Use of contrast-enhanced intraoperative ultrasonography during liver surgery for colorectal cancer liver metastases - Its impact on operative outcome. Analysis of a prospective cohort study

Abstract Background Preliminary reports led to discordant conclusions concerning the use of contrast-enhanced intraoperative ultrasonography (CE-IOUS) during surgery for colorectal liver metastases (CLM). The aim of this study was to evaluate the impact of CE-IOUS in patients undergoing surgery for CLM using an advanced preoperative imaging work-up, and well-established reference standards. Materials and methods Forty-seven consecutive patients underwent liver resection using IOUS and CE-IOUS for CLM. All patients underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI) within 2 weeks prior to surgery. CE-IOUS was performed by injecting intravenously 4.8 ml of sulphur-hexafluoride microbubbles (SonoVue, Bracco, Italy). Reference standards were histology, and 6-month imaging follow-up. Results IOUS discovered 43 additional lesions in 20 patients. CE-IOUS found 10 additional lesions not seen at IOUS in four patients, and confirmed all the IOUS findings. Fourteen CLM in 10 patients appeared within 6 months after surgery. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were, respectively: 66%, 0%, 98%, 0% and 65% for CT + MRI; 88%, 100%, 100%, 8%, 88% for IOUS and 93%, 100%, 100%, 13%, 93% for IOUS + CE-IOUS. In nine patients CE-IOUS afforded better definition of tumour margins thus helping in resection guidance. Conclusions CE-IOUS improves IOUS findings both for detection and for resection guidance. The combination of IOUS and CE-IOUS should be considered routinely in patients operated for CLM

Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma

Efficacy of trabectedin in advanced soft tissue sarcoma: Beyond lipo- and leiomyosarcoma

OBJECTIVE: Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific subgroups of patients with soft tissue sarcomas (STS). METHODS: Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m(2) every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS). RESULTS: Median age was 48 (range, 20–75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0–5). Median number of trabectedin cycles was 3 (range, 1–17). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 2–23) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively. CONCLUSION: Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma

Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors

Risk factors for hepatic immune-related adverse events (HIRAEs) in patients with advanced/unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are unclear. We investigated: (i) clinical and morpho-pathological predictors of HIRAEs in 27 pretreatment tumor specimens, including surrogate biomarkers of the HCC immune class (based on intratumoral tertiary lymphoid structures, and glutamine synthase, CD3, and CD79 expression); and (ii) the relationship between HIRAE onset and subsequent treatment outcomes. Fifty-eight patients were included—20 (34%) received ICIs alone, and 38 (66%) received ICIs plus targeted agents as first- or further-line treatment. After a median time of 0.9 months (range, 0.4–2.7), nine patients (15.5%) developed grade ≥ 3 hepatitis, which was significantly associated with higher baseline ALT levels (p = 0.037), and an infectious HCC etiology (p = 0.023). ICIs were safely resumed in six out of nine patients. Time to treatment failure (TTF) was not significantly different in patients developing grade ≥ 3 hepatitis vs. lower grades (3.25 vs. 3.91 months, respectively; p = 0.81). Biomarker surrogates for the HCC immune class were not detected in patients developing grade ≥ 3 hepatitis. Grade ≥ 3 hepatitis has a benign course that does not preclude safe ICI reintroduction, without any detrimental effect on TTF