Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview.

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV). Continuous oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental factors or cellular mitochondrial dysfunction, has recently been associated with hepatocarcinogenesis. On the other hand, a distinctive pathological hallmark of HCC is a dramatic down-regulation of oxido-reductive enzymes that constitute the most important free radical scavenger systems represented by catalase, superoxide dismutase and glutathione peroxidase. The multikinase inhibitor sorafenib represents the most promising target agent that has undergone extensive investigation up to phase III clinical trials in patients with advanced HCC. The combination with other target-based agents could potentiate the clinical benefits obtained by sorafenib alone. In fact, a phase II multicenter study has demonstrated that the combination between sorafenib and octreotide LAR (So.LAR protocol) was active and well tolerated in advanced HCC patients. The detection of molecular factors predictive of response to anti-cancer agents such as sorafenib and the identification of mechanisms of resistance to anti-cancer agents may probably represent the direction to improve the treatment of HCC.

Prognosis of patients with spontaneous rupture of hepatocellular carcinoma in cirrhosis.

The treatment of cirrhotic patients with spontaneous rupture of hepatocellular carcinoma (HCC) is controversial and largely dependent on general conditions of the patients and compensation of the underlying cirrhosis. We retrospectively reviewed clinical, imaging and surgical records of 24 consecutive cirrhotic patients (17 males, 7 females; age range 52-88 years) with hemoperitoneum from spontaneous rupture of HCC observed from June 2004 to January 2010 at our Institution. When indicated, patients were referred to surgery or trans-arterial embolization (TAE). Advanced decompensated patients were conservatively treated and clinically followed up. Spontaneous rupture of HCC was assessed by aspiration of bloody ascites at paracentesis in all cases. The presence of large blood-clots over HCC and liver surface at US and/or CT was considered a specific sign of ruptured HCC in 14 cases. In two out of four patients who underwent TAE active bleeding from tumor surface could be demonstrated. In 2 cases, the active hemorrhage from the HCC surface could be assessed by contrast-enhanced ultrasonography. Four out of 24 patients underwent surgery. Three out of four of these patients died within 2 weeks, 8 months, and 20 months after operation, respectively. The remaining patient is still alive at 52 months follow-up. Four patients underwent TAE and died at 1, 2, 6 and 10 months after treatment, because of recurrent peritoneal bleeding and/or liver failure. Sixteen patients with ruptured HCC in the advanced Child C cirrhosis were treated conservatively with blood derivative transfusion and with procoagulant drugs. All patients, but one died within 2-18 days. One patient survived the acute hemorrhage from ruptured HCC and died of liver failure after 3 months. We concluded that spontaneous rupture of HCC is usually a fatal event in patients with poor liver function, even after successful TAE. In compensated patients, timely surgical treatment can result in long term and even tumor-free survival of the patient.

Percutaneous ethanol injection of hyperfunctioning thyroid nodules: long-term follow-up in 125 patients.

OBJECTIVE: The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules. MATERIALS AND METHODS: One hundred twenty-five patients (88 women, 37 men; age range, 17-76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2-90 mL; mean, 10.3 mL) were treated with PEI. There were 1-11 PEI sessions per patient (average, 3.9) performed, with injection of 1-14 mL of ethanol per session (total injected ethanol per patient, 3-108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9-144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter. RESULTS: Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients-115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules < or = 10 mL, 63 (94.0%) of 67; nodules > 10 to < or = 30 mL, 32 (91.4%) of 35; nodules > 30 to < or = 60 mL, 17 (89.5%) of 19; nodules > 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12, 18, 18, and 48 months' follow-up, respectively. However, all patients remained euthyroid (low or normal TSH and normal FT3 and FT4) during follow-up. CONCLUSION: PEI of hyperfunctioning thyroid nodules seems to be an effective and safe alternative to traditional treatment. It also appears to be effective in patients with hyperfunctioning thyroid nodules larger than 30 mL.

Surgical treatment of differentiated thyroid carcinoma: a retrospective study.

A retrospective study was carried out to assessed reliability of the prognostic factors (histology, age, sex, and stage), and standard procedures for the surgical treatment of differentiated thyroid cancers (DTC). From the 144 DTC cases reviewed with follow-up ranging from 1 to 25 years (m = 6.33 years), total mortality for cancer was found to be 55% (8 patients), with a predictive positive value for recurrence of 95.4% and 91.8% at 12 and 24 months, respectively. Median survival was 8.8 years (range 1 to 25 years). The multivariate analysis showed that factors such as age > 45 years, histology of intermediate malignancy, size up to 1.5 cm, and presence of metastases, significantly worsened the prognosis, regardless of the intervention that was carried out. We suggest total thyroidectomy for the treatment of benign pathologies and confirmed or suspected cases of cancer. We reserve loboisthmectomy for the treatment of benign pathologies confined to one lobe or those with FNAB suggesting a follicular neoplasm.