Baseline Characteristics and Outcomes of Cancer Patients Infected with SARS-CoV-2 in the Lombardy Region, Italy (AIOM-L CORONA): A Multicenter, Observational, Ambispective, Cohort Study.

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12-218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32-2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11-0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Microwave ablation of hepatocellular carcinoma.

Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA.

Microwave ablation of hepatocellular carcinoma using a new percutaneous device: preliminary results.

BACKGROUND: Thermal ablative techniques have gained increasing popularity as safe and effective options for patients with unresectable solid malignancies. Microwave ablation has emerged as a relatively new technique with the promise of larger and faster ablation areas without some of the limitations of radiofrequency thermal ablation. Herein, we report our preliminary results on the feasibility and efficacy of thermal ablation for hepatocellular carcinoma (HCC) with a new 2.45-MHz microwave generator. PATIENTS AND METHODS: Under ultrasound guidance 194 HCCs in 144 patients were treated through a percutaneous approach. The median diameter of lesions was 2.7 cm (range=2.0-11.0 cm); 68 lesions had a diameter greater than 30 mm. We used a microwave generator (AMICA-GEM, Apparatus for MICrowave Ablation) connected to a 14- or 16-gauge coaxial antenna endowed with a miniaturized sleeve choke to reduce back heating effects and increase the sphericity of the ablated area. Contrast-enhanced computed tomography scan was carried out one month after treatment, and then every three months to assess efficacy. RESULTS: Complete ablation was achieved in 94.3% of the lesions after a mean of 1.03 percutaneous sessions. For small HCCs (diameter <3 cm) complete necrosis was obtained in 100%. Local tumor progressions were found in 10 treated lesions (5.1%) a median of 19.5 months after ablation. Minor complications occurred in 5.1% procedures. No deaths, or other major complications occurred. CONCLUSION: In our experience, the new device for microwave ablation proved to provide an effective and safe percutaneous ablative method, capable of producing large areas of necrosis.

Simultaneous measurement of doxorubicin and reduced metabolite doxorubicinol by UHPLC-MS/MS in human plasma of HCC patients treated with TACE.

A sensitive, selective, accurate and precise method for simultaneous quantification of doxorubicin (DOX) and doxorubicinol (DOXol) in human plasma of patients diagnosed as having intermediate stage unresectable hepatocellular carcinoma (HCC) was developed. The method was based on electrospray tandem mass spectrometry in selected reaction monitoring mode. DOX, DOXol and trofosfamide, an internal standard, were extracted from plasma by using a simple solid phase extraction (SPE) procedure after the addition of 0.1 M hydrochloric acid. A 200-µL aliquot of the extracted sample reconstituted in mobile phase was analyzed on a Zorbax SB-C18 UHPLC column (50 mm × 2.1 mm, 1.8 µm particle size) in 8 min. The mobile phase consisted of acetonitrile and 0.1% formic acid pH 4.5 (95:05 v/v). Good accuracy and precision of this method were demonstrated by determination of spiked plasma QC samples in four consecutive days. The SPE extraction recoveries ranged from 72.3 to 77.3% and 75.5 to 98.4% for doxorubicin and doxorubicinol, respectively. The intra-day and inter-day precisions were less than 11.4%. The limit of quantitation was 1.0 ng/mL for both compounds. The calibration curves of DOX and DOXol were analyzed by weighted linear regression with 1/x as a weighting factor. They were linear over the concentration range of 1.0-100.0 ng/mL with R(2) greater than 0.99. This developed method was successfully applied to study plasma pharmacokinetics in patients affected by HCC and treated with transarterial chemoemolization practices (TACEs) using HepaSphere™ pre-loaded with DOX in a standardized procedure.

Serum pharmacokinetics in patients treated with transarterial chemoembolization (TACE) using two types of epirubicin-loaded microspheres.

AIM: The purpose of this study was the pharmacokinetic (PK) profile assessment in the serum of patients affected by hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) with drug-eluting beads. PATIENTS AND METHODS: This study included 20 patients, 12 treated with DC Bead® and 8 with HepaSphere Microsphere®, preloaded with epirubicin. No patient randomization was used for the inclusion in one group or in the other. Peripheral blood samples were obtained from all patients after the treatment, until 24 hours past the procedure. RESULTS: The pharmacokinetic study showed low peak serum epirubicin concentrations with greater drug exposure for the DC Bead® group (p<0.05). The highest drug concentration after microsphere injection was observed at 5 minutes in all 20 patients. In the time interval between 1 and 24 hours after TACE, persisting levels of epirubicin were detected in peripheral blood samples. CONCLUSION: A persistent and sustained drug elution for both types of microparticles was found.

Intravenous or oral vinorelbine plus capecitabine as first-line treatment in HER2- metastatic breast cancer: joint analysis of 2 consecutive prospective phase II trials.

BACKGROUND: The purpose of this study was to assess the activity and safety of the combination of vinorelbine (VNR) and capecitabine (CAP) as first-line treatment in HER2-negative (HER(-)) metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients (42) enrolled in trial A received intravenous (i.v.) VNR 25 mg/m2 on days 1 and 8 of a 21-day cycle combined with CAP 1000 mg/m2 twice daily for 14 consecutive days followed by 1 week of rest. Trial B (46 patients) followed trial A when the oral formulation of VNR became available at our institution. Patients received oral VNR (60 mg/m(2) on days 1-8) combined with the same CAP schedule as in trial A. RESULTS: The response rate (RR) in trial A was 73.2% (95% confidence interval [CI], 56.4-82.8), including 12.2% complete responses (CRs). Clinical benefit was achieved in 78% of patients (95% CI, 63.2-87.9). In trial B, overall RR was 76% (95% CI, 62.0-86.0), with 13% CRs and clinical benefit of 80.4% (95% CI, 66.8-89.3). In trial A, median progression-free survival (PFS) was 8.2 months (range, 6-14+ months) and median overall survival (OS) was 32.4 months (range, 17-36+ months). In trial B, median PFS and OS were 8.8 months (range, 8-21+ months) and 34.3 months (14-39+ months), respectively. Treatment-related toxicity was manageable. Quality of life assessment showed a statistically significant difference regarding body image (p = .001), sexual functioning (p = .02), and future perspectives (p = .03) in women receiving chemotherapy fully by the oral route. CONCLUSION: This joint analysis shows that both tested schedules can produce high objective RRs with encouraging PFS, manageable toxicity profile, and suggested benefit on some aspects of quality of life for the fully oral combination.

Hepatic intra-arterial cetuximab in combination with 5-fluorouracil and cisplatin as salvage treatment for sorafenib-refractory hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only therapy approved for advanced hepatocellular carcinoma no longer eligible for transcatheter arterial chemoembolization. Hepatic intra-arterial chemotherapy has been shown to be an effective and safe therapy for advanced hepatocellular carcinoma. Cetuximab has been administered intravenously to patients with advanced hepatocellular carcinoma, showing encouraging results in terms of its safety and toxicity profile. AIM: Our purpose was to evaluate the safety and feasibility of hepatic arterial chemotherapy with cetuximab, cisplatin and 5-fluoruracil for patients with advanced hepatocellular carcinoma, not responsive or not eligible for sorafenib therapy. PATIENTS AND METHODS: From January 2010 to January 2011, 12 patients received a 2-day course of chemotherapy consisting of repeated daily hepatic arterial administration of 20 mg of cisplatin as 2-h infusion, 5-fluorouracil at 500 mg/m(2) as 5-h infusion and cetuximab 500 mg/m(2) as 12-h infusion. Cycles were repeated every 14 days. RESULTS: After a mean of four months of therapy, computed tomography revealed five partial responses, five cases of stable disease and two of progressive disease. The toxicity profile was favourable, with no G4 gastrointestinal, hematologic or skin side-effects, or severe deterioration of liver function. CONCLUSION: Hepatic intra-arterial chemotherapy with cetuximab is a safe and feasible treatment for advanced hepatocellular carcinoma, with promising results in patients with initial poor prognosis.

Acute thrombocytopenia: an unusual complication occurring after drug-eluting microspheres transcatheter hepatic chemoembolization.

Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver.

BACKGROUND: Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and for adequate preservation of liver function. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of the complications associated with TACE therapy and to correlate it with certain risk factors, either well-known or not yet evaluated. PATIENTS AND METHODS: A total of 330 chemoembolization procedures performed in 170 patients (117 males and 53 females) over a period of 64 months were retrospectively analysed. Among the patients, 123 had hepatocellular carcinoma, 10 had intrahepatic cholangiocarcinoma and 37 had hepatic metastases. The variables considered were: tumour histotype, bilioenteric anastomosis, previous or combined treatment with radiofrequency thermal ablation, antibiotic prophylaxis, chemotherapeutic agents, use of new drug-eluting microspheres, comorbidities such as diabetes, patient age and the presence of vascular anatomical variations. RESULTS: A total of 30 complications occurred in 27 procedures. The total complication rate per procedure was 9.1% and approximately 75% of patients had postembolization syndrome. The difference in the prevalence of complications was statistically significant in the group of diabetic patients (13.3%) compared to the remaining patients (6.3%) (p = 0.002) and in patients with biliary stents (25%) compared to those without stents (7.75%) (p = 0.027). CONCLUSION: These data show that diabetes mellitus and the presence of bilioenteric anastomosis are risk factors for developing complications after TACE. The use of new drug-eluting microspheres did not increase the risk of complications.

Treatment of chronic hepatitis C in a patient affected by systemic sclerosis.

The currently recommended treatment for patients infected with hepatitis C virus (HCV) is pegilated interferon alpha (IFN alpha) plus ribavirin. Despite the numerous benefits of this therapy, there is an increasing concern regarding his tolerance. Among the most common side effects, interferon may trigger the onset or exacerbation of autoimmune diseases. When chronic hepatitis C coexists with an autoimmune disorder, it is not clear whether using interferon is better than avoiding it. We evaluated the disease state of a 55-year old female affected by sistemic sclerosis (SSc), during and after therapy with IFNalpha pegilated plus ribavirin for chronic HCV infection. We were worried about the potential worsening of the autoimmune disease during the therapy, but we were confident that we would give our patient a short course of peginterferon and ribavirin. A mild, asymptomatic worsening of lung SSc was observed during IFN administration, without life threatening symptoms. After 24 months follow up we observed the maintenance of the virological response and a good control of the rheumatological disease. Thus, in liver disease at high risk of progression and concomitant SSc, the antiviral therapy with IFNalpha is a feasible approach.

Validation of an LC-MS/MS method for the determination of epirubicin in human serum of patients undergoing drug eluting microsphere-transarterial chemoembolization (DEM-TACE).

Drug Eluting Microsphere-Transarterial Chemoembolization (DEM-TACE) is a new delivery system to administrate drugs in a controlled manner useful for application in the chemoembolization of colorectal cancer metastases to the liver. DEM-TACE is focused to obtain higher concentrations of the drug to the tumor with lower systemic concentrations than traditional cancer chemotherapy. Therefore a specific, precise and sensitive LC-ESI-MS/MS assay procedure was properly designed to detect and quantify epirubicin at the concentrations expected from a transarterial chemoembolization with microspheres. Serum samples were kept acidic (pH approximately of 3.5) and sample preparation consisted of a solid phase extraction (SPE) procedure with HLB OASIS cartridges using a methylene chloride/2-propanol/methanol mixture solution to recover epirubicin. The analyses consisted of reversed-phase high-performance liquid chromatography (rp-HPLC) coupled with tandem mass spectrometry (MS/MS). Accuracy, precision and matrix effect of this procedure were carried out by analyzing four quality control samples (QCs) on five separate days. The validation parameters were assessed by recovery studies of spiked serum samples. Recoveries were found to vary between 92 and 98% at the QC levels (5, 40, 80 and 150 microg/L) with relative standard deviation (RSD) always less than 3.7%. The limit of detection (LOD) was set at 1 microg/L. The developed procedure has been also applied to investigate the different capability of two types of commercially available microspheres to release epirubicin into the human circulatory system.

White matter hyperintensities and their associations with suicidality in patients with major affective disorders.

INTRODUCTION: A large body of evidence suggests that predisposition to suicide, an important public health problem, is mediated to a certain extent by neurobiological factors. The objective of this cross-sectional study was to compare the prevalence of white matter hyperintensities (WMH) in patients with major affective disorders with and without histories of suicide attempts. METHODS: T2-weighted magnetic resonance images (MRI) of 65 psychiatric inpatients with major depressive disorder or bipolar disorder were rated for the presence of WMH. Diagnoses, presence or absence of suicide risk and substance abuse were determined by the Mini International Neuropsychiatric Interview (MINI). Medical charts were reviewed to ascertain history of suicide attempt and basic clinical variables. Fisher's Exact Tests and logistic regression modeling were used to test the association between WMH and suicidality. Suicidal patients and controls were not matched for demographic variables and exposure to some risk factors. RESULTS: Bivariate analysis showed that the prevalence of WMH was significantly higher in subjects with past suicide attempts (Fisher's Exact Test, p = 0.01) and other clinical indicators of elevated suicide risk. Logistic regression analyses controlling for age, sex, and several clinical risk factors supported this finding (odds ratio = 4.7; 95% confidence interval: 1.4, 16.1). CONCLUSIONS: The increased prevalence of WMH in adults with major affective disorders and a history of suicide attempt, compared to similar patients without such a history, is consistent with previous findings in depressed children, youth and young adults. However, the association between WMH and suicidality holds true for both, depressed and bipolar patients. Our results suggest that WMH in patients with major affective disorders might be useful biological markers of suicidality.