Survivin： Potential role in diagnosis, prognosis and targeted therapy of gastric cancer

Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.     

Multidisciplinary approach to understand the pathogenesis of gastric cancer

Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cancer death in the world. Although the incidence and mortality of gastric carcinoma are decreasing in many countries, gastric cancer still represents the second most frequent malignancies in the world and the fourth in Europe. The 5-year survival rate of gastric carcinoma is low. The etiology and pathogenesis are not yet fully known. The study of gastric cancer is important in clinical medicine as well as in public health. Over the past 15 years, integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. Gastric cancer, as all cancers, is the end result of the interplay of many risk factors as well as protective factors. Although epidemiological evidence indicates that environmental factors play a major role in gastric carcinogenesis, the role of immunological, genetic, and immunogenetic factors are thought to contribute to the pathogenesis of gastric carcinoma. Among the environmental factors, diet and Helicobacter pylori are more amenable to intervention aimed at the prevention of gastric cancer. The aim of the present paper is to review and include the most recent published evidence to demonstrate that only a multidisciplinary approach will lead to the advancement of the pathogenesis and prevention of gastric cancer. On the immunogenetic research it is clear that evidence is accumulating to suggest that a genetic profile favoring the proinflammatory response increases the risk of gastric carcinoma.     

E-cadherin in gastric cancer

Cadherin is an adhesion molecule and a superfamily of calcium-mediated membrane glycoproteins. E-cadherin is the prototype of the class E-cadherin that links to catenins to form the cytoskeleton. Recent evidence has shown that E-cadherin not only acts as an adhesive, but also plays important roles in growth development and carcinogenesis. It has been recently viewed as an invasion as well as a growth suppressor gene. This review summarizes the recent discoveries on E-cadherin and its role in gastric cancer. In particular, our work on E-cadherin in gastric cancer, including its relation with Helicobacter pylori and clinical applications, are described in detail.     

Immunotherapy in gastric cancer

Gastric cancer is the second most common of cancerrelated deaths worldwide.In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved,survival rates remain poor.Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer,prostate cancer and melanoma.Here,we provide an overview of concepts of modern cancer immunotherapy including the theory,current approaches,remaining hurdles to be overcome,and the future prospect of cancer immunotherapy in the treatment of gastric cancer.Adaptive cell therapies,cancer vaccines,gene therapies,monoclonal antibody therapies have all been used with some initial successes in gastric cancer.However,to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response.Here,we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy.We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment.We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells.Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being.Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.     

Role of symptoms in diagnosis and outcome of gastric cancer

Gastric cancer is one of the most common cancers and the second most common cause of cancer deaths worldwide. Apart from Japan, where screening programmes have resulted in early diagnosis in asymptomatic patients, in most countries the diagnosis of gastric cancers is invariably made on account on dyspeptic and alarm symptoms, which may also be of prognostic significance when reported by the patient at diagnosis. However, their use as selection criteria for endoscopy seems to be inconsistent since alarm symptoms are not sufficiently sensitive to detect malignancies. In fact, the overall prevalence of these symptoms in dyspeptic patients is high, while the prevalence of gastro-intestinal cancer is very low. Moreover, symptoms of early stage cancer may be indistinguishable from those of benign dyspepsia, while the presence of alarm symptoms may imply an advanced and often inoperable disease. The features of dyspeptic and alarm symptoms may reflect the pathology of the tumour and be of prognostic value in suggesting site, stage and aggressiveness of cancer. Alarm symptoms in gastric cancer are independently related to survival and an increased number, as well as specific alarm symptoms, are closely correlated to the risk of death. Dysphagia, weight loss and a palpable abdominal mass appear to be major independent prognostic factors in gastric cancer, while gastro-intestinal bleeding, vomiting and also duration of symptoms, do not seem to have a relevant prognostic impact on survival in gastric cancer.     

Role of cyclooxygenase-2 in gastric cancer development and progression

Although the incidence of gastric cancer has been declining in recent decades,it remains a major public health issue as the second leading cause of cancer death worldwide.In China,gastric cancer is still the main cause of death in patients with malignant tumors.Most patients are diagnosed at an advanced stage and mortality is high.Cyclooxygenase-2(COX-2)is a ratelimiting enzyme in prostanoid synthesis and plays an important role in the development and progression of gastric cancer.The expression of COX-2 in gastric cancer is upregulated and its molecular mechanisms have been investigated.Helicobacter pylori infection,tumor suppressor gene mutation and the activation of nuclear factor-kappa B may be responsible for the elevated expression of COX-2 in gastric cancer.The mechanisms of COX-2 in the development and progression of gastric cancer are probably through promoting the proliferation of gastric cancer cells,while inhibiting apoptosis,assisting angiogenesis and lymphatic metastasis,and participating in cancer invasion and immunosuppression.This review is intended to discuss,comment and summarize recent research progress on the role of COX-2 in gastric cancer development and progression,and elucidate the molecular mechanisms which might be involved in the carcinogenesis.     

Eradication of H pylori for the prevention of gastric cancer

Infection with H pylori is the most important known etiological factor associated with gastric cancer. While colonization of the gastric mucosa with H pylori results in active and chronic gastritis in virtually all individuals infected, the likelihood of developing gastric cancer depends on environmental, bacterial virulence and host specific factors. The majority of all gastric cancer cases are attributable to H pylori infection and therefore theoretically preventable. There is evidence from animal models that eradication of H pylori at an early time point can prevent gastric cancer development. However, randomized clinical trials exploring the prophylactic effect of H pylori eradication on the incidence of gastric cancer in humans remain sparse and have yielded conflicting results. Better markers for the identification of patients at risk for H pylori induced gastric malignancy are needed to allow the development of a more efficient public eradication strategy. Meanwhile, screening and treatment of H pylori in first-degree relatives of gastric cancer patients as well as certain high-risk populations might be beneficial.     

Non-microbial approach for Helicobacter pylori as faster track to prevent gastric cancer than simple eradication

Although the International Agency for Research on Cancer declared Helicobacter pylori(H.pylori)as a definite human carcinogen in 1994,the Japanese Society for Helicobacter Research only recently(February 2013)adopted the position that H.pylori infection should be considered as an indication for either amelioration of chronic gastritis or for decreasing gastric cancer mortality.Japanese researchers have found that H.pylori eradication halts progressive mucosal damage and that successful eradication in patients with non-atrophic gastritis most likely prevents subsequent development of gastric cancer.However,those who have already developed atrophic gastritis/gastric atrophy retain potential risk factors for gastric cancer.Because chronic perpetuated progression of H.pylori-associated gastric inflammation is associated with increased morbidity culminating in gastric carcinogenesis,a non-microbial approach to treatment that provides long-term control of gastric inflammation through nutrients and other interventions may be an effective way to decrease this morbidity.This non-microbial approach might represent a new form of prerequisite"rescue"therapy that provides a quicker path to the prevention of gastric cancer as compared to simple eradication.     

Clinical significance of lymph node metastasis in gastric cancer

Gastric cancer,one of the most common malignancies in the world,frequently reveals lymph node,peritoneum,and liver metastases.Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection,which results in poor prognosis.Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer.Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials,it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year followup study.Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide,but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis.It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer.Besides,the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer.     

Sister Mary Joseph��s nodule as a first sign of pancreatic cancer

Sister Mary Joseph’s nodule (SMJN) refers to a metastatic tumor of the umbilicus. It is a rare entity which arises from a malignancy in the intra-abdominal cavity. We herein describe a patient who presented with SMJN as his first sign of pancreatic cancer. It is an even more unusual case of SMJN. We therefore, suggest that pancreatic cancer should be included in the differential diagnosis when an umbilical mass is found. With the progress made in surgical procedures and other modalities, an early diagnosis will dramatically improve the prognosis of the patients.     

A case of Sister Mary Joseph's nodule as a presenting sign of gastric cancer]

The cutaneous metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph's nodule (SMJN)". It is considered to be a predictor of poor prognosis because it mostly occurs in advanced, metastasizing cancer. However, it is a very rare condition as an initial presenting sign of primary cancer. We recently encountered a 48-year-old man presented with an umbilical lump. The lesion was a firm, ill-delineated, painful nodule with regular surface in the umbilicus. Abdominal computed tomography showed a 2.2 cm sized, ill-defined, delayed enhancing mass at the periumbilical area accounting for umbilical nodule. Diffuse irregular thickening of peritoneum and diffuse wall thickening of stomach implied the diagnosis of gastric cancer. Esophagogastroduodenoscopy revealed diffuse nodular infiltrative lesion from cardia through body of the stomach, compatible with Bormann type 4 advanced gastric cancer. Later, histopathologic confirmation showed a presence of signet ring cell adenocarcinoma from biopsy specimens. We experienced a case presenting with an umbilical metastasis as the first sign of gastric adenocarcinoma. It is thought that direct extension of tumor through the peritoneum might be the route for umbilical metastasis. Careful examination of all umbilical lesions must be needed for the early diagnosis of internal malignancy.     

Forgotten node： A case report

Sister Mary Joseph nodule or node refers to a palpable nodule bulging into the umbilicus and is usually a result of a malignant cancer in the pelvis or abdomen. Traditionally it has been considered a sign of ominous prognosis. Gastrointestinal malignancies, most commonly gastric, colon and pancreatic cancer account for about 52% of the underlying sources. Gynecological cancers, most commonly ovarian and uterine cancers account for about 28% of the sources.     

A simple assessment of lung nodule location for reduction in unnecessary invasive procedures

BackgroundCT screening for lung cancer results in a significant mortality reduction but is complicated by invasive procedures performed for evaluation of the many detected benign nodules. The purpose of this study was to evaluate measures of nodule location within the lung as predictors of malignancy.MethodsWe analyzed images and data from 3,483 participants in the National Lung Screening Trial (NLST). All nodules (4–20 mm) were characterized by 3D geospatial location using a Cartesian coordinate system and evaluated in logistic regression analysis. Model development and probability cutpoint selection was performed in the NLST testing set. The Geospatial test was then validated in the NLST testing set, and subsequently replicated in a new cohort of 147 participants from The Detection of Early Lung Cancer Among Military Personnel (DECAMP) Consortium.ResultsThe Geospatial Test, consisting of the superior-inferior distance (Z distance), nodule diameter, and radial distance (carina to nodule) performed well in both the NLST validation set (AUC 0.85) and the DECAMP replication cohort (AUC 0.75). A negative Geospatial Test resulted in a less than 2% risk of cancer across all nodule diameters. The Geospatial Test correctly reclassified 19.7% of indeterminate nodules with a diameter over 6mm as benign, while only incorrectly classifying 1% of cancerous nodules as benign. In contrast, the parsimonious Brock Model applied to the same group of nodules correctly reclassified 64.5% of indeterminate nodules as benign but resulted in misclassification of a cancer as benign in 18.2% of the cases. Applying the Geospatial test would result in reducing invasive procedures performed for benign lesions by 11.3% with a low rate of misclassification (1.3%). In contrast, the Brock model applied to the same group of patients results in decreasing invasive procedures for benign lesion by 39.0% but misclassifying 21.1% of cancers as benign.ConclusionsUtilizing information about geospatial location within the lung improves risk assessment for indeterminate lung nodules and may reduce unnecessary procedures.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT00047385","term_id":"NCT00047385"}}NCT00047385, {"type":"clinical-trial","attrs":{"text":"NCT01785342","term_id":"NCT01785342"}}NCT01785342.     

Nodule‐aggregating lesion of the ileum: Report of a case and a review of the literature

We describe here a rare case of nodule‐aggregating lesion of the terminal ileum detected by colonoscopy. An 82‐year‐old Japanese woman was admitted to our hospital with diarrhea. Colonoscopy revealed a flat elevated tumor with conglomerated nodular surface involving the entire circumference of the terminal ileum, suggesting a nodule‐aggregating lesion. Magnifying the colonoscopic view showed the branch‐like or gyrus‐like pits. On biopsy, the tumor was diagnosed as a tubulovillous adenoma. Retrograde ileogram using a colonoscope revealed an elevated tumor with nodular irregularity, measuring 5 cm in length. Ileocecal resection was performed. Macroscopically, the tumor in the terminal ileum, 8 cm distant from the ileocecal valve, showed a nodule‐aggregating lesion, measuring 44 × 60 × 6 mm in size. Histologically, the tumor showed a focal carcinoma in tubulovillous adenoma. To our knowledge, this is the fifth case of early cancer of the ileum in Japan, and the first case of nodule‐aggregating lesion of the ileum detected by colonoscopy in the world.     

螺旋CT对外周型小肺癌的诊断价值(附50例分析)

目的 研究螺旋CT对外周型小肺癌的诊断价值。方法 从100例经CT、手术和病理证实的外周型肺癌中，挑选出直径≤3cm的小肺癌的CT片进行分析研究。结果 发现以下CT表现：小结节征、深分叶、棘状突起、胸膜凹陷征、小泡征以及支气管充气征和磨玻璃密度病变共存，对外周型小肺癌有诊断价值。结论 螺旋CT扫描对诊断外周型小肺癌具有很大价值，应作为发现和诊断小肺癌的首选方法。     

甲状腺结节与甲状腺癌的鉴别和最新诊疗方案——中国甲状腺结节和分化型甲状腺癌诊治指南解读

甲状腺结节是一种临床常见病,近年来我国检出率明显增高,甲状腺癌的发病率也呈现增高的趋势。经B超检查发现的甲状腺结节患病率为20％76％,其中甲状腺癌的患病率约为5％～15％。鉴别甲状腺结节的良恶性和评估对周围组织的损害是诊断的重点。收集完整病史有助于甲状腺结节发生甲状腺癌的危险评估。高分辨率超声检查是评估甲状腺结节的首选方法。穿刺活检是评估甲状腺结节良恶性准确性（83％）、特异性（92％）最高的检查。手术治疗、术后^131I治疗和促甲状腺激素（TSH）抑制治疗是甲状腺癌的治疗方法。甲状腺结节和甲状腺癌应视具体情况安排不同时间间隔的随访。与中青年人群相比老年人群甲状腺结节的患病率增高,甲状腺癌的发生率低,治疗原则相同。     

Fluorodeoxyglucose (FDG) uptake in pulmonary rheumatoid nodules diagnosed by video-assisted thoracic surgery lung biopsy: two case reports and a review of the literature

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.     

Primary Gastric Carcinoma with the Bull's eye Sign in a Case of Breast Cancer — Immunohistochemical Differentiation from Metastatic Cancer—

Abstract: A 53-year-old female, who had undergone a mastectomy for breast cancer 4 years previously, was found to have gastric cancer. Judging from the Bull's eye sign of the upper GI series and endoscopy, it appeared to be a metastatic gastric cancer. Histopathological findings of biopsy specimens revealed adenocarcinoma and metastases from the breast cancer were not negligible. However, the surgically resected specimen had different immunohistochemical staining for CEA, Alcian blue, 115D8, and C-erb B2 from the breast cancer. The tumor was finally diagnosed as a primary gastric carcinoma. This case shows that immunohistochemical studies are useful for differentiation between metastatic and primary gastric cancer     

血清肿瘤标志物与肺癌高危因素的临床分析

目的探讨血清肿瘤标记物在高危及肺癌人群中的应用价值,及肺癌高危因素的检测方法。方法选取成都市第三人民医院2013年1月至2014年2月住院患者230例;依据纳入标准进入高危因素组随访观察;对照人群为70例良性疾病患者;采用电化学发光免疫法分析血清肿瘤标志物CEA、细胞角蛋白19片段、神经特异性烯醇化酶、鳞状上皮细胞癌抗原及铁蛋白的水平。结果纳入高危因素的患者230例,其中经气管镜或胸腔镜即确诊肺癌160例,6~22个月期间随访病例70例,后期确诊肺癌12例;因肺部结节病变入院,确诊肺癌88例,占位病变中有8例随访观察中确诊肺癌;多项肿瘤标志物联合铁蛋白增高,能有效判定肺部结节的良恶性(P0.05)。胸部结节合并铁蛋白增高对诊断肺癌具有显著意义(P=0.021)。结论肿瘤标志物和铁蛋白增高是肺癌的独立危险因素。单纯铁蛋白增高对判定肺部占位的良恶性并无意义,如联合肺部占位结节检测肿瘤良恶性,其诊断意义可大为提高。