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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.

Neuroendocrine neoplasms of the lung represent about 20% to 30% of all neuroendocrine tumors. On the basis of clinical and pathologic characteristics, 2 different categories of tumors may be defined: poorly differentiated neuroendocrine neoplasms, characterized by a high rate of recurrences and poor prognosis, and well-differentiated neuroendocrine neoplasms (typical carcinoids and atypical carcinoids), which generally display an indolent course. Lung carcinoids represent only 1% to 5% of all lung malignancies, but their incidence has significantly increased over the past 30 years. Surgery is the reference standard of treatment for lung carcinoids with locoregional disease. For advanced or unresectable lung carcinoids, several therapeutic options are available, but the choice should be shared within a multidisciplinary team to ensure optimal therapeutic outcomes. We describe the current management of these rare neoplasms.

Splenic artery steal syndrome is a rare complication after liver transplant. It could lead to rapidly evolving major issues such as ischemic cholangiopathy and acute graft failure. Although the pathophysiology is not yet well understood, if diagnosed in time it could be easily managed with interventional radiology treatments. We present a case of a 47-year-old man presented to our institute with radiological findings typical for multifocal hepatocellular carcinoma in a cirrhotic liver. After therapy he underwent transplant. Some days after surgery he developed signs of acute liver failure. Steal syndrome was suspected by laboratory tests and radiology exams. The syndrome was confirmed by angiography and treated. The graft was saved, and the patient is still alive and free of disease. The purpose of this paper is to explain the importance of radiology exams in the diagnosis of splenic steal syndrome, explain its pathogenesis and describe the interventional management of this complication.

Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/

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.

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.

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.

To support laparoscopic post-chemotherapy retroperitoneal lymph-node dissection (L-PC-RPLND) as a potential new standard, we report on a large dataset of patients systematically undergoing L-PC-RPLND.Patients with unilateral residual mass (≥1 cm), normalized markers, limited encasement (30%) of gross retroperitoneal vessels underwent unilateral L-PC-RPLND with no adjuvant chemotherapy. Surgical performances, histology, hospital stay, complications within 30 days and follow-up visits were recorded. Multivariable linear and logistic regression models were used.Between February 2011 and January 2021, 151 consecutive patients underwent L-PC-RPLND. Median size of the residual mass was 25 mm (interquartile range [IQR] 20-35 mm). Overall median operative time was 208 min (IQR 177-241) and was 51 min longer (p-value0.001) for right L-PC-RPLNDs. Eleven procedures were converted to open surgery. Median number of removed and positive nodes was 11 (IQR 8-16) and 1 (IQR 1-2), respectively. Mean hospital stay was 2 days (IQR 2-3). Nine complications (6%) occurred: two were Clavien-Dindo grade III. Definitive pathology revealed post-pubertal teratoma in 65.6%, fibro-necrotic tissue in 23.8%, teratoma with malignant somatic component in 6.6% and viable tumour in 4.0% patients. In multivariable linear regression models, fibro-necrotic tissue (32 min, CI 8.5-55.5; p 0.01) and residual volume (1.05 min, CI 0.24-1.85; p 0.01) achieved independent predictor status for longer operative time. All patients, but one, are alive and disease-free after a median follow-up of 22 months (IQR 10, 48).L-PC-RPLND, when adequately planned, is safe and effective for most patients with low to medium volume residual masses.

In this confirmatory study, we tested if a calculation that included the non-uniformity of dose deposition through a voxel-based dosimetric variable

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.

Different types of drug-eluting beads have been proposed for hepatocellular carcinoma (HCC) treatment, but long-term results are not well known. We report safety, efficacy and long-term overall survival of HCC patients not amenable of curative therapies treated with transcatheter arterial chemoembolization (TACE) using drug-eluting beads sized 70–150 micron. This single-center retrospective study included 125 patients with Barcelona Clinic Liver Cancer stage A (80), B (45) and compensated cirrhosis. TACE was executed injecting drug-elutings microparticles loaded with 75 mg of Doxorubicine and was repeated in patients with partial response or stable disease after one month. Adverse events, response according to modified Response Evaluation Criteria in Solid Tumors and overall survival were assessed. Chemoembolization with 70–150 micron beads revealed an objective response rate of 88% according to mRECIST criteria and complete response was 60%. After a median follow-up of 53.3 months, overall survival was 36.6 months. Data were censored at the date of liver transplantation in 35 patients. 33 on 125 patients (26,4%) experienced at least one adverse event. We recorded a total of 102 adverse events and 18 were of a high grade (G3–G4). 30 day mortality was 0%. Chemoembolization with very small particles (70–150 µm) is an effective and safe treatment in unresectable HCC both as a primary therapy or as bridge to transplantation.

Key Points • Recurrent HCC after OLT management is challenging and notoriously difficult. • High oncologic-risk patient identification and close follow-up are essential. • Recurrences diagnosed within the first 2 years after OLT can be classified as early-onset and are associated with poor prognosis. • Surgical resection should be the first curative attempt when it is technically feasible. • TACE in patients who have undergone OLT appears to be effective and safe. • Sorafenib can be used as systemic therapy in cases with multi-organ recurrence; newer therapies are emerging. • The benefit of immunosuppression with an mTOR inhibitor has not been established. • In the posttransplant setting, a combination treatment approach is warranted.

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 p = 0.045) and the risk of liver decompensation ( p 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.

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.

The prostate and bladder are the most common primary cancer sites for penile metastases. Here, we describe an unusual case of metastases from renal cell carcinoma to the penis discovered 1 month after nephrectomy in a 60-year-old man. The diagnosis was achieved using B-mode and contrast-enhanced ultrasound.

Background and Aim Solid demonstrations of superior efficacy of drug-eluting beads transarterial chemoembolization with respect to conventional chemoembolization in hepatocellular carcinoma patients are lacking. The aim of the study was to compare these two techniques in two large cohorts of unresectable hepatocellular carcinoma patients. Methods A single center series of 249 early/intermediate hepatocellular carcinoma patients who underwent “on demand” chemoembolization in the period 2007–2011 was analyzed. Overall survival, time to progression, tumor response rate, and safety were compared between 104 patients who underwent conventional chemoembolization and 145 who underwent drug-eluting beads chemoembolization. Time-to-event data were analyzed using the Cox univariate and multivariate regression. Results The two cohorts resulted balanced for liver function and tumor stages. Objective response rate was 85.3% after conventional and 74.8% after drug-eluting beads chemoembolization (P = 0.039), and median time to progression was 17 (95% confidence interval: 14–21) versus 11 months (9–12), respectively (P

In planning Yttrium-90 ((90)Y)-radioembolizations, strategy problems arise in tumours with multiple arterial supplies. We aim to demonstrate that tumours can be treated via one main feeding artery achieving flow redistribution by embolizing accessory vessels.One hundred (90)Y-radioembolizations were performed on 90 patients using glass microspheres. In 19 lesions/17 patients, accessory branches were found feeding a minor tumour portion and embolized. In all 17 patients, the assessment of the complete perfusion was obtained by angiography and single photon emission computerized tomography-computerized tomography (SPECT-CT). Dosimetry, toxicity, and tumor response rate of the patients treated after flow redistribution were compared with the 83 standard-treated patients. Seventeen lesions in 15 patients with flow redistribution were chosen as target lesions and evaluated according to mRECIST criteria.In all patients, the complete tumor perfusion was assessed immediately before radioembolization by angiography in all patients and after the (90)Y-infusion by SPECT-CT in 15 of 17 patients. In the 15 assessable patients, the response rate in their 17 lesions was 3 CR, 8 PR, and 6 SD. Dosimetric and toxicity data, as well tumour response rate, were comparable with the 83 patients with regular vasculature.All embolization procedures were performed successfully with no complications, and the flow redistribution was obtained in all cases. Results in term of toxicity, median dose administered, and radiological response were comparable with standard radioembolizations. Our findings confirmed the intratumoral flow redistribution after embolizing the accessory arteries, which makes it possible to treat the tumour through its single main feeding artery.

Purpose To check the impact on toxicity and on overall survival (OS) of a personalized two compartment (tumor vs non tumor) dosimetric treatment planning method in the treatment of hepatocarcinoma with 90Y glass microspheres. Methods 43 Child A strictly selected patients (series 1) had been previously treated with 90Y glass microspheres according to the standard mono-compartment planning of 120 Gy to the injected liver lobe. A retrospective analysis of 99mTc-MAA pre-treatment SPECT/CT images had allowed to determine NTCP and TCP [1] . A decompensation risk of 15% was adopted as planning limit, corresponding to NTCP15 = 75 Gy. Liver absorbed dose is averaged on the organ volume excluding tumors. Such planning method was then applied to 116 less selected Child A patients (series 3, comparable to series 1). Results With respect to series 1, administered activity in series 3 was doubled in half of patients, reduced of 50% in a quarter of patients. Toxicity rate was maintained below 15%. Patient were stratified as advanced (with Portal Vein Thrombosis (PVT)) vs intermediate (NO PVT). In the PVT subgroups, lesions had the same size distribution. Treatment planning improved median OS from 8 to 12 months (with Mantel Cox test (p = 0.067) i.e. close to significance). In the NO PVT subgroups the median OS was 17 vs 15 months (n.s.) i.e. maintained, despite the larger tumor sizes. Conclusions methodological limits were absence of scatter correction and mismatch between simulation and 90Y PET dosimetry. Results are really encouraging, since are the first indications of improved outcome thanks to dosimetric treatment planning.

To evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT). Forty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response. All patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures). DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

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.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.MESD values (mean 0.96 ± 0.42 Gy) were2 Gy without relevant dependence on procedure complexity. Local DRL values for kerma area product (KAP), fluoroscopy time (FT), and number of frames (NFR) were 269 Gy cm(2), 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, p0.05) and NFR overexposures (OR 10.8, 95 % CI 1.1-109.5, p0.05). 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 NFR 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.Skin doses are not problematic in CAS with EPD because these procedures rarely lead to doses2 Gy.

Visceral artery pseudoaneurysms (PA) are a rare complication of abdominal surgery. Their natural history is generally unknown and unpredictable, so a repair is recommended. We report the case of a 77-year-old male with a huge PA of the hepatic artery diagnosed by computed tomography (CT) and treated successfully with percutaneous exclusion using a pericardium-covered stent. A staged CT confirmed the good result of the procedure.