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  • ISSN: 2373-9436
    Molecular aspects of Colorectal Carcinogenesis: A Review
    Authors: Ernst Fredericks*, Gill Dealtry and Saartjie Roux
    Abstract: Colon cancer is a common malignancy associated with significant mortality. Colon carcinogenesis generally occurs in a slow and stepwise process of accumulating mutations under the influence of genetic and environmental factors, the so-called adenoma-carcinoma sequence.
    Fertility Preservation for Cancer Patients
    Authors: Sherman Silber* and Christina Usher
    Abstract: Freezing of eggs or ovarian tissue to preserve fertility for cancer patients has been studied since 1994 with Gosden's original paper in sheep, and before that in smaller mammals for decades prior. Clinically, this tactic has enjoyed great success.
    Latest Articles
    Research Article
    Serkan Akan and Caner Ediz*
    Objective: In this study, we examined histopathologically the tumour components or combinations of these components and analysed to changes of pathological findings with aging in the patients diagnosed with testicular mixed germ cell tumour (MGCT) in the last 10 years.
    Materials and methods: 207 patients who underwent radical inguinal orchiectomy due to testicular cancer between 2010 and 2019 were retrospectively reviewed and 107 cases with MGCT whose data were fully available were included in the study. Age, primary tumour localization, primary tumour size, histopathological components and combinations of these components were analyzed. To compare the change of tumour components with aging, patients were divided into two groups according to patients age, Group 1 was younger than 25 years of age and group 2 was = 25 years old.
    Results: The mean age of the patients was 24.67 4.31 years. Tumour component of MGCT included embryonal carcinoma in 87 patients (81.3%), teratoma in 72 patients (67.3%), yolk sac carcinoma in 66 patients (61.7%), choriocarcinoma in 17 patients (15.9%) and seminoma in 44 patients (41.1%). Current combination of these tumours was analyzed and the most common combination was found as embryonal carcinoma + teratoma + yolk sac carcinoma in 26 patients (24.3%) and the second most common combination was found as embryonal carcinoma + seminoma in 17 patients (15.9%). The incidence of three or more components was significantly higher in group 2 (57.8%) than in group 1 (51.6%) (p<0.05). The mean follow-up of the patients was 43.37 months (3-113) and 2 patients died for testicular cancer in follow-up period.
    Conclusion: In 10-year series, the most common MGCT component was found as embryonal carcinoma and teratoma, while the most common combination was embryonal carcinoma + teratoma + yolk sac carcinoma. Combination of three or more components in MGCT may be more reported with increasing age (especially over 25 years old).
    Nicholas M. Schlaeger, Carmen Berkan, Ingrid Albu, Aaron P. Monte, and Cheng-chen Huang*
    Within melanoma tumors are a small subpopulation of cells called cancer stem cells (CSC). They can be categorized by two fundamental properties, self-renewal and differentiation. CSC play a vital role in metastasis, tumor relapse and chemotherapeutic resistance. Here we identified compounds that seem to specifically target the melanoma CSC population. B16F10 mouse melanoma cells treated with synthetic compounds SK0408 or SK0459 first showed reduction of proliferation in the MTT and anti-phophohistone H3 immunostaining assays. Western blotting revealed that SK0408 and SK0459 has no effect on phosphorylated MAPK level but significant decrease of phophorylated Akt and increase of phosphorylated b-catenin. Using melanoma stem cell markers CD133, CD271, and CD20, we found that SK0408 and SK0459 indeed cause a 54-79% reduction in the melanoma stem cells population. Cell invasion assay showed reduced metastatic potential in treated cells. Furthermore, we observed an increase of the epithelial marker E-cadherin but a decrease in the mesenchymal marker vimentin in the treated cells. Additionally, western blotting and RT-qPCR showed an elevated level of differentiation gene expression of Pax-3, MITF, DCT, and tyrosinase. Our results demonstrate the therapeutic potential of these compounds in suppressing melanoma cell growth and metastasis by reducing melanoma stem cells through promoting melanocyte differentiation.
    Marwa A. Suliman*, Maha L. Zamzam, Omar AT, and Fahmy NM
    Introduction: Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer death worldwide. In Egypt, it is the six cancers in both males and females. This study was performed to define the epidemiological and clinicopathological characteristics of CRC in Egypt.
    Material and Methods: Retrospective study included all patients diagnosed with colorectal carcinoma at Suez Canal University Hospitals, Egypt from January 2006 to December 2016.
    Results: A total of 193 patients were included in this study, 57% were females and 43% were males. Colon cancer were more common than those located in the rectum, (58.6% vs. 25.4%), the ascending colon was the commonest location (56.2%). Descending colon and rectum were equally the commonest in females (29.1%) while the ascending colon was the commonest in males (28.9%). Most tumors were adenocarcinoma (76.2%). In terms of tumor markers, CEA was elevated in 45.6% and CA19.9 was elevated in 40.9% in preoperative evaluation. Most patients presented with stage II (30.6%). Liver was the most common metastatic site (67.6%). The overall survival was 18.8 month.
    Conclusion: Colon cancer is more frequent than rectum cancer where ascending colon is the most affected sub site. The mean age at diagnosis was 52.6 years with female predominance. Most patients had tumors that were adenocarcinoma, low grade and most presented in stage II. Liver is the commonest metastatic site. The overall survival was 18.8 month. Three-year and 5-years survival rate were 16.1% and 3.6%.
    Joel B. Epstein*, Dana Villines MA, Geena L. Epstein RN, and Gregory Smutzer
    Objective: The purpose of this paper is to present patient reported outcomes (PRO) of oral function and toxicity in head and neck cancer (HNC) patients and the clinical oral conditions affecting diet and maintenance of body weight during and following cancer therapy.
    Study design: Patients with HNC were evaluated during and following cancer therapy. Oral conditions affecting taste and oral diet, including taste and smell function were assessed.
    Results: The participating patients reported appetite decline and taste loss in 50% of patients during and in 62.5% following treatment. Decreased food intake and altered food choice were reported as severe by 50% of patients. Throat and mouth pain affected 67% of acute and 42% of post-treatment patients. The spicy perception of capsaicin was reported to have severe impact for 80% of acute and 70% of post-treatment patients. Bitter taste perception affected oral diet either often or all the time in 33% of acute and in 83% of post-treatment patients. Weight loss occurred in 5% during treatment and in 12% post-treatment.
    Conclusions: This is the first report of clinical oral function including taste and smell testing, saliva production and patient reported outcomes. Oral complications including mucositis and saliva affect taste change throughout cancer treatment and in the first two years of survivorship. This study provides initial suggestions that may guide diet and food intake and in product development for HNC patients.
    Weiyu Wang*, Yang Yang*, Shengyao Ma, Huaijie Wang, Hanyue Li, Qingtao Yan, Kunning Yang, Zhigin Gao, Mei-Hua Qu
    Objective: To study the clinical significance of CD4 and CD45 expression in patients with non-small cell lung cancer.
    Methods: Biopsies from 140 patients with non-small cell lung cancer in Weifang Second Peoples Hospital from January 2011 to December 2015 were collected and made into tissue microarray. The expression of CD4 and CD45 in tissue microarray was detected by immunohistochemistry. The overall survival (OS) of patients was followed up by telephone in August 2020. Graphpad primes 8 and BIM SPSS statistics 22 were used for statistical analysis.
    Results: Immunohistochemical staining showed a significant positive correlation between the expression of CD4 and CD45 from the same patients (Person correlation=0.4, P<0.0001). Kaplan-Meier survival analysis showed that the OS of CD4high patients was higher than that of CD4low patients (log-rank=0.0456); the OS of CD4highCD45high patients was higher than that of CD4lowCD45low patients (log-rank=0.0362). No significant difference was found in OS between CD45high and CD45low patients (log-rank = 0.5454).
    Conclusion: There was a positive correlation between CD4 and CD45 in non-small cell lung cancer, and the expression of CD4 and CD45 in tumor tissue was positively correlated with OS.
    Case Report
    Alparslan Serarslan*, Deniz Meydan, Bilge Gursel, Nilgun Ozbek Okumus, Mehmet Koyuncu, Yurdanur Sullu, Cetin Celenk
    Maxillary sinus malignancies are uncommon. They are separated into squamous and non-squamous cells histopathologically, with most of them being squamous cell carcinomas. Maxillary sinus transitional cell carcinoma is extremely rare and is classified as primary (sinusal origin) or secondary (non-sinusal origin). Herein, we report the long-term control of primary maxillary sinus transitional cell carcinoma with surgery followed by radiotherapy. A 31-year-old female patient was admitted with a complaint of swelling on the right side of her face. Paranasal sinus computed tomography showed a right-sided maxillary sinus tumor. Biopsy revealed transitional cell carcinoma, following which the patients right maxilla was totally removed with negative surgical margins. The final histological diagnosis was consistent with the previous diagnosis. The patient underwent postoperative radiotherapy. She remained disease-free at the 14-year follow-up. Knowledge concerning the treatment of maxillary sinus transitional cell carcinoma is limited. The combination of surgery and radiotherapy seems to be successful for this rare maxillary malignancy.
    Review Article
    Kritin Vasamreddy1, Aritra Mullick1, Inamul Haque1, Syed Shadaan1, Seth Acup1, Younggi D. Moon1, Suman Kambhampati1,2*, Snigdha Banerjee, Mohiuddin Quadir4 and Sushanta K. Banerjee*
    Multiple Myeloma (MM) is a malignant B neoplasm that can be characterized as a plasma cell dyscrasia in the bone marrow. Though there has been a significant improvement in the prognosis of the disease in the past decade, it is still incurable, as most patients relapse or become refractory to standard treatment. MicroRNAs (miRNAs) are short, single-stranded, highly conserved, non-coding RNAs that play a vital role in the post-transcriptional regulation of gene expression. Over the past decade, miRNAs have been investigated to see the potential impacts on hematological malignancies such as MM. Since their discovery in 1993, a significant volume of work has been done to figure out the Role of miRNAs in controlling MM. MicroRNAs can upregulate or downregulate the expression of a gene, and their Dysregulation is associated with clinical disease. They play a significant role in cellular signaling and various biological processes like cellular proliferation, aging, maturation, and apoptosis. They are critical to the normal functioning and development of the human body. This review will provide insight into the roles that miRNAs play in general cancer cell biology with a particular focus on MM, its clinical course, and management and highlight potential treatment options for using miRNA for the treatment of MM. Tumor suppressor microRNAs (TS miRNAs) and oncogenic microRNAs (Onco miRNAs) and their significance in the development and treatment of MM are also discussed. The use of miRNA in distinguishing MGUS (monoclonal gammopathy of undetermined significance) from MM is also discussed, and a possibility to prevent the progression of MGUS to MM is highlighted in this review.
    Special Issue on Breast Cancer Therapeutics
    Masataka Sawaki*
    Recently, two pivotal papers with Intraoperative radiotherapy (IORT) are published [1,2]. The standard treatment for early breast cancer is breast-conserving therapy (BCT) with whole breast external irradiation therapy (WBI) [3]. Even in highly selected patients, omission of radiotherapy increases the risk of local recurrence [4].
    Manuel Ruiz-Borrego*
    The publication of the BOLERO 2 trial [1], made progress in identifying a way to approach different from the patients who make resistance to hormone therapy, everolimus is a drug that acts on the m- Tor [2] complex, which is in the center of the PI3K signaling pathway. Today is underway BOLERO 6 trial [3] , ("A phase II , randomized, open-label, three-arm , of everolimus in combination with exemestane versus everolimus monotherapy versus capecitabine , for the treatment of postmenopausal women with breast cancer with estrogen receptor positive , locally advanced , recurrent or metastatic after recurrence or progression to letrozole or anastrozole prior") that attempt to clarify its advantage over chemotherapy (capecitabine) in first line in patients with breast cancer metastatic hormone receptor-positive who have resorted to treatment with an aromatase inhibitor .
    Case Report
    Hussein A Assi, Katia E Khoury,Tarek H Mouhieddine, Lana E Khalil and Nagi S El Saghir*
    Abstract: Metastasis to the breast represents 0.4-1.3% of all breast malignancies. In those rare instances, the primary site is usually leukemia, lymphoma, or melanoma. Lung cancer, mostly adenocarcinoma, has been reported to be associated with metastasis to the breast. We report the first case of a female patient with a rapidly growing breast metastasis from a small cell lung cancer, as a first site of recurrence, misread as a triple negative breast cancer. We include clinical, radiological, pathological and immunohistochemical features of differential diagnosis.
    Sameer Berry1,2*
    Breast cancer represents the most common non-cutaneous cancer amongst women in the United States with over 300,000 cases diagnosed each year [1]. Breast Conserving Therapy (BCT) represents a breakthrough in the management of breast cancer allowing women to preserve their breast without compromising their cancer outcomes based on long term follow up from several randomized Phase III trials [2,3].
    Short Communication
    Yong Zhao1*, Chengfeng Yang2, Sandra Z Haslam2 and Richard C Schwartz3
    The heterogeneous disease Breast Cancer (BC) is an ancient disease which was noted 3500 years ago by ancient Egyptians [1] .The heterogeneity, including intratumor heterogeneity and intertumor heterogeneity, is influenced by genetic and non-genetic factors. Furthermore, BC is the most common malignant tumor and the second leading cause of cancer death in women.
    Mini Review
    Melissa R Gillette1 and Tracy Vargo-Gogola1,2*
    Abstract: Deregulation of Rho GTPase expression and activity levels is found in a number of cancers, including breast cancers. Aberrant Rho GTPase signaling promotes tumorigenic behaviors in a cell-autonomous manner. The development of conditional knockout and over expression mouse models of Rho GTPases and their regulators has allowed for investigation of the impact of aberrant Rho signaling in the context of the complex in vivo environment. These studies, including studies from our laboratory investigating the effects of Cdc42 and p190B RhoGAP over expression in the developing mammary gland, indicate that altered Rho signaling in the epithelium impacts the microenvironment. We propose that hyperactivated Rho signaling in neoplastic cells may contribute to tumor formation by promoting the development of a pro-tumorigenic and pro-invasive microenvironment. The availability of conditional Rho GTPase mouse models will facilitate these studies in the future.
    Review Article
    Nada Alwan*
    Breast cancer is the commonest malignancy among women in countries within the Eastern Mediterranean Regions (EMR). In Iraq, it comprises approximately one third of the registered female cancers. Other features that justify increasing efforts for breast cancer control in the EMR include the obvious rise in the incidence rates, the higher frequencies of younger ages and advanced stages at the time of presentation and the likely prevalence of more aggressive tumors resulting in high mortality/incidence ratios.
    At the level of national registration, most of the cancer registries of those countries lack data regarding tumour staging and mortality rates. In fact, within the hospital records, there is no proper documentation on critically important risk factors and clinical characteristics of the disease including stage distribution at the time of initial diagnosis, hormonal receptor status, proportion of women presenting with distant metastases, treatment modalities and survival rates.
    In an attempt to address the aforementioned information needs on the clinical profile of breast cancer patients, and emphasizing the role of research as one of the basic pillars in the adoption of the cancer control strategy, a "National Breast Cancer Research Program-NBCRP" was established in Iraq in 2009. In collaboration with the International Agency for Research on Cancer (IARC) and WHO, the Iraqi researchers developed a comprehensive information system for Iraqi patients diagnosed with breast cancer. Thereafter, that data base model was utilized to compare the demographic characteristics, clinicopathological presentations and management outcomes of breast cancer patients inhabiting selected countries in the EMR (so far Iraq, Jordan, Lebanon and Egypt are included).
    Zachary C. VanGundy1#, Joseph Markowitz2#, Julie D. Baker1, Heather R. Strange1 and Tracey L. Papenfuss1*
    In cancer, immune dysfunction and immunosuppression contributes to the failure of cancer therapies and cancer-related mortality. Myeloid derived suppressor cells (MDSCs) are a potently immunosuppressive population of cells which contribute to dysfunction and immunosuppression. In breast cancer, MDSC levels are clinically relevant and correlate with disease outcome and response to treatment. In this study, the E0771 breast cancer adenocarcinoma cell line was used to induce MDSCs in vitro to recapitulate the in vivo induction of MDSC in immunocompetent C57BL/6 mice. In vivo, approximately 25% of splenocytes derived from the E0771 breast cancer model are phenotypically (CD11b+ GR-1+) and functionally MDSCs with the level of induction dependent on tumor location and burden. Approximately 70% of the cells differentiated in vitro from bone marrow precursors were phenotypically MDSCs and found to suppress the proliferation of responder immune cells. In this study, we describe a parallel in vivo and in vitro model system of MDSC induction utilizing the E0771 breast cancer cell line. The development of this model system in immunocompetent mice is a useful new method to investigate mechanistic questions of MDSC development and MDSC-immune interactions in breast cancer.
    Kara Britt1*, Wendy Ingman2, Cecilia Huo3, Grace Chew3 and Erik Thompson3,4
    High mammographic density confers a significantly increased risk of breast cancer. As it is relatively common in the normal population the risk of cancer attributable to increased mammographic density could potentially account for an important percentage of total BCa cases. The underlying cause for high mammographic density and its association with increased BCa risk and progression is unknown. In this review we describe the work that has been done to define the histopathological characteristics of mammographic density. Mammograms define breast tissues with areas of high density due to an increased amount of radio-opaque tissue (stromal and epithelial cells) and also less areas of radiolucent fat. Histological work however can define the roles played by each cell type. We review the work that has been performed assessing changes in epithelial cells, stromal cells, the extracellular matrix, and immune infiltrate. To determine how these changes may be increasing breast cancer risk we also discuss the roles of each of the cell types in breast cancer initiation and progression.
    Amy L Strong1, Matthew E Burow2, Jeffrey M Gimble1,3 and Bruce A Bunnell1,4*
    Abstract: Obesity increases the incidence of many types of cancers, and as the incidence of obesity continues to rise, the frequency of obesity-associated cancers will likely increase. While obesity increases postmenopausal breast, endometrial, pancreatic, colorectal, and renal carcinomas, understanding the effects of obesity on postmenopausal breast cancer remains a priority, as it is the most common diagnosed cancer in women. Obesity is defined by the rapid expansion of adipose tissue, resulting in inflammation of the adipose tissue. This inflammatory environment may, in t urn, alter the Adipose-derived Stromal Cells (ASCs) within adipose tissue, influencing their effects on breast cancer cells. Recent studies demonstrate that ASCs in obese patients traffic through the circulation and into the tumor more frequently compared to lean patients. Furthermore, once at the tumor site, ASCs have been shown to alter the gene expression profile of cancer cells, leading to the expansion and enhanced invasiveness of these cancer cells. Together, these results suggest that obesity alters the ASCs within the tumor stroma, which in turn alters the cancer cells and leads to the development of aggressive breast cancer. Future studies investigating the precise mechanisms by which ASCs isolated from obese patients enhances breast cancer cell growth and developing new therapies to target these ASCs will decrease the morbidity and mortality from obesity-associated breast cancers.
    Special Issue on Lung Cancer
    Case Report
    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.
    Short Communication
    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].
    Review Article
    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.
    Research Article
    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
    Short Communication
    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].
    Review Article
    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.
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