Andras G. Lacko*
Neuroblastoma (NB) is the most common cancer diagnosed in infants and the most common extra-cranial solid tumor in children. The clinical course of the disease is highly variable with frequent spontaneous regressions observed in patients less than 1 year of age, while it presents with a much higher risk of a poor prognosis in older pediatric patients. Due to the heterogeneous presentation of NB, stratification of patients via numerous diagnostic procedures, and subsequent appropriate treatment strategies conforming to the varying stages of aggressiveness of the disease have been developed.
Design and execution and evaluation of the findings of clinical studies involving NB patients have been performed largely by a select groups of experts leading to substantially deeper knowledge of the pathophysiological mechanism(s) and the diagnosis of NB while still leaving a lot more effort to be expanded for substantially improving the prognoses for patients, especially those with medium and high risk disease.
Several exhaustive reviews are currently available on NB therapeutics including accounts of clinical trials. This brief overview intends to examine only some of the currently available treatment strategies, regarding their respective therapeutic efficacies, including a focus on long and short term toxic off target effects. A brief assessment of potential opportunities, with a special emphasis on nanotherapeutics, for achieving improved outcomes for NB patients is also included.
Special Issue on Breast Cancer Therapeutics
Special Issue on Lung Cancer
Hiroshi Hirano1*, Manabu Ninaka2, Muneyoshi Kuroyama2, Akitoshi Satomi2, Soichiro Yokota2, Toshiko Yamaguchi2 and Masahide Mori2
Abstract: We herein present three autopsy cases of unusual malignant mesotheliomas with peculiar histological features.
Case 1: The patient was a 69-year-old female. The tumor encased the entire left lung, and metastasized to multiple organs. Histologically, more than 80% of the tumor was occupied by large discohesive pleomorphic cells with single or multiple irregular nuclei, and the remaining part of the tumor showed a tubulopapillary and sarcomatoid pattern. The tumor of this case was pleomorphic mesothelioma.
Case 2: The patient was a 64-year-old male. A pleural biopsy disclosed malignant spindle cells, but a definitive diagnosis was not obtained until his death. The tumor encased the right lung invading the right chest wall, and had metastasized to multiple organs. Histologically, the tumor consisted of neoplastic spindle cells with foci of osseous and cartilaginous differentiations. The tumor of this case was a sarcomatoid mesothelioma with osseous and cartilaginous differentiations.
Case 3: The patient was a 75-year-old male, who had pleural effusion in the right thoracic cavity. A definitive diagnosis was not obtained by the cytological examination of the effusion or the tumor biopsy. During autopsy, it was found that the tumor encased the right lung, invading the diaphragm. Metastases were seen in the liver. The histological examination showed that the tumor was a desmoplastic mesothelioma.
Yoshitomo Okumura1*, Taichi Koyama2, Masaki Hashimoto3 and Seiki Hasegawa3
Abstract: A 75-year-old man complained of pain and swelling of the right shoulder for 2 months. Plain chest radiography revealed a mass in the right upper lung field and dissolution of several ribs. Bronchoscopic brush cytology showed class V squamous cell carcinoma. The patient was diagnosed with clinical stage IIIA (cT4N0M0) lung cancer. After induction chemoradiotherapy, right upper lobectomy was performed and the chest wall was reconstructed. The successful outcomes suggest that the combined transmanubrial-Paulson approach in a half-lateral decubitus position is safe and suitable for resecting superior sulcus tumors.
Fayez Kheir1*, Khaled Eissa1 and Jaime Palomino2
Lung cancer is the leading cause of cancer related deaths in the United States. The estimated number of lung cancer deaths in 2012 was higher than the total combined number of deaths from breast, prostate and colon cancer. In 2012, according to the published data from the American Cancer Society, a total of 226,160 new cases of lung cancer had been diagnosed with a total death of 160,340 secondary to lung cancer. It was estimated that about 1 person out of 2000 in the US died because of lung cancer in 2012 [1-2].
Kozo Kuribayashi1* and Chiharu Tabata2
Abstract: The advent of molecular targeted drugs and effective second-line treatment for inoperable, advanced, Non-Small Cell Lung Cancer (NSCLC) has rapidly improved treatment outcomes. Conventional first-line chemotherapy regimens included all NSCLC, with the same treatment methods for squamous cell and non-squamous cell carcinomas. In addition, second-line or later treatment was not very effective in improving prognosis. However, there has been a recent paradigm shift in treatment options for NSCLC. In other words, 1) age and Performance Status (PS), 2) presence or absence of co-existing disease, 3) first-line vs. second-line or later treatment, 4) gene profiling for Epidermal Growth Factor Receptor (EGFR) gene mutations, and 5) squamous cell carcinomas vs. non-squamous cell carcinomas have become important factors in selecting treatment regimens.
Recent advances in research have shown that the presence or absence of the EML4-ALK fusion gene is important genetic information when considering the use of Anaplastic Lymphoma Kinase (ALK) inhibitors. Previously, the same regimens were selected for NSCLC regardless of tissue type, but clinical trial results of new drugs like pemetrexed and bevacizumab have now shown that the optimal treatment method differs for squamous cell vs. non-squamous cell carcinomas. This paper presents an overview, based on the most up-to-date knowledge, on selecting treatment in lung cancer, particularly advanced NSCLC.
Kozo Kuribayashi1* and Kazuya Fukuoka2
Abstract: Malignant Pleural Mesothelioma (MPM) is a highly lethal and refractory malignancy that is caused by asbestos exposure. Surgical resection, radiotherapy, and other local treatments are of limited efficacy. Therefore, systemic chemotherapy plays an important role in improving of treatment outcomes for MPM. The findings of a large-scale phase III study led to the approval of a novel antifolate, pemetrexed, by the U.S. Food and Drug Administration (FDA), making pemetrexed the world's first therapeutic agent for MPM. Further, the combination treatment of pemetrexed plus cisplatin has been recognized as standard chemotherapy for this disease in the first-line setting. Recent studies have provided evidence that second-line chemotherapy is associated with prolonged survival among patients with various malignancies, including MPM. To date, however, no chemotherapeutic regimens have been recommended for MPM in the second-line setting. Furthermore, although, systemic chemotherapy is carried out in the majority of medical cases of MPM, it has not been established whether this systemic chemotherapy contributes to prolonged survival. This article reviews the latest findings regarding chemotherapy in cases of MPM and focuses on new medical treatments including molecular targeted therapies.
Hokkaido chest surgery group, Masahiro Miyajima1, Atsushi Watanabe1*, Kichizo Kaga2, Masahiro Kitada3, Takafumi Kondoh4, Akihiko Tanaka5, Yoshiaki Narita6, Shinichi Matsuge7, Mitsuhito Kaji8, Eiji Yatsuyanagi9, Norio Inoue10, Taijiro Mishina1, Junji Nakazawa1, Mayuko Uehara1, Yoshihiko Kurimoto1 and Nobuyoshi Kawaharada1
Background: Postoperative acute exacerbation of Idiopathic Interstitial Pneumonia (IIP) is known to be a catastrophic complication in the surgical treatment for primary lung cancer with concomitant IIP. Investigation of clinical factors associated with postoperative acute exacerbation of IIP in primary lung cancer patients was conducted.
Methods: Between 2000 and 2009, 5630 lung cancer patients underwent surgical resection in ten institutes in north Japan (Hokkaido); wherein, 249 patients (4.4%) had concomitant IIP. Univariate logistic regression models were used to determine risk factors for exacerbation of IIP in 36 clinicopathological factors (preoperative demographic data, serum data, pulmonary function, comorbidity, operative data, and pathological data).
Results: Nine of 249 patients (3.6%) developed acute exacerbation of IIP and 7/9 patients died of the exacerbation. The univariate analyses showed no risk factor for postoperative acute exacerbation of IIP.
Conclusion: It is very difficult to predict the occurrence of acute exacerbation of interstitial pneumonia after surgical treatment of patients with lung cancer and interstitial pneumonia. Further factors or parameters should be investigated to predict the occurrence.
Masahide Mori1*, Toshihiko Yamaguchi1, Hiroshi Hirano3 and Soichiro Yokota1
Abstract: Conventionally, it has been believed that oncogenesis accompanying chromosomal translocations such as BCR-Abl in CML is limited to particular tumors such as hematologic diseases, etc. However, the presence of the EML4-ALK fusion gene in lung cancer induced by chromosomal translocations in chromosome 2q was reported in 2007. This is present in approximately 5% of pulmonary adenocarcinomas in which ALK inhibitor, crizotinib, is greatly responsive with respect to EML4-ALK lung cancer. Crizotinib was approved by the FDA in 2012 at an unprecedented speed. A summary of EML4-ALK lung cancer is provided in this report.
Yoshitomo Okumura1*, Shoji Nakata1, Seiki Hasegawa2 and Fumihiro Tanaka3
Abstract: Despite recent advances in surgical and multimodality treatments, lung cancer is still the leading cause of death due to malignant disease worldwide. In Japan, the number of surgical procedures for lung cancer has been steadily increasing (31,303 in 2009; 32,801 in 2010), totaling 33,878 in 2011. Lobectomy is a standard operating procedure commonly performed worldwide, which is recommended as the first choice of treatment for operable patients with clinical stage I or II non-small cell lung cancer. The proportion of Video-Assisted Thoracic Surgery (VATS) procedures increasing from 59.6% in 2010 to 62.9% in 2011. However, the treatment of choice varies depending on the extent of N2 lymph node involvement. Adjuvant therapy is generally administered to improve these outcomes, although its long-term effectiveness has not yet been demonstrated in lung cancer patients. Accordingly, there are great expectations regarding the potential of induction therapy and neo-adjuvant therapy. Nevertheless, the increased risk associated with surgery following induction therapy is a concern, attributable to possible surgical complications, especially after combined chemo-radiation therapy, and surgery-related death. Therefore, accurate mediastinal lymph node staging is one of the most important factors that can affect the patient outcome, as it not only determines the prognosis but also dictates the most suitable treatment strategy. We report on the status of surgical therapy and postoperative adjuvant chemotherapy for lung cancer patients in Japan. It is important to carefully select the most appropriate therapy on the basis of reliable evidence after considering the advantages as well as the potential therapeutic to improve the prognosis of each patient.
Hiroshi Hirano1*, Hajime Maeda2, Yukiyasu Takeuchi2, Yoshiyuki Susaki2, Ryozi Kobayashi2, Akio Hayashi2, Naoko Ose2, Manabu Ninaka3, Toshihiko Yamaguchi3, Soichiro Yokota3 and Masahide Mori3
Abstract: A Large Cell Neuroendocrine Carcinoma (LCNEC) of the lung is highly malignant. Reduced or abnormal expression of adhesion molecules, such as E-cadherin and b-catenin, on the cell membrane is associated with the aggressiveness of its tumor cells, while nuclear b-catenin activates the WNT signaling pathway. To examine the mechanism of LCNEC aggressiveness, we used immunohistochemistry to examine the expressions of E-cadherin and b-catenin in the membrane, as well as the nuclear expression of b-catenin and Ki-67 labeling index in 12 pathological (p)-stage I LCNEC specimens. As a control, we used solid-sheet components from 19 p-stages I solid predominant Poorly Differentiated Adenocarcinomas (PDAs), as that tumor is the most aggressive among non-small cell carcinomas of various histological types. The disease-free rate of patients with LCNEC was much lower than that of patients with PDA. In the LCNECs, there was no significant difference in the frequency of membrane-expression of E-cadherin and b-catenin, though all specimens predominantly showed disrupted patterns of membrane staining for both E-cadherin and b-catenin, while 16 of 19 PDAs predominantly showed a linear pattern. Nuclear b-catenin staining was found in 4 of 13 LCNECs, but in none of the PDAs. The Ki-67 labeling index of the LCNEC specimens was about 4-fold greater than that of the PDAs. The present results suggest that abnormal membrane expression of E-cadherin and b-catenin, nuclear b-catenin expression, and high proliferative potential are associated with LCNEC aggressiveness.
Gen Yamada1*, Yasuo Kitamura2, Masami Kameda1, Kimiyuki Ikeda1, Yasuyuki Umeda1, Makoto Shioya1, Yuki Mori1, Yu-ichi Yamada1 and Hiroki Takahashi1
Objectives: Endocytoscopy is a new endoscopic imaging device for in vivo visualizing cellular structures. The aim of this study was to observe lung cancer cells using an endocytoscopy and compare them with the microscopic findings.
Methods: Between July 2009 and April 2011, 12 patients with lung cancer (5 with squamous cell carcinoma, 4 with small cell carcinoma and 3 with adenocarcinoma) and 3 control subjects who had no abnormal findings in large airway were examined. The patients had endobronchial lesions of lung cancer. After conventional bronchoscopy, the lesions were stained with 0.25% methylene blue dye and examined with endocytoscopy. The endocytoscopic images of the lesions were compared with the corresponding microscopic findings of the biopsy and/or brushing specimen. In the same way, normal bronchial mucosa in the control subjects were examined by endocytosocpy and compared with the microscopic findings of the biopsy specimen.
Results: Endocytoscopy showed columnar epithelial cells on the normal bronchial mucosa in the control subjects. These cells were arranged regularly. On the other hand, in patients with lung cancer, polymorphic or oval cells were observed in squamous cell carcinoma, and round or oval cells were observed in both small cell carcinoma and adenocarcinoma. The heterogeneity in the cell distribution was found. In quantitative analysis, the cell area (p<0.002) and the nucleus-cytoplasm ratio (p<0.002) of tumor cells in the endoscopic images were significantly higher than those of normal bronchial epithelial cells, respectively.
Conclusion: Endocytoscopy was supposed to have the potential to provide in vivo microscopic diagnosis during bronchoscopy.
Special Issue on Lung Cancer China
Wanqing Chen*, Rongshou Zheng, Hongmei Zeng and Siwei Zhang
Cancer is an emerging health issue in China and many other countries of the world. Lung cancer is the first leading cancer diagnosed and cause of cancer death for many years in China with a rapid increasing trend during the past several decades [1,2]. The incidence rate of lung cancer in China was relatively higher and also increasing with a more rapid rate than in western countries. Lots of risk factors such as cigarette smoking, air pollution has been proved as the risk factor of the disease [3-6].
Jingjing Liu, Ying Cheng*, Hui Li and Shuang Zhang
Abstract: Small Cell Lung Cancer (SCLC) account for almost 15% of lung cancers, which is strongly associated with cigarette smoking. It has a high propensity for early metastatic dissemination. Since few improvements in treatment effectiveness have been seen over the past 30 years new treatment strategies for improving therapeutic effect were urgently needed. China is the second most populous in the world and has many smokers. The morbidity and mortality of lung cancer are higher than the worldwide average. Because the government didn't take effective measures for smoking cessation, so the morbidity of SCLC has no downward trend. The progresses of studies in SCLC are slowly, such as diagnose, treatment and translational medicine. In recent years, with the emphasis of the society and the public on early diagnosis and early treatment of tumors and the progress of medical diagnosis technology, Chinese scholars have made many attempts in the treatment and research of SCLC.
Xiu-Yi Zhi1*, Xiao-Nong Zou2, Mu Hu1, Yuan Jiang3 and You-lin Qiao4
Abstract: In recent decades the age-specific mortalities of lung cancer in China have been increased to 9 times in men and women and it become one of the most important public health issues. The high prevalence of smoking in men and more than 70% of nonsmokers, both men and women, could be the biggest contributable factor for those consequences. While the abundant evidence on the health risks of exposure to smoking were available in both international and domestic studies the awareness on the health hazards from tobacco use were quit low in Chinese peoples, even in the health providers. Changes in the contents and the process of the tobacco products in Chinese tobacco product markets were accompanied by increased numbers of the lung cancer cases, increased adenocarcinoma and decreased squamous cell carcinoma of the lung, rather than reducing the overall lung cancer cases. Those suggested that comprehensive smoking-free policy should be implemented in all public places and the process of smoking-free legislation should put forward to create the legal environment and provide effective protection for reducing the incidence of lung cancer. Popularized health education should be also enhanced to raise the public awareness on smoking hazards.