Stripping the catheter: A new device for an old technique.

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).

Safety and antitumor activity of metformin plus lanreotide in patients with advanced gastro-intestinal or lung neuroendocrine tumors: the phase Ib trial MetNET2.

In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58-97) and 49% (95% CI 31-77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials.

Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial.

BACKGROUND: Well-differentiated (WD) neuroendocrine tumors (NETs) are a group of rare neoplasms with limited therapeutic options. Cabozantinib is an inhibitor of multiple tyrosine kinases with a pivotal role in NET pathogenesis, including c-MET and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). LOLA is the first prospective phase II trial aiming to assess the safety and activity of cabozantinib combined with lanreotide in WD NETs of gastroenteropancreatic (GEP), thoracic and of unknown origin. METHODS: This is a multicenter, open-label, double-cohort, non comparative, non-randomized, three-stage phase II trial. Eligible patients have to meet the following inclusion criteria: diagnosis of advanced or metastatic, progressive, non-functioning WD thoracic NETs, GEP-NETs or NETs of unknown origin with Ki67 ≥ 10%; positive 68 Ga-PET uptake or somatostatin receptor 2 immunohistochemical (IHC) stain; maximum 1 prior systemic regimen for metastatic disease. Two cohorts will be considered: pNETs and carcinoids (typical or atypical lung and thymus NETs, gastro-intestinal NETs or NETs of unknown origin). In stage I, the primary objective is to find the optimal dose of cabozantinib in combination with lanreotide and to evaluate the safety of the combination (percentage of patients experiencing grade 3-5 toxicities according to NCI-CTCAE version 5.0). Starting dose of cabozantinib is 60 mg/day continuously, plus lanreotide 120 mg every 28 days. In stage II and III, co-primary endpoints are safety and overall response rate (ORR) according to RECIST version 1.1. The uninteresting antitumor activity is fixed in ORR ≤ 5%. Secondary endpoints are progression-free survival and overall survival. Exploratory objectives include the assessment of c-MET, AXL and VEGFR2 IHC expression, to identify predictive or prognostic tissue biomarkers. Enrolment started in July 2020, with an expected trial duration of 42 months comprehensive of accrual, treatment and follow-up. Considering a drop-out rate of 5%, the maximum number of enrolled patients will be 69. DISCUSSION: Supported by a solid rationale, the trial has the potential to generate milestone data about the synergistic effects of cabozantinib plus lanreotide in a group of NET patients with relatively aggressive disease and limited therapeutic options. TRIAL REGISTRATION: LOLA is registered at ClinicalTrials.gov (NCT04427787) and EudraCT (2019-004506-10).

Textbook Outcome After Trans-arterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: Textbook Outcome (TO) is inclusive of quality indicators and it not been provided for trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data on treatment-naïve HCC patients receiving TACE from 10 centers were reviewed. TO was defined as "no post-TACE grade 3-4 complications, no prolonged hospital stay (defined as a post-procedure stay ≤ 75th percentile of the median values from the total cohort), no 30-day mortality/readmission and the achievement of an objective response (OR) at post-TACE imaging." Grade of adverse event was classified according to the Common Terminology Criteria for Adverse Events and short-term efficacy was assessed by response. Pooled estimates were calculated to account for hospital's effect and risk-adjustment was applied to allow for diversity of patients in each center. RESULTS: A total of 1124 patients (2014-2018) fulfilling specific inclusion criteria were included. Baseline clinical features showed considerable heterogeneity (I2 > 0.75) across centers. TACE-related mortality was absent in 97.6%, readmission was not required after 94.9% of procedures, 91.5% of patients had no complication graded 3-4, 71.8% of patients did not require prolonged hospitalization, OR of the target lesion was achieved in 68.5%. Risk-adjustment showed that all indicators were achieved in 43.1% of patients, and this figure was similar across centers. The median overall survival for patients who achieved all indicators was 33.1 months, 11.9 months longer than for patients who did not. CONCLUSIONS: A useful benchmark for TACE in HCC patients has been developed, which provides an indication of survival and allows for a comparison of treatment quality across different hospitals.

Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial).

BACKGROUND: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. PATIENTS AND METHODS: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). RESULTS: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). CONCLUSION: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

A "blood theft" after liver transplantation: the role of interventional radiology in the management and treatment of splenic artery steal syndrome.

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.

Renal tumor biopsy in patients with cT1b-T4-M0 disease susceptible to radical nephrectomy: analysis of safety, accuracy and clinical impact on definitive management.

PURPOSE: Renal tumor biopsy was provided in patients candidate to radical nephrectomy for a renal mass ≥4 cm, to evaluate treatment deviation. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Radioembolization of Hepatocellular Carcinoma with 90Y Glass Microspheres: No Advantage of Voxel Dosimetry with Respect to Mean Dose in Dose-Response Analysis with Two Radiological Methods.

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.

Long Term Survival Analysis in a Cohort of 125 Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using Small Drug Eluting Beads.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Inter-center agreement of mRECIST in transplanted patients for hepatocellular carcinoma.

OBJECTIVES: To evaluate the inter-observer reliability of modified Response Evaluation Criteria In Solid Tumours (mRECIST) of patients with hepatocellular carcinoma (HCC) undergoing neo-adjuvant treatments before liver transplant (LT). The agreement of tumor number, size, transplant criteria, and the radiological-pathological concordance were also assessed. METHODS: A total of 180 radiological studies before/after neo-adjuvant therapies performed on 90 patients prior to LT were reviewed from three expert centers. Kappa-statistic and intraclass correlation (ICC) were evaluated on mRECIST and on tumoral features. Complete radiological response (CR) was compared with complete pathological response (CPR). RESULTS: Before neo-adjuvant therapies, the agreement on tumor number, size, and transplant criteria ranged from moderate (defined as ICC of 0.41-0.60) to almost perfect (ICC of 0.81-0.99), being higher with magnetic resonance imaging (MRI) than CT (0.657-0.899 and 0.422-0.776, respectively). After neo-adjuvant therapies, the agreement decreased, as ICCs ranged between 0.518 and 0.663 with MRI and between 0.508 and 0.677 with CT. Concordant mRECIST pairs were 201 of 270 reviews (76.3%) with a kappa of 0.648 indicating substantial agreement. When the three observers completely agreed on CR, the positive predictive value for CPR was 51.6%. The negative predictive value was 94.2% with a kappa of 0.512 indicating fair agreement between radiology and pathology. CONCLUSIONS: mRECIST agreement was substantial among the three observers involved. The agreement on tumor number, size, and transplant criteria ranged from moderate to almost perfect, with the highest ICCs obtained with MRI before neo-adjuvant therapies. Finally, the predictive value of mRECIST in the diagnosis of CPR was only fair. KEY POINTS: • The review of 180 radiological exams of patients with hepatocellular carcinoma before and after neo-adjuvant therapies showed that the concordance among three different raters on mRECIST diagnosis was substantial. • The inter-observer reliability on fulfilment of transplant criteria slightly decreased when evaluated through CT and after loco-regional therapies. • The radiological diagnosis of complete response after neo-adjuvant therapies was predictive of complete pathological response in only 51.6% of cases.

Recent Advances in the Management of Typical and Atypical Lung Carcinoids.

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.

Including mRECIST in the Metroticket 2.0 criteria improves prediction of hepatocellular carcinoma-related death after liver transplant.

BACKGROUND & AIMS: In the context of liver transplantation (LT) for hepatocellular carcinoma (HCC), prediction models are used to ensure that the risk of post-LT recurrence is acceptably low. However, the weighting that 'response to neoadjuvant therapies' should have in such models remains unclear. Herein, we aimed to incorporate radiological response into the Metroticket 2.0 model for post-LT prediction of "HCC-related death", to improve its clinical utility. METHODS: Data from 859 transplanted patients (2000-2015) who received neoadjuvant therapies were included. The last radiological assessment before LT was reviewed according to the modified RECIST criteria. Competing-risk analysis was applied. The added value of including radiological response into the Metroticket 2.0 was explored through category-based net reclassification improvement (NRI) analysis. RESULTS: At last radiological assessment prior to LT, complete response (CR) was diagnosed in 41.3%, partial response/stable disease (PR/SD) in 24.9% and progressive disease (PD) in 33.8% of patients. The 5-year rates of "HCC-related death" were 3.1%, 9.6% and 13.4% in those with CR, PR/SD, or PD, respectively (p <0.001). Log10AFP (p <0.001) and the sum of number and diameter of the tumour/s (p <0.05) were determinants of "HCC-related death" for PR/SD and PD patients. To maintain the post-LT 5-year incidence of "HCC-related death" <30%, the Metroticket 2.0 criteria were restricted in some cases of PR/SD and in all cases with PD, correctly reclassifying 9.4% of patients with "HCC-related death", at the expense of 3.5% of patients who did not have the event. The overall/net NRI was 5.8. CONCLUSION: Incorporating the modified RECIST criteria into the Metroticket 2.0 framework can improve its predictive ability. The additional information provided can be used to better judge the suitability of candidates for LT following neoadjuvant therapies. LAY SUMMARY: In the context of liver transplantation for patients with hepatocellular carcinoma, prediction models are used to ensure that the risk of recurrence after transplantation is acceptably low. The Metroticket 2.0 model has been proposed as an accurate predictor of "tumour-related death" after liver transplantation. In the present study, we show that its accuracy can be improved by incorporating information relating to the radiological responses of patients to neoadjuvant therapies.

Patients with Barcelona Clinic Liver Cancer Stages B and C Hepatocellular Carcinoma: Time for a Subclassification.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) intermediate and advanced stages (BCLC B and C) of hepatocellular carcinoma (HCC) both include heterogeneous populations. Patients classified as BCLC stage B present with different tumour burdens, and the recommended treatment is transarterial chemoembolization (TACE). A similar heterogeneity of tumour burden and liver function can be found among patients classified as BCLC stage C, which includes diverse clinical features (performance status [PS] 1-2), macrovascular invasion (MVI) including portal vein tumour (PVT) thrombosis, and/or extra-hepatic spread. Nonetheless, the anti-tumoural treatment formally recommended by Western guidelines is systemic therapy with sorafenib. SUMMARY: Several proposals of subclassification for both these stages have been suggested in recent years, differentiating the more appropriate treatments for each substage. In particular, for BCLC stage C patients with PVT, therapeutic indications, clinical outcomes, and response to locoregional therapy are notably different in the presence of subsegmental, segmental or main PVT. Accordingly, liver resection and transarterial therapies, such as TACE or transarterial embolization (TAE) and 90Y-radioembolization (TARE), can be performed in locally advanced HCC with intrahepatic MVI according to its extent. In fact, surgery and TACE/TAE/TARE have no contraindications in the presence of PVT limited to the subsegmental or segmental branches in Child-Pugh class A patients, whereas only TARE should be utilized when there is lobar branch involvement. The presence of PS 1 should not be sufficient to allocate patients to the advanced stage since this would preclude any potential treatment for HCC. Patients should be properly classified as BCLC C only in cases of main portal trunk PVT, and treated according to the guidelines, provided that they belong to Child-Pugh class A. KEY MESSAGES: Subclassifications of BCLC B and C stages are urgently needed and require validation in order to guide clinicians towards the most effective treatment option.

Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.

Safety and Efficacy of Combined Peptide Receptor Radionuclide Therapy and Liver Selective Internal Radiation Therapy in a Patient With Metastatic Neuroendocrine Tumor.

Nuclear medicine treatments of well-differentiated neuroendocrine tumors (NETs) are gaining increasing acceptance among clinicians. Peptide receptor radionuclide therapy (PRRT) is an effective systemic treatment, providing a significant survival benefit and improving patients' quality of life. Locoregional selective internal radiation therapy (SIRT) is a safe and effective treatment for unresectable NET liver metastases, providing good local tumor control and symptomatic relief. Few reports in literature examine the sequential use of PRRT and SIRT in metastatic NET. We report the case of a metastatic NET patient treated with sequential PRRT-SIRT achieving a long disease control interval without cumulative toxicity issues.

Development of a prognostic score to predict response to Yttrium-90 radioembolization for hepatocellular carcinoma with portal vein invasion.

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.

Surgery of locally advanced and metastatic kidney cancer after tyrosine kinase inhibitors therapy: single institute experience.

PURPOSE:: Renal cell carcinoma (RCC) is the most common tumor of the kidney. Considering the TNM classification of 2009, locally advanced and metastatic diseases are included in the groups stage III and IV. The surgical treatment of these tumors could be divided into 3 categories: (1) curative (nephrectomy and/or metastasectomy), (2) cytoreductive, and (3) palliative. Targeted agents showed impressive antitumor efficacy and prolongation of progression-free survival. The integration between target therapy and surgery in patients with locally advanced or metastatic RCC has sometimes facilitated surgery. We aimed to evaluate patients' response to tyrosine kinase inhibitor (TKI) therapy and the feasibility of surgery after that and to observe complications related to surgery. METHODS:: From February 2007 to September 2014 in the Istituto Tumori of Milan, IRCCS, we selected patients with locally advanced or metastatic diseases, treated with target therapy before surgery (which comprised nephrectomy or partial nephrectomy, cytoreductive surgery, and metastasectomy) and cryoablation. RESULTS:: We selected 33 patients who underwent surgery after TKI therapy. As for response to TKIs, 20 patients (60%) had stable disease, 9 patients (28%) had a partial response, and 4 patients (12%) had progressive disease. A total of 17 patients (51%) presented complications directly or indirectly related to surgery and most of those were classified as grade II Clavien-Dindo score. CONCLUSIONS:: The association between TKI and surgery seems to have no contraindications. Our dataset provides an example of how surgery after TKI is possible in locally advanced metastatic tumor and does not have an excessive rate of postoperative complications.

Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma.

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.