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Sample records for advanced gastric adenocarcinoma

  1. MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2016-06-03

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  2. Intraoperative Radiotherapy Combined With Adjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma

    SciTech Connect

    Fu Shen; Lu Jiade; Zhang Qing Yang Zhe; Peng Lihua; Xiong, Fei

    2008-12-01

    Purpose: To evaluate the efficacy of intraoperative radiotherapy (IORT) followed by concurrent chemotherapy and external beam RT (EBRT) in the treatment of locally advanced gastric adenocarcinoma. Methods and Materials: A total of 97 consecutive and nonselected patients with newly diagnosed Stage T3, T4, or N+ adenocarcinoma of the stomach underwent gastrectomy with D2 lymph node dissection between March 2003 and October 2005. Of the 97 patients, 51 received adjuvant concurrent chemotherapy (5-fluorouracil, leucovorin, docetaxel, and cisplatin) and EBRT (EBRT group) and 46 received IORT (dose range, 12-15 Gy) immediately after gastrectomy and lymph node dissection before concurrent chemoradiotherapy (EBRT+IORT group). Results: After a median follow-up of 24 months, the 3-year locoregional control rate was 77% and 63% in the two groups with or without IORT, respectively (p = 0.05). The 3-year overall survival and disease-free survival rate was 47% and 36% in the EBRT group and 56% and 44% in the EBRT+IORT group, respectively (p > 0.05). Multivariate analyses revealed that the use of IORT, presence of residual disease after surgery, and pN category were independent prognostic factors for locoregional control and that IORT, pN, and pT categories were independent prognostic factors for overall survival (p < 0.05). Four patients experienced Grade 3 or 4 late complications, but no significant difference was observed between the two groups. Conclusions: Radical gastrectomy with D2 lymph node dissection and IORT followed by adjuvant chemoradiotherapy appeared to be feasible and well-tolerated in the treatment of locally advanced gastric cancer. The addition of IORT to the trimodality treatment significantly improved the 3-year locoregional control rate.

  3. Gastric Adenocarcinoma Presenting with Gastric Outlet Obstruction in a Child

    PubMed Central

    Al-Hussaini, Abdulrahman; AlGhamdi, Salem; Al-Kasim, Fawaz; Habib, Zakaria; Ourfali, Nouri

    2014-01-01

    Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5 cm × 2 cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction. PMID:24707411

  4. A Case of Long-Term Complete Remission of Advanced Gastric Adenocarcinoma with Liver Metastasis.

    PubMed

    Rim, Ch'angbum; Lee, Jung-Ae; Gong, Soojung; Kang, Dong Wook; Yang, Heebum; Han, Hyun Young; Kim, Nae Yu

    2016-06-01

    We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery. PMID:27433398

  5. A Case of Long-Term Complete Remission of Advanced Gastric Adenocarcinoma with Liver Metastasis

    PubMed Central

    Rim, Ch'angbum; Lee, Jung-Ae; Gong, Soojung; Kang, Dong Wook; Yang, Heebum; Han, Hyun Young

    2016-01-01

    We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery. PMID:27433398

  6. HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy

    PubMed Central

    Zhao, Wei; Dong, Shuang; Duan, Bensong; Chen, Ping; Shi, Lei; Gao, Hengjun; Qi, Haizhi

    2015-01-01

    Accumulating evidence suggests that long non-coding RNA (lncRNA) HOTAIR participates in many types of cancer such as gastric cancer and may confer malignant phenotype to tumor cells. Fluorouracil and platinum combination chemotherapy is the first line therapy for gastric cancer. However, it is still unknown whether HOTAIR influences the outcome of cancer patients treated with chemotherapy. This study aimed to evaluate the association of HOTAIR expression with the prognosis of patients with advanced gastric adenocarcinoma (GA) receiving fluorouracil and platinum based chemotherapy. We examined the levels of HOTAIR in 168 GA samples using quantitative real-time PCR and analyzed its relationship with clinical features and prognosis of patients with advanced GA treated with fluorouracil and platinum based chemotherapy. Compared with paracancerous tissues, HOTAIR was significantly upregulated in GA tissues, especially in more advanced cases. High HOTAIR expression was an independent poor prognostic factor for patients with advanced GA. Further stratification analyses revealed that the association between HOTAIR expression and survival in patients with advanced GA remained significant in the subgroup of patients with TNM stages IIIA and IIIB, poorly differentiated, and smaller tumors. In conclusion, our results provide first evidence that HOTAIR may be served as a biomarker that predicts which patient with advanced GA will benefit from fluorouracil and platinum combination chemotherapy. PMID:26328013

  7. Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

    ClinicalTrials.gov

    2013-06-03

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  8. Paranuaclear E-cadherin in gastric adenocarcinoma.

    PubMed

    Carpenter, Philip M; Al-Kuran, Rasha A; Theuer, Charles P

    2002-12-01

    Decreased E-cadherin expression permits dissociation and widespread dissemination of gastric adenocarcinoma cells. We studied the relationship between paranuclear E-cadherin distribution and the histopathologic characteristics of gastric adenocarcinomas. E-cadherin immunostains of 173 gastric adenocarcinoma sections revealed paranuclear; punctate to vesicular staining in 18% (16/87) of the intestinal-type adenocarcinomas, 30% (17/56) of the diffuse-type adenocarcinomas, and 30% (9/30) of the mired adenocarcinomas. These data suggest that in some gastric adenocarcinomas, there is a defect in transport of E-cadherin to the cell surface, which may prevent intercellular adhesion and encourage dissemination. Of 34 cancers with paranuclear E-cadherin staining, 20 (59%) had paranuclear staining within the nonneoplastic epithelium, but only 22.0% of 100 carcinomas with absent or membranous E-cadherin staining were accompanied by morphologically benign epithelium with paranuclear E-cadherin. In surface epithelium, paranuclear E-cadherin staining colocalized with Griffonia simplicifolia lectin II in the Golgi apparatus. The presence of paranuclear E-cadherin in cancer-associated benign epithelium suggests that the alteration in the E-cadherin molecule responsible for the paranuclear distribution may be an early change in gastric adenocarcinoma progression. PMID:12472282

  9. Choroidal and cutaneous metastasis from gastric adenocarcinoma.

    PubMed

    Kawai, Shoichiro; Nishida, Tsutomu; Hayashi, Yoshito; Ezaki, Hisao; Yamada, Takuya; Shinzaki, Shinichiro; Miyazaki, Masanori; Nakai, Kei; Yakushijin, Takayuki; Watabe, Kenji; Iijima, Hideki; Tsujii, Masahiko; Nishida, Kohji; Takehara, Tetsuo

    2013-03-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions. PMID:23538460

  10. S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study

    PubMed Central

    Sun, Guoping; Lu, Huishan; Liu, Yunpeng; Zhong, Meizuo; Zhang, Helong; Yu, Shiying; Li, Wei; Hu, Xiaohua; Wang, Jiejun; Cheng, Ying; Zhou, Juntian; Guo, Zengqing; Guan, Zhongzhen; Xu, Ruihua

    2015-01-01

    The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China. PMID:26439700

  11. Ramucirumab for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma

    PubMed Central

    Young, Kate; Smyth, Elizabeth; Chau, Ian

    2015-01-01

    Ramucirumab, a fully humanized monoclonal antibody directed against vascular endothelial growth factor receptor 2, is the first targeted agent to have demonstrated an improvement in survival, as a single agent or in combination, in a molecularly unselected population in gastro-oesophageal cancer. Now that second-line treatment is routinely considered for patients with advanced gastro-oesophageal cancer, ramucirumab, with its favourable toxicity profile compared with cytotoxic treatment, provides a valuable additional treatment option. PMID:26557893

  12. Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas

    ClinicalTrials.gov

    2016-06-15

    Gastric Adenocarcinoma With Peritoneal Carcinomatosis; Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis; Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis

  13. Alpha-fetoprotein-producing hepatoid gastric adenocarcinoma in a child presenting with spontaneous gastric perforation.

    PubMed

    Emir, Suna; Karakurt, Neslihan; Karakuş, Esra; Şenel, Emrah; Kırsaçlıoğlu, Ceyda; Demir, Hacı Ahmet; Orhan, Diclehan

    2014-01-01

    Gastric adenocarcinoma is a rare entity in the pediatric population. Gastric hepatoid adenocarcinoma with elevated serum alpha-fetoprotein (AFP) is seen extremely rarely in children. A 12-year-old boy was admitted to the hospital with complaint of abdominal pain. X-ray revealed free air density below the diaphragm. Emergent laparotomy showed perforated stomach. Four weeks after the operation, he was readmitted with severe gastrointestinal obstruction symptoms. He underwent an explorative laparotomy, which revealed intestinal edema and diffuse small solid nodules covering the peritoneum. Serum AFP level was mildly elevated. Endoscopic evaluation of the upper gastrointestinal tract was performed, and a gastric mass was detected. All pathological findings were compatible with gastric carcinoma showing hepatoid differentiation. We report an unusual case of AFP-producing hepatoid gastric adenocarcinoma presenting with gastric perforation. This is, to the best of our knowledge, the first reported case of AFP- producing hepatoid gastric adenocarcinoma presenting with gastric perforation in a child. PMID:24827954

  14. Comprehensive molecular characterization of gastric adenocarcinoma

    PubMed Central

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  15. Oesophageal adenocarcinoma and gastric cancer: should we mind the gap?

    PubMed

    Hayakawa, Yoku; Sethi, Nilay; Sepulveda, Antonia R; Bass, Adam J; Wang, Timothy C

    2016-04-26

    Over recent decades we have witnessed a shift in the anatomical distribution of gastric cancer (GC), which increasingly originates from the proximal stomach near the junction with the oesophagus. In parallel, there has been a dramatic rise in the incidence of oesophageal adenocarcinoma (OAC) in the lower oesophagus, which is associated with antecedent Barrett oesophagus (BO). In this context, there has been uncertainty regarding the characterization of adenocarcinomas spanning the area from the lower oesophagus to the distal stomach. Most relevant to this discussion is the distinction, if any, between OAC and intestinal-type GC of the proximal stomach. It is therefore timely to review our current understanding of OAC and intestinal-type GC, integrating advances from cell-of-origin studies and comprehensive genomic alteration analyses, ultimately enabling better insight into the relationship between these two cancers. PMID:27112208

  16. Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma

    ClinicalTrials.gov

    2015-04-15

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  17. Phase II Trial of Preoperative Irinotecan-Cisplatin Followed by Concurrent Irinotecan-Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

    SciTech Connect

    Rivera, Fernando; Galan, Maica; Tabernero, Josep; Cervantes, Andres; Vega-Villegas, M. Eugenia; Gallego, Javier; Laquente, Berta; Rodriguez, Edith; Carrato, Alfredo; Escudero, Pilar; Massuti, Bartomeu; Alonso-Orduna, Vicente; Cardenal, Adelaida; Saenz, Alberto; Giralt, Jordi; Yuste, Ana Lucia

    2009-12-01

    Purpose: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. Results: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.

  18. Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports

    PubMed Central

    HINO, MAYO; YAMAGUCHI, KEN; ABIKO, KAORU; YOSHIOKA, YUMIKO; HAMANISHI, JUNZO; KONDOH, EIJI; KOSHIYAMA, MASAFUMI; BABA, TSUKASA; MATSUMURA, NORIOMI; MINAMIGUCHI, SACHIKO; KIDO, AKI; KONISHI, IKUO

    2016-01-01

    Our group previously documented the first, very rare case of primary gastric-type mucinous adenocarcinoma of the uterine corpus. Although this type of endometrial cancer appears to be similar to the gastric-type adenocarcinoma of the uterine cervix, its main symptoms, appearance on magnetic resonance imaging (MRI) and prognosis have not been fully elucidated due to its rarity. We herein describe an additional case of gastric-type mucinous adenocarcinoma of the endometrium and review the relevant literature. The two cases at our institution (Kyoto University Hospital, Kyoto, Japan) involved postmenopausal women with a primary complaint of abnormal genital bleeding. Microscopic examination of the hysterectomy specimens indicated a highly differentiated mucinous adenocarcinoma with a desmoplastic stromal reaction. Immunohistochemistry for HIK1083 and/or MUC6 was positive in both cases, suggesting a gastric phenotype. Both patients were diagnosed at an advanced stage, they relapsed or recurred immediately after adjuvant chemotherapy, and eventually succumbed to the disease. The main symptom of gastric-type mucinous adenocarcinoma of the uterine cervix is watery discharge, whereas abnormal genital bleeding in addition to watery discharge is mainly observed in the mucinous type of endometrial adenocarcinoma. Cystic cavities in the tumor are present on MRI in cases of endometrial origin, and prognosis is very poor due to resistance to chemotherapy. Thus, gastric-type mucinous adenocarcinoma of the uterine endometrium exhibits a clinical behavior that is similar to tumors originating from the uterine cervix, but is associated with distinguishing clinical symptoms. The incidence of gastric-type endometrial adenocarcinoma may be higher than expected. PMID:27123265

  19. OTUB1 promotes tumor invasion and predicts a poor prognosis in gastric adenocarcinoma

    PubMed Central

    Weng, Weiwei; Zhang, Qiongyan; Xu, Midie; Wu, Yong; Zhang, Meng; Shen, Chen; Chen, Xiaochen; Wang, Yiqin; Sheng, Weiqi

    2016-01-01

    Backgrounds: The deubiquitinating enzyme OTUB1 participates in multiple cellular processes. However, its expression and functions in gastric adenocarcinoma remains unknown. The aim of this study was to investigate the expression of OTUB1 and its biological role in gastric adenocarcinoma. Methods: We used immunohistochemistry to analyze OTUB1 expressions levels in 80 paired samples of gastric adenocarcinoma and adjacent normal tissue (ANT) and 30 samples of intraepithelial neoplasia (IN). We also analyzed the correlation between OTUB1 expression and clinicopathological parameters and patient survival status. Moreover, we performed wound-healing, transwell, RT-qPCR and Western blot assays to evaluate the impact of OTUB1 on tumor migration and invasion. Results: In gastric adenocarcinomas, staining for OTUB1 was localized in the cytoplasm. The proportion of samples that expressed OTUB1 and the intensity of its expression were much higher in gastric adenocarcinoma tissues (61 out of 80, 76.25%) than that in either IN (10 out of 30, 33.33%, p<0.001) or ANT (7 out of 80, 8.75%, p<0.001) samples. In malignant cases, higher expression OTUB1 levels were significantly associated with deeper tumor invasion depths (p=0.02), advanced lymph node status (p=0.008) and TNM stage (p=0.001), lymph duct invasion (p<0.001) and nerve invasion (p=0.013). Univariate and multivariate Cox regression analyses revealed that OTUB1 was an independent risk factor for disease-specific survival but not disease-free survival. In vitro wound-healing and transwell assays showed that OTUB1 overexpression promoted tumor cell migration and invasion in gastric cancer cells. Conclusion: OTUB1 contributes to gastric cancer development by enhancing tumor invasiveness. Targeting OTUB1 should be considered in future molecular therapies. PMID:27347330

  20. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    PubMed

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain

    2014-04-01

    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity. PMID:24440764

  1. Poorly Differentiated Gastric Adenocarcinoma Can Mimic Hilar Cholangiocarcinoma.

    PubMed

    Urasaki, Tetsuya; Kodaira, Makoto; Hibino, Masaki; Yamagata, Shingo; Watanabe, Yukihiro; Terazawa, Yasuyuki; Sano, Munetaka; Kuriki, Ken

    2016-01-01

    This report describes two cases with obstructive jaundice caused by poorly differentiated gastric adenocarcinoma. Computed tomography scans showed circumferential stenosis in the hilar bile ducts. Endoscopic retrograde cholangiopancreatography showed dilatation of the bilateral hepatic ducts and stenosis of the common hepatic ducts from the bifurcation of the bilateral hepatic ducts. The first diagnoses were hilar cholangiocarcinoma and biliary drainage decreased serum bilirubin; however, both patients died of cancer within a short period of time. Autopsies revealed lymphatic vessel invasion and possible subepithelial invasion by gastric adenocarcinoma into the hilar bile ducts. A differential diagnosis should thus be required in suspected cases of hilar cholangiocarcinoma. PMID:27301505

  2. Inhibitory effects of dobutamine on human gastric adenocarcinoma

    PubMed Central

    Zheng, Hui-Xia; Wu, Li-Na; Xiao, Hong; Du, Qian; Liang, Jian-Fang

    2014-01-01

    AIM: To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells. METHODS: Dobutamine was used to treat gastric adenocarcinoma cells (SGC-7901) and cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of dobutamine combined with cisplatin on cell viability were also analyzed. Cell migration was studied using the wound healing assay, and cell proliferation was analyzed using the colony formation assay. A cell invasion assay was carried out using Transwell cell culture chambers. The cell cycle and cell apoptosis were analyzed by flow cytometry. Western blot and immunocytochemistry were performed to determine the expression of Yes-associated protein (YAP) in treated cells. RESULTS: Dobutamine significantly inhibited cell growth, migration, cell colony formation, and cell invasion into Matrigel. Dobutamine also arrested the cell cycle at G1/S phase, and increased the rate of apoptosis of gastric adenocarcinoma cells. The expression of YAP was detected mainly in the nucleus in the absence of dobutamine. However, reduced expression of phosphorylated YAP was mainly found in the cytosol following treatment with dobutamine. CONCLUSION: Dobutamine has significant inhibitory effects on gastric adenocarcinoma cells and may be used in neoadjuvant therapy not only for gastric cancer, but also for other tumors. PMID:25493021

  3. Opium: an emerging risk factor for gastric adenocarcinoma.

    PubMed

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Aghcheli, Karim; Sotoudeh, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M; Abnet, Christian C; Kamangar, Farin

    2013-07-15

    Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance. PMID:23319416

  4. Expression of bile acid receptor TGR5 in gastric adenocarcinoma.

    PubMed

    Cao, Weibiao; Tian, Wei; Hong, Jie; Li, Dan; Tavares, Rosemarie; Noble, Lelia; Moss, Steven F; Resnick, Murray B

    2013-02-15

    Bile reflux is a risk factor in the development of intestinal metaplasia in the stomach and is believed to function as an initiator of gastric carcinogenesis. However, whether the G protein-coupled bile acid receptor TGR5 is expressed in this tumor is not known. In this study, we determined the expression of TGR5 in gastric adenocarcinoma and examined the role of TGR5 in cell proliferation. Strong TGR5 staining was present in 12% of cases of intestinal metaplasia but in no cases of normal gastric epithelium (P < 0.01). Moderate to strong TGR5 membranous and cytoplasmic staining was present in 52% of the intestinal but in only 25% of the diffuse subtype of adenocarcinomas (P < 0.001). Kaplan-Meier univariate survival analysis revealed that moderate to strong TGR5 staining was associated with decreased patient survival (P < 0.05). Treatment with taurodeoxycholic acid (TDCA, a bile acid) significantly increased thymidine incorporation in the AGS gastric adenocarcinoma cell line, suggesting that bile acids may increase cell proliferation. This increase was significantly decreased by knockdown of TGR5 with TGR5 small-interfering RNA (siRNA). In addition, overexpression of TGR5 significantly enhanced TDCA-induced increases in thymidine incorporation. TGR5 is coupled with G(q)α and Gα(i-3) proteins. TDCA-induced increase in thymidine incorporation was significantly decreased by knockdown of G(q)α and Gα(i-3) with their siRNAs. We conclude that TGR5 is overexpressed in most gastric intestinal-type adenocarcinomas, and moderate to strong TGR5 staining is associated with decreased patient survival in all gastric adenocarcinomas. Bile acids increase cell proliferation via activation of TGR5 receptors and G(q)α and Gα(i-3) proteins. PMID:23238937

  5. Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-06-27

    Adenocarcinoma of the Gastroesophageal Junction; Gastric Cardia Adenocarcinoma; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer

  6. Allelotype analysis of adenocarcinoma of the gastric cardia.

    PubMed Central

    Gleeson, C. M.; Sloan, J. M.; McGuigan, J. A.; Ritchie, A. J.; Weber, J. L.; Russell, S. E.

    1997-01-01

    To identify chromosomal loci involved in the development of proximal gastric adenocarcinoma, this study delineated the pattern of allelic imbalance in a series of 38 adenocarcinomas arising in the gastric cardia. A total of 137 microsatellite markers covering all autosomal arms, excluding acrocentric arms, were analysed. A mean of 35 out of a total of 39 chromosomal arms studied were informative for each patient. The tumour group demonstrated a high level of allelic imbalance, with an observed median fractional allelic imbalance of 0.47 for the 29 intestinal-type adenocarcinomas and 0.54 for the nine diffuse-type adenocarcinomas. Allelic imbalance was detected in >50% of informative cases in both histological subtypes on a number of chromosomal arms. In the intestinal subtype, these included, 3p (61%), 4q (71%), 5q (59%), 8p (60%), 9p (65%), 9q (83%), 12q (52%), 13q (52%), 17p (78%) and 18q (70%). A higher incidence of allelic imbalance was detected on chromosome 16q in tumours of the diffuse type relative to those of the intestinal type. A more detailed mapping on chromosomes 4q and 6q identified a number of cases with subchromosomal breakpoints. In conclusion, this analysis has indicated regions of the genome potentially involved in the development of proximal gastric carcinomas. Images Figure 1 Figure 2 Figure 4 PMID:9400942

  7. Gastric adenocarcinoma presenting with thromboembolism in a 13-year-old boy.

    PubMed

    Hunter, Wendy L M

    2015-03-01

    Abdominal pain is a frequent complaint in the pediatric emergency department. A 13-year-old boy presented with complaints of abdominal pain, hematemesis, headache, and leg pain. Further investigation revealed an advanced-stage gastric adenocarcinoma with multiple thromboembolism including the greater saphenous vein and nonbacterial thrombotic endocarditis. This case points out the challenges of diagnosing this rare condition and treating the primary tumor and thromboembolism in the setting of both hypercoagulable state and gastrointestinal bleeding. PMID:25738239

  8. Gastric adenocarcinoma concurrent with paravertebral plasmacytoma: A case report

    PubMed Central

    Du, Fengcai; Jiang, Lixin; Zhu, Fangqing; Gong, Zhao Hua; Chen, Jian; Zhang, Liangming

    2016-01-01

    Here, we report the case of a 77-year-old male patient who was revealed to have an unsuspected case of gastric adenocarcinoma with paravertebral plasmacytoma following biopsy. Plasmacytoma may be classified into two main groups: Multiple myeloma and plasmacytoma without marrow involvement. It comprises isolated plasmacytoma of the bone and extramedullary plasmacytoma. Extramedullary plasmacytoma (EMP) accounts for 3% of all plasmacytomas; however, ~80% are located in the upper respiratory tract and upper gastrointestinal tract. It occurs extremely rarely in paravertebral areas. Case reports of EMP and other types of malignant tumor occurring at the same time have not been identified in searches of the literature. In the present study, we describe the diagnosis and treatment process of a case of gastric adenocarcinoma concurrent with paravertebral plasmacytoma. It may be helpful for early clinical diagnosis and treatment of such cases. PMID:27446469

  9. Gastric adenocarcinoma of fundic gland type: Endoscopic and clinicopathological features.

    PubMed

    Tohda, Gen; Osawa, Takeshi; Asada, Yasuyuki; Dochin, Masaki; Terahata, Shintarou

    2016-02-25

    Gastric adenocarcinoma of fundic gland type (GA-FG) with chief cell differentiation was recently proposed as an extremely rare type of gastric adenocarcinoma. Here, we report 4 cases of GA-FG with chief cell differentiation. Endoscopic features included a submucosal tumor shape or a flat shape, whitish discoloration and dilated vessels on the surface. The tumors were located in the upper or middle third of the stomach. All cases were preoperatively diagnosed as GA-FG by biopsy, and endoscopic submucosal dissection was performed. Resected specimens revealed well-differentiated adenocarcinomas resembling chief cells. Tumor cells were diffusely positive for pepsinogen-I, but partially positive for H(+)/K(+)-ATPase in scattered locations around the tumor margin. Despite the presence of minimal invasion of the carcinoma into the submucosal layer, which was observed in two cases, neither lymphatic nor venous invasion was detected in any of the cases. Finally, all cases showed less aggressive clinical behavior with low grade malignancy. PMID:26962407

  10. Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma

    PubMed Central

    Eivaz-Mohammadi, Sahar; Tarar, Omer; Malik, Khurram; Syed, Amer K.

    2014-01-01

    A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma. PMID:25349615

  11. HER 2 Expression in Gastric and Gastro-esophageal Junction (GEJ) Adenocarcinomas

    PubMed Central

    Rajagopal, Indu; Sahadev, R; Nagappa, Preethan Kamagere; Rajendra, Sowmya Goddanakoppal

    2015-01-01

    Introduction: Gastric cancer is one of the leading causes of cancer mortality in the world/India with majority being diagnosed at an advanced stage. Various chemotherapeutic regimens have modestly improved overall survival leading to quest for novel therapeutic agents. Overexpression of HER2 in many gastric cancers has lead to the advent of targeted therapy with anti HER2 antibody like Trastusumab which has improved the overall survival. Materials and Methods: Sixty cases of gastric adenocarcinomas (44 biopsies and 16 gastrectomies) over the past five years ( June 2009 to June 2014),were included in the study. Diagnosis was confirmed by review of slides and IHC with anti HER2 antibodies was performed using Dako Real Envision Detection system and scoring was done by Hoffmann et al., scoring system. Results: Of the 60 cases, majority were males (60%),with a mean age of 65.65 yrs. Tumours in antrum (76.7%) formed the major bulk. HER2 expression was observed in 26.7% of Tumours, predominantly in males (p=0.006) and intestinal type (p= 0.054). HER2 expression correlated with Tumour grade (moderately differentiated and well differentiated, p= 0.042). Tumours of gastro-esophageal junction (GEJ) showed HER2 expression in 45.5% as opposed to 22.4% in gastric location. Poorly differentiated and diffuse type of adenocarcinomas did not express HER2. Two of three Tumours from patients in the age group 31-40 y expressed HER2. Conclusion: Male gender, intestinal-type and moderately differentiated gastric cancers may be the ones that can be targeted for therapy using Herceptin. Though trastusumab is approved for advanced gastric and GEJ cancers, it’s role in adjuvant / neo-adjuvant setting in early stages needs to be evaluated with newer agents like Pertuzumab, Bevacizumab, especially in young patients. PMID:25954623

  12. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    PubMed

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  13. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

    PubMed Central

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  14. Postoperative adjuvant radiotherapy for patients with gastric adenocarcinoma.

    PubMed

    Lim, Do Hoon

    2012-12-01

    In gastric adenocarcinoma, high rates of loco-regional recurrences have been reported even after complete resection, and various studies have been tried to find the role of postoperative adjuvant therapy. Among them, Intergroup 0116 trial was a landmark trial, and demonstrated the definite survival benefit in adjuvant chemoradiotherapy, compared with surgery alone. However, the INT 0116 trial had major limitation for global acceptance of the INT 0116 regimen as an adjuvant treatment modality because of the limited lymph node dissection. Lately, several randomized studies that were performed to patients with D2-dissected gastric cancer were published. This review summarizes the data about patterns of failure after surgical resection and the earlier prospective studies, including INT 0116 study. Author will introduce the latest studies, including ARTIST trial and discuss whether external beam radiotherapy should be applied to patients receiving extended lymph node dissection and adjuvant chemotherapy. PMID:23346491

  15. Identification of Differentiation-Related Proteins in Gastric Adenocarcinoma Tissues by Proteomics.

    PubMed

    Zhou, Xin; Yao, Kun; Zhang, Lang; Zhang, Ying; Han, Yin; Liu, Hui-Ling; Liu, Xiang-Wen; Su, Gang; Yuan, Wen-Zhen; Wei, Xiao-Dong; Guan, Quan-Lin; Zhu, Bing-Dong

    2016-10-01

    There is a significant correlation between the degree of tumor differentiation and the survival of patients with gastric cancers. In this report, we compared proteomic differences between poorly differentiated gastric adenocarcinoma tissues and well-differentiated gastric adenocarcinoma tissues in order to identify differentiation-related proteins that may be closely correlated with differentiation of gastric cancer pathogenesis. We identified 7 proteins, of which calreticulin precursor, tapasinERP57 heterodimer, pyruvate kinase isozymes M1/M2 isoform M2, class Pi glutathione S-transferase, and chain A crystal structure of human enolase 1 were upregulated in poorly differentiated gastric adenocarcinoma compared with well-differentiated gastric adenocarcinoma, while myosin-11 isoform SM2A and actin alpha cardiac were downregulated. Two of them, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 are enzymes involved in glycolytic pathway. The upregulation of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 in poorly differentiated gastric adenocarcinoma was confirmed by Western blotting and immunohistochemistry. Furthermore, we observed 107 cases with gastric adenocarcinoma and found that the high expression of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 correlates with tumor size (P = .0001 and P = .0017, respectively), depth of invasion (P = .0024 and P = .0261, respectively), and poor prognosis of patients. In conclusion, with this proteomic analysis, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 were identified upregulated in poorly differentiated gastric adenocarcinoma comparing with well-differentiated gastric adenocarcinoma. The expression level of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 was significantly correlated with overall survival. Some of them would be differentiation-related cancer biomarkers and are associated with tumor metastasis, invasion, and prognosis. PMID:27624754

  16. Distal Esophageal Adenocarcinoma and Gastric Adenocarcinoma: Time for a Shared Research Agenda.

    PubMed

    Jansen, Marnix; Wright, Nicholas A

    2016-01-01

    The key insight that sparked Darwin's theory of descent with modification was that he compared and contrasted differences between living and extinct species across time and space. He likely arrived on this theory in large part through his culinary experiences, set against the background of the rugged Patagonian landscape of Southern Argentina. We feel that further integration of research into gastric and esophageal adenocarcinoma may benefit both fields and similarly lead to a coherent understanding of cancer progression in the upper gastrointestinal tract across time and space. Although the environmental trigger differs between carcinogenesis of the stomach and distal esophagus, there remain many important lessons to be learned from comparing precursor stages, such as intestinal metaplasia, across anatomic borders. This analysis will absolutely require detailed sampling within and between these related species, but most importantly we need higher resolution clinical phenotyping to relate genomic differences to drivers of morphologic evolution. In the end, this may provide us with a new phylogeny showing key differences between esophageal and gastric adenocarcinoma. PMID:27573764

  17. The role of the obestatin/GPR39 system in human gastric adenocarcinomas

    PubMed Central

    Alén, Begoña O.; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S.; Beiras, Andrés; Casanueva, Felipe F.; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P.; Pazos, Yolanda

    2016-01-01

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. PMID:26716511

  18. Gastric hepatoid adenocarcinoma: a computed tomography report of six cases.

    PubMed

    Ren, An; Cai, Feng; Shang, Yan-Ning; Ma, En-Sen; Huang, Zhen-Guo; Wang, Wu; Luo, Jie

    2014-10-28

    We describe the computed tomography (CT) imaging findings in six cases (five males and one female; age range 61-78 years; mean age 67.3 years) with histologically proven hepatoid adenocarcinoma of the stomach (HAS). Five of the six patients had elevated serum alpha-fetoprotein levels. The most common type of gross appearance HAS on CT is a polypoid mass (83%, 5/6). The most common contrast enhancement pattern was heterogeneous. All six patients had a regional lymphadenopathy larger than 6 mm in its short axis. Liver metastases (n = 3) were noted. Venous tumor thrombosis was identified in the portal vein (n = 2) of the regions near primary gastric tumors or metastatic masses. Our findings suggest in an elderly, male patients with a large heterogeneous enhancement tumor, the presence of distant metastases, regional lymphadenopathy and characteristically increased serum alpha-fetoprotein levels indicates a high likelihood of HAS. PMID:25356063

  19. A case of gastric adenocarcinoma in a Shih Tzu dog: successful treatment of early gastric cancer.

    PubMed

    Lee, Hee-Chun; Kim, Ji-Hyun; Jee, Cho-Hee; Lee, Jae-Hoon; Moon, Jong-Hyun; Kim, Na-Hyun; Sur, Jung-Hyang; Cho, Kyu-Woan; Kang, Byeong-Teck; Ha, Jeongim; Jung, Dong-In

    2014-07-01

    A 9-year-old castrated male Shih Tzu dog was referred to us, because of chronic vomiting. The patient's hematological, radiographic, ultrasonographic, endoscopic and histological examinations were evaluated for diagnosis. Hematologic analysis indicated moderate anemia and azotemia. Based on the imaging studies, an oval-shaped mass was identified in the gastric pylorus area. A proliferative mass was found on endoscopic examination, and we performed biopsy using grasping forceps. The histopathological findings of the biopsy specimens indicated hypertrophic gastritis, and Y-U pyloroplasty was performed. However, histopathological examination of the surgically resected mass revealed tubular adenocarcinoma of the stomach. Then, carboplatin chemotherapy was performed 4 times for 13 weeks. Clinical signs, such as vomiting, were resolved gradually after surgery and chemotherapy, and the patient's condition was managed favorably until recently (30 months after surgery). This case report describes clinical features, imaging studies, endoscopic characteristics and histopathological and immunohistochemical features of gastric tubular adenocarcinoma as early gastric cancer in a dog. PMID:24646602

  20. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon. PMID:26457350

  1. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    PubMed Central

    2011-01-01

    Background 18-Fluorodeoxyglucose-PET (18F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. Methods/Design The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a < 35% decrease of SUV two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. 18FDG-PET scans will be performed before ( = Baseline) and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1) and at the end of radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference ΔSUV = 100 (SUVBaseline - SUV

  2. Comparison of p53 and DNA content abnormalities in adenocarcinoma of the oesophagus and gastric cardia.

    PubMed Central

    Gleeson, C. M.; Sloan, J. M.; McManus, D. T.; Maxwell, P.; Arthur, K.; McGuigan, J. A.; Ritchie, A. J.; Russell, S. E.

    1998-01-01

    This study examined the association between 17p allelic loss, p53 gene mutation, p53 protein expression and DNA aneuploidy in a series of adenocarcinomas arising in the oesophagus and gastric cardia. 17p allelic loss was detected in 79% (15 of 19) of oesophageal and in 83% (29 of 35) of gastric adenocarcinomas. p53 mutations were detected in 70% (14 of 20) and 63% (26 of 41) of oesophageal and of gastric adenocarcinomas respectively. Both tumour types were associated with a predominance of base transitions at CpG dinucleotides. In five cases of oesophageal adenocarcinoma, the same mutation was detected both in tumour and in adjacent dysplastic Barrett's epithelium. Diffuse p53 protein expression was detected in 65% (13 of 20) and 59% (24 of 41) of oesophageal and of gastric tumours, respectively, and was associated with the presence of p53 missense mutation (Chi-squared, P < 0.0001). DNA aneuploidy was detected in 80% (16 of 20) of oesophageal and in 70% (28 of 40) of gastric tumours. No association was found between p53 or DNA content abnormalities and tumour stage or histological subtype. In conclusion, this study detected a similar pattern of p53 alterations in adenocarcinoma of the oesophagus and gastric cardia--molecular data consistent with the observation that these tumours demonstrate similar clinical and epidemiological features. Images Figure 1 Figure 4 PMID:9460999

  3. Remnant cystic duct adenocarcinoma presenting as gastric outlet obstruction

    PubMed Central

    Lo, Samuel Tsoon Wuan; Cheng, Yue; Cheung, Frances; Tang, Chung Ngai

    2016-01-01

    Only a few case reports of remnant cystic duct carcinoma exist. The presented case of remnant cystic duct carcinoma with invasion to pylorus and bulbus of duodenum leading to gastric outlet obstruction was the first of its kind. We reviewed all cases of remnant cystic duct carcinoma that we found in the literature and summarized its definition, presentation, extent of invasion and clinical outcome after operation. The diagnosis can be difficult due to the rarity of disease, locally advanced nature of disease and distorted postoperative anatomy. A high index of suspicion can increase the likelihood of a preoperative diagnosis. PMID:27154747

  4. Gastric adenocarcinoma: the role of Helicobacter pylori in pathogenesis and prevention efforts.

    PubMed

    Laird-Fick, Heather S; Saini, Shivani; Hillard, James Randolph

    2016-08-01

    Gastric cancer is the third most common cause of cancer deaths in the world, prompting high-risk countries like South Korea and Japan to establish nationwide screening programmes. Helicobacter pylori is linked to the majority of gastric adenocarcinoma cases and to the vast majority of non-cardia gastric adenocarcinomas. Several studies have demonstrated the effectiveness of 'test-and-treat' programmes for H. pylori infection to prevent gastric cancer in high-risk populations. While this strategy has gained momentum, providers in low-risk developed countries may be unaware of the risk individual patients face, particularly those who have emigrated from high-risk regions and members of economically disadvantaged minority groups. Rapidly evolving science in recent years has made it difficult for clinicians to keep up with the current best practices. This article reviews the epidemiology of H. pylori and gastric cancer, screening and diagnostic tests and the current treatment regimens for clinicians. PMID:27222587

  5. Gastric mucous neck cell and intestinal goblet cell phenotypes in gastric adenocarcinoma.

    PubMed Central

    Hughes, N R; Bhathal, P S

    1997-01-01

    AIM: To investigate the phenotype of cells comprising diffuse and intestinal-type gastric cancers using monoclonal antibodies to two antigens. One antigen (designated D10) is characteristic of gastric mucous neck cells, cardiac glands, pyloric glands, and Brunner's glands. The second antigen (designated 17NM) is specific to the mucous vacuole of intestinal goblet cells. METHODS: Thirty two gastrectomy specimens with adenocarcinoma were studied. Serial paraffin sections were stained immunohistochemically for D10 and 17NM and histochemically for acid and neutral mucins. The cancers were classified histologically as of either diffuse or intestinal type according to Lauren. RESULTS: Of 15 diffuse-type gastric carcinomas, 11 showed the majority of cancer cells staining for D10 while four were typical signet ring cell cancers staining predominantly for 17NM; five tumours displayed both phenotypes with the two phenotypes segregated in different areas of the tumours. In contrast, of 16 intestinal-type cancers, six expressed 17NM, three D10, five neither antigen, and two expressed both antigens. One indeterminate-type cancer expressed both antigens. The staining of individual cells for D10 and 17NM was mutually exclusive in both diffuse and intestinal types. In contrast to the diffuse cancers, intestinal-type cancers typically expressed either antigen only in occasional small groups of cells and individual cells. CONCLUSIONS: In disease, the gastric stem cell can assume the capacity of the duodenal stem cell for divergent differentiation into either intestinal goblet cells (for example, as in intestinal metaplasia) or Brunner's gland cells (for example, as in pyloric gland/Brunner's gland metaplasia). With neoplastic transformation, this potential for divergent differentiation is maintained and gives rise to diffuse-type cancers that display either the D10 phenotype, the 17NM phenotype, or the clonal expression of both phenotypes. In the more cell cohesive (intestinal

  6. Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

    PubMed Central

    Liu, Shin-Yun; Shun, Chia-Tung; Hung, Kuan-Yu; Juan, Hsueh-Fen; Hsu, Chia-Lang; Huang, Min-Chuan; Lai, I-Rue

    2016-01-01

    Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression. PMID:26848976

  7. A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas.

    PubMed

    Carleton, Claire; Hoang, Lien; Sah, Shatrughan; Kiyokawa, Takako; Karamurzin, Yevgeniy S; Talia, Karen L; Park, Kay J; McCluggage, W Glenn

    2016-05-01

    Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV)-related cervical adenocarcinoma. They comprise a spectrum from a well-differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly differentiated overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumors have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphologic overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover, they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, nongynecologic sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas, and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were cytokeratin (CK)7, CK20, CDX2, carcinoembryonic antigen, CA125, CA19.9, p16, estrogen receptor, progesterone receptor, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta, carbonic anhydrase IX, human epidermal receptor 2 (HER2), and mismatch repair (MMR) proteins. All markers were classified as negative, focal (<50% of tumor cells positive), or diffuse (≥50% tumor cells positive) except for p53 (classified as "wild-type" or "mutation-type"), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas), and MMR proteins (categorized as retained or lost). There was positive staining with CK7 (47/47-45 diffuse, 2 focal), MUC6 (17/21-6 diffuse, 11 focal), carcinoembryonic antigen (25/31-12 diffuse, 13 focal

  8. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

    PubMed Central

    Gunduz, Seyda; Elpek, Gulsum Ozlem; Uysal, Mukremin; Goksu, Sema Sezgin; Tatli, Murat; Arslan, Deniz; Coskun, Hasan Senol; Bozcuk, Hakan; Savas, Burhan; Ozdogan, Mustafa

    2012-01-01

    Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein. PMID:23525369

  9. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

    PubMed

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-08-01

    Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  10. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

    PubMed Central

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-01-01

    Abstract Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear. In this study, the Kaplan–Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM. CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245–0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma. A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  11. Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.

    PubMed

    Zhang, Bingchang; Wang, Fen; Dai, Lianzhi; Cai, Heguo; Zhan, Yanyan; Gang, Song; Hu, Tianhui; Xia, Chun; Zhang, Bing

    2016-02-16

    Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma. PMID:26811493

  12. Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma

    PubMed Central

    Zhang, Bingchang; Wang, Fen; Dai, Lianzhi; Cai, Heguo; Zhan, Yanyan; Gang, Song; Hu, Tianhui; Xia, Chun; Zhang, Bing

    2016-01-01

    Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma. PMID:26811493

  13. Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma

    PubMed Central

    2014-01-01

    Introduction The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. Materials and methods Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n = 173), including paired samples of benign-appearing squamous epithelium (n = 51), gastric mucosa (n = 114), Barrett’s esophagus (BE) or intestinal metaplasia (IM) (n = 57) and lymph node metastases (n = 75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. Results PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p < 0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p = 0.002) and inversely associated with involved margins (p = 0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a

  14. Goiter Frequency Is More Strongly Associated with Gastric Adenocarcinoma than Urine Iodine Level

    PubMed Central

    Tabaeizadeh, Mohammad; Haghpanah, Vahid; Keshtkar, Abbasali; Semnani, Shahryar; Roshandel, Gholamreza; Adabi, Khadijeh; Heshmat, Ramin; Rohani, Davood; Kia, Alireza; Hatami, Ehsan; Jahangirrad, Ataollah; Nabizadeh, Ramin

    2013-01-01

    Purpose We designed our study to evaluate the hypothesis that gastric cancer is correlated with iodine deficiency or thyroid dysfunction. Materials and Methods We investigated the total body iodine reserve, thyroid function status and autoimmune disorder in 40 recently diagnosed gastric adenocarcinoma cases versus 80 healthy controls. The participants came from a region with high gastric cancer rate but sufficient iodine supply due to salt iodination. The investigation included urine iodine level, thyroid gland clinical and ultrasonographic examination, and thyroid function tests. Results Goiter was detected more frequently in the case group (P=0.001); such a finding, however, was not true for lower than normal urine iodine levels. The free T3 mean level was significantly lower in the case group compared to the control group (P=0.005). Conclusions The higher prevalence of goiter rather than low levels of urinary iodine in gastric adenocarcinoma cases suggests that goiter, perhaps due to protracted but currently adjusted iodine deficiency, is more likely to be associated with gastric adenocarcinoma compared to the existing iodine deficiency itself. PMID:23844325

  15. Invasive mouse gastric adenocarcinomas arising from Lgr5+ stem cells are dependent on crosstalk between the Hedgehog/GLI2 and mTOR pathways

    PubMed Central

    Syu, Li-Jyun; Zhao, Xinyi; Zhang, Yaqing; Grachtchouk, Marina; Demitrack, Elise; Ermilov, Alexandre; Wilbert, Dawn M.; Zheng, Xinlei; Kaatz, Ashley; Greenson, Joel K.; Gumucio, Deborah L.; Merchant, Juanita L.; di Magliano, Marina Pasca; Samuelson, Linda C.; Dlugosz, Andrzej A.

    2016-01-01

    Gastric adenocarcinoma is the third most common cause of cancer-related death worldwide. Here we report a novel, highly-penetrant mouse model of invasive gastric cancer arising from deregulated Hedgehog/Gli2 signaling targeted to Lgr5-expressing stem cells in adult stomach. Tumor development progressed rapidly: three weeks after inducing the Hh pathway oncogene GLI2A, 65% of mice harbored in situ gastric cancer, and an additional 23% of mice had locally invasive tumors. Advanced mouse gastric tumors had multiple features in common with human gastric adenocarcinomas, including characteristic histological changes, expression of RNA and protein markers, and the presence of major inflammatory and stromal cell populations. A subset of tumor cells underwent epithelial-mesenchymal transition, likely mediated by focal activation of canonical Wnt signaling and Snail1 induction. Strikingly, mTOR pathway activation, based on pS6 expression, was robustly activated in mouse gastric adenocarcinomas from the earliest stages of tumor development, and treatment with rapamycin impaired tumor growth. GLI2A-expressing epithelial cells were detected transiently in intestine, which also contains Lgr5+ stem cells, but they did not give rise to epithelial tumors in this organ. These findings establish that deregulated activation of Hedgehog/Gli2 signaling in Lgr5-expressing stem cells is sufficient to drive gastric adenocarcinoma development in mice, identify a critical requirement for mTOR signaling in the pathogenesis of these tumors, and underscore the importance of tissue context in defining stem cell responsiveness to oncogenic stimuli. PMID:26859571

  16. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  17. Synchronous occurrence of a primary colon adenocarcinoma and a gastric stromal tumor. A case report.

    PubMed

    Tzilves, D; Moschos, J; Paikos, D; Tagarakis, G; Pilpilidis, I; Soufleris, K; Kadis, S; Tarpagos, A; Katsos, I

    2008-03-01

    Gastrointestinal stromal tumors are currently the object of a great clinical and experimental interest. We are presenting the case of a 69-year-old patient, who was presented with lower gastrointestinal bleeding and dyspeptic symptoms over the last six months. The colonoscopy showed a large tumor of the sigmoid and the gastroscopy a large gastric tumor of the antrum, which were histologically diagnosed as colonic adenocarcinoma and gastric stromal tumor respectively. The patient underwent a sigmoidectomy and a partial gastrectomy. Six months after surgery were the clinical condition, abdominal CT, gastroscopy and colonoscopy without pathological findings. To our best knowledge, this is the second report of a synchronous gastric stromal tumor and a colonic adenocarcinoma in medical literature. PMID:18299673

  18. Peritoneal metastatic adenocarcinoma possibly due to a gastric duplication cyst: a case report and literature review

    PubMed Central

    2014-01-01

    Background Gastric duplication cysts are rare congenital abnormalities, and malignant transformation of these duplications is also thought to be rare. Case presentation During a routine health checkup, a 28-year-old man underwent abdominal sonography followed by computed tomography (CT) with contrast agent, which revealed a cystic lesion with no enhancement. Laparoscopic surgery showed a 10 × 10 cm cyst adhering to the gastric corpus. However, attempts to remove the lesion en bloc were unsuccessful, and the ruptured cyst had contaminated the peritoneal cavity. Gastric duplication was diagnosed from microscopic examination of the cyst. Seven months later, the patient suffered a progressive increase in ascites, and repeated cytological analysis showed small nests of adenocarcinoma cells, with primary lesion unknown. Diagnostic laparoscopy showed multiple white nodules scattered over the surface of the liver, greater omentum, and peritoneum. Biopsy of the omental nodules confirmed adenocarcinoma, while carcinomatosis was diagnosed in the peritoneum. Conclusions Clinical presentation and chronological developments indicated that the malignancy probably originated from the gastric duplication cyst. This case highlights the importance of accurate preoperative diagnosis and optimal surgical management for gastric duplication as well as considering the potential existence of malignant transformation during surgical evaluation of adult patients with gastric duplication cysts. PMID:24641252

  19. Intracellular and Interstitial Expression of Helicobacter pylori Virulence Genes in Gastric Precancerous Intestinal Metaplasia and Adenocarcinoma

    PubMed Central

    Semino-Mora, Cristina; Doi, Sonia Q.; Marty, Aileen; Simko, Vlado; Carlstedt, Ingemar; Dubois, Andre

    2008-01-01

    Gastric intestinal metaplasia (IM) and gastric cancer are associated with Helicobacter pylori, but the bacterium often is undetectable in these lesions. To unravel this apparent paradox, IM, H. pylori presence, and the expression of H. pylori virulence genes were quantified concurrently using histologic testing, in situ hybridization, and immunohistochemistry. H. pylori was detected inside metaplastic, dysplastic, and neoplastic epithelial cells, and cagA and babA2 expression was colocalized. Importantly, expression of cagA was significantly higher in patients with IM and adenocarcinoma than in control subjects. The preneoplastic “acidic” MUC2 mucin was detected only in the presence of H. pylori, and MUC2 expression was higher in patients with IM, dysplasia, and cancer. These novel findings are compatible with the hypothesis that all stages of gastric carcinogenesis are fostered by persistent intracellular expression of H. pylori virulence genes, especially cagA inside MUC2-producing precancerous gastric cells and pleomorphic cancer cells. PMID:12695995

  20. Adenocarcinoma arising from gastric duplication: a case report with literature review.

    PubMed

    Fukumoto, Kazuhiko; Suzuki, Shohachi; Sakaguchi, Takanori; Morita, Yoshifumi; Oishi, Kosuke; Suzuki, Atsushi; Inaba, Keisuke; Kamiya, Kinji; Miura, Katsutoshi; Konno, Hiroyuki

    2008-12-01

    Gastric duplication is a rare congenital malformation. We report the case of a 50-year-old man with adenocarcinoma derived from gastric duplication. He was referred to our institute because of persistent vomiting due to pyloric stenosis. Abdominal computed tomography revealed two cystic lesions: a 2-cm mass located along the greater curvature of the upper gastric corpus and a 3-cm mass adjacent to the bulbus. Under the diagnosis of gastric duplication cysts, the oral cyst was removed with the gastric wall and the other cyst lesion firmly adhered to the bulbus was treated with distal gastrectomy. Based on histological findings showing adenocarcinoma in the anal duplication cyst wall and regional lymph node metastases and cancer invasion into the duodenal stump, pancreatoduodenectomy was performed 9 days after the initial surgery. Invasion into the pancreas head and duodenal walls was seen in the resected specimen. Although the postoperative course was uneventful, he died of local recurrence and multiple liver metastases 14 months after surgical treatment. This case report with literature review indicates that alimentary tract duplication cysts should be recognized as risky lesions of cancer development in patients aged 50 years or over. PMID:26193693

  1. Intestinal-type gastric adenocarcinoma without Helicobacter pylori infection successfully treated with endoscopic submucosal dissection.

    PubMed

    Kotani, Satoshi; Miyaoka, Youichi; Fujiwara, Aya; Tsukano, Kousuke; Ogawa, Sayaka; Yamanouchi, Satoshi; Kusunoki, Ryusaku; Fujishiro, Hirofumi; Kohge, Naruaki; Ohnuma, Hideyuki; Kinoshita, Yoshikazu

    2016-08-01

    A 67-year-old woman was admitted to our hospital for further examination and for treatment of gastric neoplasia located on the posterior wall of the antrum of the stomach, as revealed by screening esophagogastroduodenoscopy. The patient had no history of Helicobacter pylori (H. pylori) eradication. Her serum H. pylori antibody and urea breath test results were negative, histopathological findings revealed no H. pylori bacteria, and endoscopic findings revealed no chronic gastritis. We performed endoscopic submucosal dissection (ESD). Histological examination of the resected tissues revealed the tumor to be composed of a well-differentiated tubular adenocarcinoma with a tubular-type adenoma confined to the mucosa. This adenocarcinoma exhibited immunohistochemical expression of CD10, MUC2, and Cdx2, but not MUC5AC or MUC6. This is an extremely rare case of H. pylori infection-negative, intestinal-type, differentiated gastric adenocarcinoma revealed by detailed immunohistochemical examination that was treated with ESD. The patient has had no recurrence of adenocarcinoma after ESD. PMID:27259702

  2. Advances in gastric cancer prevention

    PubMed Central

    Giordano, Antonio; Cito, Letizia

    2012-01-01

    Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori (H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin (E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decision cannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled. PMID:23061031

  3. Diffusion MRI on lymph node staging of gastric adenocarcinoma

    PubMed Central

    Akcakaya, Adem; Memmi, Naim; Turkmen, Ihsan; Cipe, Gokhan; Yildiz, Pelin; Arici, Dilek Sema; Muslumanoglu, Mahmut

    2015-01-01

    Objective The purpose of this study was to evaluate the accuracy of diffusion weighted magnetic resonance imaging (MRI) in preoperative assessment of metastatic lymph nodes of gastric cancer. Methods A total of 23 gastric cancer patients with a mean age of 59.4±10.9 years were analyzed. Lymph nodes were grouped as perigastric lesser curvature (Group Ia), perigastric greater curvature (Group Ib), D1+/D2 lymph nodes (Group II). Identification of histologically metastatic lymph nodes by diffusion weighted MRI was regarded as the main outcome. Results A total of 1,056 lymph nodes including 180 histologically proven metastatic lymph nodes were dissected. Although diffusion weighted MRI could identify the metastatic lymph nodes in 18 out of 23 patients (77.8%), only 69 of total 1,056 nodes (6.53%), either metastatic or non-metastatic, could be detected. There was no correlation between histopathology and diffusion weighted MRI with regard to lymph node groups (P>0.05 for all). Overall accuracy was calculated as 69.56, 65.21 and 52.17 for Groups II, Ib and Ia lymph nodes, respectively. Apparent diffusion coefficient (ADC) values could not be helpful to differentiate metastatic lymph nodes (P=0.673). Conclusions Diffusion weighted MRI has low accuracy to detect or to differentiate metastatic and non-metastatic lymph nodes based on their ADC values in gastric cancer. PMID:26029642

  4. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

  5. Morphological evidence of neutrophil-tumor cell phagocytosis (cannibalism) in human gastric adenocarcinomas.

    PubMed

    Caruso, R A; Muda, A O; Bersiga, A; Rigoli, L; Inferrera, C

    2002-01-01

    The phenomenon of neutrophil-tumor cell emperipolesis or phagocytosis has been documented by light microscopy in various human carcinomas, but little is known about the cellular pathological processes and the morphological changes involved. In an attempt to clarify the nature of this phenomenon, the authors' ultrastructural studies on the relationships among neutrophils and tumor cells in human gastric carcinomas are reviewed and analyzed. At the electron microscopy level, apoptotic neutrophils were found within vacuoles of adenocarcinoma cells in 2 cases. They showed either early apoptotic morphology with perinuclear chromatin aggregation but cytoplasm integrity or late apoptotic morphology with uniform, collapsed nucleus and tightly packed cytoplasmic granules. A light microscopy review of 200 cases of resected gastric carcinomas identified 22 cases (11%) that were characterized by neutrophil-tumor cell phagocytosis (cannibalism). TUNEL staining confirmed the presence of apoptotic neutrophils within the cytoplasm of the tumor cells. This study provides light and electron microscopic evidence of apoptotic neutrophils phagocytosed by gastric adenocarcinoma cells. The morphological features of neutrophil-tumor cell phagocytosis (cannibalism) would suggest a particular mechanism of tumor-immune escape in human gastric carcinoma. PMID:12396242

  6. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma.

    PubMed

    Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

    2016-08-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

  7. De novo gastric adenocarcinoma 1 year after sleeve gastrectomy in a transplant patient

    PubMed Central

    Masrur, M.; Elli, E.; Gonzalez-Ciccarelli, L.F.; Giulianotti, P.C.

    2016-01-01

    Introduction It has been reported in the literature that upper gastrointestinal malignancies after bariatric surgery are mostly gastro-esophageal, although it is not clear whether bariatric surgery represents a risk factor for the development of esophageal and/or gastric cancer. We report a case of a de novo gastric adenocarcinoma occurring in a transplant patient 1 year after a laparoscopic sleeve gastrectomy. Presentation of case A 44 year-old woman with a BMI of 38 kg/m2, hypertension, type 1 diabetes mellitus, multiple malignancies and a pancreas transplant underwent laparoscopic sleeve gastrectomy. The patient presented with intense dysphagias during the follow up. Studies were performed and the diagnoses of grade 2/3 adenocarcinoma were made. The patient underwent a robotic assisted total gastrectomy with a roux-en-y intracorporeal esophagojejunostomy. The procedure resulted in multiple metastasic lymph nodes, focal and transmural invasions to multiple organs with a tumor free margin resection. The patient presented with a postoperative pleural effusion, with no further complications. Discussion The diagnosis of gastroesophageal cancer after bariatric surgery is usually late since these patients have common upper gastrointestinal symptoms related to the procedure that could delay the diagnosis. De novo gastric cancer after sleeve gastrectomy has only been reported in one instance, in contrast with other bariatric surgery procedures. Conclusions No direct relation has been established between sleeve gastrectomy and the development of gastric cancer. Robotic procedures allow for complex multiorgan resections, while preserving the benefits of minimally invasive surgery. PMID:26774417

  8. HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily

    PubMed Central

    IENI, A.; BARRESI, V.; GIUFFRÈ, G.; CARUSO, R.A.; LANZAFAME, S.; VILLARI, L.; SALOMONE, E.; ROZ, E.; CABIBI, D.; FRANCO, V.; CERTO, G.; LABATE, A.; NAGAR, C.; MAGLIOLO, E.; BROGGI, B.; FAZZARI, C.; ITALIA, F.; TUCCARI, G.

    2013-01-01

    According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki-67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki-67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC. PMID:24260051

  9. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  10. New advances in targeted gastric cancer treatment.

    PubMed

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-08-14

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  11. Preoperative Gross Classification of Gastric Adenocarcinoma: Comparison of Double Contrast-Enhanced Ultrasound and Multi-Detector Row CT.

    PubMed

    Yan, Caoxin; Bao, Xiaofeng; Shentu, Weihui; Chen, Jian; Liu, Chunmei; Ye, Qin; Wang, Liuhong; Tan, Yangbin; Huang, Pintong

    2016-07-01

    The aim of this study was to compare the accuracy of multi-detector computed tomography (MDCT) with double contrast-enhanced ultrasound (DCEUS), in which intravenous microbubbles are used alongside oral contrast-enhanced ultrasound, in determining the gross classification of patients with gastric carcinoma (GC). Altogether, 239 patients with GC proved by histology after endoscopic biopsy were included in this study. DCEUS and MDCT were performed pre-operatively. The diagnostic accuracies of DCEUS and MDCT in determining the gross classification were calculated and compared. The overall accuracy of DCEUS in determining the gross appearance of GC was higher than that of MDCT (84.9% vs. 79.9%, p < 0.001). There was no significant difference in accuracy between DCEUS and MDCT for Borrmann I and IV classifications of advanced gastric cancer (χ(2), p = 0.323 for Borrmann type I, p = 0.141 for Borrmann type IV). The accuracy of DCEUS for early GC and Borrmann II and III classifications of GC was higher than that of MDCT (χ(2), p = 0.000 for all). DCEUS may be regarded as a valuable complementary tool to MDCT in determining the gross appearance of gastric adenocarcinoma pre-operatively. PMID:27072076

  12. P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome.

    PubMed

    Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

    2015-01-01

    We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA. PMID:26191312

  13. P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome

    PubMed Central

    Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

    2015-01-01

    We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA. PMID:26191312

  14. Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

    PubMed Central

    2015-01-01

    Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

  15. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    SciTech Connect

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  16. Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

    PubMed

    De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Chang, Yu-Hui H

    2014-10-01

    Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues. PMID:24788529

  17. Adenocarcinoma arising from a gastric duplication cyst with invasion to the stomach: a case report with literature review

    PubMed Central

    Kuraoka, K; Nakayama, H; Kagawa, T; Ichikawa, T; Yasui, W

    2004-01-01

    This report describes a rare case of adenocarcinoma arising from a gastric duplication cyst, with invasion to the stomach wall, in a 40 year old Japanese man. A cystic lesion was found between the stomach and the spleen. The cyst had a well circumscribed smooth muscle layer, corresponding to the muscularis propria of the stomach and the mucosa of the alimentary tract. A well differentiated adenocarcinoma was found within the duplication cyst, invading its serosa. Well differentiated adenocarcinoma was independently found in the fundus of the stomach; the tumour of the cyst was connected by fibrous tissue. Microscopically, there was neither adenocarcinoma in situ nor precancerous lesions, such as epithelial dysplasia, suggesting that the carcinoma derived from a gastric duplication cyst that invaded the stomach. Duplication cysts should be included in the differential diagnosis of cystic masses of the gastrointestinal tract, and the possibility of malignancy within these cysts should be considered. PMID:15047751

  18. Advanced gastric cancer and a concomitant pregnancy associated with disseminated intravascular coagulation.

    PubMed

    Kurabayashi, Takumi; Isii, Keisuke; Suzuki, Mina; Takakuwa, Koichi; Shibazaki, Yasuhiko; Ozawa, Tsunenori; Narisawa, Rintaro; Sekizuka, Naoto; Tanaka, Kenichi

    2004-07-01

    Gastric cancer associated with pregnancy is extremely rare and the prognosis is generally grave. A 31-year-old Japanese women, 41 weeks pregnant, displayed disseminated intravascular coagulation (DIC), although clinical symptoms and diagnostic examinations did not indicate an obstetrical cause. She went into labor spontaneously and vaginally delivered a 3248-g normal female infant, after receiving a blood transfusion. On the day 5 postpartum, a gastroduodenal fiberscope examination indicated advanced gastric cancer. She was also diagnosed with bilateral chronic subdural hematoma and underwent an operation to allow drainage. It was not possible to treat her curatively, so she was treated conservatively for DIC. She died on day 13 postpartum. Necropsy of the iliac bone indicated bone marrow metastasis of adenocarcinoma. This is the first known case of a pregnant woman with DIC occurring as the first manifestation of advanced gastric cancer. PMID:15232763

  19. THE PRESENCE OF METASTASES IN REGIONAL LYMPH NODES IS ASSOCIATED WITH TUMOR SIZE AND DEPTH OF INVASION IN SPORADIC GASTRIC ADENOCARCINOMA

    PubMed Central

    CAMBRUZZI, Eduardo; de AZEREDO, Andreza Mariane; KRONHART, Ardala; FOLTZ, Katia Martins; ZETTLER, Cláudio Galeano; PÊGAS, Karla Lais

    2014-01-01

    Background Gastric adenocarcinoma is more often found in men over 50 years in the form of an antral lesion. The tumor has heterogeneous histopathologic features and a poor prognosis (median survival of 15% in five years). Aim To estimate the relationship between the presence of nodal metastasis and other prognostic factors in sporadic gastric adenocarcinoma. Method Were evaluated 164 consecutive cases of gastric adenocarcinoma previously undergone gastrectomy (partial or total), without clinical evidence of distant metastasis, and determined the following variables: topography of the lesion, tumor size, Borrmann macroscopic configuration, histological grade, early or advanced lesions, Lauren histological subtype, presence of signet ring cell, degree of invasion, perigastric lymph node status, angiolymphatic/perineural invasion, and staging. Results Were found 21 early lesions (12.8%) and 143 advanced lesions (87.2%), with a predominance of lesions classified as T3 (n=99/60, 4%) and N1 (n=62/37, 8%). The nodal status was associated with depth of invasion (p<0.001) and tumor size (p<0.001). The staging was related to age (p=0.048), histological grade (p=0.003), and presence of signet ring cells (p = 0.007), angiolymphatic invasion (p = 0.001), and perineural invasion (p=0.003). Conclusion In gastric cancer, lymph node involvement, tumor size and depth of invasion are histopathological data associated with the pattern of growth/tumor spread, suggesting that a wide dissection of perigastric lymph nodes is a fundamental step in the surgical treatment of these patients. PMID:24676292

  20. A phase II study of 5-fluorouracil, leucovorin, adriamycin, and cisplatin (FLAP) for metastatic gastric and gastroesophageal junction adenocarcinoma. A Penn Cancer Clinical Trial Group and Roswell Park Cancer Institute Community Oncology Research Program Trial.

    PubMed

    Vaughn, D J; Meropol, N J; Holroyde, C; Mintzer, D; Nuamah, I; Armstead, B; Douglass, H O; Haller, D G

    1997-06-01

    A Phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil, leucovorin, Adriamycin, and cisplatin combination chemotherapy (FLAP) in patients with previously untreated advanced gastric and gastroesophageal (GE) junction adenocarcinoma. Forty-two consecutive patients were enrolled to received FLAP in this multi-institutional trial. Response, toxicity, and survival data were noted. Fifteen of 42 (36%) patients demonstrated objective responses, with two complete responses (5%) and 13 partial responses (31%). The median time to disease progression was 17 weeks, and the overall survival duration was 30 weeks. Myelosuppression was significant, requiring dose modifications, but there were no treatment-related deaths. FLAP is an active regimen in the treatment of advanced gastric and GE junction adenocarcinoma. We are presently using this regimen in the neoadjuvant setting in patients with gastric and GE junction cancers. PMID:9167745

  1. Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

    PubMed Central

    Suzuki, Akira; Koide, Naohiko; Kitazawa, Masato; Mochizuka, Akiyoshi; Ota, Hiroyoshi; Miyagawa, Shinichi

    2012-01-01

    Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component. PMID:22482081

  2. Total laparoscopic subtotal gastrectomy with transvaginal specimen extraction is feasible in advanced gastric cancer

    PubMed Central

    Sumer, Fatih; Kayaalp, Cuneyt; Ertugrul, Ismail; Yagci, Mehmet Ali; Karagul, Servet

    2015-01-01

    Purpose Natural orifice specimen extraction (NOSE) is an ever-evolving advanced laparoscopic technique. NOSE minimizes surgical injury, involving a low risk of wound complications, fewer incisional hernias, faster recovery and less postoperative pain. Laparoscopic gastrectomy combined with NOSE is a procedure that can potentiate the advantages of both minimal invasive techniques. We aim to demonstrate the feasibility of laparoscopic subtotal gastrectomy with transvaginal specimen extraction in advanced gastric cancer. Case A 72-year-old woman with a 2 cm adenocarcinoma in gastric antrum was treated by laparoscopic subtotal gastrectomy and lymph node dissection. A totally laparoscopic Roux-en-Y gastrojejunostomy was constructed. Specimen was extracted through the posterior fornix of vagina without difficulty. Histopathology confirmed pT3pN0 tumor. After a 10-month follow-up the patient was asymptomatic and getting adjuvant chemoradiotherapy. Conclusions Transvaginal specimen extraction after laparoscopic gastric resection for advanced gastric cancer is a feasible procedure. It is offered to selected patients and of course only to female patients. Natural orifice surgery may provide faster recovery and decrease the wound related complications which may cause a delay on postoperative adjuvant chemo–radio therapies. We have presented, as far as we know, the first human case of a transvaginal extraction of an advanced gastric cancer after laparoscopic gastrectomy. PMID:26413924

  3. Adenocarcinoma of the cervical esophagus arising from ectopic gastric mucosa: report of two cases and review of the literature.

    PubMed

    Nomura, Kosuke; Iizuka, Toshiro; Inoshita, Naoko; Kuribayashi, Yasutaka; Toba, Takahito; Yamada, Akihiro; Yamashita, Satoshi; Furuhata, Tsukasa; Kikuchi, Daisuke; Matsui, Akira; Mitani, Toshifumi; Ogawa, Osamu; Hoteya, Shu; Ueno, Masaki; Udagawa, Harushi; Kaise, Mitsuru

    2015-12-01

    Esophageal adenocarcinoma arising from ectopic gastric mucosa (EGM) is extremely rare. We describe here two Japanese patients with adenocarcinoma of the cervical esophagus arising from EGM. Case 1 is a 62-year-old man who had slightly red EGM in the cervical esophagus on upper gastrointestinal endoscopy (UGE). Because the biopsy showed atypical glands that were suspicious for adenocarcinoma, endoscopic submucosal dissection was performed. Histopathological examination revealed that the lesion was a well-differentiated adenocarcinoma (pT1a MM). Lymphovascular invasion was absent, and the margins were free from carcinoma. Case 2 is a 57-year-old man who had an elevated lesion with a bleeding tendency in an area of EGM in the cervical esophagus on UGE. Adenocarcinoma was diagnosed in the biopsy. Because of the presence of enlarged lymph nodes (#106recL), preoperative chemoradiotherapy was performed to reduce the size of the adenocarcinoma and lymph nodes prior to resection of the cervical esophagus and reconstruction with free jejunal grafts. Histopathological examination revealed moderately differentiated adenocarcinoma (0-I, pT2N1M0, pStage II). In both cases, adenocarcinoma was surrounded by EGM, which led to the diagnosis of EGM-derived esophageal adenocarcinoma. Here, we report its immunohistochemical characteristics in the present cases and discuss the histogenesis. PMID:26476962

  4. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer

    PubMed Central

    Bennett, M; O'Connell, J; O'Sullivan, G; Roche, D; Brady, C; Kelly, J; Collins, J; Shanahan, F

    1999-01-01

    Background—Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. 
Aim—To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. 
Specimens—Thirty paraffin wax embedded human gastric adenocarcinomas. 
Methods—FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). 
Results—Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. 
Conclusions—Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer. 

 Keywords: Fas ligand; gastric cancer; immune escape; apoptosis; tumour; mRNA PMID:9895372

  5. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma

    PubMed Central

    Yu, Ji-wei; Wu, Ju-gang; Zheng, Lin-hai; Zhang, Biao; Ni, Xiao-chun; Li, Xiao-qiang; Jiang, Bo-jian

    2009-01-01

    Background To investigate influencing factors of the metastatic lymph nodes ratio (MLR) and whether it is related to survival in patients with gastric adenocarcinoma. Methods We retrospectively evaluated the clinical features of 121 patients with gastric adenocarcinoma enrolled in our hospital between 2000 and 2007. The receiver operating characteristic (ROC) curve was used to determine the cutoff of the MLR, and CK20 immunohistochemical staining was used to detect micrometastasis of the lymph nodes. Results The areas under the ROC curve of MLR used to predict the death of 3-year and 5-year postoperative patients were 0.826 ± 0.053 and 0.896 ± 0.046. Thus MLR = 30.95% and MLR = 3.15% were designated as cutoffs. The MLR was then classified into three groups: MLR1 (MLR<3.15%); MLR2(3.15% ≤ MLR ≤ 30.95%); and MLR3 (MLR>30.95%). We found that patients with a higher MLR demonstrated a much poorer survival period after radical operation than those patients with a lower MLR (P = 0.000). The COX model showed that MLR was an independent prognostic factor (P = 0.000). The MLR could also discriminate between subsets of patients with different 5-year survival periods within the same N stage (P < 0.05). The MLR has been shown to be 34.7% (242/697) by HE staining and 43.5% (303/697) by CK staining (P = 0.001). The clinicopathological characteristics of lymph vessel invasion and the depth of invasion could significantly affect the MLR. Conclusion MLR is an independent prognostic factor in gastric cancer. The combined ROC curve with MLR is an effective strategy to produce a curve to predict the 3-year and 5-year survival rates. PMID:19393100

  6. Cutaneous Metastasis from Signet-ring Gastric Adenocarcinoma in a Carcinoma En Cuirasse Pattern: An Unusual Clinical-diagnostic Sequence.

    PubMed

    Kaur, Sarabjit; Aggarwal, Parul; Dayal, Surabhi; Sangwan, Ankita; Jain, Vijay Kumar; Jindal, Nidhi

    2015-01-01

    Cutaneous metastasis (CM) of gastric adenocarcinoma (ADC) is rare and usually presents late in the course of the disease. We report a rare case of carcinoma en cuirasse (CEC) pattern of CM secondary to gastric malignancy in a 55-year-old male patient-the interesting part being that CM was the first-presenting sign, which on further histopathological and immunohistochemical evaluation led to the diagnosis of hidden gastric carcinoma. The finding of signet ring cells (SRCs) on cutaneous biopsy further added a differential of the rare possibility of primary cutaneous tumors. PMID:26677305

  7. Association between the expression levels of tumor necrosis factor-α-induced protein 8 and the prognosis of patients with gastric adenocarcinoma

    PubMed Central

    CHEN, LING; YANG, XIGUI; YANG, XIANGSHAN; FAN, KAIXI; XIAO, PING; ZHANG, JING; WANG, XIUWEN

    2016-01-01

    The present study aimed to investigate the expression levels of tumor necrosis factor-α-induced protein 8 (TNFAIP8) in gastric adenocarcinoma. TNFAIP8 expression levels in gastric adenocarcinoma tissue samples (with and without lymph node metastasis), adjacent normal tissue samples and metastatic lymph node tissue samples were detected by immunohistochemistry. The correlation between TNFAIP8 expression levels and clinicopathological data and gastric adenocarcinoma prognosis was analyzed. The results demonstrated that TNFAIP8 expression in gastric adenocarcinoma tissue samples and metastatic lymph node tissue samples markedly increased at a rate of 47.2% (50/106) and 81.7% (49/60), respectively, as compared with the adjacent normal tissue samples in which no TNGFAIP8 expression was detected (0%). This increase in TNFAIP8 expression was statistically significant. TNFAIP8 expression rates in the primary tumors (60%, 36/60) of patients with lymph node metastasis were significantly higher compared with the primary tumors of patients without lymph node metastasis (30.4%, 14/46). TNFAIP8 expression was associated with an increase in the severity of TNM stage, tumor grade, vascular invasion, lymph node metastasis and serum CA72-4 levels. The overall survival rate of patients with gastric adenocarcinoma and high TNFAIP8 expression was poorer compared with patients with low TNFAIP8 expression, and TNFAIP8 expression was negatively correlated with patient prognosis. The results also demonstrated that TNFAIP8 was an independent prognostic marker in gastric adenocarcinoma (relative risk, 1.736; P=0.029). In conclusion, the results of the present study demonstrated that TNFAIP8 expression was associated with the occurrence, development and metastasis of gastric adenocarcinoma, and negatively correlated with the prognosis of patients with gastric adenocarcinoma. TNFAIP8 may therefore serve as a prognostic factor for gastric adenocarcinoma. PMID:27347043

  8. Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma.

    PubMed

    Schlößer, Hans A; Drebber, Uta; Kloth, Michael; Thelen, Martin; Rothschild, Sacha I; Haase, Simon; Garcia-Marquez, Maria; Wennhold, Kerstin; Berlth, Felix; Urbanski, Alexander; Alakus, Hakan; Schauss, Astrid; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; Warnecke-Ebertz, Ute; Stippel, Dirk L; Zippelius, Alfred; Büttner, Reinhard; Hallek, Michael; Hölscher, Arnulf H; Zander, Thomas; Mönig, Stefan P; von Bergwelt-Baildon, Michael

    2016-05-01

    Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted next-generation sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumor-draining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment. PMID:27467911

  9. High Levels of Epstein-Barr Virus DNA in Latently Infected Gastric Adenocarcinoma

    PubMed Central

    Ryan, Julie L.; Morgan, Douglas R.; Dominguez, Ricardo L.; Thorne, Leigh B.; Elmore, Sandra H.; Mino-Kenudson, Mari; Lauwers, Gregory Y.; Booker, Jessica K.; Gulley, Margaret L.

    2008-01-01

    Gastric adenocarcinoma is the second leading cause of cancer death worldwide. Epstein-Barr virus (EBV) is present in the malignant cells of approximately 10% of cases. It is unclear whether EBV is being missed in some gastric adenocarcinomas due to insensitive test methods or partial EBV genome loss. In the current study, we screened 113 gastric adenocarcinomas from low and high incidence regions (United States and Central America) for the presence of EBV using a battery quantitative real-time PCR (Q-PCR) assays targeting disparate segments of the EBV genome (BamH1W, EBNA1, LMP1, LMP2, BZLF1, EBER1) and histochemical stains targeting EBV-encoded RNA (EBER), the latent proteins LMP1 and LMP2, and the lytic proteins BMRF1 and BZLF1. EBV DNA was detected by Q-PCR in 48/75 United States cancers (64%) and in 38/38 Central American cancers (100%), which was a significant differrence. EBER was localized to malignant epithelial cells in 8/48 (17%) United States and 3/38 (8%) Central American cancers. Viral loads were considerably higher for EBER-positive versus EBER-negative cancers (mean 162,986 versus 62 EBV DNA copies per 100,000 cells). A viral load of 2,000 copies per 100,000 cells is recommended as the threshold distinguishing EBER-positive from EBER-negative tumors. One infected cancer selectively failed to amplify the LMP2 gene because of a point mutation, while another cancer had an atypical pattern of Q-PCR positivity suggesting deletion of large segments of the EBV genome. Three different viral latency profiles were observed in the cancers based on constant expression of EBER and focal or variable expression of LMP1 or LMP2, without lytic protein expression. We conclude that EBV DNA levels generally reflect EBER status, and a panel of at least two Q-PCR assays is recommended for sensitive identification of infected cancers. PMID:19002111

  10. Tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography: association with N categories

    PubMed Central

    Li, Hang; Chen, Xiao-li; Li, Jun-ru; Li, Zhen-lin; Chen, Tian-wu; Pu, Hong; Yin, Long-lin; Xu, Guo-hui; Li, Zhen-wen; Reng, Jing; Zhou, Peng; Cheng, Zhu-zhong; Cao, Ying

    2016-01-01

    OBJECTIVE: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories. MATERIALS AND METHODS: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories. RESULTS: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3). CONCLUSION: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories. PMID:27166769

  11. Intraoperative Gastroscopy for Tumor Localization in Laparoscopic Surgery for Gastric Adenocarcinoma.

    PubMed

    Hur, Hoon; Son, Sang-Yong; Cho, Yong Kwan; Han, Sang-Uk

    2016-01-01

    Determining resection margins for gastric cancer, which are not exposed to the serosal surface of the stomach, is the most important procedure during totally laparoscopic gastrectomy (TLG). The aim of this protocol is to introduce a procedure for intraoperative gastroscopy, in order to directly mark tumors during TLG for gastric cancer in the middle third of the stomach. Patients who were diagnosed with adenocarcinoma in the middle third of the stomach were enrolled in this case series. Before surgery, additional gastroscopy for tumor localization is not performed. Under general anesthesia, laparoscopic mobilization of the stomach is performed first. After the first portion of the duodenum is mobilized from the pancreas and clamped, the surgeon moves to the other side for the gastroscopic procedure. On the insertion of a gastroscope through the oral cavity into the stomach, 2 - 3 cc of indigo carmine is administered via an endoscopic injector into the gastric muscle layer at the proximal margin of the stomach. The location of stained serosa in the laparoscopic view is used to guide distal subtotal gastrectomy, however, total gastrectomy is performed if the tumor is too close to the esophagogastric junction. A specimen is sampled after distal gastrectomy to confirm sufficient length from resection margin to tumor before reconstruction. In our case series, all patients had tumor-free margins and required no additional resection. There was no morbidity related to the gastroscopic procedure, and the time required for the procedure has gradually decreased to about five minutes. Intraoperative gastroscopy for tumor localization is an accurate and tolerated method for gastric cancer patients undergoing totally laparoscopic distal gastrectomy. PMID:27584713

  12. Novel therapy for advanced gastric cancer

    PubMed Central

    Zhang, Yue; Wu, Shenhong

    2015-01-01

    Gastric cancer (GC) is a common lethal malignancy. Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States. Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease. The median overall survival (OS) is less than one year for advanced GC patients; thus, there is an urgent unmet need to develop novel therapy for GC. Although multiple targeted agents were studied, only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit (5.2 mo vs 3.8 mo, P = 0.047) as a single agent; 2.2 mo improvement of survival (9.6 mo vs 7.4 mo, P = 0.017) when combined with paclitaxel in previously treated advanced GC patients. It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab. Even with limited success, targeted therapy may be improved by developing new biomarkers. Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials. More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities. PMID:26600926

  13. EPO-R expression patterns in resected gastric adenocarcinoma followed by adjuvant chemoradiation treatment.

    PubMed

    Sereno, Maria; De Castro, Javier; Belda-Iniesta, Cristóbal; Garcia-Cabezas, Miguel Angel; Cejas, Paloma; Casado, Enrique; Barriuso, Jorge; Feliu, Jaime; Larrauri, Javier

    2009-03-01

    The primary aim was to determine whether Epo-R immunohistochemical expression is related to disease free survival (DFS) in specimens of GC from patients who underwent adjuvant chemoradiation. Specimens of gastric adenocarcinomas obtained from 44 patients who had undergone curative gastrectomy and adjuvant treatment were investigated immunohistochemically expression of Epo-R. Three patterns for Epo-R staining were defined: Pattern A (secretory cells-like staining), Pattern B (parietal-like staining) and Pattern C (chief-like staining). Median DFS was 38 months (CI 95%: 33-43) and 15 months (IC 95%: 3-27) in the pattern B and C, respectively, but it was not reached in the pattern A (p = 0.06). Our findings suggest that there may be a relationship between Epo-R expression and DFS in the patients with GC resected. PMID:19002606

  14. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma

    PubMed Central

    Hedner, Charlotta; Borg, David; Nodin, Björn; Karnevi, Emelie; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Background Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma. Methods Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology. Results and Discussion High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods. PMID:26844548

  15. Surgical Resection First for Localized Gastric Adenocarcinoma: Are There Adjuvant Options?

    PubMed

    Elimova, Elena; Ajani, Jaffer A

    2015-10-01

    A 55-year-old male presented with upper abdominal bloating followed by modest hematemesis that led to the diagnosis of an ulcerated poorly differentiated (with signet ring cells) adenocarcinoma in the angularis of the stomach. A contrast-enhanced positron emission tomography (PET) with computed tomography (CT) scan showed higher-than-normal physiologic avidity (standardized uptake value, 4.3) in the proximal stomach but not in the lower stomach, and the CT scan vaguely suggested a polypoid lesion in the distal stomach. Nodes were normal in size, and there were no metastases. He underwent esophagoduodenoscopy with ultrasonography (EUS) that showed a 3- x 2-cm flat nodular mass with an 8-mm ulcer in the angularis. The tumor mass was demarcated well on narrow-band imaging, and with a 20-MHz EUS probe, it was designated eusT1bN0. His case was presented to our weekly Multidisciplinary Gastric Adenocarcinoma Conference, and the consensus was to offer surgery as primary therapy. He underwent a subtotal gastrectomy with Roux-en-Y gastrojejunostomy along with D2 nodal dissection. The surgical pathology showed a poorly differentiated adenocarcinoma with signet ring cells; the primary tumor measured 2.8 x 2.2 cm in diameter with infiltration through the muscularis propria and into the subserosal fat. Seven of 53 examined lymph nodes were malignant; therefore, his cancer was staged pT3N3M0 (a higher stage than designated clinically). He recovered well without complications, and the postoperative CT scans showed no metastases. His case was represented at the tumor board meeting, and adjuvant chemotherapy with oxaliplatin and capecitabine was recommended. PMID:26324361

  16. Concurrent Gastric Adenocarcinoma of Fundic Gland Type and Carcinoma with Lymphoid Stroma: A Rare Case Report

    PubMed Central

    Cha, Hee Jeong; Kim, Kyungbin; Kim, Misung; Choi, Hyejeong; Kim, Young Min; Suh, Jae Hee

    2016-01-01

    Both gastric adenocarcinoma of fundic gland type (ADC-FG) and carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma, LELC) are relatively rare. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of LELC. However, the pathogenesis of ADC-FG, as well as the role of EBV in the carcinogenesis of LELC, remain unclear and under debate. The current study presents a case of concurrent ADC-FG and LELC in the stomach in a 69-year-old man. Total gastrectomy was performed, and two separate masses were identified. Upon histological and immunohistochemical examination, the mass located in the lower body was determined to be LELC and the mass in the upper body was diagnosed as ADC-FG. The lesions were characterized by different mucin phenotypes and EBV in situ results. In the lower-body mass, EBV in situ hybridization expression was diffusely strongly positive, but MUC2, MUC5AC, MUC6, and CD10 were all negative. On the other hand, in the upper-body mass, the results were positive for MUC6 but negative for MUC2, MUC5AC, CD10, and EBV by in situ hybridization. The remaining gastric tissue was unremarkable, and perigastric lymph node metastases were absent. Seven months after the gastrectomy, a postoperative computed tomography scan revealed no recurrence or metastasis. PMID:27462199

  17. Gastric-type extremely well-differentiated adenocarcinoma arising in the blind pouch of a bypassed stomach, presenting as colonic pseudo-obstruction.

    PubMed

    McFarland, Sarah; Manivel, Carlos J; Ramaswamy, Archana; Mesa, Hector

    2015-01-01

    Gastric carcinoma after gastric bypass is rare. Extremely well-differentiated adenocarcinoma (EWDA) of the stomach is a rare variant that has been mostly reported in Japan. We present a case of a 68-year-old man with EWDA arising in the bypassed stomach that presented as a colonic pseudo-obstruction (CPO). Several imaging, endoscopic and pathologic studies performed in the course of 2 months were non-diagnostic. An iatrogenic duodenal perforation during a diagnostic procedure led to an emergent exploratory laparotomy in which the dilated colonic segment was resected. Pathologic examination showed metastatic EWDA in the colonic wall. Post-operative complications led to the patient's demise. At autopsy the primary tumor was identified in the blind pouch of the bypassed stomach. A literature review on gastric EWDA and carcinomas arising in bypassed stomachs is discussed. EWDA of the stomach is rare, difficult to diagnose, and shows an aggressive clinical course discordant with its near-benign histology. Gastric cancer arising in a bypassed stomach is uncommon; when it occurs it is usually diagnosed at advanced stage. Surveillance of the blind pouch is not currently recommended. Malignant infiltration of the colonic wall should be included in the differential diagnosis of CPO of unclear etiology. PMID:26424554

  18. The Value of miR-299-5p in Diagnosis and Prognosis of Intestinal-Type Gastric Adenocarcinoma.

    PubMed

    Azarbarzin, Shirin; Hosseinpour Feizi, Mohammad Ali; Safaralizadeh, Reza; Ravanbakhsh, Reyhaneh; Kazemzadeh, Mina; Fateh, Alavieh; Karimi, Nasibeh; Moaddab, Yaghoub

    2016-08-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs, containing about 22 nucleotides and having a pivotal function in various cellular processes. The oncogenic and tumor suppressor roles of miRNAs have been identified in cancers especially in gastric cancer, which is one of the most prevalent cancers. MiR-299-5p is located in the imprinted Dlk1-Dio3 region in chromosome 14q32. Aberrant expression of miR-299-5p was determined in solid and blood cancers. The current study was performed to assess the expression pattern of miR-299-5p in intestinal-type gastric adenocarcinoma and compare it with the normal adjacent counterparts. The expression level of miR-299-5p was investigated in forty fresh specimens which were obtained from gastric cancer patients during endoscopy. Moreover, the association of aberrant expression of miR-299-5p and clinicopathological features, as well as the susceptibility of miR-299-5p as a tumor marker, was determined. The result of qRT-PCR revealed the downregulation of miR-299-5p in intestinal-type gastric adenocarcinoma compared with adjacent tumor-free tissues (P < 0.001); this misregulation can be used as a tumor marker. Analysis of miR-299-5p misregulation did not reveal a significant correlation with clinical features. The result obtained from the present study revealed the significant downregulation of miR-299-5p in intestinal-type gastric adenocarcinoma which is consistent with previous studies showing miR-299-5p downregulation in other types of cancers. The data obtained from the current study suggest basic information which can be very helpful for future research in the field of diagnosis and treatment of gastric cancer. PMID:27007598

  19. Gastric adenocarcinoma in Zambia: a case-control study of HIV, lifestyle risk factors, and biomarkers of pathogenesis

    PubMed Central

    Kayamba, Violet; Asombang, Akwi W; Mudenda, Victor; Lisulo, Mpala Mwanza; Sinkala, Edford; Mwanamakondo, Stayner; Mweemba, Isaac; Kelly, Paul

    2013-01-01

    Background Gastric cancer is a leading cause of cancer deaths worldwide but there are few data from Africa. We have recently observed a trend towards diagnosis in younger patients. Objective To test the hypothesis that HIV may have altered risk factors for acquisition of gastric cancer, in a case-control study in the University Teaching Hospital, Lusaka, Zambia. Methods Cases (n=52) with confirmed gastric adenocarcinoma and controls (n=94) undergoing endoscopy but with no macroscopic gastric pathology. Established risk factors and HIV status were compared. Results HIV status did not differ significantly in cases and controls (Odds Ratio 1·03; 95% CI 0·2–4·3; P=1·00) and seroprevalence in cases was similar to the Zambian population. Smoking, regular alcohol intake, and gastric atrophy were all associated with cancer in univariate and multivariate analysis. H. pylori serology was positive in 84% of patients studied and cagA serology in 66%; neither serological marker was associated with cancer. Atrophy, assessed serologically, was common in cases (57%) and controls (30%). In controls, both smoking and alcohol use were associated with atrophy, and intestinal metaplasia was present in 17% but was not associated with atrophy. Conclusions HIV was not associated with gastric cancer and does not explain the apparent change in age distribution in Zambia. Atrophy was common and was not essential for the development of intestinal metaplasia, suggesting that gastric carcinogenesis in Africa does not always follow the Correa pathway. PMID:23547703

  20. Primary vaginal mucinous adenocarcinoma of gastric type arising in adenosis: a report of 2 cases, 1 associated with uterus didelphys.

    PubMed

    Talia, Karen L; Scurry, James; Manolitsas, Thomas; McCluggage, W Glenn

    2012-03-01

    We report 2 cases of primary vaginal mucinous adenocarcinoma arising in adenosis in nondiethylstilbestrol-exposed women, 1 with uterus didelphys. Both tumors exhibited morphologic and immunohistochemical features (MUC6 and/or HIK 1083 positivity) identical to the recently described cervical gastric-type adenocarcinoma, a subtype of mucinous adenocarcinoma that is non-human papillomavirus related and possibly related to adenoma malignum. Both neoplasms were intensely p53 positive, suggesting that TP53 mutation may be implicated in their development. We believe that the vaginal tumors arose from adenosis through atypical adenosis, as benign and atypical glands were present at the periphery of the neoplasms. In reporting these cases, we discuss atypical adenosis and other types of non-diethylstilbestrol-associated vaginal adenocarcinomas. At least 9 other examples of primary vaginal, or more uncommonly cervical, adenocarcinomas arising in non-diethylstilbestrol-exposed women with congenital genitourinary malformations have been reported, suggesting a probable causal association between congenital malformation, vaginal adenosis, and vaginal adenocarcinoma. PMID:22317878

  1. Salt-Inducible Kinase 1 (SIK1) Is Induced by Gastrin and Inhibits Migration of Gastric Adenocarcinoma Cells

    PubMed Central

    Selvik, Linn-Karina M.; Rao, Shalini; Steigedal, Tonje S.; Haltbakk, Ildri; Misund, Kristine; Bruland, Torunn; Prestvik, Wenche S.; Lægreid, Astrid; Thommesen, Liv

    2014-01-01

    Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase (AMPK) family of kinases, all of which play major roles in regulating metabolism and cell growth. Recent studies have shown that reduced levels of SIK1 are associated with poor outcome in cancers, and that this involves an invasive cellular phenotype with increased metastatic potential. However, the molecular mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide hormone gastrin regulates cellular processes involved in oncogenesis, including proliferation, apoptosis, migration and invasion. The aim of this study was to examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J, AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER). We demonstrate that gastrin-mediated signalling induces phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic expression of SIK1 increases gastrin-induced phosphorylation of histone deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE-, SRE-, AP1- and NF-κB-driven luciferase reporter plasmids. We also show that gastrin induces phosphorylation and nuclear export of HDACs. Next we find that siRNA mediated knockdown of SIK1 increases migration of the gastric adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is regulated by gastrin and influences gastrin elicited signalling in gastric adenocarcinoma cells. The results from the present study are relevant for the understanding of molecular mechanisms involved in gastric adenocarcinomas. PMID:25384047

  2. Primary advanced esophago-gastric melanoma: A rare case

    PubMed Central

    Wang, Lin; Zong, Liang; Nakazato, Hidetsugu; Wang, Wen-Yue; Li, Chao-Feng; Shi, Yan-Fen; Zhang, Guo-Chao; Tang, Tao

    2016-01-01

    Primary esophageal or gastric melanoma is a very rare disease with early metastasis. Due to its atypical symptom and less efficiency of chemotherapy and radiotherapy, the prognosis of esophageal or gastric melanoma is still very poor. Surgical resection remains the preferential treatment for esophageal or gastric melanoma. Here we present an extremely rare case of primary advanced esophago-gastric melanoma. Debulking surgery was performed without chemotherapy or radiotherapy. However, abdominal recurrence and hepatic metastases were found within one month by a postoperative follow-up computed tomography. Three and a half months after surgical resection, the patient died of extensive abdominal metastasis. PMID:27004009

  3. Impact of Perioperative Blood Transfusion on Postoperative Complications and Prognosis of Gastric Adenocarcinoma Patients with Different Preoperative Hemoglobin Value

    PubMed Central

    Xue, Lian; Wei-Han, Zhang; Yang, Kun; Chen, Xin-Zu; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Background. The impact of perioperative blood transfusion on the prognosis of gastric adenocarcinoma patients is still controversial. The aim of this study was to elucidate the impact of perioperative blood transfusion on postoperative complications and prognosis of patients who underwent gastrectomy for gastric adenocarcinoma with different levels of preoperative hemoglobin value (POHb). Method. From 2003 to 2011, 1199 patients who underwent curative gastrectomy were retrospectively enrolled and followed up to December 2014. Clinicopathological features and survival outcomes were compared between transfused and nontransfused patients. Results. In this study, transfused patients had more postoperative complications than nontransfused ones (P = 0.002). In survival analysis, the difference was not significant between transfused and nontransfused patients with POHb between 70 and 100 g/L (P = 0.191). However, in patients with POHb >100 g/L, transfused patients had significantly worse prognosis (P < 0.001), especially in TNM III stage patients (P = 0.002). And intraoperative blood transfusion predicted poor prognosis (P = 0.001). Conclusion. Perioperative blood transfusion might lead to poor survival in gastric adenocarcinoma patients with POHb >100 g/L and transfused patients had more postoperative complications; thus it is better to refrain from unnecessary perioperative blood transfusion especially intraoperative transfusion. PMID:26819609

  4. Expression of SPARC like protein 1 (SPARCL1), extracellular matrix-associated protein is down regulated in gastric adenocarcinoma

    PubMed Central

    Jakharia, Aniruddha; Borkakoty, Biswajyoti

    2016-01-01

    Background SPARC-like protein 1 (SPARCL1/Hevin), a member of the SPARC family is defined by the presence of a highly acidic domain-I, a follistatin-like domain, and an extracellular calcium (EC) binding domain. SPARCL1 has been shown to be down-regulated in many types of cancer and may serve as a negative regulator of cell growth and proliferation. Methods Both tumor and adjacent normal tissue were collected from patients with gastric adenocarcinoma. Monoclonal antibody developed against recombinant SPARCL1 was used to analyze the expression of SPARCL1 by immunohisto chemical and western blotting (WB) analysis. Results The expression of SPARCL1 was found to be significantly lower or negligible in gastric adenocarcinoma tissues in nearly all of the cases in comparison with adjacent normal tissue. This comparison was found to be independent of the patient’s age, sex, and stage of cancer. Conclusions We postulate that down regulation of SPARCL1 may be related to inactivation of its tumor suppressor functions and might play an important role in the development of gastric adenocarcinoma. PMID:27034797

  5. The inhibition of histone deacetylase 8 suppresses proliferation and inhibits apoptosis in gastric adenocarcinoma.

    PubMed

    Song, Shiyuan; Wang, Ying; Xu, Po; Yang, Ruina; Ma, Zhikun; Liang, Shuo; Zhang, Guangping

    2015-11-01

    Histone deacetylase 8 (HDAC8), a unique member of class I HDACs, shows remarkable correlation with advanced disease stage. The depletion of HDAC8 leads to inhibition of proliferation, apoptosis and cell cycle arrest in multiple malignant tumors. However, little is known about the contribution of HDAC8 to the tumorigenesis of gastric cancer (GC). The present study investigated expression of HDAC8 in GC cell lines and tissues, and the roles of HDAC8 inhibition in the proliferation, cell cycle and apoptosis of gastric cancer cells and explored the potential mechanisms. In the present study, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry were used to examine the mRNA and protein expression of HDAC8 in GC cell lines and tissues. Then, the correlation between the clinicopathological parameters and the expression of HDAC8 was assessed. Finally, siRNA transfection and HDAC8 plasmid was performed to explore the functions of HDAC8 in GC progression in vitro. We found that the expression of HDAC8 was significantly upregulated both in GC cell lines and tumor tissues compared to human normal gastric epithelial cell, GES-1 and matched non-tumor tissues. Furthermore, depletion of HDAC8 remarkably inhibited GC cell proliferation, increased the apoptosis rate and G0/G1 phase percentage in vitro. Western blotting showed that the expression of protein promoting apoptosis such as, Bmf, activated caspase-3, caspase-6 were elevated following HDAC8 depletion. Our data exhibited an important role of HDAC8 in promoting gastric cancer tumorigenesis and identify this HDAC8 as a potential therapeutic target for the treatment of gastric cancer. PMID:26412386

  6. Genetic variations in angiogenesis pathway genes associated with clinical outcome in localized gastric adenocarcinoma

    PubMed Central

    Lurje, G.; Husain, H.; Power, D. G.; Yang, D.; Groshen, S.; Pohl, A.; Zhang, W.; Ning, Y.; Manegold, P. C.; El-Khoueiry, A.; Iqbal, S.; Tang, L. H.; Shah, M. A.; Lenz, H.-J.

    2010-01-01

    Background: Angiogenesis has been attributed to be a well-recognized aspect of human cancer biology. As such, proteinase-activated receptor (PAR)-1, endostatin (ES) and interleukin-8 (IL-8) mediate the regulation of early-onset angiogenesis and in turn impact the process of tumor-growth and disease progression. Patients and methods: Formalin-fixed paraffin-embedded tissues were obtained from 137 patients with localized gastric cancer at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was extracted and genotyping was carried out using PCR–restriction fragment length polymorphism-based protocols. Results: In false discovery rate-adjusted univariate analysis, PAR-1 −506 ins/del (P < 0.001), ES +4349 G>A (P = 0.004), and IL-8 −251 T>A (P < 0.0001) were associated with time to tumor recurrence (TTR). Further, PAR-1 −506 ins/del and IL-8 −251 were associated with overall survival (OS). After adjusting for covariates, IL-8 remained significantly associated with TTR (adjusted P = 0.003) and OS (adjusted P = 0.049), whereas ES was significantly associated with TTR (adjusted P = 0.026). Conclusions: Polymorphisms in PAR-1, ES, and IL-8 may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinoma. The assessment of the patients’ individual risk on the basis of interindividual genotypes may therefore help to identify patient subgroups at high risk for poor clinical outcome. PMID:19622587

  7. Increased expression of IDO associates with poor postoperative clinical outcome of patients with gastric adenocarcinoma

    PubMed Central

    Liu, Hao; Shen, Zhenbin; Wang, Zhenglin; Wang, Xuefei; Zhang, Heng; Qin, Jing; Qin, Xinyu; Xu, Jiejie; Sun, Yihong

    2016-01-01

    Clinical significance of 2,3-dioxygenase (IDO) has been studied in types of tumors, but the role that IDO played in gastric adenocarcinoma (GAC) is still unclear. Here, we aim to investigate the prognostic value of IDO expression in patients with GAC. We examined intratumoral IDO expression in retrospectively enrolled 357 patients with GAC undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochemical staining. The Kaplan-Meier method and Cox regression models were used to evaluate the prognostic value of IDO expression and its association with clinical pathological factors. We generated a predictive nomogram by integrating IDO expression with the TNM staging system for overall survival of GAC patients. High expression of intratumoral IDO predicted a dismal outcome. Intratumoral IDO expression gave a further discrimination for the prognosis of GAC patients. By Cox multivariate analysis, IDO expression was defined as an independent prognosticator. The generated nomogram performed well in predicting the 3- and 5-year overall survival of GAC patients. Conclusively, IDO is a potential prognostic biomarker for overall survival of patients with GAC after gastrectomy. PMID:26887337

  8. Deconvolution Analysis for Classifying Gastric Adenocarcinoma Patients Based on Differential Scanning Calorimetry Serum Thermograms

    PubMed Central

    Vega, Sonia; Garcia-Gonzalez, María Asuncion; Lanas, Angel; Velazquez-Campoy, Adrian; Abian, Olga

    2015-01-01

    Recently, differential scanning calorimetry (DSC) has been acknowledged as a novel tool for diagnosing and monitoring several diseases. This highly sensitive technique has been traditionally used to study thermally induced protein folding/unfolding transitions. In previous research papers, DSC profiles from blood samples of patients were analyzed and they exhibited marked differences in the thermal denaturation profile. Thus, we investigated the use of this novel technology in blood serum samples from 25 healthy subjects and 30 patients with gastric adenocarcinoma (GAC) at different stages of tumor development with a new multiparametric approach. The analysis of the calorimetric profiles of blood serum from GAC patients allowed us to discriminate three stages of cancer development (I to III) from those of healthy individuals. After a multiparametric analysis, a classification of blood serum DSC parameters from patients with GAC is proposed. Certain parameters exhibited significant differences (P < 0.05) and allowed the discrimination of healthy subjects/patients from patients at different tumor stages. The results of this work validate DSC as a novel technique for GAC patient classification and staging, and offer new graphical tools and value ranges for the acquired parameters in order to discriminate healthy from diseased subjects with increased disease burden. PMID:25614381

  9. Genetic variations in MTHFR and gastric cardia adenocarcinoma susceptibility in the Chinese Han population

    PubMed Central

    Wang, Yafeng; Chen, Shuchen; Kang, Mingqiang; Tang, Weifeng; Gu, Haiyong; Yin, Jun; Huang, Ziyang

    2015-01-01

    Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are associated with many types of cancers. The purpose of our study was to evaluate the effect of MTHFR single nucleotide polymorphisms (SNPs) on gastric cardia adenocarcinoma (GCA). We conducted a hospital-based case-control study. Three hundred and thirty cases with GCA and 608 controls were recruited. The ligation detection reaction (LDR) method was used to determine genotypes. The genotype MTHFR rs1801133 TT was significantly more frequent in cases than in controls (adjusted odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.04-2.05, P = 0.029) in a recessive model, after adjusting for age, sex and smoking and alcohol use. The haplotype MTHFR Grs4845882Ars4846048Trs1801133Crs9651118Ars3753584 was more frequent in cases than in controls (crude OR = 5.32, 95% CI = 2.34-12.10, P < 0.001). No association between other genotypes and haplotypes was observed. Our results suggest that the genotype MTHFR rs1801133 TT and the MTHFR Grs4845882Ars4846048Trs1801133Crs9651118Ars3753584 haplotype may be associated with susceptibility to GCA. Further studies are needed to confirm these findings. PMID:26770518

  10. Clinical management of advanced gastric cancer: The role of new molecular drugs

    PubMed Central

    De Vita, Ferdinando; Di Martino, Natale; Fabozzi, Alessio; Laterza, Maria Maddalena; Ventriglia, Jole; Savastano, Beatrice; Petrillo, Angelica; Gambardella, Valentina; Sforza, Vincenzo; Marano, Luigi; Auricchio, Annamaria; Galizia, Gennaro; Ciardiello, Fortunato; Orditura, Michele

    2014-01-01

    Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual “scenario” of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice. PMID:25356019

  11. A Phase II Study of Sequential Capecitabine Plus Oxaliplatin Followed by Docetaxel Plus Capecitabine in Patients With Unresectable Gastric Adenocarcinoma: The TCOG 3211 Clinical Trial.

    PubMed

    Chen, Ming-Huang; Lin, Johnson; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

    2016-01-01

    Fluorouracil and platinum are considered the standard treatment options for advanced gastric cancer. Docetaxel is also an effective agent and it shows no cross-resistance with fluorouracil and platinum. The combination treatment of docetaxel with fluorouracil and platinum has been explored, but it demonstrated intolerable toxicities. An alternative approach in the first-line treatment of gastric adenocarcinoma may be to use these agents sequentially. We aimed to evaluate the activity and safety profile of sequential chemotherapy with capecitabine plus oxaliplatin, followed by docetaxel plus capecitabine in the first-line treatment of unresectable gastric cancer.We conducted a phase II study of sequential first-line chemotherapy in advanced gastric cancer. Treatment consisted of 6 cycles of capecitabine plus oxaliplatin (capecitabine 1000 mg/m bid on days 1-10 and oxaliplatin 85 mg/m on day 1, every 2 weeks), followed by 4 cycles of docetaxel plus capecitabine (docetaxel 30 mg/m on days 1 and 8, capecitabine 825 mg/m bid on days 1-14, every 3 weeks). The primary end-point was the objective response rate.Fifty-one patients were enrolled: median age, 63 years; male/female: 37/14. The main grade 3 to 4 toxicities were a decreased absolute neutrophil count (25.4%), diarrhea (9.8%), and hand-foot syndrome (15.7%). The objective response rate was 61.7%. The median progression-free survival and overall survival were 8.6 and 11.0 months, respectively. Six patients (11.8%) received surgery after chemotherapy and 5 are still disease-free.This sequential treatment demonstrated feasibility with a favorable safety profile and produced encouraging results in terms of activity and efficacy. PMID:26817912

  12. Impact of marital status on survival of gastric adenocarcinoma patients: Results from the Surveillance Epidemiology and End Results (SEER) Database

    PubMed Central

    Qiu, Miaozhen; Yang, Dajun; Xu, Ruihua

    2016-01-01

    Marital status was found to be an independent prognostic factor for survival in various cancer types. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among different marital status in the United States. Gastric adenocarcinoma patients from 2004–2012 were enrolled for study. The 5-year cause specific survival (CSS) was our primary endpoint. Totally 29,074 eligible patients were identified. We found that more male patients were married than female. Asian patients had the highest percentages of married than the other races. More married patients were covered by the insurance. Married patients had better 5-year CSS than unmarried, 30.6% vs 25.7%, P < 0.001. The median overall CSS was 17.87 and 13.61 months for the married and unmarried patients, hazard ratio: 1.09 (95% confidence interval: 1.01–1.17), P = 0.027. The survival difference was significant in the insured but not in the uninsured patients. Widowed patients had the worst prognosis compared with other groups even though they had more stage I disease and more well / moderate differentiated tumors. These results indicated that unmarried gastric adenocarcinoma patients were at greater risk of cancer specific mortality. We recommend every patient should have access to best available gastric cancer therapy. PMID:26876653

  13. [A Case of Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy].

    PubMed

    Okamoto, Tatsuya; Tanaka, Keita; Yonemitsu, Kimihiro; Munechika, Taro; Nomi, Masako; Maeno, Hiroshi; Nagao, Shuji; Kawamoto, Shunji; Sasaguri, Takakazu; Sueishi, Katsuo

    2015-11-01

    A 60s male was admitted to our hospital because of appetite loss and nausea. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum. Abdominal computed tomography showed gastric cancer invasion to the left liver lobe. We initiated neoadjuvant chemotherapy using S-1 plus CDDP after laparoscopic gastrojejunostomy. S-1 was orally administered for 3 weeks followed by a 2-week drug-free period. CDDP was administered intravenously on day 8 of each course. After 5 courses of chemotherapy, the gastric cancer was reduced in size. We therefore performed total gastrectomy with D2-affiliated left liver resection. S-1 plus CDDP is expected to improve outcomes in unresectable or locally advanced gastric cancer. PMID:26805257

  14. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment

    PubMed Central

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  15. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment.

    PubMed

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  16. microRNA-25 Inhibits Cell Apoptosis of Human Gastric Adenocarcinoma Cell Line AGS via Regulating CCNE1 and MYC

    PubMed Central

    Zhang, Yong; Peng, Zheng; Zhao, Yunshan; Chen, Lin

    2016-01-01

    Background Gastric carcinoma is the second leading cause of cancer death. microRNAs play vital roles in regulating expression of related oncogenes. microRNA-25 (miR-25) has been found to be up-regulated in gastric carcinoma. However, its roles in affecting cell apoptosis of gastric carcinoma and the related mechanism remain elusive. This study aimed to uncover the influences of miR-25 on gastric carcinoma cell apoptosis and the possible functional mechanisms involved. Material/Methods Human gastric adenocarcinoma cell line AGS was used and transfected with lentivirus containing miR-25-specifc inhibitor sponge or expression vector to analyze the effects of miR-25. Results miR-25 had higher expression in AGS than in human gastric epithelial cell line GES-1 (P<0.01). Inhibition of miR-25 by its sponge in AGS cells resulted in suppressed cell viability (P<0.01) and promoted cell apoptosis (P<0.01), while overexpression of miR-25 abrogated these effects (P<0.01 and P<0.05), indicating that miR-25 can promote cell viability and inhibit cell apoptosis in AGS cells. Expression analysis of related factors by Western blot showed that inhibiting miR-25 led to the up-regulation of F-box and WD repeat domain-containing 7 (FBXW7, P<0.01) and the down-regulation of FBXW7 substrates, cyclin E1 (CCNE1, P<0.01), and v-myc avian myelocytomatosis viral oncogene homolog (MYC, P<0.001). Conclusions These results indicate that miR-25 has anti-apoptosis roles in AGS cells, possibly via inhibiting FBXW7 and thus promoting oncogenes, such as CCNE1 and MYC. This study provides basic evidence for using miR-25 as a possible therapeutic target in treating gastric carcinoma. PMID:27120728

  17. Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

    PubMed Central

    Yang, Shi Bin; Han, Fanghai; Wu, Jian Hai; Zhao, Zhi; Zhan, Wenhua

    2016-01-01

    C-X-C motif chemokine receptor type 2 (CXCR2), a key regulatory protein, has been associated with multiple roles in the progression of numerous tumors, including gastric adenocarcinoma (GA). However, the mechanism of CXCR2 in the development of tumors remains controversial and unclear. In a previous study, the expression of CXCR2 and interleukin-22 receptor 2 (IL-22BP) was observed in GA. This promoted the present study, which aimed to explore the association between the two proteins, and to further analyze their roles in GA. CXCR2 and IL-22BP protein expression was analyzed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in gastric cancer (GC) tissue, additionally confirmed via western blotting and immunocytochemical analysis in the MKN-45, BGC-823 and SGC-7901 cell lines. The association between expression levels and clinicopathological characteristics was evaluated by the Mann-Whitney U and Kruskal-Wallis tests. Using Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with non-cancerous tissue, CXCR2 and IL-22BP were over expressed (P<0.001 and P<0.001, respectively), and were observed mainly in the cytoplasm (P=0.022 and P=0.014, respectively) in GA. The associated protein and messenger RNA levels were analyzed, and coexpression was identified. Increased expression and more positive cases of CXCR2 and IL-22BP were observed with advanced pathological tumor-node-metastasis (p-TNM) stage in GC (P<0.001 and P<0.001, respectively), as well as the presence and absence of lymph node metastasis (LNM) (P=0.003 and P=0.041, respectively) and deep or superficial muscular invasion (P=0.002 and P=0.004, respectively). In addition, an association between IL-22BP and tumor diameter was indicated (P=0.021). In a Kaplan-Meier analysis, compared with negative expression, the two proteins identified a group of patients with the shortest OS. Cox proportional hazard models revealed that

  18. Long-Term Progression-Free Survival in a Patient with Locally Advanced, Unresectable Pancreatic Adenocarcinoma

    PubMed Central

    Kahn, Leonel A; Matin, Mahan; Bold, Richard J; Tanaka, Michael I; Monjazeb, Arta M

    2015-01-01

    Pancreatic adenocarcinoma is amongst the most lethal malignancies with dismal five-year survival rates. Surgical excision is the mainstay of therapy and unresectable disease is considered incurable. Herein, we describe a patient with unresectable, advanced stage pancreatic adenocarcinoma with a remarkable clinical course following definitive chemoradiotherapy. PMID:26824007

  19. Methylation-mediated downregulation of long noncoding RNA LOC100130476 in gastric cardia adenocarcinoma.

    PubMed

    Guo, Wei; Dong, Zhiming; Shi, Yabin; Liu, Shengnan; Liang, Jia; Guo, Yanli; Guo, Xin; Shen, Supeng; Wang, Guiying

    2016-06-01

    Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardia adenocarcinoma (GCA) has remained unknown. The present study investigated the role and methylation status of LOC100130476 in the pathogenesis of GCA, and further evaluated the potential prognostic role of LOC100130476 in GCA. Significant downregulation of LOC100130476 was detected in SGC-7901 and BGC-823 cell lines and primary GCA tissues. Methylation frequency of LOC100130476 was gradually increased from exon 1 to exon 2 both in tumor tissues and corresponding normal tissues; however, methylation status of region 1 closing to the transcription start site was more tumor-specific among the three regions examined. The findings of the association between LOC100130476 expression, methylation and TNM stage, pathological differentiation, and GCA patients' survival further identified the role of LOC100130476 as a tumor suppressor gene. Furthermore, the hypermethylation of LOC100130476 was also detected in peripheral white blood cells of GCA cases. Thus, LOC100130476 may be act as a tumor suppressor gene in GCA carcinogenesis and aberrant methylation at the CpG sites near the transcription start site within exon 1 may be critical for gene silencing. In addition, aberrant methylation of LOC100130476 in peripheral white blood cells and GCA tissues may be used as a potential valuable biomarker in GCA diagnosis and prognosis. PMID:27189370

  20. NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma-Very good response predominantly in patients with intestinal type tumors.

    PubMed

    Schulz, Christoph; Kullmann, Frank; Kunzmann, Volker; Fuchs, Martin; Geissler, Michael; Vehling-Kaiser, Ursula; Stauder, Heribert; Wein, Axel; Al-Batran, Salah-Eddin; Kubin, Thomas; Schäfer, Claus; Stintzing, Sebastian; Giessen, Clemens; Modest, Dominik Paul; Ridwelski, Karsten; Heinemann, Volker

    2015-08-01

    Perioperative treatment is a standard of care in locally advanced gastroesophageal cancer (GEC) (gastric adenocarcinoma and gastroesophageal junction (GEJ) adenocarcinoma). While preoperative treatment can be applied to the majority of patients, postoperative chemotherapy can be given only to a fraction. The NeoFLOT-study therefore investigates the application of prolonged neoadjuvant chemotherapy (NACT). Patients with T3, T4, and/or node-positive adenocarcinoma (GEC) were eligible for this multicenter phase II trial. NACT consisted of 6 cycles of oxaliplatin 85 mg/m(2) , leucovorin 200 mg/m(2) , 5-fluorouracil 2600 mg/m(2) and docetaxel 50 mg/m(2) (FLOT) applied q 2 wks. Application of adjuvant chemotherapy was explicitly not part of the protocol. R0-resection rate was evaluated as a primary endpoint. Of 59 enrolled patients, 50 patients underwent surgery and were assessable for the primary endpoint. R0-resection rate was 86.0% (43/50). Pathologic complete response (pCR) was 20.0% (10/50) and a further 20% (10/50) of patients achieved near complete histological remission (<10% residual tumor). Among these very good responders, 85% (17/20) had intestinal type tumors, 10% (2/20) had diffuse and 5% (1/20) had mixed type tumors. After 3 cycles of NACT, 6.9% (4/58) of patients developed progressive disease. Median disease-free survival was 32.9 months. The 1-year survival-rate was 79.3%. Grade 3-4 toxicities included neutropenia 29.3%, febrile neutropenia 1.7%, diarrhea 12.1% and mucositis 6.9%. This study indicates that intensified NACT with 6 cycles of FLOT is highly effective and tolerable in resectable GEC. Very good response (pCR and <10% residual tumor) was predominantly observed in patients with intestinal type tumors. PMID:25530271

  1. Exceptional Response to Systemic Therapy in Advanced Metastatic Gastric Cancer: A Case Report

    PubMed Central

    Hartley, Marion; Manning, Maria A; Carroll, John E; Xiu, Joanne; Smaglo, Brandon G; Mikhail, Sameh; Salem, Mohamed E

    2016-01-01

    Gastroesophageal adenocarcinomas represent one of the top five most common types of cancer worldwide. Despite significant advancement, it is still not known which first-line chemotherapy option is best matched to an individual patient. The vast advances in molecular biology have led to the discovery of many potential predictive biomarkers, such as HER-2 neu, thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and topoisomerase-1 (TOPO1). These markers could allow us to select treatment based on an individual’s tumor profile, resulting in an improvement of outcome. Our report highlights two patients with metastatic gastric cancer that achieved an exceptional response with traditional therapy and provides insights into the future perspectives of molecular profile-directed chemotherapy. PMID:26918225

  2. Synchronous gastric and ampullary adenocarcinomas in a hairy cell leukemia patient treated with pentostatin eight years prior.

    PubMed

    Senatore, Frank J; Dasanu, Constantin A

    2016-06-01

    Hairy cell leukemia patients are at increased risk for second malignancies, including both solid and lymphoid neoplasms. Along with other factors, multiple immune defects present in hairy cell leukemia likely contribute to subsequent carcinogenesis. We report herein a case of synchronous high-grade gastric and ampullary adenocarcinomas in a patient with a history of hairy cell leukemia treated eight years prior with pentostatin. We include a review of immune alterations induced by both hairy cell leukemia and its therapies, and link them with the occurrence of second cancers in these patients. PMID:25712625

  3. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  4. Clinical utility of ramucirumab in advanced gastric cancer

    PubMed Central

    Chan, Matthew MK; Sjoquist, Katrin M; Zalcberg, John R

    2015-01-01

    Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer. PMID:26451083

  5. Combination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer

    ClinicalTrials.gov

    2015-12-16

    Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  6. Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit.

    PubMed

    Geyer, Philipp Emanuel; Maak, Matthias; Nitsche, Ulrich; Perl, Markus; Novotny, Alexander; Slotta-Huspenina, Julia; Dransart, Estelle; Holtorf, Anne; Johannes, Ludger; Janssen, Klaus-Peter

    2016-05-01

    The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node-metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endoplasmic reticulum. Treatment of the Gb3-expressing gastric carcinoma cell line St3051 with STxB coupled to SN38, the active metabolite of the topoisomerase type I inhibitor irinotecan, resulted in >100-fold increased cytotoxicity, as compared with irinotecan alone. No cytotoxicity was observed on gastric cancer cell lines lacking Gb3 expression, demonstrating receptor specificity of the STxB-SN38 compound. Thus, STxB is a highly specific transport vehicle for cytotoxic agents in gastric carcinoma. Mol Cancer Ther; 15(5); 1008-17. ©2016 AACR. PMID:26826119

  7. [A Case Report of Advanced Gastric Cancer Demonstrating CR after Treatment with S-1 and Paclitaxel].

    PubMed

    Kudoh, Keisuke; Ogata, Kenichi; Ohchi, Tetsufumi; Ootao, Ryu; Koga, Yuki

    2015-11-01

    Here, we report a case of advanced gastric cancer that demonstrated CR after treatment with S-1 and paclitaxel. The patient was an 80-year-old woman with gastric cancer in whom upper gastrointestinal endoscopy (GIF) revealed a type 3 tumor in the cardia of the stomach that was pathologically diagnosed as a well-differentiated adenocarcinoma. Computed tomography showed no lymph node involvement or metastasis. Considering her advanced age and cardinal functional disorder, she was administered chemotherapy consisting of S-1 and paclitaxel. Depending on a state, a side effect, I changed a dose and inter-dose interval from head to foot and I treated it by foreign going to hospital and continued it. Gradual tumor reduction was observed on GIF (2011/1/25). CR was diagnosed without tumor disappearance, with accepted malignant findings on biopsy. The patient has now survived for 7 years 9 months after diagnosis. The present case demonstrates that combination therapy of S-1 and paclitaxel is safe and useful for patients with risk factors such as advanced age and underlying disease. PMID:26805267

  8. 64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

    ClinicalTrials.gov

    2016-06-27

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer

  9. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Steffen, Annika; Huerta, José-Maria; Weiderpass, Elisabete; Bueno-de-Mesquita, H B As; May, Anne M; Siersema, Peter D; Kaaks, Rudolf; Neamat-Allah, Jasmine; Pala, Valeria; Panico, Salvatore; Saieva, Calogero; Tumino, Rosario; Naccarati, Alessio; Dorronsoro, Miren; Sánchez-Cantalejo, Emilio; Ardanaz, Eva; Quirós, J Ramón; Ohlsson, Bodil; Johansson, Mattias; Wallner, Bengt; Overvad, Kim; Halkjaer, Jytte; Tjønneland, Anne; Fagherazzi, Guy; Racine, Antoine; Clavel-Chapelon, Françoise; Key, Tim J; Khaw, Kay-Tee; Wareham, Nick; Lagiou, Pagona; Bamia, Christina; Trichopoulou, Antonia; Ferrari, Pietro; Freisling, Heinz; Lu, Yunxia; Riboli, Elio; Cross, Amanda J; Gonzalez, Carlos A; Boeing, Heiner

    2015-08-01

    General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation. PMID:25598323

  10. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids

    PubMed Central

    Mukaisho, Ken-ichi; Nakayama, Takahisa; Hagiwara, Tadashi; Hattori, Takanori; Sugihara, Hiroyuki

    2015-01-01

    Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori–negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids. PMID:26029176

  11. Progressing Sclerosing Mesenteritis (Mesenteric Panniculitis) Mimics Progression of Malignancy After Neoadjuvant Chemotherapy for Gastric Adenocarcinoma on Serial 18F-FDG PET/CT.

    PubMed

    Makis, William

    2016-04-01

    A 62-year-old man was diagnosed with a moderately differentiated gastric adenocarcinoma in the proximal stomach. A staging 18F-FDG PET/CT showed an intensely FDG-avid gastric mass, as well as a mildly FDG-avid misty nodular mesentery. After 3 cycles of neoadjuvant chemotherapy, a follow-up PET/CT showed partial response of the gastric primary, with increase in the size of nodules in the mesentery and increased FDG uptake, raising concern of secondary malignancy. Biopsy of the mesentery revealed xanthogranulomatous inflammation, consistent with sclerosing mesenteritis. PMID:26359565

  12. In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

    SciTech Connect

    Gunassekaran, G.R.; Kalpana Deepa Priya, D.; Gayathri, R.; Sakthisekaran, D.

    2011-08-12

    Highlights: {yields} Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. {yields} Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. {yields} In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. {yields} So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C{sub 30}H{sub 30}O{sub 8}, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in patients

  13. Borrmann Type 4 Advanced Gastric Cancer: Focus on the Development of Scirrhous Gastric Cancer

    PubMed Central

    Jung, Kyoungwon; Park, Moo In; Kim, Sung Eun; Park, Seun Ja

    2016-01-01

    Early diagnosis of Borrmann type 4 advanced gastric cancer (AGC) is very important for improving the prognosis of AGC patients. Because there is no definite mass in most cases of Borrmann type 4 AGC, its accurate diagnosis via endoscopy requires an understanding of its pathogenesis and developmental process. Moreover, many people confuse linitis plastica (LP) type gastric cancer (GC), scirrhous GC, and Borrmann type 4 AGC. To distinguish each of these cancers, knowledge of their endoscopic and pathological differences is necessary, especially for LP type GCs in the developmental stage. In conclusion, diagnosis of pre-stage or latent LP type GC before progression to typical LP type GC requires the detection of IIc-like lesions in the fundic gland area. It is also crucial to identify any abnormalities such as sclerosis of the gastric wall and hypertrophy of the mucosal folds during endoscopy. PMID:27456608

  14. Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies

    PubMed Central

    Teague, Andrea; Lim, Kian-Huat

    2015-01-01

    Pancreatic adenocarcinoma is one of the deadliest solid malignancies. A large proportion of patients are diagnosed with locally advanced or metastatic disease at the time of presentation and, unfortunately, this severely limits the number of patients who can undergo surgical resection, which offers the only chance for cure. Recent therapeutic advances for patients with advanced pancreatic cancer have extended overall survival, but prognosis still remains grim. Given that traditional chemotherapy is ineffective in curing advanced pancreatic adenocarcinoma, current research is taking a multidirectional approach in the hopes of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. We also review the current ongoing clinical trials, which include the use of agents targeting the oncogenic network signaling of K-Ras, agents targeting the extracellular matrix, and immune therapies. PMID:25755680

  15. Recent advances in gastric floating drug delivery technology: a review.

    PubMed

    Pahwa, Rakesh; Bisht, Seema; Kumar, Vipin; Kohli, Kanchan

    2013-06-01

    Gastric floating drug delivery systems have been an avenue of considerable interest in terms of their immense potential for better pharmacotherapeutic interventions along with site-specific absorption. These buoyant systems significantly enhance the bioavailability and controlled delivery of several drug molecules. Scientific investigators have also carried out substantial research endeavours worldwide in order to design a more systematic and intellectual floating systems. The present manuscript is an attempt to highlight numerous recent advancements in the design of gastric floating drug delivery systems along with various available commercial preparations. Salient applications, characterization aspects and future perspectives of these multifarious systems have also been addressed. PMID:23808593

  16. Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma

    PubMed Central

    Subbannayya, Yashwanth; Syed, Nazia; Barbhuiya, Mustafa A; Raja, Remya; Marimuthu, Arivusudar; Sahasrabuddhe, Nandini; Pinto, Sneha M; Manda, Srikanth Srinivas; Renuse, Santosh; Manju, HC; Zameer, Mohammed Abdul Lateef; Sharma, Jyoti; Brait, Mariana; Srikumar, Kotteazeth; Roa, Juan Carlos; Vijaya Kumar, M; Kumar, KV Veerendra; Prasad, TS Keshava; Ramaswamy, Girija; Kumar, Rekha Vijay; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi

    2015-01-01

    Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer. PMID:25756516

  17. Duodenal adenocarcinoma: Advances in diagnosis and surgical management

    PubMed Central

    Cloyd, Jordan M; George, Elizabeth; Visser, Brendan C

    2016-01-01

    Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma (DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multi-institutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles. PMID:27022448

  18. [A Case of Isolated Leptomeningeal Carcinomatosis from Advanced Gastric Cancer].

    PubMed

    Ji, Jung Geun; Chung, Joo Won; Nam, Seung Woo; Choi, Seung Kyu; Lee, Dong Won; Kim, Dae In; Jeon, Byung Gwan; Shin, Yun Jae

    2016-08-25

    Leptomeningeal carcinomatosis (LMC) is rare metastatic form of gastric cancer. Most cases are diagnosed in the final stage after multiple distant metastasis. An 84-year-old woman was admitted with melena, headache and vomiting. Esophagogastroduodenoscopy showed an ulceroinfiltrating lesion at the stomach (Borrmann class III), and biopsy revealed a signet ring cell carcinoma. The abdominal-pelvic CT showed no evidence of metastasis. A sudden decrease of consciousness was noted, but the brain CT showed no active lesion while the brain MRI revealed enhancement of leptomeninges. A lumbar puncture was performed and the cerebrospinal fluid study revealed malignant neoplastic cells. With family consent, no further evaluation and treatment were administered and she died six weeks after the diagnosis of gastric cancer. We report an extremely rare case of a patient who initially presented with neurologic symptoms, and was diagnosed LMC from advanced gastric cancer without any evidence of metastasis in abdomen and pelvis. PMID:27554216

  19. Association of KRAS and EGFR Mutations with Survival in Patients with Advanced Lung Adenocarcinomas

    PubMed Central

    Johnson, Melissa L.; Sima, Camelia S.; Chaft, Jamie; Paik, Paul K.; Pao, William; Kris, Mark G.; Ladanyi, Marc; Riely, Gregory J.

    2014-01-01

    Background Lung adenocarcinomas can be distinguished by identifying mutated driver oncogenes including EGFR and KRAS. Mutations in EGFR are associated with both an improved survival as well as response to treatment with erlotinib and gefitinib. However, the prognostic significance of KRAS has not been evaluated in large numbers of patients and remains controversial. We examined the association of EGFR and KRAS mutations with survival among patients with advanced lung adenocarcinomas. Methods We analyzed data from patients with advanced lung adenocarcinomas and known EGFR and KRAS mutation status evaluated between 2002 and 2009. We collected clinical variables including age, gender, Karnofsky Performance Status, smoking history, and treatment history. Overall survival from diagnosis of advanced disease was analyzed using Kaplan-Meier and Cox proportional hazard methods. Results We evaluated 1036 patients, including 610 women (59%) and 344 never-smokers (33%). Patients had a median age of 65 (range, 25–92) and the majority (81%) had a KPS ≥80%. In multivariate analysis, EGFR mutations were associated with a longer overall survival (HR= 0.6, p<0.001) and KRAS mutations with a shorter survival (HR=1.21, p=0.048). Conclusions KRAS mutations predict shorter survival for patients with advanced lung adenocarcinomas. The presence of EGFR and KRAS mutations define distinct subsets of patients with lung adenocarcinomas, and should be determined in patients upon diagnosis of advanced disease. Clinical trial reports should include EGFR and KRAS mutation status along with other prognostic factors. PMID:22810899

  20. Requirement for a standardised definition of advanced gastric cancer

    PubMed Central

    DE SOL, ANGELO; TRASTULLI, STEFANO; GRASSI, VERONICA; CORSI, ALESSIA; BARILLARO, IVAN; BOCCOLINI, ANDREA; DI PATRIZI, MICOL SOLE; DI ROCCO, GIORGIO; SANTORO, ALBERTO; CIROCCHI, ROBERTO; BOSELLI, CARLO; REDLER, ADRIANO; NOYA, GIUSEPPE; KONG, SEONG-HO

    2014-01-01

    Each year, ~988,000 new cases of stomach cancer are reported worldwide. Uniformity for the definition of advanced gastric cancer (AGC) is required to ensure the improved management of patients. Various classifications do actually exist for gastric cancer, but the classification determined by lesion depth is extremely important, as it has been shown to correlate with patient prognosis; for example, early gastric cancer (EGC) has a favourable prognosis when compared with AGC. In the literature, the definition of EGC is clear, however, there is heterogeneity in the definition of AGC. In the current study, all parameters of the TNM classification for AGC reported in each previous study were individually analysed. It was necessary to perform a comprehensive systematic literature search of all previous studies that have reported a definition of ACG to guarantee homogeneity in the assessment of surgical outcome. It must be understood that the term ‘advanced gastric cancer’ may implicate a number of stages of disease, and studies must highlight the exact clinical TNM stages used for evaluation of the study. PMID:24348842

  1. Irinotecan Hydrochloride With or Without Alvocidib in Treating Patients With Advanced Stomach or Gastroesophageal Junction Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-05-09

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  2. Reduced MUTYH, MTH1, and OGG1 expression and TP53 mutation in diffuse-type adenocarcinoma of gastric cardia.

    PubMed

    Kohno, Yukiko; Yamamoto, Hidetaka; Hirahashi, Minako; Kumagae, Yoshiteru; Nakamura, Masafumi; Oki, Eiji; Oda, Yoshinao

    2016-06-01

    The effects of oxidative stress in adenocarcinomas of gastric cardia (AGCs) have not been fully elucidated. With a strict definition of AGC, we examined the immunohistochemical expressions of inducible nitric oxide synthase; 8-hydroxy-deoxyguanosine; and the base excision repair enzymes such as MUTYH, MTH1, and OGG1, and TP53 mutational status. Sixty-three cases of AGC were characterized by younger patient age (P = .0227) and more frequent venous invasion (P = .0106) compared with the adenocarcinomas of pylorus (APs). 8-hydroxy-deoxyguanosine was accumulated (P = .0011), whereas MUTYH (P = .0325) and OGG1 (P = .0007) were decreased, in the AGCs compared with the adjacent mucosa, but these differences were not detected in the APs. Among the AGCs, lower expressions of MUTYH (P = .0013) and MTH1 (P = .0059) were each significantly associated with diffuse-type histology. A lower expression of OGG1 was correlated with higher T-stage (P = .0011), lymphatic invasion (P = .004), and lymph node metastasis (P = .0094). In addition, the presence of TP53 mutation was associated with diffuse-type histology (P = .0153) and a lower level of MUTYH (P = .0221). The AGCs also showed a relatively high rate of a transversion-type mutation of TP53 (50%), whereas all TP53 mutations in the APs were transition type. Age 62years or older (P = .0073), diffuse-type histology (P = .0020), and TP53 mutation (P = .0066) were each associated with worse survival in the AGC patients. Our results indicate that oxidative stress accumulation and a downregulation of base excision repair enzymes may play an important role in the pathogenesis of AGC, in particular diffuse-type AGCs. Diffuse-type AGC might involve molecular pathways different from those of other subsets of gastric cancer. PMID:26980051

  3. [Advanced Adenocarcinoma of the Bladder after Augmentation Gastrocystoplasty].

    PubMed

    Kono, Yuka; Terada, Naoki; Takashima, Yasushi; Hikami, Kensuke; Hida, Takuya; Goto, Shuhei; Sunada, Takuro; Okada, Yoshiyuki; Shibasaki, Noboru; Negoro, Hiromitsu; Kobayashi, Takashi; Yamasaki, Toshinari; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Ogawa, Osamu

    2016-01-01

    A 29-year-old woman had undergone gastrocystoplasty with Mitrofanoff appendicovesicostomy for urethral trauma at 9 years of age. Since then, she was being followed up for performing clean intermittent self-catheterization at regular intervals. Twenty years after the surgery, she presented with gross hematuria. Ultrasonographic findings revealed bilateral hydronephrosis. Cystoscopy and computed tomography (CT) revealed invasive bladder cancer with pelvic lymph node metastases. A biopsy confirmed the diagnosis of adenocarcinoma with signet ring cell carcinoma. Subsequently, neo-adjuvant combination chemotherapy with TS-1 and cisplatin (CDDP) was initiated, which was followed by open radical cystectomy with extended pelvic lymphadenectomy. The tumor was found to infiltrate from the anastomotic site into the entire native bladder and histopathological diagnosis was muscle invasive adenocarcinoma with neuroendocrine differentiation and lymph node metastasis (ypT3bN2). TS-1 was continued as adjuvant chemotherapy and the patient did not have any evidence of recurrence for 12 months postoperatively. PMID:26932334

  4. Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100).

    PubMed

    Sousa, J M C; Matos, L A; Alcântara, D F A; Ribeiro, H F; Santos, L S; Oliveira, M N; Brito-Junior, L C; Khayat, A S; Guimarães, A C; Cunha, L A; Burbano, R R; Bahia, M O

    2013-01-01

    There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions. PMID:24114206

  5. New Alkyl Phloroglucinol Derivatives from Rhus trichocarpa Roots and Their Cytotoxic Effects on Human Gastric Adenocarcinoma AGS Cells.

    PubMed

    Lee, Ki Yong; Choi, Ji Hoon; Kim, Hyeon Woo; Yan, Xi-Tao; Shin, Hyeji; Jeon, Young Ho; Sung, Sang Hyun

    2016-05-01

    The phytochemical investigation of the roots of Rhus trichocarpa led to this isolation of five new alkyl phloroglucinol derivatives, characterized as (Z)-15-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol A, 1), (Z)-15-hydroxy-1-(2,6-dihydroxy-4-methoxyphenyl)-9-octadecen-1-one (named trichocarpol B, 2), (Z)-17-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol C, 3), (Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol D, 4), and (9Z,12Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9,12-octadecadien-1-one (named trichocarpol E, 5), together with a known compound, 4-(2,6-dihydroxy-4-methoxyphenyl)-4-oxobutanoic acid (6). In vitro cytotoxic activity of compounds 1-6 was evaluated in the human gastric adenocarcinoma AGS cell line and compounds 1-5 showed significant cytotoxicity. Our results indicate that R. trichocarpa, especially the alkyl phloroglucinol derivatives in it, is a good source of promising natural agents for the treatment of gastric cancer. PMID:26845711

  6. Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma

    SciTech Connect

    Lee, Na Keum; Lee, Jung Hwa; Park, Chan Hyuk; Yu, Dayeon; Lee, Yong Chan; Cheong, Jae-Ho; Noh, Sung Hoon; Lee, Sang Kil

    2014-08-22

    Highlights: • HOTAIR expression was tested in fifty patients with gastric cancer. • Cell proliferation was measured after HOTAIR silencing in gastric cancer cell line. • siRNA–HOTAIR suppresses cell invasiveness and capacity of migration. • Knock down of HOTAR leads to decreased expression of EMT markers. • Inhibition of HOTAIR induces apoptosis and cell cycle arrest. - Abstract: Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastric cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.

  7. Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma

    PubMed Central

    Li, Ming; Deng, Fang; Qian, Li-Ting; Meng, Shui-Ping; Zhang, Yang; Shan, Wu-Lin; Zhang, Xiao-Lei; Wang, Bao-Long

    2016-01-01

    Previous studies have demonstrated an association between human papillomavirus (HPV) and mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer patients; however, few studies have investigated this association in advanced lung adenocarcinoma patients undergoing gefitinib treatment. The present study investigated the association between HPV and EGFR mutations in advanced lung adenocarcinoma patients. A total of 95 advanced lung adenocarcinoma patients were enrolled in the study. The HPV infection status and presence of EGFR mutations in tumor tissue was evaluated. Patient clinical characteristics were also determined and compared with HPV infection and EGFR mutation status to analyze their impact on progression-free survival. HPV DNA was identified in 27/95 (28.4%) lung adenocarcinoma tumors and was most common in patients with lymph node metastasis (P=0.016). A total of 44/95 (46.3%) cases exhibited EGFR mutations, which were predominantly observed in female patients and non-smokers. The presence of HPV DNA was significantly associated with EGFR mutations (P=0.012) and multivariate analysis also revealed that HPV DNA was significantly associated with EGFR mutations (odds ratio=3.971) in advanced lung adenocarcinoma. Patients with both HPV infections and EGFR mutations exhibit a marked decrease in the risk of lung cancer progression when compared with those without HPV infection or EGFR mutations (adjusted HR=0.640; 95% confidence interval: 0.488–0.840; P=0.001). HPV infection was significantly associated with EGFR mutations in advanced lung adenocarcinoma patients. Furthermore, patients with HPV infections exhibited the longest progression-free survival times, which may be due to good response to tyrosine kinase inhibitor- or platinum-based-adjuvant therapy in these patients. Patients with EGFR mutations exhibited a better prognosis when compared with those exhibiting wild-type EGFR, regardless of HPV status. PMID:27602120

  8. Proteasome inhibitor MG-132 lowers gastric adenocarcinoma TMK1 cell proliferation via bone morphogenetic protein signaling

    SciTech Connect

    Wu, William Ka Kei; Sung, Joseph Jao Yiu; Yu Le; Cho, C.H.

    2008-06-27

    Proteasome inhibitor is a novel class of cancer therapeutics, of which the mechanism of action is not fully understood. It is reported that proteasome inhibitor enhances bone morphogenetic protein (BMP) signaling in osteoblasts to stimulate bone formation. BMP signaling is also an important tumor-suppressing pathway in gastric carcinogenesis. We therefore sought to determine the anti-mitogenic effect of proteasome inhibition in relation to BMP signaling in gastric cancer cells. Results showed that proteasome inhibitor MG-132 significantly suppressed the proliferation and the colony-forming ability of gastric cancer TMK1 cells. In this connection, MG-132 activated BMP signaling, manifested as an increase in Smad1/5/8 phosphorylation and up-regulation of p21{sup Waf1/Cip1} mRNA and protein expression. Knockdown of BMP receptor II by RNA interference abolished Smad1/5/8 phosphorylation, p21{sup Waf1/Cip1} induction, and the inhibition of cell proliferation induced by MG-132. Further analysis revealed that MG-132 up-regulated the expression of BMP1 and BMP4 and suppressed the expression of Smad6. Knockdown of Smad6 also mimicked the effect of MG-132 on BMP signaling. Collectively, these findings suggest that inhibition of proteasome suppresses gastric cancer cell proliferation via activation of BMP signaling. This discovery may open up a novel therapeutic avenue to proteasome inhibitors for the management of gastric cancer.

  9. Advanced Mucinous Adenocarcinoma Arising from a Mature Cystic Teratoma: A Case Report and Literature Review

    PubMed Central

    Miyasaka, Aki; Nishikawa, Tadaaki; Kozawa, Eito; Yasuda, Masanori; Fujiwara, Keiichi; Hasegawa, Kosei

    2016-01-01

    Purpose To describe the postoperative progressive course of advanced-stage adenocarcinoma arising from a mature cystic teratoma (MCT) and review the literature regarding this disease. Methods A 59-year-old woman visited our hospital with an abdominal mass. Laparotomy showed enlargement of the left ovary and dissemination throughout the abdominal and pelvic cavities. The diagnosis was FIGO stage IIIB adenocarcinoma arising from a MCT. We report this case in detail with a review of the literature. Results A literature search yielded 9 cases of stage III adenocarcinoma with malignant transformation. Six of these 9 patients died within 12 months after diagnosis. Of the 8 patients who underwent postoperative chemotherapy, 3 survived for over 39 months. The review indicates that prognosis of adenocarcinoma is as poor as that for squamous cell carcinoma arising from a MCT. Conclusions In general, as with this case, prognosis of advanced adenocarcinoma associated with a MCT is poor. However, we should be aware that not all patients are resistant to chemotherapy. PMID:27462234

  10. c-Met targeting in advanced gastric cancer: An open challenge.

    PubMed

    Marano, Luigi; Chiari, Rita; Fabozzi, Alessio; De Vita, Ferdinando; Boccardi, Virginia; Roviello, Giandomenico; Petrioli, Roberto; Marrelli, Daniele; Roviello, Franco; Patriti, Alberto

    2015-08-28

    Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC) remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. High-quality research and advances in technology have contributed to the elucidation of molecular pathways underlying disease progression and have stimulated many clinical studies testing target therapies in an advanced disease setting. In particular, strong preclinical evidence for the aberrant activation of the HGF/c-Met signaling pathways in GC cancers exists. This review will cover the c-Met pathway, the mechanisms of c-Met activation and the different strategies of its inhibition. Next, we will focus on the current state of the art in the clinical evaluation of c-Met-targeted therapies and the description of ongoing randomized trials with the idea that in this disease, high quality translational research to identify and validate biomarkers is a priority task. PMID:26049023

  11. Total versus subtotal gastrectomy for adenocarcinoma of the gastric antrum. A French prospective controlled study.

    PubMed Central

    Gouzi, J L; Huguier, M; Fagniez, P L; Launois, B; Flamant, Y; Lacaine, F; Paquet, J C; Hay, J M

    1989-01-01

    In a multicentric trial the postoperative mortality and the 5-year survival of elective total gastrectomy (TG) was compared with subtotal gastrectomy (SG) for adenocarcinoma of the antrum operated on with intent of cure. Two hundred and one patients were included in the study; 32 were excluded after pathologic examination (linitis plastica, superficial cancer, lymphoma). One hundred sixty-nine patients remained for analysis, with 93 undergoing TG and 76 undergoing SG. Elective TG did not increase postoperative mortality (1.3%) compared with SG (3.2%). There was no difference in the 5-year survival rate (48%). Analysis of survival showed no difference in the two techniques when related to nodal involvement and serosal extension. It is concluded that both TG and SG can be performed safely in patients with adenocarcinoma of the antrum; however TG did not increase the survival rate. PMID:2644898

  12. Postoperative Chemoradiotherapy Combined with Epirubicin-Based Triplet Chemotherapy for Locally Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction

    PubMed Central

    Li, Guichao; Zhang, Zhen; Ma, Xuejun; Zhu, Ji; Cai, Gang

    2013-01-01

    Background Due to low tolerance to chemotherapy, the maximum number of cycles of postoperative adjuvant chemotherapy is 4 in adjuvant gastric clinical trials. The aim of this study is to retrospectively evaluate the safety and efficacy of adjuvant epirubicin-based triplet chemotherapy and radiotherapy in the treatment of resected locally advanced stomach or gastroesophageal junction adenocarcinoma. Methodology/Principal Findings From January 2004 to July 2008, ninety-seven consecutive gastric or gastroesophageal junction adenocarcinoma patients in stages T3–4/N+ were treated with postoperative radiotherapy and chemotherapy. The recommended treatment plan was radical resection followed by 1–2 cycles of adjuvant chemotherapy (ACT), postoperative chemoradiotherapy (CRT), and, finally, 4–5 cycles of ACT. The patients were classified into two groups depending on the number of cycles of ACT: group 1 received 4–6 cycles (n = 59), and group 2 received 0–3 cycles (n = 38). The detailed grouping is as follows: RT alone, 2; RT and CT, 18; concurrent RTCT and CT, 41; and CRT, 36. Of the 97 patients, 77 patients received concurrent therapy (CRT, (5-fluorouracil or capecitabine), and 20 received radiotherapy alone because of patient refusal (n = 15) or treatment toxicity (n = 5). After a median follow-up of 44 months, the 3-year disease free survival(DFS) and overall survival (OS) were 66.5% and 69.5% for group 1 and 45.5% and 50% for group 2, respectively (p = 0.005 and p = 0.024). Multivariate analysis revealed that 4–6 cycles of ACT, lymphovascular invasion, or peritoneal metastasis were independent prognostic factors for disease-free survival or overall survival (p<0.05). Conclusions/Significance This study demonstrates that concurrent chemoradiation with adjuvant epirubicin-based triplet chemotherapy is feasible and tolerable for gastric or gastroesophageal junction carcinoma patients. Patients can benefit from more cycles of ACT. PMID

  13. Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data

    PubMed Central

    Janowitz, Tobias; Thuss-Patience, Peter; Marshall, Andrea; Kang, Jung Hun; Connell, Claire; Cook, Natalie; Dunn, Janet; Park, Se Hoon; Ford, Hugo

    2016-01-01

    Background: Second-line chemotherapy treatment of patients with relapsed gastric and oesophageal cancers in comparison with supportive care (SC) alone has been supported by recent phase 3 clinical trials, but a meta-analysis of patient-level data is lacking. Methods: We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science for phase 3 clinical trials that compared second-line chemotherapy with SC alone for gastric and oesophageal cancers. A meta-analysis of the comprehensive patient-level data from the three identified trials was performed. Results: A total of 410 patients with gastric (n=301), gastroesophageal junction (n=76), or oesophageal (n=33) adenocarcinoma were identified. In all, 154 patients received single-agent docetaxel and 84 patients received single-agent irinotecan, each with SC. SC alone was given to 172 patients. Chemotherapy significantly reduced the risk of death (hazard ratio (HR)=0.63, 95% confidence interval (CI)=0.51–0.77, P<0.0001). This effect was observed for treatment with docetaxel (HR=0.71, 95% CI=0.56–0.89, P=0.003) and irinotecan (HR=0.49, 95% CI=0.36–0.67, P<0.001). Overall survival (OS) benefit was greatest for patients who progressed 3–6 months following first-line chemotherapy (HR=0.39, 95% CI=0.26–0.59, P<0.0001). Performance status (PS) 0–1 compared with PS 2 (HR=0.66, 95% CI=0.46–0.94, P=0.02), locally advanced disease compared with metastatic disease (HR=0.41, 95% CI=0.25–0.67, P=0.0004) and older age (HR=0.94 per 5 years, 95% CI=0.90–0.99, P=0.01) were significant predictors of improved OS. Progression of disease during first-line treatment (HR=1.24, 95% CI=0.96–1.59) or within the first 3 months of completion of first-line treatment (HR=1.42, 95% CI=1.09–1.83) were predictors of an increased risk of death compared with progression between 3 and 6 months (P=0.03). Health-related quality of life outcomes were reported in only one of the three trials

  14. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma

    PubMed Central

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-01-01

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

  15. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma.

    PubMed

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-08-21

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

  16. Advances in the management of Barrett’s esophagus and early esophageal adenocarcinoma

    PubMed Central

    Singh, Ajaypal; Chak, Amitabh

    2015-01-01

    The incidence of esophageal adenocarcinoma (EAC) has markedly increased in the United States over the last few decades. Barrett’s esophagus (BE) is the most significant known risk factor for this malignancy. Theoretically, screening and treating early BE should help prevent EAC but the exact incidence of BE and its progression to EAC is not entirely known and cost-effectiveness studies for Barrett’s screening are lacking. Over the last few years, there have been major advances in our understanding of the epidemiology, pathogenesis and endoscopic management of BE. These developments focus on early recognition of advanced histology and endoscopic treatment of high-grade dysplasia. Advanced resection techniques now enable us to endoscopically treat early esophageal cancer. In this review, we will discuss these recent advances in diagnosis and treatment of Barrett’s esophagus and early esophageal adenocarcinoma. PMID:26486568

  17. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

    PubMed

    Li, Jun; Woods, Susan L; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing; Lee, Jason S; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A; Kaurah, Pardeep; Mackenzie, Robertson; Heravi-Moussavi, Alireza; Hansford, Samantha; Lannagan, Tamsin R M; Spurdle, Amanda B; Simpson, Peter T; da Silva, Leonard; Lakhani, Sunil R; Clouston, Andrew D; Bettington, Mark; Grimpen, Florian; Busuttil, Rita A; Di Costanzo, Natasha; Boussioutas, Alex; Jeanjean, Marie; Chong, George; Fabre, Aurélie; Olschwang, Sylviane; Faulkner, Geoffrey J; Bellos, Evangelos; Coin, Lachlan; Rioux, Kevin; Bathe, Oliver F; Wen, Xiaogang; Martin, Hilary C; Neklason, Deborah W; Davis, Sean R; Walker, Robert L; Calzone, Kathleen A; Avital, Itzhak; Heller, Theo; Koh, Christopher; Pineda, Marbin; Rudloff, Udo; Quezado, Martha; Pichurin, Pavel N; Hulick, Peter J; Weissman, Scott M; Newlin, Anna; Rubinstein, Wendy S; Sampson, Jone E; Hamman, Kelly; Goldgar, David; Poplawski, Nicola; Phillips, Kerry; Schofield, Lyn; Armstrong, Jacqueline; Kiraly-Borri, Cathy; Suthers, Graeme K; Huntsman, David G; Foulkes, William D; Carneiro, Fatima; Lindor, Noralane M; Edwards, Stacey L; French, Juliet D; Waddell, Nicola; Meltzer, Paul S; Worthley, Daniel L; Schrader, Kasmintan A; Chenevix-Trench, Georgia

    2016-05-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present. PMID:27087319

  18. Gastric signet-ring cell adenocarcinoma presenting with left arm deep-vein thrombosis and bilateral chylothorax.

    PubMed

    Kayacan, Oya; Karnak, Demet; Ayşe Can, Berna; Dizbay Sak, Serpil; Beder, Sumru

    2008-10-01

    A 28-year-old housewife, a life-long nonsmoker, presented with 3 weeks of pleuritic chest pain along with swollen right leg, left arm, and left breast. Six months previously she had left subclavian vein thrombosis. On admission, bilateral supraclavicular lymphedema on right leg and left arm and breast was observed and bilateral pleural fluid, chylous exudates, was detected. Abdomen computed tomography revealed abundant ascites and right ovarian enlargement. Whole body bone scintigraphy showed bone metastases on left humerus, right femur, and pelvis. Bronchial biopsy, obtained from edematous, hyperemic-irregular mucosa, revealed a carcinoma composed of signet-ring cells with intracytoplasmic mucin. Breast biopsy also showed signet-ring cells within the lymphatics. Pleural fluid cytology showed similar malignant cells. The patient was diagnosed as gastric signet-ring cell adenocarcinoma with endobronchial, mammary, ovarian, pleural, pericardial, peritoneal, and osteal metastases. The authors recommend that deep-vein thrombosis in unusual sites deserves further evaluation for an occult malignancy. PMID:18263634

  19. Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells

    PubMed Central

    Hahm, Sahng-Wook; Park, Jieun; Park, Kun-Young; Son, Yong-Suk; Han, Hyungchul

    2016-01-01

    Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF (100 μg/mL) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF (200 μg/mL) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells. PMID:27069903

  20. A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

    ClinicalTrials.gov

    2015-06-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  1. Prognostic role of telomerase activity in gastric adenocarcinoma: A meta-analysis

    PubMed Central

    LÜ, MU-HAN; DENG, JIA-QI; CAO, YA-LING; FANG, DIAN-CHUN; ZHANG, YAO; YANG, SHI-MING

    2012-01-01

    Activation of telomerase is involved in carcinogenesis in most types of cancers. However, the prognostic value of telomerase activity (TA) in patients with gastric carcinoma (GC) remains controversial. We conducted a meta-analysis to assess the relationship between TA and the clinical outcome of GC. A meta-analysis of 18 studies (886 patients) was performed to evaluate the association between TA and metastasis-related parameters in GC patients by searching databases, including PubMed, MEDLINE, EMBASE, Web of Science databases, Cochrane Library and the Chinese Biomedical Literature database (CBM) (last search updated in October 2011). We used the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between TA and metastasis of GC. Our analysis results indicated that high telomerase activity expression tended to be associated with the presence of lymph node metastasis (866 patients) (OR=2.03, 95% CI 1.21–3.39, p=0.007), the depth of invasion (886 patients) (OR=1.87, 95% CI 1.30–2.70, p=0.0007), distant metastasis (407 patients) (OR=2.71, 95% CI 1.59–4.63, p=0.0002), tumor size (466 patients) (OR=2.14, 95% CI 1.31–3.50, p=0.002) and TNM stage (711 patients) (OR=2.39, 95% CI 1.30–4.41, p=0.005). However, high TA expression was not associated with the presence of histologic differentiation (791 patients) (OR=1.51, 95% CI 0.73–3.11, p=0.26). In conclusion, telomerase overexpression not only plays a key role in primary initiation, but also promotes invasion and metastatic progression of GC. These findings raise the possibility of using TA to screen for the prognosis of gastric cancer. PMID:22969960

  2. Update on phase I studies in advanced pancreatic adenocarcinoma. Hunting in darkness?

    PubMed

    Strimpakos, Alexios S; Saif, Muhammad Wasif

    2013-07-01

    Over the last twenty years, there is a limited number of effective cytotoxic or biological agents that managed to get approval in advanced pancreatic ductal adenocarcinoma. Despite numerous trials, investments in translational research and generally in health care, the survival of pancreatic cancer patients has improved by a few only months. This disappointing reality necessitates a better understanding of the pathogenesis of this disease and the identification of targetable alterations which might lead to development of more effective drugs or better combinations. At the 2013 Annual Meeting of the American Society of Clinical Oncology, few novel agents and new therapeutic concepts, tested in phase I studies in advanced pancreatic ductal adenocarcinoma, were presented. The first notable phase I study referred to the combination of chemotherapy with local delivery of silencing RNA against the K-ras mutation G12D, in advanced pancreatic ductal adenocarcinoma, which was well tolerated and promising (Abstract #4037). The second one referred to a combination of gemcitabine with pegylated recombinant human hyaluronidase (PEGPH20), an inhibitor of hyaluronan which as a matrix glycosaminoglycan is believed to play role in the reduced drug delivery to cancer (Abstract #4010). The other notable abstract was related to an early phase study which tested the safety and toxicity of arctigenin, a traditional herbal agent found in Arctium lappa Linné, administered as an oral formulation (GMS-01) in pancreatic ductal adenocarcinoma patient resistant to standard chemotherapy (Abstract #2559). The aforementioned early phase studies open new therapeutic approaches which deserve further testing in advanced pancreatic cancer. PMID:23846926

  3. Synthesis of CdTe quantum dot-conjugated CC49 and their application for in vitro imaging of gastric adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, Yun-Peng; Sun, Peng; Zhang, Xu-Rui; Yang, Wu-Li; Si, Cheng-Shuai

    2013-06-01

    The purpose of this experiment was to investigate the visible imaging of gastric adenocarcinoma cells in vitro by targeting tumor-associated glycoprotein 72 (TAG-72) with near-infrared quantum dots (QDs). QDs with an emission wavelength of about 550 to 780 nm were conjugated to CC49 monoclonal antibodies against TAG-72, resulting in a probe named as CC49-QDs. A gastric adenocarcinoma cell line (MGC80-3) expressing high levels of TAG-72 was cultured for fluorescence imaging, and a gastric epithelial cell line (GES-1) was used for the negative control group. Transmission electron microscopy indicated that the average diameter of CC49-QDs was 0.2 nm higher compared with that of the primary QDs. Also, fluorescence spectrum analysis indicated that the CC49-QDs did not have different optical properties compared to the primary QDs. Immunohistochemical examination and in vitro fluorescence imaging of the tumors showed that the CC49-QDs probe could bind TAG-72 expressed on MGC80-3 cells.

  4. [A Case of Advanced Gastric Cancer with Peritoneal Dissemination Effectively Treated with S-1 and Docetaxel Combination Chemotherapy].

    PubMed

    Saito, Hiroyuki; Suematsu, Yuki; Hiratsuka, Miyuki; Suda, Hiroshi; Takahashi, Miyuki; Omori, Keita; Ishibashi, Yuji; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

    2015-11-01

    A 72-year-old man underwent surgery for advanced gastric cancer. Systemic chemotherapy was started, using a regimen of S-1/CDDP for 4 courses, followed by 8 courses of S-1. Three years and 8 months after the surgery, abdominal CT demonstrated ascites, and the serum CA19-9 level was abnormally high (1,165.1 U/mL). Adenocarcinoma cells were found in the ascites. Treatment with S-1/docetaxel (DOC) was started. After 10 courses, the ascites disappeared and the serum CA19-9 value returned to normal. Four years and 7 months after the operation, the patient has been in good health, with no signs of recurrence. PMID:26805261

  5. UFT plus leucovorin in advanced hepatobiliary tumors and pancreatic adenocarcinomas.

    PubMed

    Mani, S

    1997-09-01

    UFT (tegafur and uracil) has been studied extensively in Japan, with documented efficacy in hepatobiliary and pancreatic cancer. In the United States, UFT with or without leucovorin has not undergone phase II testing in these malignancies. Our current trial is designed primarily to assess the efficacy in terms of response rates to UFT with leucovorin in patients with advanced hepatobiliary and pancreatic cancer. Secondary objectives include determining response duration, time to disease progression, overall survival, quality of life, and toxicity. PMID:9348584

  6. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-02-16

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  7. Neoadjuvant chemotherapy for high-grade advanced gastric cancer.

    PubMed

    Yonemura, Y; Sawa, T; Kinoshita, K; Matsuki, N; Fushida, S; Tanaka, S; Ohoyama, S; Takashima, T; Kimura, H; Kamata, T

    1993-01-01

    Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered. PMID:8511923

  8. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  9. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas

    PubMed Central

    Lin, Suling J; Gagnon-Bartsch, Johann A; Tan, Iain Beehuat; Earle, Sophie; Ruff, Louise; Pettinger, Katherine; Ylstra, Bauke; van Grieken, Nicole; Rha, Sun Young; Chung, Hyun Cheol; Lee, Ju-Seog; Cheong, Jae Ho; Noh, Sung Hoon; Aoyama, Toru; Miyagi, Yohei; Tsuburaya, Akira; Yoshikawa, Takaki; Ajani, Jaffer A; Boussioutas, Alex; Yeoh, Khay Guan; Yong, Wei Peng; So, Jimmy; Lee, Jeeyun; Kang, Won Ki; Kim, Sung; Kameda, Yoichi; Arai, Tomio; zur Hausen, Axel; Speed, Terence P; Grabsch, Heike I; Tan, Patrick

    2015-01-01

    Objective Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. Design We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665). Results Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes. Conclusions Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology. PMID:25385008

  10. An Unusual Recurrence of Signet Ring Cell Gastric Adenocarcinoma Treated by Right Hemicolectomy, Pancreaticoduodenectomy, and IVC Resection: Controversies and Dilemmas of Following Standard Treatment Pathways.

    PubMed

    Sodergren, Mikael; Brammer, Kirsty; Zentler-Munro, Patrick L; Cunningham, David; Mudan, Satvinder

    2015-01-01

    We present the case of a 67-year-old male patient with a past history of previously resected T3 right adrenocortical carcinoma and T3N1 signet ring cell adenocarcinoma of the stomach who presented with recurrence of gastric cancer in the form of a large solitary mass in the right abdomen. He was treated with ECX (epirubicin, cisplatin and capecitabine) chemotherapy and multivisceral resection. This recurrence pattern is the first such description in the literature, and we discuss the controversies and arguments in favour of offering surgical resection. PMID:26848413

  11. Molecular classification and prediction in gastric cancer

    PubMed Central

    Lin, Xiandong; Zhao, Yongzhong; Song, Won-min; Zhang, Bin

    2015-01-01

    Gastric cancer, a highly heterogeneous disease, is the second leading cause of cancer death and the fourth most common cancer globally, with East Asia accounting for more than half of cases annually. Alongside TNM staging, gastric cancer clinic has two well-recognized classification systems, the Lauren classification that subdivides gastric adenocarcinoma into intestinal and diffuse types and the alternative World Health Organization system that divides gastric cancer into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas. Both classification systems enable a better understanding of the histogenesis and the biology of gastric cancer yet have a limited clinical utility in guiding patient therapy due to the molecular heterogeneity of gastric cancer. Unprecedented whole-genome-scale data have been catalyzing and advancing the molecular subtyping approach. Here we cataloged and compared those published gene expression profiling signatures in gastric cancer. We summarized recent integrated genomic characterization of gastric cancer based on additional data of somatic mutation, chromosomal instability, EBV virus infection, and DNA methylation. We identified the consensus patterns across these signatures and identified the underlying molecular pathways and biological functions. The identification of molecular subtyping of gastric adenocarcinoma and the development of integrated genomics approaches for clinical applications such as prediction of clinical intervening emerge as an essential phase toward personalized medicine in treating gastric cancer. PMID:26380657

  12. Gastric cáncer: Overview.

    PubMed

    Piazuelo, M Blanca; Correa, Pelayo

    2013-07-01

    Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer. PMID:24892619

  13. Helicobacter pylori in gastric carcinogenesis

    PubMed Central

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-01-01

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  14. Helicobacter pylori in gastric carcinogenesis.

    PubMed

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-12-15

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  15. Fever as a first manifestation of advanced gastric adenosquamous carcinoma: A case report

    PubMed Central

    Ajoodhea, Harsha; Zhang, Ren-Chao; Xu, Xiao-Wu; Jin, Wei-Wei; Chen, Ke; He, Yong-Tao; Mou, Yi-Ping

    2014-01-01

    Gastric adenosquamous carcinoma (ASC) is a rare type of gastric cancer. It is a mixed neoplasm, consisting of glandular cells and squamous cells. It is often diagnosed at an advanced stage, thus carrying a poor prognosis. We describe a case of a 73-year-old male, who presented with refractory fever and an intra-abdominal mass on imaging. He underwent a laparoscopic exploration followed by a successful totally laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer. Postoperative pathology revealed primary gastric ASC (T4aN0M0). The patient received adjuvant radiotherapy and chemotherapy with S1 and is alive 20 mo after surgery without recurrence. This is the first case of advanced gastric ASC with fever as the initial presentation treated with totally laparoscopic total gastrectomy reported in the English literature. PMID:25110448

  16. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  17. Prognostic value of serum leptin in advanced lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy

    PubMed Central

    MOU, WENJUN; XUE, HUI; TONG, HONGLI; SUN, SHENGJIE; ZHANG, ZHUHONG; ZHANG, CHUNYAN; SUN, QIYU; DONG, JING; WEN, XINYU; YAN, GUANGTAO; TIAN, YAPING

    2014-01-01

    Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in lung adenocarcinoma. However, the response to the cisplatin/pemetrexed combination varies considerably among patients due to individual variations. Thus, novel biomarkers are required to aid the prediction of the response to the cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a determinant for prognosis in lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung adenocarcinoma were obtained for the measurement of leptin and associated tumor biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4, cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression were determined by electrochemiluminescence immunoassays. Serum squamous cell carcinoma antigen levels were measured using a microparticle enzyme immunoassay. The associations between serum leptin and tumor biomarker expression were evaluated by Spearman’s correlation analysis. Serum CEA, CA19-9, CA15-3, CA125, CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients. However, a trend towards an improved prognosis was observed in patients with lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed chemotherapy. The results indicated that the serum leptin level has prognostic indications in patients with advanced lung adenocarcinoma during cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker for the prognosis of cancer patients undergoing chemotherapy treatment. PMID:24932291

  18. Prognostic value of serum leptin in advanced lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy.

    PubMed

    Mou, Wenjun; Xue, Hui; Tong, Hongli; Sun, Shengjie; Zhang, Zhuhong; Zhang, Chunyan; Sun, Qiyu; Dong, Jing; Wen, Xinyu; Yan, Guangtao; Tian, Yaping

    2014-06-01

    Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in lung adenocarcinoma. However, the response to the cisplatin/pemetrexed combination varies considerably among patients due to individual variations. Thus, novel biomarkers are required to aid the prediction of the response to the cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a determinant for prognosis in lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung adenocarcinoma were obtained for the measurement of leptin and associated tumor biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4, cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression were determined by electrochemiluminescence immunoassays. Serum squamous cell carcinoma antigen levels were measured using a microparticle enzyme immunoassay. The associations between serum leptin and tumor biomarker expression were evaluated by Spearman's correlation analysis. Serum CEA, CA19-9, CA15-3, CA125, CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients. However, a trend towards an improved prognosis was observed in patients with lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed chemotherapy. The results indicated that the serum leptin level has prognostic indications in patients with advanced lung adenocarcinoma during cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker for the prognosis of cancer patients undergoing chemotherapy treatment. PMID:24932291

  19. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; de Mello, Ramon Andrade

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs. PMID:26838766

  20. miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells

    SciTech Connect

    Zhang, Mingjun; Wang, Xiaolei; Li, Wanhu; Cui, Yongchun

    2015-05-08

    Although a series of oncogenes and tumor suppressors were identified in the pathological development of gastric adenocarcinoma (GAC), the underlying molecule mechanism were still not fully understood. The current study explored the expression profile of miR-107 and miR-25 in GAC patients and their downstream regulative network. qRT-PCR analysis was performed to quantify the expression of these two miRNAs in serum samples from both patients and healthy controls. Dual luciferase assay was conducted to verify their putative bindings with LATS2. MTT assay, cell cycle assay and transwell assay were performed to explore how miR-107 and miR-25 regulate proliferation and invasion of gastric cancer cells. Findings of this study demonstrated that total miR-107 or miR-25 expression might be overexpressed in gastric cancer patients and they can simultaneously and synchronically regulate LATS2 expression, thereby affecting gastric cancer cell growth and invasion. Therefore, the miR-25/miR-107-LATS2 axis might play an important role in proliferation and invasion of the gastric cancer cells. - Highlights: • Total miR-107 and miR-25 expression is significantly increased in GAC patients. • Both miR-107 and miR-25 can promote proliferation and invasion of GAC cells. • Both miR-107 and miR-25 can target LATS2 and regulate its expression. • miR-107 and miR-25 regulate proliferation and invasion of GAC cells though LATS2.

  1. Advanced gastric cancer: What we know and what we still have to learn

    PubMed Central

    Coccolini, Federico; Montori, Giulia; Ceresoli, Marco; Cima, Simona; Valli, Maria Carla; Nita, Gabriela E; Heyer, Arianna; Catena, Fausto; Ansaloni, Luca

    2016-01-01

    Gastric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amongst geographic areas. The definition of advanced gastric cancer is still debated. Different stadiating systems lead to slightly different stadiation of the disease, thus leading to variations between the single countries in the treatment and outcomes. In the present review all the possibilities of treatment for advanced gastric cancer have been analyzed. Surgery, the cornerstone of treatment for advanced gastric cancer, is analyzed first, followed by an investigation of the different forms and drugs of chemotherapy and radiotherapy. New frontiers in treatment suggest the growing consideration for intraperitoneal administration of chemotherapeutics and combination of traditional drugs with new ones. Moreover, the necessity to prevent the relapse of the disease leads to the consideration of administering intraperitoneal chemotherapy earlier in the therapeutical algorithm. PMID:26811653

  2. Treatment of Gastric Adenocarcinoma May Differ Among Hospital Types in the United States, a Report from the National Cancer Data Base

    PubMed Central

    Gay, Greer; Patel-Parekh, Lina; Ajani, Jaffer A.; Donohue, John H.

    2007-01-01

    The concept that complex surgical procedures should be performed at high-volume centers to improve surgical morbidity and mortality is becoming widely accepted. We wanted to determine if there were differences in the treatment of patients with gastric cancer between community cancer centers and teaching hospitals in the United States. Data from the 2001 Gastric Cancer Patient Care Evaluation Study of the National Cancer Data Base comprising 6,047 patients with gastric adenocarcinoma treated at 691 hospitals were assessed. The mean number of patients treated was larger at teaching hospitals (14/year) when compared to community centers (5–9/year) (p < 0.05). The utilization of laparoscopy and endoscopic ultrasonography were significantly more common at teaching centers (p < 0.01). Pathologic assessment of greater than 15 nodes was documented in 31% of specimen at community hospitals and 38% at teaching hospitals (p < 0.01). Adjusted for cancer stage, chemotherapy and radiation therapy were utilized with equal frequency at all types of treatment centers. The 30-day postoperative mortality was lowest at teaching hospitals (5.5%) and highest at community hospitals (9.9%) (p < 0.01). These data support previous publications demonstrating that patients with diseases requiring specialized treatment have lower operative mortality when treated at high-volume centers. PMID:17436123

  3. Pulmonary adenocarcinoma: implications of the recent advances in molecular biology, treatment and the IASLC/ATS/ERS classification

    PubMed Central

    Thakur, Priyanka; Bhardwaj, Bhaskar; Susheela, Sridhar Papaiah; Madabhavi, Irappa

    2014-01-01

    A decade ago, lung cancer could conveniently be classified into two broad categories—either the small cell lung carcinoma (SCLC), or the non-small cell lung carcinoma (NSCLC), mainly to assist in further treatment related decision making. However, the understanding regarding the eligibility of adenocarcinoma histology for treatments with agents such as pemetrexed and bevacizumab made it a necessity for NSCLC to be classified into more specific sub-groups. Then, the availability of molecular targeted therapy with oral tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib not only further emphasized the need for accurate sub-classification of lung cancer, but also heralded the important role of molecular profiling of lung adenocarcinomas. Given the remarkable advances in molecular biology, oncology and radiology, a need for felt for a revised classification for lung adenocarcinoma, since the existing World Health Organization (WHO) classification of lung cancer, published in the year 2004 was mainly a pathological system of classification. Thus, there was a combined effort by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS) and the European Respiratory Society (ERS) with an effort to inculcate newly established perspectives from clinical, molecular and radiological aspects in evolving a modern classification for lung adenocarcinomas. This review provides a summary of the recent advances in molecular biology and molecular targeted therapy with respect to lung adenocarcinoma. Also, a brief summation of the salient recommendations provided in the IASLC/ATS/ERS classification of lung adenocarcinomas is provided. Lastly, a discussion regarding the future prospects with lung adenocarcinoma is included. PMID:25349702

  4. DAG/PKCδ and IP3/Ca2+/CaMK IIβ Operate in Parallel to Each Other in PLCγ1-Driven Cell Proliferation and Migration of Human Gastric Adenocarcinoma Cells, through Akt/mTOR/S6 Pathway

    PubMed Central

    Dai, Lianzhi; Zhuang, Luhua; Zhang, Bingchang; Wang, Fen; Chen, Xiaolei; Xia, Chun; Zhang, Bing

    2015-01-01

    Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca2+/calmodulin-dependent protein kinase II (CaMK II) axes to regulate import events in some cancer cells, including gastric adenocarcinoma cells. However, whether DAG/PKCδ and IP3/Ca2+/CaMK IIβ axes are simultaneously involved in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells and the underlying mechanism are not elucidated. Here, we investigated the role of DAG/PKCδ or CaMK IIβ in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells, using the BGC-823 cell line. The results indicated that the inhibition of PKCδ and CaMK IIβ could block cell proliferation and migration of BGC-823 cells as well as the effect of inhibiting PLCγ1, including the decrease of cell viability, the increase of apoptotic index, the down-regulation of matrix metalloproteinase (MMP) 9 expression level, and the decrease of cell migration rate. Both DAG/PKCδ and CaMK IIβ triggered protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 pathway to regulate protein synthesis. The data indicate that DAG/PKCδ and IP3/Ca2+/CaMK IIβ operate in parallel to each other in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells through Akt/mTOR/S6 pathway, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance. PMID:26633375

  5. Role of Helicobacter pylori in gastric cancer: advances and controversies.

    PubMed

    Meng, Wenbo; Bai, Bing; Sheng, Liang; Li, Yan; Yue, Ping; Li, Xun; Qiao, Liang

    2015-11-01

    Gastric cancer is one of the most common cancers of digestive system globally and Helicobacter pylori (HP) infection is believed to be a major risk factor. HP can be classified into different types based on the presence and expression level of CagA and VacA, and, when exposed to adverse environment, HP changes its phenotype from helical type to coccoid type, with each having different pathogenicity. The mechanisms of HP-induced gastric carcinogenesis and progression are complicated, including DNA nitration and oxidation induced by mutagenic factors, HP-induced epigenetic modifications, HP-induced disruption of the balance between cell proliferation and apoptosis, and HP-induced cancer cell invasion and metastasis. HP may also affect the biological function of cancer stem cells and induction of cell autophagy. The lipopolysaccharide produced by HP can act through toll-like receptor-4 (TLR-4) to induce gastric mucosal inflammation and is thereby linked to the development of gastric cancer. PMID:26645900

  6. Endoscopic therapy for early gastric cancer: Standard techniques and recent advances in ESD

    PubMed Central

    Kume, Keiichiro

    2014-01-01

    The technique of endoscopic submucosal dissection (ESD) is now a well-known endoscopic therapy for early gastric cancer. ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precision of histologic diagnosis and can also reduce the recurrence rate. However, the drawback of ESD is its technical difficulty, and, consequently, it is associated with a high rate of complications, the need for advanced endoscopic techniques, and a lengthy procedure time. Various advances in the devices and techniques used for ESD have contributed to overcoming these drawbacks. PMID:24914364

  7. Genetically engineered Newcastle disease virus expressing human interferon-λ1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response.

    PubMed

    Bu, Xuefeng; Li, Mi; Zhao, Yinghai; Liu, Sha; Wang, Mubin; Ge, Jinying; Bu, Zhigao; Yan, Yulan

    2016-09-01

    Interferon-λ1 (IFN-λ1), a recently discovered cytokine of the type III IFN family, was found to be a therapeutic alternative to type I IFN in terms of tumors. Using reverse genetics technique, we generated a recombinant Newcastle disease virus (NDV) LaSota strains named as human IFN‑λ1 recombinant adenovirus (rL-hIFN-λ1) containing human IFN-λ1 gene and further evaluated the expressing of IFN-λ1 in human gastric adenocarcinoma cell line SGC-7901 after infected with rL-hIFN-λ1 by using western blot analysis, RT-PCR and immunofluorescence analyses. IFN-λl specific receptor IFNLR1 was detected on several gastric tumor cell lines including SGC-7901 and AGS and on PBMCs.The expression of the IFN-λ1 proteins reached a high level detected in the supernatant harvested 24 h after the infection of tumor cells. The proliferation changes of SGC infected with rL-hIFN-λ1 was significantly inhibited compared with NDV-infected group. Apoptosis was significantly induced by rL-hIFN-λ1 in gastric cancer cells compared with NDV virus tested by TUNEL assay, western blot analysis and Annexin V flow cytometry. Due to the high dose of IFN-λ1 expressed by the rL-hIFN-λ1-infected tumor cells, the immune study showed that rL-hIFN-λ1 increased IFN-γ production [the T helper cell subtype 1 (Th1) response] and inhibited interleukin (IL)-13 production [the T helper cell subtype 2 (Th2) response] to change the Th1/Th2 response of tumor microenvironment which inhibited tumor growth. This study aims at building recombinant NDV rL-hIFN-λ1 as an efficient antitumor agent. PMID:27430534

  8. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells

    SciTech Connect

    Yi, Ho-Keun; Kim, Sun-Young; Hwang, Pyoung-Han; Kim, Chan-Young; Yang, Doo-Hyun; Oh, Youngman; Lee, Dae-Yeol . E-mail: leedy@chonbuk.ac.kr

    2005-05-13

    PTEN is a tumor suppressor gene that is frequently mutated or deleted in a variety of human cancers including human gastric cancer. PTEN functions primarily as a lipid phosphatase and plays a key role in the regulation of the PI3 kinase/Akt pathway, thereby modulating cell proliferation and cell survival. On the other hand, the IGF system plays an important role in cell proliferation and cell survival via the PI3 kinase/Akt and MAP kinase pathways in many cancer cells. To characterize the impact of PTEN on the IGF-IGFR-IGFBP axis in gastric cancer, we overexpressed PTEN using an adenovirus gene transfer system in human gastric adenocarcinoma cells, SNU-484 and SNU-663, which lack PTEN. Overexpression of PTEN inhibited serum-induced as well as IGF-I-induced cell proliferation as compared to control cells. PTEN overexpression resulted in a significant decrease in the expression of IGF-I, -II, and IGF-IR. Interestingly, amongst the six IGFBPs, only IGFBP-3 was upregulated by PTEN, whereas IGFBP-4 and -6 were reduced. The IGFBP-3 promoter activity assay and Western immunoblotting demonstrate that PTEN regulates IGFBP-3 at the transcriptional level. In addition, the PI3 kinase inhibitor, LY294002, upregulates IGFBP-3 expression but downregulates IGF-I and IGF-II, indicating that PTEN controls IGFBP-3 and IGFs by an Akt-dependent pathway. These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the IGF-IGFR-induced Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF-dependent and IGF-independent mechanisms in cancer cells.

  9. Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns.

    PubMed

    Treece, Amanda L; Duncan, Daniel L; Tang, Weihua; Elmore, Sandra; Morgan, Douglas R; Dominguez, Ricardo L; Speck, Olga; Meyers, Michael O; Gulley, Margaret L

    2016-06-01

    MicroRNA expression in formalin-fixed paraffin-embedded tissue (FFPE) or plasma may add value for cancer management. The GastroGenus miR Panel was developed to measure 55 cancer-specific human microRNAs, Epstein-Barr virus (EBV)-encoded microRNAs, and controls. This Q-rtPCR panel was applied to 100 FFPEs enriched for adenocarcinoma or adjacent non-malignant mucosa, and to plasma of 31 patients. In FFPE, microRNAs upregulated in malignant versus adjacent benign gastric mucosa were hsa-miR-21, -155, -196a, -196b, -185, and -let-7i. Hsa-miR-18a, 34a, 187, -200a, -423-3p, -484, and -744 were downregulated. Plasma of cancer versus non-cancer controls had upregulated hsa-miR-23a, -103, and -221 and downregulated hsa-miR-378, -346, -486-5p, -200b, -196a, -141, and -484. EBV-infected versus uninfected cancers expressed multiple EBV-encoded microRNAs, and concomitant dysregulation of four human microRNAs suggests that viral infection may alter cellular biochemical pathways. Human microRNAs were dysregulated between malignant and benign gastric mucosa and between plasma of cancer patients and non-cancer controls. Strong association of EBV microRNA expression with known EBV status underscores the ability of microRNA technology to reflect disease biology. Expression of viral microRNAs in concert with unique human microRNAs provides novel insights into viral oncogenesis and reinforces the potential for microRNA profiles to aid in classifying gastric cancer subtypes. Pilot studies of plasma suggest the potential for a noninvasive addition to cancer diagnostics. PMID:26950485

  10. Gemcitabine-Based Regional Intra-Arterial Infusion Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Liu, Xiaoyu; Yang, Xuerong; Zhou, Guofeng; Chen, Yi; Li, Changyu; Wang, Xiaolin

    2016-01-01

    Abstract The present study was carried out to investigate the prognostic factors in patients who received intra-arterial infusion for advanced pancreatic cancer. In addition, the detailed procedure of intra-arterial infusion chemotherapy was described. A total of 354 patients with advanced unresectable pancreatic adenocarcinoma were recruited from January 2012, to April 2015, at Zhongshan Hospital Fudan University, Shanghai, China. Demographic and clinic characteristics of the patients were extracted from electronic medical records. Restricted cubic spline was used to assess the nonliner regression between baseline CA19-9 value and overall survival. Kaplan–Meier analysis and Cox proportional hazard models were used to estimate the association between overall survival and clinical characteristics. Of all 354 included patients, 230 (65%) were male (male/female ratio = 1.8), and 72 (20%) patients were diagnosed with detectable distant metastases. Pretreatment CA19-9 value of patients with metastases was significantly higher as compared to those with locally advanced cancer (median: 922.30 vs 357.00 U/mL, P = 0.0090). Totally 274 patients completed 1 cycle of intra-arterial infusion, whereas 80 patients received 2 or more cycles of the chemotherapy. For all the 354 patients, median OS was 7.0 months (95% CI: 6.0, 8.0 months) with a 6-, 12-, and 18-month survival rate of 0.48, 0.28, and 0.18, respectively. The median OS of patients, who received 1 cycle of intra-arterial infusion therapy, was 6.0 months (95% CI: 5.0, 8.0 months), which was similar to 7.0 months (95% CI: 6.0, 9.0 months) in patients who received 2 or more cycles. Restricted cubic spline revealed the nonline association between baseline CA19-9 and prognosis. The Cox proportional hazard model showed that age, CA19-9 baseline, CA19-9 value, and tumor location were significantly associated with the OS. In conclusion, the gemcitabine-based RIAC presented a potential treatment method for advanced

  11. High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death

    PubMed Central

    2014-01-01

    Background High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma. Material and methods Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett’s esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS). Results RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS). Conclusion High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence

  12. Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary.

    PubMed

    Mikhail, Sameh; Lustberg, Maryam B; Ruppert, Amy S; Mortazavi, Amir; Monk, Paul; Kleiber, Barbara; Villalona-Calero, Miguel; Bekaii-Saab, Tanios

    2015-11-01

    Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity. PMID:26416564

  13. Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2013-09-27

    Adenocarcinoma of the Gastroesophageal Junction; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  14. Effect of pravastatin on the survival of patients with advanced gastric cancer

    PubMed Central

    Bujanda, Luis; Rodríguez-González, Araceli; Sarasqueta, Cristina; Eizaguirre, Emma; Hijona, Elizabeth; Marín, José J.G.; Perugorria, María J.; Banales, Jesús M.; Cosme, Angel

    2016-01-01

    Objectives A fluoropyrimidine plus cisplatin combined with surgery is standard first-line treatment for advanced gastric cancer. We evaluated the effect of pravastatin on overall survival in patients with advanced gastric cancer in a prospective cohort study. Methods At the time of surgery, we assigned 60 patients with advanced gastric cancer (stage III or IV) to receive standard first-line treatment (control group) or standard first-line treatment plus pravastatin at a dose of 40 mg once daily (pravastatin group). The minimum follow-up period was 4 years and the maximum of 6 years. Results The mean of age was 66 years and the TNM stage was III and IV in 65% and 35% of patients, respectively. There was no significant difference between the two groups (control vs pravastatin) in median overall survival (15 vs 14 months; P = 0.8). Predictors of survival were the stage (hazard ratio of death stage IV (III stage as reference): 4.4; 95% CI: 2–9.7; p < 0.05) and older age (hazard ratio of death ≥ 65 years (< 65 years as reference): 2.8; 95% CI: 1.3–6; p < 0.05). Conclusions Pravastatin did not improve outcome in patients with advanced gastric cancer. PMID:26735890

  15. Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

    PubMed Central

    Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

    2014-01-01

    Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

  16. Not all gastric masses are gastric cancer.

    PubMed

    Del Rosario, Michael; Tsai, Henry

    2016-01-01

    Lung cancer metastasising to the gastrointestinal tract normally does not occur. However, as clinicians, we must be aware that lung adenocarcinoma, as in all cancers, can and will metastasise to any part of the body. We describe a case of a patient with a presumed primary gastric adenocarcinoma who presented with shortness of breath due to pleural effusion. Pathology from the pleural effusion was positive for primary lung adenocarcinoma. Further investigation revealed that the patient's gastric mass was misdiagnosed as gastric adenocarcinoma. We correctly diagnosed the mass as metastatic lung adenocarcinoma. This was very significant because the patient was transitioning to palliative care with possible tube feeding. After the correct diagnosis, her management drastically changed and her health improved. Clinical, pathological and medical management of lung cancer metastasis to the stomach are discussed. PMID:26976833

  17. Targeted therapy for advanced gastric cancer: A review of current status and future prospects

    PubMed Central

    Kanat, Ozkan; O’Neil, Bert; Shahda, Safi

    2015-01-01

    In the West in particular, the vast majority of gastric cancer (GC) patients present with advanced-stage disease. Although combination chemotherapy is still the most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted therapeutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC. PMID:26690491

  18. Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

    PubMed

    Lee, Hyun Sook; Hong, Ji Eun; Kim, Eun Ji; Kim, Sun Hyo

    2014-01-01

    Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer. PMID:24911042

  19. Tissue Inhibitor of Metalloproteinase-1 Is Confined to Tumor-Associated Myofibroblasts and Is Increased With Progression in Gastric Adenocarcinoma.

    PubMed

    Alpízar-Alpízar, Warner; Laerum, Ole Didrik; Christensen, Ib J; Ovrebo, Kjell; Skarstein, Arne; Høyer-Hansen, Gunilla; Ploug, Michael; Illemann, Martin

    2016-08-01

    The tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the extracellular matrix-degrading activity of several matrix metalloproteinases, thereby regulating cancer cell invasion and metastasis. Studies describing the expression pattern and cellular localization of TIMP-1 in gastric cancer are, however, highly discordant. We addressed these inconsistencies by performing immunohistochemistry and in situ hybridization analyses in a set of 49 gastric cancer lesions to reexamine the TIMP-1 localization. In addition, we correlated these findings to clinicopathological parameters. We show that strong expression of TIMP-1 protein and mRNA was observed in a subpopulation of stromal fibroblast-like cells at the periphery of the cancer lesions. In a few cases, a small fraction of cancer cells showed weak expression of TIMP-1 protein and mRNA. The stromal TIMP-1-expressing cells were mainly tumor-associated myofibroblasts. In the normal-appearing mucosa, scattered TIMP-1 protein was only found in chromogranin A positive cells. TIMP-1-positive myofibroblasts at the invasive front of the tumors were more frequently seen in intestinal than in diffuse histological subtype cases (p=0.009). A significant trend to a higher number of cases showing TIMP-1 staining in myofibroblasts with increasing tumor, node, metastasis (TNM) stage was also revealed (p=0.041). In conclusion, tumor-associated myofibroblasts are the main source of increased TIMP-1 expression in gastric cancer. PMID:27370797

  20. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer

    PubMed Central

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo

    2015-01-01

    Objective To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Methods According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. Results In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Conclusions Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies. PMID:26157320

  1. Recent advances in the molecular diagnostics of gastric cancer

    PubMed Central

    Kanda, Mitsuro; Kodera, Yasuhiro

    2015-01-01

    Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined. PMID:26379391

  2. Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma

    SciTech Connect

    Safran, Howard . E-mail: hsafran@lifespan.org; Di Petrillo, Thomas; Akerman, Paul; Ng, Thomas; Evans, Devon; Steinhoff, Margaret; Benton, David; Purviance, John; Goldstein, Lisa; Tantravahi, Umadevi; Kennedy, Teresa R.N.

    2007-02-01

    Purpose: To determine the overall survival for patients with locally advanced, HER2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a Phase I-II study. Methods and Materials: Patients with adenocarcinoma of the esophagus without distant organ metastases and 2+/3+ HER2 overexpression by immunohistochemistry (IHC) were eligible. All patients received cisplatin 25 mg/m{sup 2} and paclitaxel 50 mg/m{sup 2} weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg. Results: Nineteen patients were entered: 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. Fourteen of 19 patients (74%) had either 3+ HER2 expression by immunohistochemistry, or an increase in HER2 gene copy number by HER2 gene amplification or high polysomy by fluorescence in situ hybridization. The median survival of all patients was 24 months and the 2-year survival was 50%. Conclusions: Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing HER2 is limited by the small number of patients in this study. Overall survival, however, was similar to prior studies without an increase in toxicity. Evaluation of HER2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family.

  3. GNAS mutation as an alternative mechanism of activation of the Wnt/β-catenin signaling pathway in gastric adenocarcinoma of the fundic gland type.

    PubMed

    Nomura, Ryosuke; Saito, Tsuyoshi; Mitomi, Hiroyuki; Hidaka, Yasuhiro; Lee, Se-yong; Watanabe, Sumio; Yao, Takashi

    2014-12-01

    Gastric adenocarcinoma of the fundic gland type (GAFG) is a rare variant of gastric tumor. We have recently reported the frequent accumulation of β-catenin in GAFGs and showed that approximately half of the cases studied harbored at least 1 mutation in CTNNB1/AXINs/APC, leading to the constitutive activation of the Wnt/β-catenin pathway. However, the mechanisms of Wnt signaling activation in the remaining cases are unknown. Accumulating evidence showed that the activating mutation in GNAS promotes tumorigenesis via the activation of the Wnt/β-catenin pathway or the ERK1/2 MAPK pathway. Therefore, we analyzed the mutations in GNAS (exons 8 and 9) and in KRAS (exon 2) in 26 GAFGs. Immunohistochemistry revealed nuclear β-catenin expression in 22 of 26 GAFGs, and 10 (38.5%) of 26 cases harbored at least 1 mutation in CTNNB1/AXINs/APC. Activating mutations in GNAS were found in 5 (19.2%) of 26 GAFGs, all of which harbored R201C mutations. Activating mutations in KRAS were found in 2 (7.7%) of 26 GAFGs, and both of these also contained GNAS activating mutations. Four of 5 cases with GNAS mutation showed nuclear β-catenin expression, and presence of GNAS mutation was associated with β-catenin nuclear expression (P = .01). Furthermore, 3 of these 4 cases did not harbor mutations in CTNNB1, APC, or AXINs, suggesting that mutations in the Wnt component genes and those in GNAS occur almost exclusively. These results suggest that GNAS mutation might occur in a small subset of GAFG as an alternative mechanism of activating the Wnt/β-catenin signaling pathway. PMID:25288233

  4. Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

    PubMed Central

    Ratosa, Ivica; Oblak, Irena; Anderluh, Franc; Velenik, Vaneja; But-Hadzic, Jasna; Ermenc, Ajra Secerov; Jeromen, Ana

    2015-01-01

    Background. To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Patients and methods. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4–6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Results. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five

  5. Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

    ClinicalTrials.gov

    2016-07-20

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

  6. Erlotinib versus carboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504.

    PubMed

    Cadranel, Jacques; Gervais, Radj; Merle, Patrick; Moro-Sibilot, Denis; Westeel, Virginie; Bigay-Game, Laurence; Quoix, Elisabeth; Friard, Sylvie; Barlesi, Fabrice; Lethrosne, Claire; Moreau, Lionel; Monnet, Isabelle; Salaun, Mathieu; Oliviero, Gérard; Souquet, Pierre-Jean; Antoine, Martine; Langlais, Alexandra; Morin, Franck; Wislez, Marie; Zalcman, Gérard

    2015-11-01

    The IFCT-0504 phase II trial evaluated the efficacy of erlotinib versus carboplatin-paclitaxel (CP) as first-line treatment in 130 cases of advanced lepidic-predominant adenocarcinoma (ADC).The primary objective of the study was treatment efficacy, evaluated based on an end-point of disease control at 16 weeks.The primary objective was met, with a disease control in 35 (53%) out of 66 patients treated with CP and in 25 (39.1%) out of 64 patients treated with erlotinib. Median progression-free survival (PFS) for the total population was 3.6 months. The disease control rate did not differ between either the therapeutic arms or pathological subtypes, whereas there was a strong interaction between treatment arms and tumour pathological subtypes for PFS (p=0.009). Mucinous tumour patients treated with erlotinib exhibited an increased progression risk (hazard ratio 3.4, 95% CI 1.7-6.5; p≤0.001). The PFS for nonmucinous tumour patients was similar in both arms. Median overall survival was 20.1 months and did not differ between therapeutic arms. These findings were not further elucidated by molecular analyses and the toxicity profiles were as expected.Our study demonstrated the dominant role of CP alongside erlotinib in the management of advanced lepidic ADC. Based on these findings, erlotinib should not be administered in first-line therapy to patients with lepidic ADC in the absence of an epidermal growth factor receptor mutation. PMID:26381515

  7. Regulation of Desmocollin3 Expression by Promoter Hypermethylation is Associated with Advanced Esophageal Adenocarcinomas

    PubMed Central

    Wang, Qinggang; Peng, DunFa; Zhu, Shoumin; Chen, Zheng; Hu, TianLing; Soutto, Mohammed; Saad, Rama; Zhang, Shutian; EI-Rifai, Wael

    2014-01-01

    BACKGROUND: Desmocollin3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and plays an important role in tumor invasion and metastasis. In this study, we investigated the epigenetic mechanism that regulates DSC3 expression in esophageal adenocarcinomas (EACs). METHODS: Expression of DSC3 was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The promoter DNA methylation level of DSC3 was examined using quantitative bisulfite pyrosequencing. RESULTS: The qRT-PCR analysis demonstrated significant down-regulation of the DSC3 mRNA levels in human EAC cell lines and tissue samples (P<.001). In addition, the EAC cell lines and tumor samples have aberrant promoter hypermethylation as compared to normal esophageal samples (P<.001). DSC3 promoter hypermethylation (>10% methylation level) was detected in 97.5% (39/40) of EAC samples whereas none of the normal tissue samples showed hypermethylation (P<.0001). There was a significant inverse correlation between promoter DNA methylation levels and mRNA expression folds for DSC3 (coefficient r=-0.685, P<.0001). Treatment of FLO-1 and SKGT4 EAC cells with 5-Aza-deoxytidine led to a significant reduction in the promoter DNA methylation levels with restoration of the DSC3 expression, suggesting that promoter DNA methylation is a key epigenetic mechanism regulating DSC3 expression. High DSC3 promoter DNA methylation levels were significantly correlated with advanced tumor stage (P<.001) and lymph node metastasis (P<.001). CONCLUSION: Taken together, our results demonstrate that epigenetic silencing of DSC3 is a frequent finding in EAC that is possibly associated with advanced stages. PMID:24847386

  8. Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells.

    PubMed

    Fuentes, Rolly G; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2015-04-24

    Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL. PMID:25793965

  9. Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population

    PubMed Central

    Zhang, Sheng; Tang, Weifeng; Ding, Guowen; Liu, Chao; Liu, Ruiping; Chen, Suocheng; Gu, Haiyong

    2015-01-01

    Objective To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nucleotide polymorphisms (SNPs), including TP53BP1 rs560191 G>C, CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A, and six C1orf10/CRNN variants. We performed a hospital-based case-control study to evaluate the genetic effects of these SNPs. Methods Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex SNPscanTM Kit was used to determine their genotypes. Results When the TP53BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A or the six C1orf10/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. Conclusions The results demonstrated that the functional polymorphism TP53BP1 rs560191 G>C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well-designed studies and further functional investigations are needed to confirm our findings. PMID:25937777

  10. Trousseau’s syndrome in a patient with advanced stage gastric cancer

    PubMed Central

    Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

    2015-01-01

    Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau’s syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered. PMID:26379411

  11. Inhibition of neutrophil elastase and metalloprotease-9 of human adenocarcinoma gastric cells by chamomile (Matricaria recutita L.) infusion.

    PubMed

    Bulgari, Michela; Sangiovanni, Enrico; Colombo, Elisa; Maschi, Omar; Caruso, Donatella; Bosisio, Enrica; Dell'Agli, Mario

    2012-12-01

    This study investigated whether the antiinflammatory effect of chamomile infusion at gastric level could be ascribed to the inhibition of metalloproteinase-9 and elastase. The infusions from capitula and sifted flowers (250-1500 µg/mL) and individual flavonoids (10 µM) were tested on phorbol 12-myristate 13-acetate-stimulated AGS cells and human neutrophil elastase. The results indicate that the antiinflammatory activity associated with chamomile infusions from both the capitula and sifted flowers is most likely due to the inhibition of neutrophil elastase and gastric metalloproteinase-9 activity and secretion; the inhibition occurring in a concentration dependent manner. The promoter activity was inhibited as well and the decrease of metalloproteinase-9 expression was found to be associated with the inhibition of NF-kB driven transcription. The results further indicate that the flavonoid-7-glycosides, major constituents of chamomile flowers, may be responsible for the antiinflammatory action of the chamomile infusion observed here. PMID:22407864

  12. Prognostic implications of immunohistochemistry markers for EGFR-TKI therapy in Chinese patients with advanced lung adenocarcinoma harboring EGFR mutations

    PubMed Central

    Zhang, Ruiguang; Li, Yan; Nie, Xiu; Dong, Xiaorong; Wu, Gang

    2016-01-01

    Background Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict dramatic clinical responses to tyrosine kinase inhibitor (TKI) treatment. The conclusion on EGFR mutation-specific antibodies by immunohistochemistry (IHC) is not consistent. We evaluated the clinical availability of EGFR mutation-specific antibodies, investigating the prediction role of mutant EGFRs and other IHC markers in TKI therapy in patients with advanced lung adenocarcinoma. Materials and methods We analyzed 637 primary lung adenocarcinomas from an unselected Chinese population. For IHC, antibodies against EGFR exon 19 E746_A750 deletions, exon 21 L858R mutations, thyroid transcription factor-1 (TTF-1), and Napsin-A were applied. Positivity was defined as staining score >0. Results Specificities of E746_A750 and L858R antibodies were 99.6% and 99.3%, while sensitivities were 86.0% and 82.7%, respectively. Tumors with Napsin-A positivity, TTF-1 positivity, EGFR mutations, and lepidic pattern showed a lower marker of proliferation index (Ki67). Higher expression scores of mutant EGFR protein, TTF-1 positivity, lower Ki67 proliferation index, and lepidic pattern were associated with longer progression-free survival. Conclusion High scores of mutant EGFR, Napsin-A positivity, TTF-1 positivity, lower Ki67 index, and lepidic pattern were favorable predictors for TKI therapy in patients with advanced lung adenocarcinoma. PMID:26848271

  13. A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer.

    PubMed

    LaBonte, Melissa J; Yang, Dongyun; Zhang, Wu; Wilson, Peter M; Nagarwala, Yasir M; Koch, Kevin M; Briner, Colleen; Kaneko, Tomomi; Rha, Sun-Young; Gladkov, Oleg; Urba, Susan G; Sakaeva, Dina; Pishvaian, Michael J; Hsieh, Ruey-Kuen; Lee, Wei-Ping; Lenz, Heinz-Josef

    2016-09-01

    An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. Mol Cancer Ther

  14. Optimal Number of Endoscopic Biopsies in Diagnosis of Advanced Gastric and Colorectal Cancer

    PubMed Central

    Choi, Yeowon; Choi, Hyo Sun; Jeon, Woo Kyu; Kim, Byung Ik; Park, Dong Il; Cho, Yong Kyun; Kim, Hong Joo; Park, Jung Ho

    2012-01-01

    Endoscopic biopsy is necessary to confirm a histopathologic diagnosis. Currently, 6 to 8 biopsies are recommended for diagnosis of a suspected malignant lesion. However, multiple biopsies may result in several problems, such as an increased risk of bleeding, procedure prolongation, and increased workload to pathologists. The aim of this study was to clarify the optimal number of endoscopic biopsy specimens required in diagnosis of advanced gastrointestinal cancer. Patients who were diagnosed with advanced gastrointestinal cancer during endoscopy were included. Five specimens were obtained sequentially from viable tissue of the cancer margin. Experienced pathologists evaluated each specimen and provided diagnoses. A total of 91 patients were enrolled. Fifty-nine subjects had advanced gastric cancer, and 32 had advanced colon cancer. Positive diagnosis rates of the first, second, and third advanced gastric cancer specimens were 81.3%, 94.9%, and 98.3%, respectively, while positive diagnosis rates of advanced colon cancer specimens were 78.1%, 87.5%, and 93.8%. Further biopsies did not increase positive diagnosis cumulative rates. This study demonstrated that three specimens were sufficient to make correct pathologic diagnoses in advanced gastrointestinal cancer. Therefore, we recommend 3 or 4 biopsies from viable tissue in advanced gastrointestinal cancer to make a pathologic diagnosis during endoscopy. PMID:22219611

  15. Neoadjuvant therapy for gastroesophageal adenocarcinoma.

    PubMed

    Samalin, Emmanuelle; Ychou, Marc

    2016-06-10

    Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions. PMID:27298768

  16. Neoadjuvant therapy for gastroesophageal adenocarcinoma

    PubMed Central

    Samalin, Emmanuelle; Ychou, Marc

    2016-01-01

    Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions. PMID:27298768

  17. C-Met Inhibitor AMG 337, Oxaliplatin, Leucovorin Calcium, and Fluorouracil in Treating Patients With Advanced Stomach or Esophageal Cancer

    ClinicalTrials.gov

    2015-01-16

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Gastrointestinal Cancer; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  18. [Weekly administration of paclitaxel with a short course of premedication for advanced or recurrent gastric cancer].

    PubMed

    Yamamoto, Shigetaka; Tanaka, Yasuhiro; Ito, Toshinori; Nakai, Sumio; Morimoto, Yoshikazu; Kitagawa, Tohru; Kurihara, Youjirou; Nishimura, Junichi

    2003-01-01

    Weekly administration of paclitaxel with a short course of premedication was performed for 8 patients with advanced or recurrent gastric cancer. In this regimen, 500 ml of physiological saline with vitamins was administered in a 3-hour infusion. After 30 minutes of infusion, dexamethasone 10 mg, chlorpheniramine maleate 5 mg, famotidine 20 mg and ramosetron hydrochloride 0.3 mg were administered intravenously. After 30 more minutes of infusion, paclitaxel at a dose of 65 mg/m2 was admixed in the residual normal physiological saline and administered over 2 hours. Administration was continued for 3 weeks with a 1 week rest. Though the partial response rate was 25%, clinical symptoms improved in all patients. Moreover, both hematological and non-hematological toxicities were mild. Weekly administration of paclitaxel with a short course of premedication is an effective and well-tolerated method for patients with advanced or recurrent gastric cancer. PMID:12557707

  19. A Prognostic Model Using Inflammation- and Nutrition-Based Scores in Patients With Metastatic Gastric Adenocarcinoma Treated With Chemotherapy.

    PubMed

    Hsieh, Meng-Che; Wang, Shih-Hor; Chuah, Seng-Kee; Lin, Yu-Hung; Lan, Jui; Rau, Kun-Ming

    2016-04-01

    The outcomes of patients with metastatic gastric cancer (mGC) are poor. Recent studies have identified the prognostic impact of inflammatory response and nutritional status on survival for patients with gastric cancer. This study aims to create a prognostic model using inflammatory- and nutrition-based scores to predict survival in patients with mGC treated with chemotherapy.After institutional review board approval, patients who had mGC and were treated with chemotherapy from 2007 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regression analyses. Based on these variables, a prognostic model using inflammatory- and nutrition-based scores was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The c-statistic values with 95% confidence interval (CI) were also calculated to access their predicting performances.Our study consisted of 256 patients with a median age of 60 years and a median follow-up visit of 18.5 months. Multivariate analyses showed that neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and Patient-Generated Subjective Global Assessment (PG-SGA) were independently related to survival. After computing these scores, patients were classified into favorable-, intermediate-, and poor-risk groups. The median overall survival were 27.6 versus 13.2 versus 8.2 months in favorable, intermediate, and poor-risk groups, respectively. The 2-year survival rate was 52% versus 16% versus 3% in favorable-, intermediate-, and poor-risk groups, respectively. (P < 0.001). The c-statistic value of our model at 2 years is 0.8 (95% CI, 0.75-0.86).NLR, mGPS, and PG-SGA were independently related to survival. Our prognostic model using inflammatory- and nutrition-based scores could provide prognostic information to patients and physicians. PMID:27124056

  20. A Prognostic Model Using Inflammation- and Nutrition-Based Scores in Patients With Metastatic Gastric Adenocarcinoma Treated With Chemotherapy

    PubMed Central

    Hsieh, Meng-Che; Wang, Shih-Hor; Chuah, Seng-Kee; Lin, Yu-Hung; Lan, Jui; Rau, Kun-Ming

    2016-01-01

    Abstract The outcomes of patients with metastatic gastric cancer (mGC) are poor. Recent studies have identified the prognostic impact of inflammatory response and nutritional status on survival for patients with gastric cancer. This study aims to create a prognostic model using inflammatory- and nutrition-based scores to predict survival in patients with mGC treated with chemotherapy. After institutional review board approval, patients who had mGC and were treated with chemotherapy from 2007 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regression analyses. Based on these variables, a prognostic model using inflammatory- and nutrition-based scores was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The c-statistic values with 95% confidence interval (CI) were also calculated to access their predicting performances. Our study consisted of 256 patients with a median age of 60 years and a median follow-up visit of 18.5 months. Multivariate analyses showed that neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and Patient-Generated Subjective Global Assessment (PG-SGA) were independently related to survival. After computing these scores, patients were classified into favorable-, intermediate-, and poor-risk groups. The median overall survival were 27.6 versus 13.2 versus 8.2 months in favorable, intermediate, and poor-risk groups, respectively. The 2-year survival rate was 52% versus 16% versus 3% in favorable-, intermediate-, and poor-risk groups, respectively. (P < 0.001). The c-statistic value of our model at 2 years is 0.8 (95% CI, 0.75–0.86). NLR, mGPS, and PG-SGA were independently related to survival. Our prognostic model using inflammatory- and nutrition-based scores could provide prognostic information to patients and physicians. PMID:27124056

  1. Paclitaxel combined with capecitabine as first-line chemotherapy for advanced or recurrent gastric cancer.

    PubMed

    Yuan, Meiqin; Yang, Yunshan; Lv, Wangxia; Song, Zhengbo; Zhong, Haijun

    2014-07-01

    Chemotherapy is of crucial importance in advanced gastric cancer (AGC) patients, in order to obtain palliation of symptoms and improve survival. To date, no standard chemotherapy regimen has been established for AGC. The purpose of the present study was to evaluate the efficacy and toxicity of the combination regimen of paclitaxel and capecitabine (PX) as first-line chemotherapy in patients with advanced or recurrent gastric cancer. Patients with advanced or recurrent gastric cancer who were treated with PX as first-line chemotherapy between January 2001 and December 2012 at the Zhejiang Cancer Hospital (Hangzhou, China) were retrospectively investigated. Survival was evaluated using the Kaplan-Meier method. In total, 36 patients were enrolled, with a median age of 53.5 years and a Karnofsky performance status (KPS) score of ≥80. A median of 4 PX cycles were administered (range, 2-8 cycles). The median progression-free survival time was 3.7 months [95% confidence interval (CI), 2.9-4.5 months) and the median overall survival time was 12.0 months (95% CI, 9.8-14.1 months). From the 36 patients evaluated, one (2.8%) achieved a complete response, seven (19.4%) achieved a partial response, 24 (66.7%) exhibited stable disease and four (11.1%) exhibited progressive disease. The objective response rate was 22.2% (8/36), and the disease control rate was 88.9% (32/36). All 36 patients were assessed for treatment toxicity. Grade 3 or 4 adverse events included neutropenia (2.8% of patients), hand-foot syndrome (2.8%) and vomiting (2.8%). No neutropenic fever or treatment-related mortalities were observed. PX combination chemotherapy may be a valuable first-line therapy for advanced or recurrent gastric cancer. PMID:24959275

  2. Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination

    PubMed Central

    Yi, Eunjue; Kim, Daejoong; Cho, Sukki; Kim, Kwhanmien

    2016-01-01

    Background This study aimed to investigate the safety and feasibility of intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive surgery as a part of multimodal strategy for the treatment of advanced lung adenocarcinoma. Methods Medical records of advanced lung cancer patients with pleural dissemination who underwent surgical treatment between 2003 and 2013 were reviewed retrospectively. Enrolled patients were divided into a surgery group comprising patients who underwent surgery only and an IPHC group, which consisted of patients who underwent surgery combined with IPHC. Results A total of 33 patients were enrolled in this study. Twenty-three patients underwent IPHC after surgical resection, and 10 patients underwent surgical resection only. The complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of which included postoperative mortality. The complication rate of the surgery group was 40.0% (4 cases), which included one postoperative mortality. The 6-month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%, 91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0% and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%, 33.3% and 0.0%, respectively. There were significant differences in overall survival rates between two groups (P=0.045); however, progression-free survival was not different between the two groups. Conclusions IPHC combined with cytoreductive surgery for advanced lung adenocarcinoma associated with pleural seeding could be performed safely and feasible. It would be part of multimodality therapy for certain category of advanced lung adenocarcinoma. However, the long-term benefits for survival is uncertain. More extensive and precisely designed studies are warranted to further evaluate the effectiveness of IPHC. PMID:27499943

  3. Strategies and Advancements in Harnessing the Immune System for Gastric Cancer Immunotherapy

    PubMed Central

    Subhash, Vinod Vijay; Yeo, Mei Shi; Tan, Woei Loon; Yong, Wei Peng

    2015-01-01

    In cancer biology, cells and molecules that form the fundamental components of the tumor microenvironment play a major role in tumor initiation, and progression as well as responses to therapy. Therapeutic approaches that would enable and harness the immune system to target tumor cells mark the future of anticancer therapy as it could induce an immunological memory specific to the tumor type and further enhance tumor regression and relapse-free survival in cancer patients. Gastric cancer is one of the leading causes of cancer-related mortalities that has a modest survival benefit from existing treatment options. The advent of immunotherapy presents us with new approaches in gastric cancer treatment where adaptive cell therapies, cancer vaccines, and antibody therapies have all been used with promising outcomes. In this paper, we review the current advances and prospects in the gastric cancer immunotherapy. Special focus is laid on new strategies and clinical trials that attempt to enhance the efficacy of various immunotherapeutic modalities in gastric cancer. PMID:26579545

  4. Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

    PubMed Central

    Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

    2010-01-01

    Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

  5. [18F]2-Fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil

    PubMed Central

    Suttie, S A; Park, K G M; Smith, T A D

    2007-01-01

    Decreased tumour [18F]2-fluoro-2-deoxy-D-glucose (18FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD10 and LD50), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. 18FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding (a measure of apoptosis). Treatment of cells for 48 and 72 h with LD50 doses of cisplatin resulted in reductions in 18FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced 18FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with 18FDG incorporation before the recovery period allowed an assessment of the predictive ability of 18FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in 18FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between 18FDG incorporation and cell cycle distribution. Our results

  6. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

    SciTech Connect

    Tey, Jeremy . E-mail: Jeremy_Tey@mail.nhg.com.sg; Back, Michael F.; Shakespeare, Thomas P.; Mukherjee, Rahul K.; Lu, Jiade J.; Lee, Khai Mun; Wong, Lea Choung; Leong, Cheng Nang; Zhu Ming

    2007-02-01

    Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

  7. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    PubMed Central

    Li, Kaichun; Li, Jin

    2016-01-01

    Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

  8. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application.

    PubMed

    Li, Kaichun; Li, Jin

    2016-01-01

    Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

  9. Whole Pelvic Radiotherapy Versus Prostate Only Radiotherapy in the Management of Locally Advanced or Aggressive Prostate Adenocarcinoma

    SciTech Connect

    Aizer, Ayal A.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Colberg, John W.; Peschel, Richard E.

    2009-12-01

    Purpose: To determine whether whole pelvic radiotherapy (WPRT) or prostate-only radiotherapy (PORT) yields improved biochemical disease-free survival (BDFS) in patients with advanced or aggressive prostate adenocarcinoma. Methods and Materials: Between 2000 and 2007, a consecutive sample of 277 patients with prostate adenocarcinoma and at least a 15% likelihood of lymph node involvement who had undergone WPRT (n = 68) or PORT (n = 209) at two referral centers was analyzed. The median radiation dose in both arms was 75.6 Gy. The outcome measure was BDFS, as determined using the prostate-specific antigen nadir + 2 ng/mL definition of failure. BDFS was calculated using the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed to assess for confounding. Treatment-related toxicity was assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events guidelines. The median follow-up was 30 months. Results: WPRT patients had more advanced and aggressive disease at baseline (p < .001). The 4-year BDFS rate was 69.4% in the PORT cohort and 86.3% in the WPRT cohort (p = .02). Within the entire cohort, after adjustment for confounding variables, the pretreatment prostate-specific antigen (p < .001), Gleason score (p < .001), use of hormonal therapy (p = .002), and use of WPRT (vs. PORT, p = .006) predicted for BDFS. Patients undergoing WPRT had increased acute gastrointestinal toxicity (p = .048), but no significant difference in acute genitourinary toxicity was seen (p = .09). No difference in late toxicity was found. Conclusion: WPRT may yield improved BDFS in patients with advanced or aggressive prostate adenocarcinoma, but results in a greater incidence of acute toxicity.

  10. Use of Respiratory-Correlated Four-Dimensional Computed Tomography to Determine Acceptable Treatment Margins for Locally Advanced Pancreatic Adenocarcinoma

    SciTech Connect

    Goldstein, Seth D.; Ford, Eric C.; Duhon, Mario; McNutt, Todd; Wong, John; Herman, Joseph M.

    2010-02-01

    Purpose: Respiratory-induced excursions of locally advanced pancreatic adenocarcinoma could affect dose delivery. This study quantified tumor motion and evaluated standard treatment margins. Methods and Materials: Respiratory-correlated four-dimensional computed tomography images were obtained on 30 patients with locally advanced pancreatic adenocarcinoma; 15 of whom underwent repeat scanning before cone-down treatment. Treatment planning software was used to contour the gross tumor volume (GTV), bilateral kidneys, and biliary stent. Excursions were calculated according to the centroid of the contoured volumes. Results: The mean +- standard deviation GTV excursion in the superoinferior (SI) direction was 0.55 +- 0.23 cm; an expansion of 1.0 cm adequately accounted for the GTV motion in 97% of locally advanced pancreatic adenocarcinoma patients. Motion GTVs were generated and resulted in a 25% average volume increase compared with the static GTV. Of the 30 patients, 17 had biliary stents. The mean SI stent excursion was 0.84 +- 0.32 cm, significantly greater than the GTV motion. The xiphoid process moved an average of 0.35 +- 0.12 cm, significantly less than the GTV. The mean SI motion of the left and right kidneys was 0.65 +- 0.27 cm and 0.77 +- 0.30 cm, respectively. At repeat scanning, no significant changes were seen in the mean GTV size (p = .8) or excursion (p = .3). Conclusion: These data suggest that an asymmetric expansion of 1.0, 0.7, and 0.6 cm along the respective SI, anteroposterior, and medial-lateral directions is recommended if a respiratory-correlated four-dimensional computed tomography scan is not available to evaluate the tumor motion during treatment planning. Surrogates of tumor motion, such as biliary stents or external markers, should be used with caution.

  11. Elevated Preoperative Serum Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) Ratio Is Associated with Better Prognosis in Patients Undergoing Curative Treatment for Gastric Adenocarcinoma

    PubMed Central

    Chen, Shu-Lin; Li, Jian-Pei; Li, Lin-Fang; Zeng, Tao; He, Xia

    2016-01-01

    The level of anine aminotransferase/aspartate aminotransferase (ALT/AST) ratio in the serum was often used to assess liver injury. Whether the ALT/AST ratio (LSR) was associated with prognosis for gastric adenocarcinoma (GA) has not been reported in the literature. Our aim was to investigate the prognostic value of the preoperative LSR in patients with GA. A retrospective study was performed in 231 patients with GA undergoing curative resection. The medical records collected include clinical information and laboratory results. We investigated the correlations between the preoperative LSR and overall survival (OS). Survival analysis was conducted with the Kaplan–Meier method, and Cox regression analysis was used to determine significant independent prognostic factors for predicting survival. A p value of <0.05 was considered to be statistically significant. A total of 231 patients were finally enrolled. The median overall survival was 47 months. Multivariate analysis indicated that preoperative LSR was an independent prognostic factor in GA. Patients with LSR ≤ 0.80 had a greater risk of death than those with LSR > 0.80. The LSR was independently associated with OS in patients with GA (hazard ratio: 0.610; 95% confidence interval: 0.388–0.958; p = 0.032), along with tumor stages (hazard ratio: 3.118; 95% confidence interval: 2.044–4.756; p < 0.001) and distant metastases (hazard ratio: 1.957; 95% confidence interval: 1.119–3.422; p = 0.019). Our study first established a connection between the preoperative LSR and patients undergoing curative resection for GA, suggesting that LSR was a simple, inexpensive, and easily measurable marker as a prognostic factor, and may help to identify high-risk patients for treatment decisions. PMID:27294917

  12. Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

    PubMed Central

    Tey, Jeremy; Choo, Bok Ai; Leong, Cheng Nang; Loy, En Yun; Wong, Lea Choung; Lim, Keith; Lu, Jiade Jay; Koh, Wee Yao

    2014-01-01

    Abstract The purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques. We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity. Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (≤39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (α/β ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia). External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (≤39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing. PMID:25396330

  13. Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

    ClinicalTrials.gov

    2015-06-03

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  14. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: Long-term results of a phase I trial

    SciTech Connect

    Allal, Abdelkarim S. . E-mail: abdelkarim.allal@hcuge.ch; Zwahlen, Daniel; Bruendler, Marie-Anne; Peyer, Raymond de; Morel, Philippe; Huber, Olivier; Roth, Arnaud D.

    2005-12-01

    Purpose: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. Methods and Materials: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m{sup 2} d1, 5FU 800 mg/m{sup 2} d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. Results: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. Conclusions: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.

  15. Laparoscopy-assisted distal gastrectomy for advanced gastric cancer with situs inversus totalis: A case report

    PubMed Central

    Ye, Min-Feng; Tao, Feng; Xu, Guan-Gen; Sun, Ai-Jing

    2015-01-01

    Situs inversus totalis (SIT) is a rare anomaly in which the abdominal and thoracic cavity structures are located opposite to their usual positions. Occasionally, patients with this condition are diagnosed with malignant tumors. We report a case of a 60-year-old woman with gastric cancer and SIT. Laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection and Billroth II anastomosis were performed successfully on the patient by careful consideration of the mirror-image anatomy. The operation required 230 min, and no intraoperative complications occurred. The final pathological report was pT4aN0M0, according to the American Joint Committee on Cancer 7th edition staging guidelines. The postoperative course was favorable, and the patient was discharged on postoperative day 8. We believe that this is the first case of LADG with D2 lymphadenectomy reported in a SIT patient with advanced gastric cancer. PMID:26401091

  16. A clinical exploration of neoadjuvant chemotherapy with tegafur, gimeracil, and oteracil potassium capsules combined with oxaliplatin for advanced gastric cancer

    PubMed Central

    Lv, Xinting; Zhang, Li; Huang, Renjun; Song, Weiyong

    2015-01-01

    Background: Advanced gastric cancer refers to tumor invasion into the gastric muscularis propria or even the layer beyond, and has low early gastric cancer diagnosis rate. Purpose: To determine the clinical efficacy and side effects of neoadjuvant chemotherapy with tegafur, gimeracil, and oteracil potassium capsules (TGOP) combined with oxaliplatin (SOX regimen) in patients with advanced gastric cancer. Methods: We evaluated 25 patients with advanced gastric cancer who were admitted and treated with neoadjuvant chemotherapy with the SOX regimen (intravenous injection of 130 mg/m2 oxaliplatin on day 1 followed by oral administration of 60 mg TGOP twice daily on days 1-14), every 3 weeks. The clinical efficacy and side effects of the SOX regimen were evaluated after two courses of treatment, before surgery. Results: Of the 25 patients enrolled in this study, 23 completed two courses of neoadjuvant chemotherapy, and of these, 12 achieved downstaging as determined by the clinical TNM stage, resulting in a total response rate of 52.2%. The 23 patients underwent surgery, with 22 receiving radical resection (95.7%). Among these 23 patients, R0 resection was achieved in 16 (69.6%) and pathological complete remission was observed in one. Conclusion: Neoadjuvant chemotherapy with TGOP combined with oxaliplatin was effective for advanced gastric cancer and had tolerable side effects. PMID:26770529

  17. Clinical role of ramucirumab alone or in combination with paclitaxel for gastric and gastro-esophageal junction adenocarcinoma

    PubMed Central

    Davidson, Michael; Smyth, Elizabeth C; Cunningham, David

    2016-01-01

    Cancers of the stomach and gastro-esophageal junction represent a significant challenge in oncology. Despite some recent advances in genetic categorization and the development of novel agents, outcomes remain poor. The vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab is the first targeted therapy to improve survival in a molecularly unselected population, and represents a valuable new treatment option. This review describes the current treatment landscape for advanced disease, evaluates existing and ongoing research into ramucirumab, and discusses its current and potential future therapeutic role. PMID:27524910

  18. Mixed gastric carcinoma with intestinal and cribriform patterns: a distinctive pathologic appearance associated with poor prognosis in advanced stages and a potential mimicker of metastatic breast carcinoma.

    PubMed

    Lino-Silva, Leonardo Saúl; Salcedo Hernández, Rosa Angélica; Molina-Frías, Ernesto

    2013-02-01

    Gastric adenocarcinoma is characterized by marked heterogeneity at cytological and architectural level and frequently shows overlap between microscopic patterns. This article describes a peculiar pattern of gastric adenocarcinoma, previously unreported, that combines intestinal type adenocarcinoma with areas of cribriform pattern that resembles both architectural and cytological in situ ductal carcinoma of the breast and to the best of the authors' knowledge, there are no earlier reports of this pattern in the stomach, which has been named "gastric carcinoma with cribriform component (CGA). The authors analyzed 12 cases of intestinal type adenocarcinoma with areas at least 20% of cribriform pattern (range from 20% to 90%) that was present in 9% of intestinal type gastric adenocarcinomas in their institution. There is slight predilection for male sex, and the median age of presentation is 55.8 years. The phenotype by immunohistochemistry is the same as with conventional (non-CGA) carcinomas. CGA shows more frequent lymphovascular invasion (P = .039), perineural invasion (P = .027) and resembles both in situ and invasive cribriform carcinoma of the breast. In clinical stage III the overall 3-year survival of CGA was worse than those with non-CGA component (38.6% vs 25%; 3-year survival, P = .010) and proves to be an independent adverse factor for overall survival in a multivariate analysis. Compared with conventional gastric carcinomas, CGA is deep infiltrating, has more nodal metastases, more lymphovascular and perineural invasion, and has decreased overall survival. Thus, proper recognition and report is important, even in small biopsies or small foci. PMID:22744963

  19. Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

    PubMed

    Garcia-Perez, Juan Carlos; Rodríguez-Perez, Rosa; Ballestero, Araceli; Zuloaga, Jaime; Fernandez-Puntero, Belen; Arias-Díaz, Javier; Caballero, María Luisa

    2015-10-01

    Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer. PMID:26448021

  20. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma.

    PubMed

    Lee, Su-Min; Joshi, Jay; Wolfe, Konrad; Acher, Peter; Liyanage, Sidath H

    2016-06-01

    We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient. PMID:27257455

  1. Degranulation patterns of eosinophils in advanced gastric carcinoma: an electron microscopic study.

    PubMed

    Caruso, R A; Ieni, A; Fedele, F; Zuccalà, V; Riccardo, M; Parisi, E; Parisi, A

    2005-01-01

    Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and degranulation patterns of eosinophils in the tumor stroma. Seven cases of advanced gastric carcinomas were found to be massively infiltrated by eosinophils and studied by light and electron microscopy. Gastric carcinomas, despite having similar numbers of tissue eosinophils, exhibited markedly different degranulation patterns. In 2 cases, resting nondegranulating eosinophils were found. Piecemeal degranulation was the predominant mode of secretion from eosinophils localized within the tumor stroma in 4 cases. Eosinophil exocytosis and cytolysis were rarely observed. In 1 case, crystals morphologically similar to Charcot-Leyden crystals were observed at the extracellular level as well as in phagosomes of tissue macrophages, confirming active sequestrations of eosinophil Charcot-Leyden protein by macrophages in vivo. In the same case, eosinophils showed characteristic features of early and late apoptotic changes, such as condensed chromatin, focal dilatation of nuclear envelope, and preserved plasma membrane. Morphological association between apoptotic eosinophils and deposition of granules in the tumor stroma was found. Extracellular deposition of intact granules from apoptotic eosinophils was distinct from eosinophilic (necrotic) cytolysis, and has reported previously in experimental studies in vitro. To the knowledge of the authors, this case represents the first report of late apoptotic eosinophils that release their granules within the tumor stroma in a human gastric carcinoma. PMID:15931778

  2. Novel targets in the treatment of advanced gastric cancer: a perspective review

    PubMed Central

    Fontana, Elisa; Smyth, Elizabeth C.

    2016-01-01

    Gastric cancer is responsible for a high burden of disease globally. Although more extensive use of chemotherapy together with the recent introduction of the two targeted agents trastuzumab and ramucirumab have contributed to marginal outcome prolongation, overall survival for patients with advanced stage disease remains poor. Over the last decade, a number of novel agents have been examined in clinical trials with largely disappointing results. Potential explanations for this are the absence of molecularly selected trial populations or weak predictive biomarkers within the context of a highly heterogeneous disease. In the recently published gastric cancer The Cancer Genome Atlas (TCGA) project a new classification of four different tumour subtypes according to different molecular characteristics has been proposed. With some overlap, several relatively distinct and potentially targetable pathways have been identified for each subtype. In this perspective review we match recent trial results with the subtypes described in the gastric cancer TCGA aiming to highlight data regarding novel agents under evaluation and to discuss whether this publication might provide a framework for future drug development. PMID:26929787

  3. A significant response to sorafenib in a woman with advanced lung adenocarcinoma and a BRAF non-V600 mutation.

    PubMed

    Sereno, María; Moreno, Victor; Moreno Rubio, Juan; Gómez-Raposo, César; García Sánchez, Sagrario; Hernández Jusdado, Rebeca; Falagan, Sandra; Zambrana Tébar, Francisco; Casado Sáenz, Enrique

    2015-10-01

    Lung adenocarcinoma includes recurrent activating oncogenic mutations (EGFR, EML4-ALK, ROS1) that have been associated with response to EGFR and ALK inhibitors. Platinum-based chemotherapy is the standard therapy for non-oncodrivers population. Sorafenib is a small molecule that blocks the activation of C-RAF, B-RAF, c-KIT, FLT-3, RET, VEGFR-2, VEGFR-3 and PDGFR approved for advanced renal cell and hepatocellular carcinoma (b, c). Many studies have evaluated sorafenib in advanced non-small-cell lung cancer (NSCLC), with different results. We present a case report of a patient with NSCLC and the BRAF G469R mutation who showed a dramatic response to sorafenib. PMID:26237499

  4. Genetic Analysis-Guided Dosing of FOLFIRABAX in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-01-13

    Adenocarcinoma of Unknown Primary; Adult Cholangiocarcinoma; Gallbladder Carcinoma; Gastric Adenocarcinoma; Malignant Gastrointestinal Neoplasm; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Stage III Ampulla of Vater Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IV Ampulla of Vater Cancer; Stage IV Gallbladder Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer

  5. Strategies of laparoscopic spleen-preserving splenic hilar lymph node dissection for advanced proximal gastric cancer.

    PubMed

    Chen, Qi-Yue; Huang, Chang-Ming; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Lu, Jun; Cao, Long-Long; Lin, Mi; Tu, Ru-Hong; Hong, Zhi-Liang

    2016-06-27

    For advanced proximal gastric cancer (GC), splenic hilar (No. 10) lymph nodes (LN) are crucial links in lymphatic drainage. According to the 14(th) edition of the Japanese GC treatment guidelines, a D2 lymphadenectomy is the standard surgery for advanced GC, and No. 10 LN should be dissected for advanced proximal GC. In recent years, the preservation of organ function and the use of minimally invasive technology are being accepted by an increasing number of clinicians. Laparoscopic spleen-preserving splenic hilar LN dissection has become more accepted and is gradually being used in operations. However, because of the complexity of splenic hilar anatomy, mastering the strategies for laparoscopic spleen-preserving splenic hilar LN dissection is critical for successfully completing the operation. PMID:27358672

  6. Strategies of laparoscopic spleen-preserving splenic hilar lymph node dissection for advanced proximal gastric cancer

    PubMed Central

    Chen, Qi-Yue; Huang, Chang-Ming; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Lu, Jun; Cao, Long-Long; Lin, Mi; Tu, Ru-Hong; Hong, Zhi-Liang

    2016-01-01

    For advanced proximal gastric cancer (GC), splenic hilar (No. 10) lymph nodes (LN) are crucial links in lymphatic drainage. According to the 14th edition of the Japanese GC treatment guidelines, a D2 lymphadenectomy is the standard surgery for advanced GC, and No. 10 LN should be dissected for advanced proximal GC. In recent years, the preservation of organ function and the use of minimally invasive technology are being accepted by an increasing number of clinicians. Laparoscopic spleen-preserving splenic hilar LN dissection has become more accepted and is gradually being used in operations. However, because of the complexity of splenic hilar anatomy, mastering the strategies for laparoscopic spleen-preserving splenic hilar LN dissection is critical for successfully completing the operation. PMID:27358672

  7. [Complete response in an elderly patient with advanced gastric cancer treated with TS-1].

    PubMed

    Harada, Katsuhisa; Noguchi, Tsuyoshi; Fujiwara, Shozo; Moriyama, Hatsuo; Kitano, Seigo; Kawahara, Katsunobu

    2007-03-01

    The patient was an 80-year-old man whose complaint was coffee-grounds vomit. He was diagnosed with advanced gastric cancer, T2N1H0P0M0, stage II. Though the curative operation was explained to the patient, he declined it because of complications of advanced age, diabetes and bronchial asthma; chemotherapy was chosen instead. TS-1 (80 mg/day) was administered for 28 days, followed by 14 days rest as one course. A partial response was observed after the first course, and no cancer cells were confirmed by endoscopic biopsy after the fifth course. Moreover, after the 14th course, CT showed a complete regression of lymph node metastasis, and no cancer cells were confirmed by endoscopic biopsy, for a complete response (CR). From now on, as society grays more and more, it is considered that elderly advanced gastric cancer patients with complications will increase. TS-1 single treatment is considered to be safe and outpatient treatment possible as one of the useful cures. PMID:17353636

  8. Isoprenaline Induces Periostin Expression in Gastric Cancer

    PubMed Central

    Liu, Guo-Xiao; Xi, Hong-Qing; Sun, Xiao-Yan; Geng, Zhi-Jun; Yang, Shao-Wei; Lu, Yan-Jie

    2016-01-01

    Purpose Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. Materials and Methods Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. Results Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. Conclusion These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. PMID:26996552

  9. LI-cadherin: a marker of gastric metaplasia and neoplasia

    PubMed Central

    Grotzinger, C; Kneifel, J; Patschan, D; Schnoy, N; Anagnostopoulos, I; Faiss, S; Tauber, R; Wiedenmann, B; Gessner, R

    2001-01-01

    BACKGROUND—Intestinal metaplasia is considered a risk factor for the development of gastric adenocarcinomas of the intestinal type and is found in approximately 20% of gastric biopsies. Conventional histology only detects advanced stages of intestinal metaplasia.
AIMS—To study expression of the enterocyte specific adhesion molecule liver-intestinal (LI)-cadherin in intestinal metaplasia as well as in gastric cancer, and to evaluate its use as a diagnostic marker molecule.
PATIENTS—Gastric biopsies (n=77) from 30 consecutive patients (n=30; aged 28-90 years) as well as surgically resected tissue samples (n=24) of all types of gastric carcinomas were analysed.
METHODS—Single and double label immunofluorescence detection on cryosections of gastric biopsies; alkaline phosphatase antialkaline phosphatase method on paraffin embedded carcinoma tissue sections.
RESULTS—Of 77 biopsies (from 30 patients), 12 (from 10 patients) stained positive for LI-cadherin. LI-cadherin staining correlated with the presence of intestinal metaplasia. Conventional histological diagnosis however failed to detect subtle gastric intestinal metaplasia (three of 10 patients). In contrast, only LI-cadherin and villin were positive in these cases whereas sucrase-isomaltase also failed to detect intestinal metaplasia in four of 10 patients. Well differentiated gastric carcinomas showed intense staining for LI-cadherin while undifferentiated carcinomas showed only weak diffuse cytoplasmic staining.
CONCLUSIONS—To detect early metaplastic changes in the gastric mucosa, LI-cadherin has a sensitivity superior to sucrase-isomaltase and conventional histology and comparable with that of villin. Its specificity exceeds that of villin. Thus LI-cadherin represents a new, reliable, and powerful marker molecule for early detection of gastric intestinal metaplasia and well differentiated adenocarcinomas.


Keywords: stomach; intestinal metaplasia; cadherins; carcinogenesis

  10. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

    PubMed Central

    2011-01-01

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561