy usually offers a modest benefit in terms of disease control rate, progression-free survival, and overall survival at the cost of a significant percentage of adverse events. Liver malignancies are mostly perfused by the hepatic artery while the normal liver parenchyma by the portal vein network. On these bases, the therapeutic strategy consisting of hepatic arterial infusion of chemotherapy takes place. This review aims to summarize the current knowledge on this approach from different points of view, such as techniques, drugs pharmacology and pharmacokinetics, and clinical outcomes for advanced hepatobiliary cancers. Most of the collected studies have several limitations: non-randomized retrospective design, a relatively small number of patients, the hepatic arterial administration of different chemotherapeutic agents, as well as its combination with a great heterogeneity of systemic agents. However, despite these limitations, the presented data show favorable results in terms of safety and efficacy for hepatic arterial infusion of chemotherapy, with respect or in alternative to the gold standard treatment, even when they are combined with systemic treatments. Therefore, this therapeutic strategy may be an alternative or an integrative treatment option for advanced hepatobiliary cancers. Further and larger prospective, randomized, multi-center studies, with well-defined inclusion criteria and treatment strategies, are required to confirm the presented data. Liver functional failure is one of the leading causes of cancer-related death. Primary liver tumors grow up mainly in the liver, and thus happens for liver metastases deriving from other organs having a lower burden of disease at the primary site. Systemic chemotherapy usually offers a modest benefit in terms of disease control rate, progression-free survival, and overall survival at the cost of a significant percentage of adverse events. Liver malignancies are mostly perfused by the hepatic artery while the normal liver parenchyma by the portal vein network. On these bases, the therapeutic strategy consisting of hepatic arterial infusion (HAI) of chemotherapy takes place. In literature, HAI chemotherapy was applied for the treatment of advanced hepatobiliary cancers with encouraging results. Different chemotherapeutic agents were used such as Oxaliplatin, Cisplatin, Gemcitabine, Floxuridine, 5-Fluorouracil, Epirubicin, individually or in combination. However, the efficacy of this treatment strategy remains controversial. Therefore, this review aims to summarize the current knowledge on this approach from different points of view, such as techniques, drugs pharmacology and pharmacokinetics, and clinical outcomes for advanced hepatobiliary cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Intravenous chemoreduction (IVCRD) has been the standard of care for treatment of retinoblastoma (RB). Since survival rates exceed 95–98%, the goals of treatment have now shifted to emphasize eye salvage and vision preservation in addition to patient survival. Consequently, there has been a shift towards combining standard IVCRD with intravitreal chemotherapy or altogether replacing IVCRD with intra-arterial chemotherapy. As more data from intravitreal chemotherapy and intra-arterial chemotherapy are being published, there are claims of improved globe salvage rates resulting in more widespread use of these newer treatment modalities. However, there are no published randomized controlled trials comparing these to IVCRD head-to-head. To evaluate the relative efficacy of these new therapies, it is critical to determine the true success rates of IVCRD regimens alone. Therefore, it is both timely and essential to determine the baseline IVCRD success rates so that an evidence-based assessment of new and emerging therapies can be determined. To evaluate the relative efficacy of novel retinoblastoma treatments, eye classification-specific success rates for current standard-of-care intravenous chemotherapy regimens must be known. This meta-analysis included studies if: (1) patients received intravenous chemotherapy for retinoblastoma, (2) globe salvage data was reported, (3) only intravenous chemoreduction (with/without local consolidation) was used. The outcome measure was globe salvage success without need for salvage radiotherapy, subdivided by disease classification and chemotherapy regimen. Data from 27 studies (1483 eyes) were pooled. By Reese–Ellsworth classification, globe salvage rates were 85% (95%CI:73–92%) for Group I, 78% (95%CI:70–85%) for Group II, 68% (95%CI:56–78%) for Group III, 47% (95%CI:34–60%) for Group IV, and 35% (95%CI:26–45%) for Group V (Va: 35% [95%CI:21–54%]; Vb: 42% [95%CI:29–56%]; those without sub-classification: 31% [95%CI:19–47%]). By International Classification, globe salvage rates were 93% (95%CI:80–97%) for Group A, 83% (95%CI:73–89%) for Group B, 73% (95%CI:54–86%) for Group C, 40% (95%CI:31–51%) for Group D, and 19% (95%CI:5–50%) for Group E. Standard carboplatin-etoposide-vincristine out-performed two-drug regimens (odds ratio (OR) = 1.9 (95%CI:1.3–3.0) for Groups I-IV and OR = 2.1 (95%CI:1.3–3.4) for Group V; p = 0.002 for each). For eyes with diffuse vitreous seeds (Vb), an enhanced regimen out-performed standard chemotherapy (OR = 2.4 [95%CI:1.3–4.7]; p = 0.004). In conclusion, two-drug regimens were less effective for all eyes, whereas enhanced regimens were more effective for eyes with vitreous seeds. Novel therapies can now be compared to these baseline globe salvage rates. [ABSTRACT FROM AUTHOR]

Radioembolization (RE) is a treatment for patients with liver cancer, one of the leading cause of cancer-related deaths worldwide. RE consists of the transcatheter intraarterial infusion of radioactive microspheres, which are injected at the hepatic artery level and are transported in the bloodstream, aiming to target tumors and spare healthy liver parenchyma. In paving the way towards a computer platform that allows for a treatment planning based on computational fluid dynamics (CFD) simulations, the current simulation (model preprocess, model solving, model postprocess) times (of the order of days) make the CFD-based assessment non-viable. One of the approaches to reduce the simulation time includes the reduction in size of the simulated truncated hepatic artery. In this study, we analyze for three patient-specific hepatic arteries the impact of reducing the geometry of the hepatic artery on the simulation time. Results show that geometries can be efficiently shortened without impacting greatly on the microsphere distribution. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy 'holiday' or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with systemic treatments such as sorafenib. Hepatic arterial infusion chemotherapy (HAIC) is the treatment using an indwelling catheter port system. The regimen of HAIC used in the study is New FP which is consisted of a fine-powder cisplatin and 5-fluorouracil. In the study, for the patients with locally progressed HCC, such as HCC with vascular invasion, initial administration of local hepatic treatment using HAIC was superior to systemic treatment using sorafenib. BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib; 1624 (New-FP, n = 644; sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months; sorafenib, 7.9 months; p < 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS. [ABSTRACT FROM AUTHOR]

Simple Summary: Contrary to other cancers, treatment of human uveal malignant melanoma metastases has not evolved sufficiently remaining as a great challenge in the field of ocular oncology. Although uveal melanoma is effectively controlled at the local level, the diagnosis of systemic disease in these patients makes its prognosis fatal, with survival rates of around 4–8 months. In this manuscript, we performed a systematic review studying comprehensively all the different treatment types for metastatic uveal melanoma disease in the last 40 years. We truly believe that our work shows a global vision of the situation, placing the reader in a concise and orderly manner in perspective of the current state of the subject. Introduction: More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease. Methods: A systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan–Meier curves or numerically. Results: After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9–22 months), isolated liver perfusion (OS: 9, 6–27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6–17 months), immunotherapy (OS: 5–19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6–12 months), without being significant. Conclusions: The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15–116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue. [ABSTRACT FROM AUTHOR]

Liver metastases (LM) are often consequences of colo-rectal cancer (CRC)and the majority of patients have unresectable LM. Oxaliplatin-based intravenous chemotherapy represents the gold standard treatment for CRC. Intravenous oxaliplatin has several side effects i.e., nephrologic, hematologic and neurological toxicity. Moreover, hepatic arterial infusion (HAI) of antitumor drugs deeply modifies the treatment of LMCRC due to the knowledge that LM are perfused by the hepatic artery network, whereas healthy tissue is perfused by the portal vein. Therefore, oxaliplatin-based HAI becomes an interesting possibility to treat LMCRC. The aim of this review is to shed light on the important impact of the oxaliplatin-based chemotherapy from a non-conventional clinical point of view, considering that, being universally accepted its antitumor effect if administered intravenously, fragmentary information are known about its clinical applications and benefits deriving from intra-arterial administration in loco-regional chemotherapy. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20–40 mg/m2, 4–6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36–40 Gy photon radiation therapy delivered to the prophylactic area, to a total dose of 70.4–74.8 Gy. The median follow-up was 33 months. The 3-year local control and overall survival rates were 69% and 59%, respectively. Major grade 3 or higher acute toxicities included mucositis, neutropenia, and dermatitis in 12 (40%), 5 (17%), and 3 (10%) patients, respectively. No grade 3 or higher late toxicities were observed. These results suggested that proton beam therapy in combination with intra-arterial infusion chemotherapy was not inferior to other treatment protocols and should be considered as a safe and effective option in patients with T4 squamous cell carcinoma of the maxillary gingiva. [ABSTRACT FROM AUTHOR]