The calm before the storm: a report from the International Liver Cancer Association Congress 2015--part 1.

International Liver Cancer Association Congress 2015, Paris, France, 4-6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4-6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.

The calm before the storm: a report from the International Liver Cancer Association Congress 2015 - part 2.

International Liver Cancer Association Congress 2015, Paris, France, 4-6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4-6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.

Functional outcomes after different types of transoral supraglottic laryngectomy.

OBJECTIVES/HYPOTHESIS: To seek a correlation between the four types of transoral supraglottic laryngectomies (TSLs) according to the European Laryngological Society (ELS) and postoperative morbidity. STUDY DESIGN: Retrospective case series at an academic institution. METHODS: Chart review was done for 96 patients affected by T1-T3 supraglottic cancers (28 pT1, 46 pT2, 22 pT3) treated by TSL (29 type I, 14 type II, 35 type III, 18 type IV) with CO2 laser. Five-year overall survival (OS), disease-specific survival (DSS), local control with laser alone (LCL), and organ preservation (OP) were calculated by Kaplan-Meier curves. Thirty-six patients were submitted to swallowing evaluation by M. D. Anderson Dysphagia Inventory (MDADI), videoendoscopy of swallow (VEES), and videofluoroscopy (VFS). Hospitalization, tracheotomy, nasogastric feeding tube (NGFT), and complications were compared between type I-II versus III-IV TSLs for the entire series. MDADI and VEES/VFS scores were compared in the subgroup of 36 patients. RESULTS: Five-year OS, DSS, LCL, and OP rates were 69%, 85.9%, 89.2%, and 92.6%. Mean hospitalization was 9 days, tracheotomy was required in 7% of patients, an NGFT was required in 33%, and 11% experienced complications. Type III-IV TSLs were associated with increased hospitalization (P < .001), more NGFTs (P = .001), and 90% of complications (P = .021). Aspiration was seen in 0% and 9% of type I-II TSLs, and in 7% and 43% of type III-IV TSLs by VEES and VFS, respectively. CONCLUSIONS: Type III-IV TSLs present higher morbidity and complications, thus confirming the utility of the ELS classification in preoperative counseling and therapeutic planning. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1131-1135, 2016.

Gefitinib plus interleukin-2 in advanced non-small cell lung cancer patients previously treated with chemotherapy.

The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m2 (Million International Unit/m2)twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3-4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2-3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2-3.8) and 4.1 (CI 95% = 2.6-5.7) months; a median overall survival of 20.1 (CI 95% = 5.1-35.1) and 6.9 (CI 95% = 4.9-8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16-0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18-0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

EASL HCC summit: liver cancer management.

EASL HCC Summit, Geneva, Switzerland, 13-16 February 2014. The European Association for the Study of the Liver (EASL) organized the 2014 EASL HCC Summit in Geneva, Switzerland. We discuss here the most interesting and provocative contents from the clinical program of the summit. The objective of this segment was to provide an in-depth review on the different management issues related to early detection, diagnosis and treatment of hepatocellular carcinoma, and, in addition, to highlight the ways of dealing with such an important and rapidly involving field.

Transarterial chemoembolization and sorafenib in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is considered as the standard therapy for patients with intermediate-stage hepatocellular carcinoma. However, given the high heterogeneity of this population, no common strategy or protocol standardization has been defined yet. In the last few years TACE treatment has been combined with sorafenib systemic therapy, reporting overall positive results both in terms of safety and efficacy. This systematic review presents and critically discusses the evidence available on the use of TACE in combination (concomitant or sequential) with sorafenib, focusing also on clinical trials currently ongoing to better define an optimal therapeutic strategy for this group of patients.

MR Imaging of Hepatocellular Adenomas and Differential Diagnosis Dilemma.

HEPATOCELLULAR ADENOMAS (HCAS) ARE CURRENTLY CATEGORIZED INTO DISTINCT GENETIC AND PATHOLOGIC SUBTYPES AS FOLLOWS: inflammatory hepatocellular adenoma, hepatocyte-nuclear-factor-1-alpha (HNF-1 α -mutated) hepatocellular adenoma, and ß -catenin-mutated hepatocellular adenomas; the fourth, defined as unclassified subtype, encompasses HCAs without any genetic abnormalities. This classification has accepted management implications due to different risks of haemorrhage and malignant transformation of the four subtypes. Imaging guided biopsy and/or surgical resection very important in obtaining definitive characterization; nevertheless, MRI with intra-extravascular and hepatobiliary (dual phase) agents, is an important tool not only in differential subtypes definition but even in surveillance with early identification of complications and discovery of some signs of HCA malignant degeneration. Inflammation, abnormal rich vascularisation, peliotic areas, and abundant fatty infiltration are pathologic findings differently present in the HCA subtypes and they may be detected by multiparametric MRI approach. Lesion enlargement and heterogeneity of signal intensity and of contrast enhancement are signs to be considered in malignant transformation. The purpose of this paper is to present the state of the art of MRI in the diagnosis of HCA and subtype characterization, with particular regard to morphologic and functional information available with dual phase contrast agents, and to discuss differential diagnosis with the most common benign and malignant lesions mimicking HCAs.

Management of pancreatic intraductal papillary mucinous neoplasm in an academic hospital (2005-2010): what follow-up for unoperated patients?

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are diagnosed frequently in asymptomatic patients. It is still not clear what follow-up is indicated for patients not undergoing surgical resection. METHODS: Review of all reports of magnetic resonance cholangiopancreatography (MRCP) from June 2005 to June 2010, identifying all patients diagnosed with IPMN; subsequent reconstruction of the initial therapeutic decision, indications for and adherence to scheduled follow-up, and IPMN evolution by morphology and by biology. RESULTS: Overall, 4943 MRCP reports were analyzed, identifying 234 patients with IPMN. Although 143 (61.1%) of these were comprised in Sendai criteria for resection, surgical resection was considered in only 42 (17.9%) patients. Of the remainder, 52 were not subjected to any control, 58 to a single short time check, 77 to MRCP-based regular annual follow-up, and 5 were treated for associated ductal adenocarcinoma. With a median follow-up of 39.5 months (range, 12-72), 37.6% of 125 patients in follow-up had a morphological evolution, but only 2.4% has developed a malignant IPMN. No deaths were recorded, directly related to IPMN, in all 187 conservatively managed patients. CONCLUSIONS: In the analyzed series, fewer patients than expected underwent surgical resection, and only 67.2% undergo regular follow-up, but no more than 2.4% developed malignancy.

Dose-finding trial of a combined regimen with bevacizumab, immunotherapy, and chemotherapy in patients with metastatic renal cell cancer: An Italian Oncology Group for Clinical Research (GOIRC) study.

The aim of this study was to look for the maximum tolerated dose (MTD) of gemcitabine and 5-fluorouracil in a new regimen also containing the antiangiogenic bevacizumab and immunotherapy (IT) for the treatment of metastatic renal cell cancer. The primary objective of this multicenter dose-finding study was to establish the MTD of chemotherapy (CT) in combination with fixed doses of IT and bevacizumab. The secondary objective was to assess the combination's activity. Five escalated dose levels of CT with intravenous gemcitabine and 5-fluorouracil (days 1 and 8 every 28 d), were associated together with intravenous bevacizumab (10 mg/kg on days 1 and 15 every 28 d), subcutaneous interleukin-2 (1 MIU/m² bid on days 8, 9, 15, 16, and 1 MIU/m²/d on days 10-12 and 17-19), and interferon-α-2a (3 MIU on days 10, 12, 17, 19). Of the 27 enrolled patients, 59% had been pretreated. The MTD was not reached. The highest CT dose studied was gemcitabine 1000 mg/m² and 5-fluorouracil 600 mg/m². More frequent grade 3 to 4 toxicities included neutropenia (63%), thrombocytopenia (33%), and fever (26%). The response rate was 33% according to the Response Evaluation Criteria in Solid Tumors. This is the first study that explored the feasibility and safety of combined bevacizumab, IT, and CT in metastatic renal cell cancer. The activity of this regimen is interesting and its efficacy warrants further trials.