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Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread. [ABSTRACT FROM AUTHOR]

Renal tumor biopsy was provided in patients candidate to radical nephrectomy for a renal mass ≥4 cm, to evaluate treatment deviation. Between 2008 and 2017, 102 patients with a solid renal mass ≥4 cm with no distant metastases underwent preliminary renal tumor biopsy. We investigated the proportion of patients who proceeded with radical nephrectomy, variables predicting non-renal cell carcinoma (RCC) and concordance between biopsy findings and definitive pathology. Median tumor size was 70 mm (IQR 55–110). Clinical stage was cT1b in 41, cT2 in 33, cT3 in 25 and cT4 in three patients. A median of three (IQR 2–3) renal tumor biopsies were taken with 16/18 Gauge needles in 97% of cases. Clavien grade I complications occurred in five cases. Malignant tumors were documented in 84 patients: 78 RCCs and six non-RCCs. Fifteen biopsies documented oncocytoma and three were non-diagnostic. Grade was reported in 50 RCCs: 42 (84%) were low and eight (16%) high grade. Eighty-three patients proceeded with radical nephrectomy; six non-RCC malignant tumors underwent combined and/or intensified treatment; 13 of 15 patients with oncocytoma did not undergo radical nephrectomy (eight underwent observation). Definitive pathology confirmed diagnosis in all cases. Grade concordance was 84%, considering two tiers (high vs low grade). No preoperative clinical variable predicted definitive pathology. Renal tumor biopsy is a safe procedure that leads to radical nephrectomy in most tumors ≥4 cm. Nonetheless, 20% of patients exhibited non-RCC histology. Renal tumor biopsy should be considered in this setting. [ABSTRACT FROM AUTHOR]

Although combination therapy is not recommended in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs), this strategy is widely used in clinical practice. This network meta-analysis of randomized trials evaluates targeted therapies and somatostatin analogues in GEP-advanced NETs, either alone or in combination, comparing the efficacy of different, single or combined treatment strategies in terms of progression-free survival (PFS). Interventions were grouped as analogs, everolimus, everolimus plus SSAs, sunitinib and placebo. In a secondary analysis, we also assessed the efficacy of individual-specific pharmacological treatments vs placebo or each other. From 83 studies identified, 8 randomized controlled trials were selected, with a total of 1849 patients with either functioning or non-functioning NETs. The analysis confirmed the superiority of all treatments over placebo (HR ranging from 0.34, 95% CI: 0.24-0.37 with the combination of everolimus plus SSAs to 0.42, 0.31-0.57 with the analogs; moderate quality of evidence). On ranking analysis, the combination of everolimus plus SSA (P score = 0.86) and then everolimus alone (P score = 0.65) ranked highest in increasing PFS. On comparative evaluation of different interventions, pasireotide (P score = 0.96) and everolimus + octreotide (P score = 0.82) ranked as the best pharmacological treatment options. Our findings support the use of combination therapy in the treatment of functioning and non-functioning GEP NETs. The role of pasireotide should be explored in selected subgroups of patients. Lastly, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice. [ABSTRACT FROM AUTHOR]

In the presence of peritoneal disease, patients often should undergo biopsy of the peritoneum for acquiring a specific pathologic diagnosis. Ultrasound is ideal for guiding peritoneal biopsy, although in some situations, it can be technically challenging. The addition of a contrast agent can improve the visualization of lesions and adjacent organs, providing radiologists increased confidence. A contrast agent can identify perfused areas within the target lesion, improving diagnostic accuracy. We present 3 cases of contrast‐enhanced ultrasound–guided peritoneal biopsy. In all cases, we gained a specific diagnosis. No immediate or delayed complications occurred. Contrast‐enhanced ultrasound–guided biopsy proved to be a simple, safe, and accurate diagnostic method. [ABSTRACT FROM AUTHOR]

Purpose: To measure the maximum entrance skin dose (MESD) on patients undergoing carotid artery stenting (CAS) using embolic-protection devices, to analyze the dependence of dose and exposure parameters on anatomical, clinical, and technical factors affecting the procedure complexity, to obtain some local diagnostic reference levels (DRLs), and to evaluate whether overcoming DRLs is related to procedure complexity. Materials and Methods: MESD were evaluated with radiochromic films in 31 patients (mean age 72 ± 7 years). Five of 33 (15 %) procedures used proximal EPD, and 28 of 33 (85 %) procedures used distal EPD. Local DRLs were derived from the recorded exposure parameters in 93 patients (65 men and 28 women, mean age 73 ± 9 years) undergoing 96 CAS with proximal (33 %) or distal (67 %) EPD. Four bilateral lesions were included. Results: MESD values (mean 0.96 ± 0.42 Gy) were <2 Gy without relevant dependence on procedure complexity. Local DRL values for kerma area product (KAP), fluoroscopy time (FT), and number of frames (N) were 269 Gy cm, 28 minutes, and 251, respectively. Only simultaneous bilateral treatment was associated with KAP (odds ratio [OR] 10.14, 95 % confidence interval [CI] 1-102.7, p < 0.05) and N overexposures (OR 10.8, 95 % CI 1.1-109.5, p < 0.05). Type I aortic arch decreased the risk of FT overexposure (OR 0.4, 95 % CI 0.1-0.9, p = 0.042), and stenosis ≥ 90 % increased the risk of N overexposure (OR 2.8, 95 % CI 1.1-7.4, p = 0.040). At multivariable analysis, stenosis ≥ 90 % (OR 2.8, 95 % CI 1.1-7.4, p = 0.040) and bilateral treatment (OR 10.8, 95 % CI 1.1-109.5, p = 0.027) were associated with overexposure for two or more parameters. Conclusion: Skin doses are not problematic in CAS with EPD because these procedures rarely lead to doses >2 Gy. [ABSTRACT FROM AUTHOR]

Simple Summary: We confirmed that the non-uniformity of an intra-lesion dose distribution, which was introduced in calculations as voxel dosimetry, did not significantly improve the AUC values of the dose–response relationship with respect to the mean dose. This was probably derived from the strong correlations (all p < 0.0001) among all voxel-based dosimetric variables (minimum Spearman correlation coefficient: 0.67) caused by the limited spatial resolution of nuclear medicine images. Responses were assessed with mRECIST and with an experimental densitometric method with a response threshold optimized at 20% HU variation. Significant dose–response agreement was obtained only with the densitometric method and only with post-therapy 90Y-PET data. More unexpectedly, the injection of Theraspheres™ on day 8 from the reference date rather than on day 4 worsened the dose–response correlation and reduced the efficacy at high doses. This may be explained by the increased non-uniformity following the non-linear mega-clustering effect triggered by the higher number of microspheres/GBq injected on day 8. In this confirmatory study, we tested if a calculation that included the non-uniformity of dose deposition through a voxel-based dosimetric variable Ψ was able to improve the dose–response agreement with respect to the mean absorbed dose D. We performed dosimetry with 99mTc-MAA SPECT/CT and 90Y-PET/CT in 86 patients treated 8 instead of 4 days after the reference date with 2.8 times more 90Y glass microspheres/GBq than in our previous study. The lesion-by-lesion response was assessed with the mRECIST method and with an experimental densitometric criterion. A total of 106 lesions were studied. Considering Ψ as a prognostic response marker, having no Ψ provided a significantly higher AUC than D. The correlation, t-test, and AUC values were statistically significant only with the densitometric method and only with post-therapy dosimetry. In comparison with our previous study, the dose–response correlation and AUC values were poorer (maximum r = 0.43, R2 = 0.14, maximal AUC = 0.71), and the efficacy at a high dose did not reach 100%. The expected advantages of voxel dosimetry were nullified by the correlation between any Ψ and D due to the limited image spatial resolution. The lower AUC and efficacy may be explained by the mega-clustering effect triggered by the higher number of microspheres/GBq injected on day 8. [ABSTRACT FROM AUTHOR]

Background & Aims Yttrium-90 transarterial radioembolization (TARE) has shown promising efficacy in the treatment of patients with hepatocellular carcinoma (HCC), associated with portal vein tumor thrombus (PVTT). The aim of this study is to identify prognostic factors for survival in patients with HCC and PVTT undergoing TARE, and build a prognostic classification for these patients. Methods This is a single center retrospective study conducted over six years (2010–2015), on consecutive patients undergoing TARE. Patients were included if they met the following criteria: presence of at least one measurable HCC, presence of PVTT not occluding the main portal trunk, absence of extrahepatic metastases, Child-Pugh score within B7, Eastern Cooperative Oncology Group performance status 0–1. Uni- and multivariable analysis was used to explore the variables that showed an independent relationship with survival. A prognostic score was then derived, and three prognostic categories were identified. Results A total of 120 patients were included in the study. Median overall survival (OS) was 14.1 months (95% CI 10.7–17.5) and median progression-free survival (PFS) was 6.5 months (95% CI 3.8–9.2). The only variables independently correlated with OS were bilirubin, extension of PVTT and tumor burden. Three prognostic categories were identified: favourable prognosis (0 points), intermediate prognosis (2–3 points) and dismal prognosis (>3 points). Median OS in the three categories was 32.2 months, 14.9 months and 7.8 months respectively ( p  <0.0001). PFS ( p  = 0.045) and the risk of liver decompensation ( p  <0.0001) also significantly differed along the same prognostic categories. Conclusions Radioembolization with Yttrium-90 is an effective therapy for patients with HCC and PVTT. The proposed prognostic stratification may help to better identify good candidates for the treatment, and those for whom TARE may be futile. Lay summary Yttrium-90 transarterial radioembolization (TARE) is a microembolic procedure that minimizes alterations to hepatic arterial flow, and thus can be safely performed in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). In this study, we retrospectively evaluated the independent predictors of long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin level, extension of PVTT and tumor burden were independently related to post-treatment survival: the combination of these factors allowed us to build a prognostic stratification that may help to better identify good candidates for the treatment, and those for whom TARE may be futile. [ABSTRACT FROM AUTHOR]

Fibroblastic sleeve is a common pathophysiological phenomenon characterized by the formation of a mixed fibrous-collagen tissue encasing the outside of venous access devices. Although it nearly always presents asymptomatically, this catheter-related complication represents one of the leading culprits of venous catheters malfunction. Several techniques have been described for the management of dysfunctional catheters secondary to fibroblastic sleeve, including medical therapy, catheter exchange, balloon angioplasty, and percutaneous stripping. However, there is no common consensus for the treatment management in patients who present contraindications to surgical port removal. This report illustrates the case of a port catheter malfunction due to a fibroblastic sleeve in an oncological patient with a high risk of bleeding. This was effectively treated with a minimally invasive stripping technique using an off-label device for mechanical thrombectomy, namely the ClotTriever system (Inari Medical, Irvine, CA)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pheochromocytomas and paragangliomas (PPGLs) can metastasize in approximately 15-20% of cases. This review discusses the available evidence on the biology and treatment of metastatic PPGLs. Chemotherapy is the first-line treatment option for this evolving and symptomatic disease. In patients with high MIBG uptake and positive PETGa-68, radiometabolic treatment may be considered. The efficacy of sunitinib has been shown in observational studies, and pembrolizumab has been evaluated in phase II clinical studies, while other agents investigated in this setting are anti-angiogenic drugs cabozantinib, dovitinib, axitinib and lenvatinib. As these agents' efficacy and safety data, alone or in combination, are scant and based on few treated patients, enrollment in clinical trials is mandatory. Future therapeutic options may be represented by DNA repair system inhibitors (such as olaparib), HIF2 inhibitors and immunotherapy.

Introduction: Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are established procedures for treating hepatocellular cancer and selected malignancies with liver metastasis. The aim of this study is to describe a monoinstitutional case series of local approaches in patients with liver metastases from rare head and neck cancers (HNCs)., Methods: This is a retrospective series of adult patients with HNC treated with liver locoregional approaches (TACE or RFA) at our institution from 2007 to 2018. In case of chemoembolization, the preferred chemotherapeutic drug was doxorubicin. Response according to RECIST (Response Evaluation Criteria in Solid Tumors) was assessed with contrast-enhanced computed tomography scans., Results: Thirty-four patients were treated (20 men, median age 58 years) with TACE (27), transarterial embolization (2), or RFA (7). Primary tumours were salivary gland (21), thyroid (6), nasopharyngeal (5), and sinonasal cancers (2). Seventeen patients (50%) had a single metastatic liver nodule; 70% of the remaining 17 patients had at least three liver metastases. The median diameter of the metastatic liver mass undergoing treatment was 39 mm (range 11-100 mm). Median follow-up was 27.6 months. Response rate was 35% (3% complete, 32% partial response). Median progression-free survival and overall survival were 6.9 and 19.6 months, respectively. Treatment-related adverse events occurred in 59% of patients (21% grade ⩾ 3; no grade 5)., Discussion: This retrospective case series demonstrates that locoregional radiologic approaches for rare HNCs with liver metastases are feasible. These procedures deserve further prospective studies before being considered safe and active in these malignancies where the availability of effective systemic treatments is lacking.

Aim: To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment., Methods: Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules., Results: DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21)., Conclusion: DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.