Transarterial chemoembolization alone or followed by bevacizumab for treatment of colorectal liver metastases.

AIMS: Bevacizumab (B) in association with systemic chemotherapy is commonly used for the treatment of colorectal cancer liver metastases. The aim of this study was to monitor tumor response, overall survival (OS) and progression-free survival (PFS) of patients with colorectal cancer liver metastases treated with transarterial chemoembolization (TACE) + B compared with TACE alone and to correlate the results with KRAS mutational status. PATIENTS & METHODS: This was an observational multicentric case-control study (NCT03732235) on the efficacy and safety of B administered after TACE. RESULTS: The disease control rate was significantly higher for the TACE + B than the TACE alone group (p < 0.001). KRAS wild-type patients had a significantly better disease control rate than those with KRAS mutations in the TACE + B group. Median OS and PFS were similar for the TACE + B and TACE groups, whereas median time to progression was significantly higher for the TACE + B group (p < 0.01). CONCLUSION: The combination of TACE with B may improve tumor response and delay disease progression.

Biliary involvement in liver metastases: long-term experience with biliary biopsy from a single center.

OBJECTIVE: To investigate long-term results of biliary biopsy performed with transluminal forceps in the setting of metastatic biliary involvement. MATERIALS AND METHODS: Between September 2014 and June 2019, 25 patients-18 males (72%)-with a mean age of 65 ± 15 years, underwent 26 biliary biopsy procedures with a dedicated forceps system. All patients presented with obstructive jaundice that was suspected of being malignant and underwent pre-procedural magnetic resonance cholangiopancreatography. The biopsies were performed during percutaneous placement of an internal-external biliary drainage catheter, under fluoroscopic guidance. RESULTS: The technical success rate was 96% (corresponding to 25 of the 26 procedures). The histological diagnosis was inflammatory biliary stricture in five cases, pancreatic adenocarcinoma in six, liver metastases from colorectal cancer in eight, and hepatocellular carcinoma in three, the biliary mucosa being categorized as normal in three cases. In one case, the sample was considered insufficient and the procedure was successfully repeated, after which a diagnosis of pancreatic adenocarcinoma was made. Over a follow-up period of 6-48 months, there were five false-negative results: two findings of inflammatory biliary stricture were later identified as liver metastases from breast and gastric cancer, respectively; and all three patients in which the biliary mucosa was categorized as normal were subsequently diagnosed with metastatic hilar lymph nodes. The procedure was found to have a sensitivity of 77%, a specificity of 100%, and an overall accuracy of 80%. The complication rate was 11.5% (mild, transient hemobilia occurring in three cases). CONCLUSION: Percutaneous transluminal forceps biopsy is a safe, effective, minimally invasive procedure for histological characterization in patients presenting with obstructive jaundice due to a non-primary biliary tumor.

OBJETIVO: Investigar os resultados a longo prazo da biópsia endobiliar realizada com um pinça tipo fórceps transluminal no diagnóstico de neoplasia biliar metastática. MATERIAIS E MÉTODOS: Entre setembro de 2014 e junho de 2019, 25 pacientes - 18 homens (72%), com idade média de 65 ± 15 anos) - foram submetidos a 26 procedimentos de biópsia endobiliar com um conjunto dedicado. Todos os pacientes apresentaram icterícia obstrutiva, suspeita de malignidade e colangiorressonância pré-procedimento. Os procedimentos foram realizados durante o posicionamento percutâneo da drenagem biliar interna-externa, sob orientação fluoroscópica. RESULTADOS: A taxa de sucesso técnico foi de 96% (25 casos), com diagnóstico histológico de estenose benigna (inflamatória) em cinco casos, adenocarcinoma pancreático em seis casos, metástases hepáticas retais no cólon em oito casos, carcinoma hepatocelular em três casos e de mucosa biliar normal em três casos. Em um caso a amostra foi considerada insuficiente pelo patologista (um adenocarcinoma pancreático) e o procedimento foi repetido com sucesso. O seguimento de 6 a 48 meses mostrou cinco casos falso-negativos, em particular dois casos de metástases hepáticas retais sem cólon (câncer de mama e gástrico) e três linfonodos hilares metastáticos. A análise estatística revelou sensibilidade de 77%, especificidade de 100% e precisão geral de 80%. A taxa de complicações foi de 11,5% (três casos com hemobilia transitória). CONCLUSÃO: A biópsia biliar transluminal realizada com pinça tipo fórceps é um procedimento minimamente invasivo, seguro e eficaz para caracterização histológica em pacientes que apresentam icterícia obstrutiva no diagnóstico de neoplasia biliar metastática.

Biliary involvement in liver metastases: long-term experience with biliary biopsy from a single center / Envolvimento biliar nas metástases hepáticas: experiência a longo prazo com biópsia endobiliar em um único centro

Abstract Objective: To investigate long-term results of biliary biopsy performed with transluminal forceps in the setting of metastatic biliary involvement. Materials and Methods: Between September 2014 and June 2019, 25 patients-18 males (72%)-with a mean age of 65 ± 15 years, underwent 26 biliary biopsy procedures with a dedicated forceps system. All patients presented with obstructive jaundice that was suspected of being malignant and underwent pre-procedural magnetic resonance cholangiopancreatography. The biopsies were performed during percutaneous placement of an internal-external biliary drainage catheter, under fluoroscopic guidance. Results: The technical success rate was 96% (corresponding to 25 of the 26 procedures). The histological diagnosis was inflammatory biliary stricture in five cases, pancreatic adenocarcinoma in six, liver metastases from colorectal cancer in eight, and hepatocellular carcinoma in three, the biliary mucosa being categorized as normal in three cases. In one case, the sample was considered insufficient and the procedure was successfully repeated, after which a diagnosis of pancreatic adenocarcinoma was made. Over a follow-up period of 6-48 months, there were five false-negative results: two findings of inflammatory biliary stricture were later identified as liver metastases from breast and gastric cancer, respectively; and all three patients in which the biliary mucosa was categorized as normal were subsequently diagnosed with metastatic hilar lymph nodes. The procedure was found to have a sensitivity of 77%, a specificity of 100%, and an overall accuracy of 80%. The complication rate was 11.5% (mild, transient hemobilia occurring in three cases). Conclusion: Percutaneous transluminal forceps biopsy is a safe, effective, minimally invasive procedure for histological characterization in patients presenting with obstructive jaundice due to a non-primary biliary tumor.

Resumo Objetivo: Investigar os resultados a longo prazo da biópsia endobiliar realizada com um pinça tipo fórceps transluminal no diagnóstico de neoplasia biliar metastática. Materiais e Métodos: Entre setembro de 2014 e junho de 2019, 25 pacientes - 18 homens (72%), com idade média de 65 ± 15 anos) - foram submetidos a 26 procedimentos de biópsia endobiliar com um conjunto dedicado. Todos os pacientes apresentaram icterícia obstrutiva, suspeita de malignidade e colangiorressonância pré-procedimento. Os procedimentos foram realizados durante o posicionamento percutâneo da drenagem biliar interna-externa, sob orientação fluoroscópica. Resultados: A taxa de sucesso técnico foi de 96% (25 casos), com diagnóstico histológico de estenose benigna (inflamatória) em cinco casos, adenocarcinoma pancreático em seis casos, metástases hepáticas retais no cólon em oito casos, carcinoma hepatocelular em três casos e de mucosa biliar normal em três casos. Em um caso a amostra foi considerada insuficiente pelo patologista (um adenocarcinoma pancreático) e o procedimento foi repetido com sucesso. O seguimento de 6 a 48 meses mostrou cinco casos falso-negativos, em particular dois casos de metástases hepáticas retais sem cólon (câncer de mama e gástrico) e três linfonodos hilares metastáticos. A análise estatística revelou sensibilidade de 77%, especificidade de 100% e precisão geral de 80%. A taxa de complicações foi de 11,5% (três casos com hemobilia transitória). Conclusão: A biópsia biliar transluminal realizada com pinça tipo fórceps é um procedimento minimamente invasivo, seguro e eficaz para caracterização histológica em pacientes que apresentam icterícia obstrutiva no diagnóstico de neoplasia biliar metastática.

The CIREL Cohort: A Prospective Controlled Registry Studying the Real-Life Use of Irinotecan-Loaded Chemoembolisation in Colorectal Cancer Liver Metastases: Interim Analysis.

PURPOSE: Transarterial chemoembolisation (TACE) using irinotecan-eluting beads is an additional treatment option for colorectal cancer liver metastases (CRLM) patients that are not eligible for curative treatment approaches. This interim analysis focuses on feasibility of the planned statistical analysis regarding data distribution and completeness, treatment intention, safety and health-related quality of life (HRQOL) of the first 50 patients prospectively enrolled in the CIrse REgistry for LifePearl™ microspheres (CIREL), an observational multicentre study conducted across Europe. METHODS: In total, 50 patients ≥ 18 years diagnosed with CRLM and decided to be treated with irinotecan-eluting LifePearl™ microspheres TACE (LP-irinotecan TACE) by a multidisciplinary tumour board. There were no further inclusion or exclusion criteria. The primary endpoint is the categorisation of treatment intention, and secondary endpoints presented in this interim analysis are safety, treatment considerations and HRQOL. RESULTS: LP-irinotecan TACE was conducted in 42% of patients as salvage therapy, 20% as an intensification treatment, 16% as a first-line treatment, 14% a consolidation treatment and 8% combination treatment with ablation with curative intent. Grade 3 and 4 adverse events were reported by 4% of patients during procedure and by 10% within 30 days. While 38% reported a worse, 62% reported a stable or better global health score, and 54% of patients with worse global health score were treated as salvage therapy patients. CONCLUSION: This interim analysis confirms in a prospective analysis the feasibility of the study, with an acceptable toxicity profile. More patients reported a stable or improved HRQOL than deterioration. Deterioration of HRQOL was seen especially in salvage therapy patients. TRIAL REGISTRATION: NCT03086096.

Gadoxetic acid magnetic-enhanced resonance imaging in the diagnosis of cholangiocarcinoma.

The use of liver magnetic resonance imaging is increasing thanks to its multiparametric sequences that allow a better tissue characterization, and the use of hepatobiliary contrast agents. This review aims to evaluate gadoxetic acid enhanced magnetic resonance imaging in the diagnosis and staging of cholangiocarcinoma and its different clinical and radiological classifications proposed in the literature. We also analyze the epidemiology, risk factors in correlation with clinical findings and laboratory data.

Chemoembolization Alone or Associated With Bevacizumab for Therapy of Colorectal Cancer Metastases: Preliminary Results of a Randomized Study.

AIM: to assess efficacy and safety of chemoembolization alone (TACE) and followed by bevacizumab (TACE-B) in patients with colorectal liver metastases (CRC-LM) (NCT03732235). PATIENTS AND METHODS: The study included 30 consecutive patients with CRC-LM. They were informed about the types of treatment available: TACE with irinotecan loaded into polythylene glycol embolics alone or followed by bevacizumab therapy. Each patient underwent self-randomization and 17 chose TACE, whereas 13 chose TACE-B. RESULTS: Tumor response at 3 months was complete response in one (6%) and four (31%) patients, and partial response in two (13%) and six (46%) patients, after TACE and TACE-B, respectively. No complications were observed during TACE. Most TACE-related adverse events were correlated with post-embolic syndrome. CONCLUSION: The preliminary results of the study showed that the TACE-B is feasible and tolerable. This study will be continued in order accrue a larger number of patients and longer follow-up.

Outcomes of percutaneous transluminal biopsy of biliary lesions using a dedicated forceps system.

BACKGROUND: Distinction between benign and malignant biliary obstruction is always challenging. PURPOSE: To evaluate outcomes of percutaneous transluminal biopsy of biliary strictures using a dedicated forceps system. MATERIAL AND METHODS: This prospective, single-center, single-arm study, included 29 consecutive patients (17 men [56.6%]; mean age = 60 ± 9 years), who underwent 30 transluminal biopsies during percutaneous transhepatic biliary drainage (PTBD) due to obstructive jaundice, between September 2014 and January 2017, using a transluminal biliary access and biopsy forceps set. The study's primary efficacy endpoint was technical success and the primary safety endpoint was the procedure-related major complications rate. The study's secondary endpoints were procedure-related minor complication rate, sensitivity, specificity, and diagnostic accuracy for the characterization of malignancy. RESULTS: Tissue samples allowed histological diagnosis in 27/30 procedures (technical success rate 90.0%), as in three cases (10.0%) the sample was characterized as non-diagnostic: one case was suspicious for pancreatic cancer and two cases were cholangiocarcinoma. In one case, biopsy was successfully repeated. The diagnosis was cholangiocarcinoma in 16 cases (53.3%), colorectal metastasis in three cases (10%), pancreatic adenocarcinoma in three cases (10.0%), and inflammation in five cases (16.6%). There were two false-negative cases of inflammation proven to be cholangiocarcinoma, resulting in sensitivity of 91.67%, specificity of 100%, and accuracy of 92.59%. No major complications were noted. There were four cases of hemobilia (13%) which auto-resolved within 48 h. CONCLUSION: Percutaneous transluminal biopsy of biliary strictures during PTBD using the specific forceps system was proven safe and resulted in high technical success and diagnostic accuracy rates.

Recent advances in non-invasive magnetic resonance imaging assessment of hepatocellular carcinoma.

Magnetic resonance (MR) imaging of the liver is an important tool for the detection and characterization of focal liver lesions and for assessment of diffuse liver disease, having several intrinsic characteristics, represented by high soft tissue contrast, avoidance of ionizing radiation or iodinated contrast media, and more recently, by application of several functional imaging techniques (i.e., diffusion-weighted sequences, hepatobiliary contrast agents, perfusion imaging, magnetic resonance (MR)-elastography, and radiomics analysis). MR functional imaging techniques are extensively used both in routine practice and in the field of clinical and pre-clinical research because, through a qualitative rather than quantitative approach, they can offer valuable information about tumor tissue and tissue architecture, cellular biomarkers related to the hepatocellular functions, or tissue vascularization profiles related to tumor and tissue biology. This kind of approach offers in vivo physiological parameters, capable of evaluating physiological and pathological modifications of tissues, by the analysis of quantitative data that could be used in tumor detection, characterization, treatment selection, and follow-up, in addition to those obtained from standard morphological imaging. In this review we provide an overview of recent advanced techniques in MR for the diagnosis and staging of hepatocellular carcinoma, and their role in the assessment of response treatment evaluation.

Transcatheter Arterial Embolization for Bleeding Peptic Ulcers: A Multicenter Study.

PURPOSE: To investigate the outcomes of transcatheter arterial embolization (TAE) for the treatment of peptic ulcer bleeding (PUB). MATERIALS AND METHODS: This is a retrospective, multicenter study, which investigated all patients who underwent TAE for the treatment of severe upper gastrointestinal hemorrhage from peptic ulcers in five European centers, between January 1, 2012 and May 1, 2017. All patients had undergone failed endoscopic hemostasis. Forty-four patients (male; mean age 74.0 ± 11.1 years, range 49-94), with bleeding from duodenum (36/44; 81.8%) or gastric ulcer (8/44; 18.2%) were followed up to 3.5 years (range 2-1354 days). In 42/44 cases, bleeding was confirmed by pre-procedural CT angiography. In 50% of the cases, coils were deployed, while in the remaining glue, microparticles, gel foam and combinations of the above were used. The study's outcome measures were 30-day survival technical success (occlusion of feeding vessel and/or no extravasation at completion DSA), overall survival, bleeding relapse and complication rates. RESULTS: The technical success was 100%. The 30-day survival rate was 79.5% (35/44 cases). No patients died due to ongoing or recurrent hemorrhage. Re-bleeding occurred in 2/44 cases (4.5%) and was successfully managed with repeat TAE (one) or surgery (one). The rate of major complications was 4.5% (2/44; one acute pancreatitis and one partial pancreatic ischemia), successfully managed conservatively. According to Kaplan-Meier analysis survival was 71.9% at 3.5 years. CONCLUSIONS: TAE for the treatment of PUB was technically successful in all cases and resulted in high clinical success rate. Minimal re-bleeding rates further highlight the utility of TAE as the second line treatment of choice, after failed endoscopy.

Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer.

AIM: To study tumor response, and tolerability of arterially directed embolic therapy (ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases (CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients. METHODS: Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, and had liver involvement < 50%. Tumor response, performance status (PS), tumor marker antigens, and quality of life (QoL) were monitored at 1, 3 and 6 mo after ADET. QoL was assessed with the Palliative Performance Scale (PPS). RESULTS: We treated 50 consecutive CRC-LM patients with ADET using polyethylene glycol embolics. Their tumor response one month after ADET was: 28% of complete response (CR), 48% of partial response (PR), 8% stable disease (SD), and 16% of progression. Tumor response 3 mo after ADET was CR 24%, PR 38%, SD 19% and progression disease (PD) 19%. Tumor response 6 mo after ADET was CR 18%, PR 44%, SD 21% and PD 18%. QoL was 90% PPS at each time point. Median time to progression for patients who progressed was 2.5 mo (range 0.8-6). Median follow-up was 14 mo (0.8-25 range). ADETs were performed with no complications. Observed side effects (mild or moderate intensity) were: Pain in 32% of patients, increase of transaminase levels in 20% and fever in 14%, whereas 30% of patients did not complain any adverse event. CONCLUSION: The treatment of unresectable CRC-LM with ADET using polyethylene glycol microspheres loaded with irinotecan was effective in tumor response and resulted in mild toxicity, and good QoL.

Myocardial iron overload assessed by magnetic resonance imaging (MRI)T2* in multi-transfused patients with thalassemia and acquired anemias.

BACKGROUND: Cardiac complications secondary to iron overload remain a significant matter in patients with transfusion dependent anemias. PATIENTS AND METHODS: To evaluate cardiac siderosis, Magnetic resonance imaging T2* (MRI T2*) was performed in 3 cohorts of transfusion dependent patients: 99 with thalassemia major (TM), 20 with thalassemia intermedia (TI), and 10 with acquired anemias (AA). Serum ferritin was measured and all patients underwent echocardiographic evaluation. RESULTS: In TM patients cardiac T2* pathologic values (below 20 ms) were found in 37 patients. Serum ferritin was negatively associated with age (r=-0.32, p=0.001) and weakly with T2* values (r=-0.19, p=0.057). A positive correlation was found between T2* and LVEF (r=0.27, p=0.006). Out of 37 patients with T2*<20 ms, 18 (48%) had serum ferritin values<1000 ng/ml. In TI cohort, 3 patients had cardiac T2* pathologic values. In AA cohort, pathologic T2* values were found in 2 patients, who received 234 and 199 PRBC units, respectively, and were both on chelation therapy (in one patient ferritin value was 399 ng/ml). T2* values were negatively associated, but not significantly, with the number of PRBC transfused (r=-0.53, p=0.07). CONCLUSION: In our experience, 37% of TM patients had a myocardial iron overload assessed by MRI T2*; this value is higher than in TI patients. Serum ferritin measurement was a poor predictor of myocardial siderosis. In patients with AA, more than 200 PRBC units transfused were required to induce cardiac hemosiderosis, in spite of chelation therapy and, in one patient, of normal ferritin values.

Preoperative assessment of stenosis of the epiaortic vessels: can colour-Doppler ultrasound really supplant angiography?

PURPOSE: To evaluate the diagnostic role of digital angiography compared with colour-Doppler US in the study of epiaortic vessel stenoses and the degree of morbidity associated with angiography. MATERIALS AND METHODS: Out of 2,000 angiographic examinations of the epiaortic vessels performed for the concurrent presence of clinical findings of cerebrovascular insufficiency and colour-Doppler US findings of carotid-vertebral stenosis, a randomized sample of 200 patients was evaluated. The retrospective review of medical records provided the surgical data of the stenosis which were subsequently compared with the angiography and colour-Doppler US findings, and with the clinical and laboratory data to identify the possible complications of angiography. RESULTS: Diagnostic agreement was 75%. Colour-Doppler US underestimated stenosis in 16.5% and overestimated stenosis in 8% of cases. In 18% of cases there was a diagnostic gain of angiography (vascular lesions associated with main lesion), which also provided clinically important incidental findings (intracranial aneurysms, meningiomas) in 6.5% of patients. No relevant complications resulting from the angiographic procedure were recorded. CONCLUSIONS: Angiography allowed a more accurate evaluation of the degree of stenosis compared with colour-Doppler ultrasound. Moreover, it allowed diagnosis of important associated conditions that may affect therapeutic planning. In our series, we recorded no important complications related to angiography. Therefore, angiography remains the standard of reference in the preoperative evaluation of patients with clinically diagnosed cerebral ischaemia. Though fairly reliable as a first-line investigation, Colour-Doppler US is not sufficiently exhaustive as a pre-operative evaluation tool.

Endovascular treatment of intracranial arterio-venous malformations with Onyx embolization: preliminary experience.

PURPOSE: Intracranial arterio-venous malformations (AVM) often represent a complex clinical problem as regards indications to treatment, the choice of treatment and the technical difficulties related to treatment. In the last twenty years, endovascular treatment of intracranial arterio-venous malformations was primarily based on an acrylic glue (Hystoacril) whose endovascular use is not free from risks. A new product for endovascular embolization, named ONYX, has been recently been made commercially available. It is a bio-compatible liquid polymer that precipitates and solidifies in contact with blood, thus forming a soft and spongy embolus. The aim of this study was to evaluate our preliminary results in the endovascular embolization of intracranial AVM with Onyx. MATERIALS AND METHODS: Ten patients were treated (7 men, 3 women; mean age: 29 years, range: 12-48 years) for a total of 37 embolizations, 22 with Onyx and 15 with acrylic resin. RESULTS: Nidus occlusion was complete in 2 cases, >90% in 2 cases, >50 and <90% in 3 cases and <50% in the remaining 3 cases. The following complications were recorded: two transient and one mild permanent neurological deficits, two clinically silent cases of moderate subarachnoid haemorrhage, four catheters glued to the injection site, three cases of treatment discontinuation due to continuous and massive reflux of Onyx into the afferent artery peduncle. CONCLUSIONS: This early experience showed that while Onyx has good embolization potential it also presents some disadvantages, which need to be overcome before this product can be considered easy and safe to use on a large scale.