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Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, and limited to the lungs. Despite the increasing research interest in the pathogenesis of IPF, unfavorable survival rates remain associated with this condition. Recently, novel therapeutic agents have been shown to control the progression of IPF. However, these drugs do not improve lung function and have not been tested prospectively in patients with IPF and coexisting lung cancer, which is a common comorbidity of IPF. Optimal management of patients with IPF and lung cancer requires understanding of pathogenic mechanisms and molecular pathways that are common to both diseases. This review article reflects the current state of knowledge regarding the pathogenesis of pulmonary fibrosis and summarizes the pathways that are common to IPF and lung cancer by focusing on the molecular mechanisms.

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Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The patatin-like phospholipase-3 (PNPLA3) I148M sequence variant is one of the strongest genetic determinants of NAFLD/NASH. PNPLA3 is an independent risk factor for HCC among patients with NASH. The obesity epidemic is closely associated with the rising prevalence and severity of NAFLD/NASH. Furthermore, metabolic syndrome exacerbates the course of NAFLD/NASH. These factors are able to induce apoptosis and activate immune and inflammatory pathways, resulting in the development of hepatic fibrosis and NASH, leading to progression toward HCC. Small intestinal bacterial overgrowth (SIBO), destruction of the intestinal mucosa barrier function and a high-fat diet all seem to exacerbate the development of hepatic fibrosis and NASH, leading to HCC in patients with NAFLD/NASH. Thus, the intestinal microbiota may play a role in the development of NAFLD/NASH. In this review, we describe recent advances in our knowledge of the molecular mechanisms contributing to the development of hepatic fibrosis and HCC in patients with NAFLD/NASH.

BackgroundTo evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer.Methodology/Principal FindingsBetween January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be medically inoperable with Charlson comorbidity index of 3 or greater. Follow-up was based primarily on computed tomography. There were 22 patients with 34 tumors who underwent 25 sessions of cryoablation treatment. Complications were pneumothoraces in 7 treatments (28%, chest tube required in one treatment), and pleural effusions in 8 treatments (31%). The observation period ranged from 12–68 months, average 29±19 months, median 23 months. Local tumor progression was observed in one tumor (3%). Mean local tumor progression-free interval was 69±2 months. One patient died of lung cancer progression at 68 months. Two patients died of acute exacerbations of idiopathic pulmonary fibrosis which were not considered to be directly associated with cryoablation, at 12 and 18 months, respectively. The overall 2- and 3-year survivals were 88% and 88%, respectively. Mean overall survival was 62±4 months. Median overall survival was 68 months. The disease-free 2- and 3-year survivals were 78% and 67%, respectively. Mean disease-free survival was 46±6 months. Pulmonary function tests were done in 16 patients (18 treatments) before and after cryoablation. Percentage of predicted vital capacity, and percentage of predicted forced expiratory volume in 1 second, did not differ significantly before and after cryoablation (93±23 versus 90±21, and 70±11 versus 70±12, respectively).Conclusions/SignificanceAlthough further accumulation of data is necessary regarding efficacy, cryoablation may be a feasible option in medically inoperable stage I lung cancer patients.

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

BackgroundAnatomic sublobar resection is being assessed as a substitute to lobectomy for primary lung cancers. However, persistent air leak after anatomic sublobar resection is prevalent and increasing surgical morbidity and costs. The use of electrocautery is being popularized recently in anatomic sublobar resection. We have retrospectively evaluated the safety and efficacy of intersegmental plane dissection using electrocautery.MethodsBetween April 2009 to September 2010, 47 patients were treated with segmentectomy for clinical T1N0M0 non-small cell lung cancers. The intersegmental plane was dissected using electrocautery alone or in combination with staplers. We evaluated the methods of dividing intersegmental plane (electrocautery alone or combination with electrocautery and staplers), intraoperative blood loss, duration of chest tube placement, duration of surgery, preoperative FEV1.0 %, incidence of prolonged air leak, length of postoperative hospital stay, postoperative pulmonary function at 6 months after surgery and the cost for sealing intersegmental plane.ResultsAmong the 47 patients, 22 patients underwent intersegmental plane dissection with electrocautery alone and 25 patients did in combination with electrocautery and staplers. The mean number of stapler cartridges used was only 1.3 in electrocautery and staplers group. Mean age, gender, number of patients whose FEV1% < 70 % were similar between two groups. There was no statistical difference between electrocautery alone and combination with electrocautery and staplers group in duration of surgery (282 vs. 290 minutes), intraoperative blood loss (203 vs.151 ml), duration of chest tube placement (3.2 vs. 3.1 days), postoperative hospital stay (11.0 vs.10.0 days), postoperative loss of FEV1.0 (13 vs.8 %), loss of FVC (11 vs. 6 %) or incidence of minor postoperative complications [9 % (2/22) vs. 16 % (4/25), p = 0.30)]. However, incidence of prolonged air leak was higher in electrocautery alone group than in combination with electrocautery and staplers group [14 % (3/22) vs. 4 % (1/25), p = 0.025)]. The cost of materials for sealing air leaks amounted to €964 per patient in the electrocautery alone group and €1594 per patient in combination with electrocautery and staplers group.ConclusionsThe number of patients with prolonged air leak was higher in the electrocautery alone group. The use of staplers in addition to electrocautery may lead to reduced prolonged air leak. However, the use of electrocautery for intersegmental plane dissection appeared to be safe with acceptable postoperative complications and effective in reducing costs.