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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. 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

  1. [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

  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. 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

  4. 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

  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 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

  10. 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

  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. 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

  2. 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

  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

    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

  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. 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

  7. 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

  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

    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

  10. 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

  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 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

  13. 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

  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. 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

  10. 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

  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. 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

  2. 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

  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. [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

  13. 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

  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. 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

  16. 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

  17. 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

  18. 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

  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. 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

  1. 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

  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. 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

  17. [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

  18. 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

  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. 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

  5. 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

  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. 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

  12. 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

  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. 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

  7. 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

  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

    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

  14. 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

  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. 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.

  8. 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

  9. 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

  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. 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

  14. 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

  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. 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

  1. 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

  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. 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

  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. 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

  8. 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

  9. 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

  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. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  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. 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

  20. 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

  1. 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

  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. 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.

  6. [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

  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. 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

  12. 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

  13. 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.

  14. 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

  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. 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

  2. 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

  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

  11. Non-platinum-based chemotherapy for treatment of advanced gastric cancer: 5-fluorouracil, taxanes, and irinotecan.

    PubMed

    Kang, Byung Woog; Kim, Jong Gwang; Kwon, Oh-Kyoung; Chung, Ho Young; Yu, Wansik

    2014-05-14

    Despite numerous advances in treatment options, advanced gastric cancer (AGC) remains a major public health issue and the leading cause of cancer-related deaths. Cisplatin is one of the most effective broad-spectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil (5FU)-based chemotherapy is generally used for treatment of patients with AGC. However, there is still no consensus on the best regimen for treating AGC. Recently, various new chemotherapeutic agents, including oral 5FU, taxanes, and irinotecan, have been identified as improving the outcomes for AGC when used as a single agent or in combination with non-platinum chemotherapy. Nonetheless, it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC. Accordingly, this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC. PMID:24833869

  12. Non-platinum-based chemotherapy for treatment of advanced gastric cancer: 5-fluorouracil, taxanes, and irinotecan

    PubMed Central

    Kang, Byung Woog; Kim, Jong Gwang; Kwon, Oh-Kyoung; Chung, Ho Young; Yu, Wansik

    2014-01-01

    Despite numerous advances in treatment options, advanced gastric cancer (AGC) remains a major public health issue and the leading cause of cancer-related deaths. Cisplatin is one of the most effective broad-spectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil (5FU)-based chemotherapy is generally used for treatment of patients with AGC. However, there is still no consensus on the best regimen for treating AGC. Recently, various new chemotherapeutic agents, including oral 5FU, taxanes, and irinotecan, have been identified as improving the outcomes for AGC when used as a single agent or in combination with non-platinum chemotherapy. Nonetheless, it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC. Accordingly, this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC. PMID:24833869

  13. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.

    PubMed

    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki

    2012-12-01

    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P < 0.0001), and tumors without vascular-poor area (P < 0.0001). Based on a multivariate analysis, presence of EGFR mutations was independently associated with never-smokers (P = 0.0046), lack of vascular-poor area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency. PMID:22492281

  14. Expression of Mismatch Repair Proteins in Early and Advanced Gastric Cancer in Poland.

    PubMed

    Karpińska-Kaczmarczyk, Katarzyna; Lewandowska, Magdalena; Ławniczak, Małgorzata; Białek, Andrzej; Urasińska, Elżbieta

    2016-01-01

    BACKGROUND Mutations in DNA of mismatch repair (MMR) genes result in failure to repair errors that occur during DNA replication in microsatellites, resulting in accumulation of frameshift mutations in these genes and leading to DNA mismatch replication errors and microsatellite instability. Gastric cancers (GCs) with high MSI (MSI-H) are a well-defined subset of carcinomas showing distinctive clinicopathological features. In this study we investigated the rate of MSI and the correlation between MSI status and clinicopathological features of GC. MATERIAL AND METHODS The study included 107 patients with GCs: 61 with advanced gastric cancers (AGC) and 46 with early gastric cancer (EGC). MSI deficiency in GCs was assessed by the immunohistochemical analysis of expression of MMR proteins - MLH1, MSH2, MSH6, and PMS2 - using formalin-fixed and paraffin-embedded tissue. RESULTS A total of 6 (5.6%) MSI-H were observed. The loss of MMR proteins expression was associated with the intestinal type of GC in Lauren classification, and tubular and papillary architecture in WHO classification. There was no statistically significant association between negative MMR expression and other selected clinical parameters: age, sex, tumor location, depth of invasion (EGC and AGC), lymph nodes status, presence of the ulceration, and lymphocytic infiltrate. CONCLUSIONS In the present era of personalized medicine, the histological type of GC and MMR proteins status in cancer cells are very important for the proper surveillance of patients with familial GC and sporadic GCs, as well as for selecting the proper follow-up and treatment. Larger collaborative studies are needed to verify the features of MSI-H GCs in Poland. PMID:27527654

  15. Expression of Mismatch Repair Proteins in Early and Advanced Gastric Cancer in Poland

    PubMed Central

    Karpińska-Kaczmarczyk, Katarzyna; Lewandowska, Magdalena; Ławniczak, Małgorzata; Białek, Andrzej; Urasińska, Elżbieta

    2016-01-01

    Background Mutations in DNA of mismatch repair (MMR) genes result in failure to repair errors that occur during DNA replication in microsatellites, resulting in accumulation of frameshift mutations in these genes and leading to DNA mismatch replication errors and microsatellite instability. Gastric cancers (GCs) with high MSI (MSI-H) are a well-defined subset of carcinomas showing distinctive clinicopathological features. In this study we investigated the rate of MSI and the correlation between MSI status and clinicopathological features of GC. Material/Methods The study included 107 patients with GCs: 61 with advanced gastric cancers (AGC) and 46 with early gastric cancer (EGC). MSI deficiency in GCs was assessed by the immunohistochemical analysis of expression of MMR proteins – MLH1, MSH2, MSH6, and PMS2 – using formalin-fixed and paraffin-embedded tissue. Results A total of 6 (5.6%) MSI-H were observed. The loss of MMR proteins expression was associated with the intestinal type of GC in Lauren classification, and tubular and papillary architecture in WHO classification. There was no statistically significant association between negative MMR expression and other selected clinical parameters: age, sex, tumor location, depth of invasion (EGC and AGC), lymph nodes status, presence of the ulceration, and lymphocytic infiltrate. Conclusions In the present era of personalized medicine, the histological type of GC and MMR proteins status in cancer cells are very important for the proper surveillance of patients with familial GC and sporadic GCs, as well as for selecting the proper follow-up and treatment. Larger collaborative studies are needed to verify the features of MSI-H GCs in Poland. PMID:27527654

  16. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  17. Evolving treatments for advanced gastric cancer: appraisal of the survival trend.

    PubMed

    Roberto, Michela; Romiti, Adriana; Onesti, Concetta Elisa; Zullo, Angelo; Falcone, Rosa; Marchetti, Paolo

    2016-07-01

    Introduction and areas covered: We analysed the results of the main clinical studies looking at patients with advanced gastric or esophagogastric junction cancer, in order to differentiate between what is already clinical evidence and what is a promise for the cure of such patients. Thus, achievements from key studies, which had been purposely directed at chemotherapy, molecular target therapies and immunotherapy in both first and second-line setting were analysed. Metronomic chemotherapy, which consists of the administration of continuative low-dose anticancer drugs, was considered also. Expert commentary: It was found that patients included in experimental arms of randomized trials compared with controls have often benefited from a statistically significant extension of overall survival. However, further studies are awaited to bring new drugs into clinical practice and to validate candidate biomarkers predictive of response. PMID:27137418

  18. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer

    PubMed Central

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-01-01

    Abstract Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients. Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS). The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC. Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts. PMID:26496252

  19. 15-PGDH expression as a predictive factor response to neoadjuvant chemotherapy in advanced gastric cancer

    PubMed Central

    Hu, Min; Li, Kai; Maskey, Ninu; Xu, Zhigao; Peng, ChunWei; Tian, Sufang; Li, Yan; Yang, Guifang

    2015-01-01

    Given the various clinical and pathologic responses to neoadjuvant chemotherapy (NACT) in gastric cancer (GC), potential biomarkers that reflecting the efficacy of NACT on GC should be investigated. The aim of this study was to investigate the 15-PGDH expression response to NACT in GC patients and its relationship with prognosis of GC. Immunohistochemical method was used to assess the level of 15-PGDH expression in 56 GC patients who received NACT before surgery and 46 patients who underwent surgical treatment without NACT as well as their corresponding adjacent non-neoplastic tissues. We found that there was no correlation of 15-PGDH expression between non-cancerous gastric tissues and GC tissues (P=0.519), while 15-PGDH expression level in NACT group was higher than that in nNACT group (P=0.015). In patients with NACT, the higher level of 15-PGDH expression was significantly associated with well-moderately differentiated grade (P=0.023), I/II stage (P=0.014) and with no lymph node metastasis (P=0.016). Moreover, statistically significant differences in overall survival (OS) were found among 15-PGDH expression (log-rank test, P<0.001) and TNM stage (log-rank test, P=0.032). Most importantly, expression of 15-PGDH was found to be an independent predictive factor by multivariate analysis (Hazard ratio (HR) 0.315 [0.120-0.827], P=0.019). These findings indicated that NACT could increase 15-PGDH expression in advanced GC patients, and 15-PGDH may serve as a candidate prognostic biomarker of advanced GC response to NACT. PMID:26261578

  20. Palliative treatment for advanced biliary adenocarcinomas with combination dimethyl sulfoxide-sodium bicarbonate infusion and S-adenosyl-L-methionine.

    PubMed

    Hoang, Ba X; Tran, Hung Q; Vu, Ut V; Pham, Quynh T; Shaw, D Graeme

    2014-09-01

    Adenocarcinoma of the gallbladder and cholangiocarcinoma account for 4% and 3%, respectively, of all gastrointestinal cancers. Advanced biliary tract carcinoma has a very poor prognosis with all current available modalities of treatment. In this pilot open-label study, the authors investigated the efficacy and safety of a combination of dimethyl sulfoxide-sodium bicarbonate (DMSO-SB) infusion and S-adenosyl-L-methionine (ademetionine) oral supplementation as palliative pharmacotherapy in nine patients with advanced nonresectable biliary tract carcinomas (ABTCs). Patients with evidence of biliary obstruction with a total serum bilirubin ≤300 μmol/L were allowed to join the study. The results of this 6-month study and follow-up of all nine patients with ABTC indicated that the investigated combination treatment improved pain control, blood biochemical parameters, and quality of life for the patients. Moreover, this method of treatment has led to a 6-month progression-free survival for all investigated patients. The treatment was well tolerated for all patients without major adverse reactions. Given that ABTC is a highly fatal malignancy with poor response to chemotherapy and targeted drugs, the authors consider that the combination of DMSO-SB and ademetionine deserves further research and application as a palliative care and survival-enhancing treatment for this group of patients. PMID:25102038

  1. Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

    PubMed Central

    Nakamura, M.; Katano, M.; Kuwahara, A.; Fujimoto, K.; Miyazaki, K.; Morisaki, T.; Mori, M.

    1998-01-01

    It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma. Images Figure 1 PMID:9823982

  2. Multidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges.

    PubMed

    Zhang, Dexin; Fan, Daiming

    2007-10-01

    Gastric cancer is the second leading cause of cancer mortality worldwide. The major cause of treatment failure for gastric cancer is the development of multidrug resistance (MDR) to chemotherapy, which is currently one of the primary treatment options. Recently, research into the MDR of gastric cancer has revealed that, in addition to the classical ATP-binding cassette transporters, such as P-glycoprotein (P-gp) and MDR-associated protein (MRP)1, a number of other molecules might mediate the drug resistance of human gastric cancer. The absence of P-gp and MRP1 expression in some gastric cancer cases also indicates that there might be other mechanisms responsible for human gastric cancer MDR. These molecules belong to different functional families and might work together to confer MDR phenotypes. The new findings may provide new clues to the mechanisms of MDR and enable the selection of new candidates for targeting MDR in human gastric cancer. PMID:17944563

  3. Oxaliplatin, Fluorouracil, Erlotinib Hydrochloride, and Radiation Therapy Before Surgery and Erlotinib Hydrochloride After Surgery in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

    ClinicalTrials.gov

    2015-07-27

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage II Esophageal Cancer; Stage II Gastric Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer

  4. PTEN polymorphisms contribute to clinical outcomes of advanced lung adenocarcinoma patients treated with platinum-based chemotherapy.

    PubMed

    Yang, Yang; Xu, Wen; Liu, Di; Ding, Xi; Su, Bo; Sun, Yifeng; Gao, Wen

    2016-06-01

    This study aimed to elucidate the impact of PTEN single nucleotide polymorphism (SNP) on clinical outcomes for advanced lung adenocarcinoma (LAC) patients treated with platinum-based chemotherapy. Three functional SNPs (rs11202607 G>A, rs701848 A>G, and rs11202592 G>C) of PTEN gene were genotyped by using DNA from blood samples of 618 advanced LAC patients, and their relationships with clinical outcomes were analyzed. The carriers of homozygous mutant of rs701848 and rs11202592 polymorphisms revealed significantly worse overall survival (OS) than those with heterozygote or wild-type homozygote (18.83 vs. 21.47 vs. 24.37 months, P = 0.034 and 13.40 vs. 19.03 vs. 21.90 months, P = 0.025, respectively). Subgroup analysis revealed that this association was particularly significant in tumor-lymph-node metastasis (TNM) stage III patients. The objective response rates (ORR) and disease control rates (DCR) of patients with genotype AA, AG, and GG in PTEN rs701848 polymorphism were statistically different (24.1 vs 16.6 vs 12.2 %, P = 0.017 and 82.7 vs 76.0 vs 70.2 %, P = 0.029, respectively). Haplotype analysis revealed a protective effect of the haplotype G-A-A (in the order of rs11202592, rs701848, and rs11202607) on chemotherapy efficacy and survival. Taken together, PTEN polymorphisms may contribute to survival and chemotherapy efficacy of advanced LAC patients treated with platinum-based agents. PMID:26695147

  5. Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model.

    PubMed

    Philips, Prejesh; Li, Yan; Li, Suping; St Hill, Charles R; Martin, Robert Cg

    2015-01-01

    Irreversible electroporation (IRE) is a promising cell membrane ablative modality for pancreatic cancer. There have been recent concerns regarding local recurrence and the potential use of IRE as a debulking (partial ablation) modality. We hypothesize that incomplete ablation leads to early recurrence and a more aggressive biology. We created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. Tumors were allowed to grow from 0.75 to 1.5 cm and then treated with the goal of complete ablation or partial ablation using standard IRE settings. Animals were recovered and survived for 2 days (n = 6), 7 (n = 6), 14 (n = 6), 21 (n = 6), 30 (n = 8), and 60 (n = 8) days. All 40 animals/tumors underwent successful IRE under general anesthesia with muscle paralysis. The mean tumor volume of the animals undergoing ablation was 1,447.6 mm(3) ± 884). Histologically, in the 14-, 21-, 30-, and 60-day survival groups the entire tumor was nonviable, with a persistent tumor nodule completely replaced fibrosis. In the group treated with partial ablation, incomplete electroporation/recurrences (N = 10 animals) were seen, of which 66% had confluent tumors and this was a significant predictor of recurrence (P < 0.001). Recurrent tumors were also significantly larger (mean 4,578 mm(3) ± SD 877 versus completed electroporated tumors 925.8 ± 277, P < 0.001). Recurrent tumors had a steeper growth curve (slope = 0.73) compared with primary tumors (0.60, P = 0.02). Recurrent tumors also had a significantly higher percentage of EpCAM expression, suggestive of stem cell activation. Tumors that recur after incomplete electroporation demonstrate a biologically aggressive tumor that could be more resistant to standard of care chemotherapy. Clinical correlation of this data is limited, but should be considered when IRE of pancreatic cancer is being

  6. Clinical benefits of combined chemotherapy with S-1, oxaliplatin, and docetaxel in advanced gastric cancer patients with palliative surgery

    PubMed Central

    Liu, Yan; Feng, Ye; Gao, Yongjian; Hou, Ruizhi

    2016-01-01

    Background and aim Advanced gastric cancer accounts for a substantial portion of cancer-related mortality worldwide. Surgical intervention is the curative therapeutic approach, but patients with advanced gastric cancer are not eligible for the radical resection. The present work aimed to investigate the efficacy and safety of palliative surgery combined with S-1, oxaliplatin, and docetaxel chemotherapy in the treatment of patients with advanced gastric cancer. Method A total of 20 patients who underwent palliative resection of gastric cancer in China–Japan Union Hospital of Jilin University from 2010 to 2011 were evaluated. Days 20–30 postoperative, these patients started to receive chemotherapy of S-1 (40 mg/m2, oral intake twice a day) and intravenous infusion of oxaliplatin (135 mg/m2) and docetaxel (75 mg/m2). After three cycles of chemotherapy (21 days/cycle), patients were evaluated, and only those who responded toward the treatment continued to receive six to eight cycles of the treatment and were included in end point evaluation. Patients’ survival time and adverse reactions observed along the treatment were compared with those treated with FOLFOX. Results Out of 20 patients evaluated, there was one case of complete response, nine cases of partial response, six cases of stable disease, and four cases of progressive disease. The total efficacy (complete response + partial response) and clinical benefit rates were 50% and 80%, respectively. Of importance, the treatment achieved a significantly longer survival time compared to FOLFOX, despite the fact that both regimens shared common adverse reactions. The adverse reactions were gastrointestinal reaction, reduction in white blood cells, and peripheral neurotoxicity. All of them were mild, having no impact on the treatment. Conclusion Combination therapy of S-1, oxaliplatin, and docetaxel improves the survival of gastric cancer patients treated with palliative resection, with adverse reactions being

  7. Prognostic Value of Baseline 18F-FDG PET/CT Functional Parameters in Patients with Advanced Lung Adenocarcinoma Stratified by EGFR Mutation Status

    PubMed Central

    Wang, Dalong; Zhang, Minghui; Gao, Xuan; Yu, Lijuan

    2016-01-01

    The study objective was to retrospectively analyze the metabolic variables derived from 18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as predictors of progression-free survival (PFS) and overall survival (OS) in advanced lung adenocarcinoma stratified by epidermal growth factor receptor (EGFR) mutation status. A total of 176 patients (91, EGFR mutation; 85, wild-type EGFR) who underwent 18F-FDG PET/CT before treatment were enrolled. The main 18F-FDG PET/CT-derived variables: primary tumor maximum standardized uptake value (SUVmaxT), primary tumor total lesion glycolysis (TLGT), the maximum SUVmax of all selected lesions in whole body determined using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (SUVmaxWBR), and whole-body total TLG determined using the RECIST 1.1 criteria (TLGWBR) were measured. Survival analysis regarding TLGWBR, and other factors in advanced lung adenocarcinoma patients stratified using EGFR mutation status, were evaluated. The results indicated that high TLGWBR (≥259.85), EGFR wild-type, and high serum LDH were independent predictors of worse PFS and OS in all patients with advanced lung adenocarcinoma. Among patients with wild-type EGFR, only TLGWBR retained significance as an independent predictor of both PFS and OS. Among patients with the EGFR mutation, high serum LDH level was an independent predictor of worse PFS and OS, and high TLGWBR (≥259.85) was an independent predictor of worse PFS but not worse OS. In conclusion, TLGWBR is a promising parameter for prognostic stratification of patients with advanced lung adenocarcinoma and EGFR status; however, it cannot be used to further stratify the risk of worse OS for patients with the EGFR mutation. Further prospective studies are needed to validate our findings. PMID:27336755

  8. Metachronous primary uterine cancer surgically resected during Crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma

    PubMed Central

    Misino, Andrea; Scattone, Anna; Caldarola, Lucia; Petroni, Stella; Logroscino, Antonio; Montagna, Elisabetta Sara; Serio, Gabriella; Simone, Giovanni; Galetta, Domenico

    2016-01-01

    Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of non-small-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slow-growing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out. PMID:26958511

  9. A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

    PubMed Central

    Kollmannsberger, C; Quietzsch, D; Haag, C; Lingenfelser, T; Schroeder, M; Hartmann, J T; Baronius, W; Hempel, V; Clemens, M; Kanz, L; Bokemeyer, C

    2000-01-01

    To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35–74) were enrolled. 5-FU 2 g/m2was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2as a 2 h infusion. Paclitaxel 175 mg/m2was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1–4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% Cl: 35.8–66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1–36+) and 14 months (range 2–36+), respectively. Neutropenia WHO III°/IV° occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III°/IV° toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive

  10. Constitutive hypophosphorylation of extracellular signal-regulated kinases-1/2 and down-regulation of c-Jun in human gastric adenocarcinoma

    SciTech Connect

    Wu, William Ka Kei; Sung, Joseph Joe Yiu; Yu Le; Li Zhijie; Chu, Kent Man; Cho, C.H.

    2008-08-22

    Hyperphosphorylation of extracellular signal-regulated protein kinases-1/2 (ERK1/2) is known to promote cancer cell proliferation. We therefore investigated the constitutive phosphorylation levels of ERK1/2 and the expression of its downstream targets c-Fos, c-Jun, and cyclooxygenase-2 (COX-2) in biopsied human gastric cancer tissues. Results showed that ERK1/2 phosphorylation and c-Jun expression were significantly lowered in gastric cancer compared with the non-cancer adjacent tissues. The expression of c-Fos, however, was not altered while COX-2 was significantly up-regulated. To conclude, we demonstrate that hypophosphorylation of ERK1/2 may occur in gastric cancer. Such discovery may have implication in the application of pathway-directed therapy for this malignant disease.

  11. Efficacy and toxicity of salvage weekly paclitaxel chemotherapy in non-Asian patients with advanced oesophagogastric adenocarcinoma

    PubMed Central

    Tarazona, Noelia; Smyth, Elizabeth C.; Peckit, Clare; Chau, Ian; Watkins, David; Rao, Sheela; Starling, Naureen; Cunningham, David

    2016-01-01

    Objectives: Survival for oesophagogastric adenocarcinoma (OGA) patients varies globally and clinical trial results are seldom replicated in clinical practice. We sought to examine the efficacy and toxicity of salvage paclitaxel chemotherapy for patients with advanced OGA at our institution. Methods: Advanced OGA patients treated with paclitaxel between June 2011 and February 2014 were identified from the electronic record at the Royal Marsden Hospital (RMH), London. Chart review was performed to obtain demographics, performance status (PS), laboratory parameters, radiological response and dates of progression, death and last follow up. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Multivariate Cox regression analysis examined the interaction between clinical and laboratory parameters and survival. Results: Fifty-seven patients were identified; OS and PFS were 5.8 and 2.6 months respectively. From first-line chemotherapy, median OS was 14.3 months. Two-year and three-year survival rates from diagnosis were 26% and 13%. More than or equivalent to Grade 3 neutropenia occurred in 13% of patients. In multivariate analysis, PS more than or equal to 2, alkaline phosphatase (ALP) more than or equal to100 U/L, and previous rechallenge with platinum were independent prognostic factors for OS. Conclusions: OGA cancer patients treated at RMH with salvage paclitaxel had an OS equivalent to patients in clinical trials with more (33%) PS = 2 patients treated and less haematological toxicity than Asian patients. Eastern Cooperative Oncology Group (ECOG) PS more than or equal to 2, ALP more than or equal to 100 U/L, and prior platinum rechallenge were associated with poor survival. However, the proportion of patients surviving more than or equal to two years from diagnosis demonstrates a clinically relevant improvement from historical controls. PMID:26929786

  12. Lauren classification and individualized chemotherapy in gastric cancer

    PubMed Central

    MA, JUNLI; SHEN, HONG; KAPESA, LINDA; ZENG, SHAN

    2016-01-01

    Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy. PMID:27123046

  13. Staging laparoscopy improves treatment decision-making for advanced gastric cancer

    PubMed Central

    Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

    2016-01-01

    AIM: To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). METHODS: Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ2 test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. RESULTS: Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. CONCLUSION: Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy. PMID:26855545

  14. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  15. KRAS G12D Mutation Subtype Is A Prognostic Factor for Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Bournet, Barbara; Muscari, Fabrice; Buscail, Camille; Assenat, Eric; Barthet, Marc; Hammel, Pascal; Selves, Janick; Guimbaud, Rosine; Cordelier, Pierre; Buscail, Louis

    2016-01-01

    Objectives: There is no molecular biomarker available in the clinical practice to assess the prognosis of advanced pancreatic carcinoma. This multicenter prospective study aimed to investigate the role of KRAS mutation subtypes within the primary tumor to determine the prognosis of advanced pancreatic cancer. Methods: The exon-2 KRAS mutation status was tested on endoscopic ultrasound-guided fine-needle aspiration biopsy material (primary tumor; restriction fragment-length polymorphism plus sequencing and TaqMan allelic discrimination) of patients with proven locally advanced and/or metastatic pancreatic ductal carcinoma. We used the Kaplan–Meier method, log-rank test, and Cox's model to evaluate the impact of KRAS status on the overall survival (OS), adjusting for age, stage of disease, clinical performance status, CA 19-9 levels, and treatment. Results: A total of 219 patients (men: 116; mean age: 67±9.4 years) were included: 147 harbored a codon-12 KRAS mutation (G12D: 73; G12V: 53; G12R: 21) and 72 had a wild-type KRAS. There was no difference in the OS between patients with a mutant KRAS (8 months; 95% confidence interval (95% CI): 8.7–12.3) and the wild-type (9 months; 95% CI: 8.7–12.8; hazard ratio (HR): 1.03; P=0.82). However, the patients with a G12D mutation had a significantly shorter OS (6 months; 95% CI: 6.4–9.7) compared with the other patients (OS: 9 months; 95% CI: 10–13; HR: 1.47; P=0.003; i.e., wild type: 9 months, G12V: 9 months, G12R: 14 months). Similar results were observed in the subgroup of 162 patients who received chemotherapy (HR: 1.66; P=0.0013; G12D (n=49): 8 months, wild type (n=56): 10 months, G12V (n=38): 10 months, G12R (n=19): 14 months). Multivariate analyses identified KRAS G12D as an independent predictor for worse prognosis within the entire series (HR: 1.44; P=0.01) and in the subgroup of patients that received chemotherapy (HR: 1.84; P=0.02). Conclusions: The KRAS G12D mutation subtype is an independent prognostic

  16. Primary adenocarcinoma of cervical esophagus.

    PubMed

    Alrawi, S J; Winston, J; Tan, D; Gibbs, J; Loree, T R; Hicks, W; Rigual, N; Lorè, J M

    2005-06-01

    Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far. PMID:16110768

  17. Pathology and Genetics of Syndromic Gastric Polyps.

    PubMed

    Brosens, Lodewijk A A; Wood, Laura D; Offerhaus, G Johan; Arnold, Christina A; Lam-Himlin, Dora; Giardiello, Francis M; Montgomery, Elizabeth A

    2016-05-01

    Gastric polyps are found in 1% to 4% of patients undergoing gastroscopy. The vast majority are sporadic, but some gastric polyps indicate an underlying syndrome. Gastric polyps can manifest in each of the gastrointestinal polyposis syndromes, including the recently described gastric adenocarcinoma and proximal polyposis of the stomach syndrome. In addition, gastric polyps occur in Lynch syndrome and in a few rare conditions that are not primarily gastrointestinal. While some of these syndromes are clearly associated with an increased risk of gastric cancer, others are not. Interestingly, even in disorders with a well-established risk of gastric cancer, the neoplastic potential and the precursor status of these gastric polyps are not always clear. Although rare, recognition of syndromic gastric polyps is important for individual patient management. These conditions also serve as important models to study gastric homeostasis and gastric tumorigenesis. PMID:26721304

  18. [Study on endoscopic features in responders to systemic chemotherapy in advanced gastric cancer].

    PubMed

    Yasutake, K; Tokisue, M; Masuda, T; Ono, S; Yoshimura, Y; Yasutake, K; Imamura, Y; Oya, M; Matsushita, K

    1990-10-20

    We studied the endoscopic features in 6 cases of advanced gastric cancer responded to chemotherapy. Patient characteristics were as follows. [table; see text] Age 43-77 (mean 63 years old) Endoscopic type Mean duration of PR was 26.6 weeks. The process of the improvement of primary lesion as judged by endoscopic findings were as follows. Firstly getting flat of wall, secondly reduction in size of ulcer, and lastly changing into scar. Number of reported cases including our case No. 6 which are diagnosed as scar endoscopically after chemotherapy and are operated successfully has been increasing. Most of them showed scar macroscopically with wide and irregular surface. Especially our case No. 6 showed keloidal scar. In these cases, the histological improvement into grade 2-3 was observed in scared tissue. Sooner or later, such a process of endoscopic improvement was observed 4-8 weeks after initiation of chemotherapy. Unless the endoscopic improvement was observed 8 weeks after initiation, regimen of chemotherapy should be changed into others. PMID:2148178

  19. Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

    ClinicalTrials.gov

    2016-03-01

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer

  20. Use of positron emission tomography scan response to guide treatment change for locally advanced gastric cancer: the Memorial Sloan Kettering Cancer Center experience

    PubMed Central

    Won, Elizabeth; Shah, Manish A.; Schöder, Heiko; Strong, Vivian E.; Coit, Daniel G.; Brennan, Murray F.; Kelsen, David P.; Janjigian, Yelena Y.; Tang, Laura H.; Capanu, Marinela; Rizk, Nabil P.; Allen, Peter J.; Bains, Manjit S.

    2016-01-01

    Background Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non-responders. Methods Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m2, cisplatin 60 mg/m2 day 1, and capecitabine 625 mg/m2 bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., ≥35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m2, irinotecan 50 mg/mg2 day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders. Results Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30–85%] in responders compared with 56% in the non-responder group (95% CI, 20–80%, P=0.93). Conclusions The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial. PMID:27563439

  1. Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

    PubMed Central

    YAMASHITA, KEISHI; SAKURAMOTO, SHINICHI; MIENO, HIROAKI; NEMOTO, MASAYUKI; SHIBATA, TOMOTAKA; KATADA, NATSUYA; OHTSUKI, SHIGEAKI; SAKAMOTO, YASUTOSHI; HOSHI, KEIKA; WANG, GUOQIN; HEMMI, OSAMU; SATOH, TOSHIHIKO; KIKUCHI, SHIRO; WATANABE, MASAHIKO

    2015-01-01

    Systemic abrogation of TGF-β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-β was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-β ranged from 1.85–43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-β between groups A and B (P=0.019). PSK reduced the plasma TGF-β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID:26137253

  2. A Phase Ib/II Study Evaluating the Combination of Weekly Docetaxel and Cisplatin Together with Capecitabine and Bevacizumab in Patients with Advanced Esophago-Gastric Cancer

    PubMed Central

    Sarfaty, Michal; Purim, Ofer; Kundel, Yulia; Amit, Limor; Abramovich, Amir; Sadeh Gonik, Udi; Idelevich, Efraim; Gordon, Noa; Medalia, Gal; Sulkes, Aaron

    2016-01-01

    Introduction Current treatment options for advanced esophagogastric cancer (AEGC) are still unsatisfactory. The aim of this prospective phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. Methods Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25–35 mg/m2, days 1,8, capecitabine 1,600 mg/m2 days 1–14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX (phase Ib part) and to determine the tumor response rate (phase II part). Results The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%), usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. The recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). Hence, the objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. For the 17 patients treated at the MTD, the objective response rate was 41% and the disease control rate was 88%. The median overall survival (OS) for these patients was 13.9 months (range, 1.5–52.2 months) and the median progression-free survival was 7.6 months (range, 1.3–26.6 months). The 2-year OS rate reached 23.7%. Conclusions AVDCX was associated with a high rate of regimen related fatal adverse events and is not appropriate for further

  3. Adjuvant therapy for gastric cancer: Current and future directions

    PubMed Central

    Foo, Marcus; Leong, Trevor

    2014-01-01

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies. PMID:25320509

  4. Maintenance therapy with capecitabine in patients with locally advanced unresectable pancreatic adenocarcinoma.

    PubMed

    Saif, Muhammad Wasif; Ledbetter, Leslie; Kaley, Kristin; Garcon, Marie Carmel; Rodriguez, Teresa; Syrigos, Kostas N

    2014-09-01

    Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following

  5. [Introduction of Chemotherapy for Advanced Gastric Cancer Showing Oncologic Emergency Caused by Peritoneal Dissemination--Report of Tow Cases].

    PubMed

    Fujiwara, Yoshiyuki; Omori, Takeshi; Sugimura, Keijiro; Miyata, Hiroshi; Miyoshi, Norikatsu; Akita, Hirofumi; Gotoh, Kunihito; Takahashi, Hidenori; Kobayashi, Shogo; Noura, Shingo; Ohue, Masayuki; Sakon, Masato; Yano, Masahiko

    2015-11-01

    Here, we report 2 patients with gastric cancer and peritoneal dissemination who were successfully treated with chemotherapy after undergoing treatment for an oncologic emergency caused by peritoneal dissemination. Case 1 involved obstruction of the sigmoid colon caused by peritoneal dissemination. After urgent colostomy, S-1/IP IV paclitaxel chemotherapy was introduced. The patient continued the therapy for 2 years and 2 months. Case 2 involved acute renal failure due to bilateral ureter obstruction and obstructive jaundice caused by peritoneal dissemination. This patient underwent emergency treatment consisting of Double-J ureteral stent insertion and endoscopic nasobiliary drainage. He was successfully started on chemotherapy with S-1/oxaliplatin/IP paclitaxel. He continued the therapy for 8 months without symptoms. Aggressive treatment might be effective for advanced gastric cancer showing oncologic emergency. PMID:26805263

  6. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas.

    PubMed

    Byun, Do-Sun; Cho, Kyucheol; Ryu, Byung-Kyu; Lee, Min-Goo; Kang, Min-Ju; Kim, Hak-Ryul; Chi, Sung-Gil

    2003-11-01

    X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects by interfering with the activities of caspases. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. To explore the candidacy of XAF1, Smac/DIABLO, and HtrA2 as a tumor suppressor in gastric tumorigenesis, we investigated the expression and mutation status of the genes in 123 gastric tissues and 15 cancer cell lines. Whereas Smac/DIABLO and HtrA2 transcripts were normally expressed in all cancer specimens we examined, XAF1 transcript was not expressed or present at extremely low levels in 40% (6 of 15) of cancer cell lines and in 23% (20 of 87) of primary carcinomas. Abnormal reduction of XAF1 expression showed a strong correlation with stage and grade of tumors, and a tumor-specific down-regulation of XAF1 was observed in 45% (9 of 20) of matched sets. Unlike XAF1, XIAP expression exhibited no detectable alteration in cancers. Whereas loss of heterozygosity within the XAF1 region or somatic mutations of the gene was not detected, expression of XAF1 transcript was reactivated in all nonexpressor cell lines after 5-aza-2-deoxycytidine treatment. The 5' upstream region of the XAF1 gene encompasses no gastric cell-rich region that rigorously satisfies the formal criteria for CpG islands. However, bisulfite DNA sequencing analysis for 34 CpG sites in the promoter region revealed a strong association between hypermethylation and gene silencing. Moreover, transcriptional silencing of XAF1 was tightly associated with hypermethylation of seven CpGs located in the 5' proximal region (nucleotides -23 to -234). Additionally, loss or abnormal reduction of XAF1 expression was found to inversely correlate with p53 mutations, suggesting that epigenetic inactivation of XAF1 and mutational alteration of p53 might be mutually exclusive

  7. [A Case of Early Gastric Cancer with Nodular Tumor-like Scalp Metastasis].

    PubMed

    Song, Young Wook; Kim, Woo Sub; Yun, Gee Young; Park, Sun Wook; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

    2016-07-25

    Many neoplasms, including lung cancer, breast cancer, melanoma, and gastrointestinal tract malignancy, possess potential for skin metastasis. Skin metastases can represent the first presentation of such malignancies and may be observed incidentally during routine exam. Skin metastases from gastric adenocarcinoma are uncommon, with a prevalence rate of 0.04-0.8%. Cutaneous metastases from gastric cancer are generally observed as the initial symptom of advanced gastric cancer. Early detection and treatment can increase patient survival. A 42-year-old woman visited our department with nodule about 1 cm in size on the right frontal scalp noticed incidentally after laparoscopy-assisted distal gastrectomy and adjuvant systemic chemo-therapy for early gastric cancer about 16 months prior. The patient was diagnosed with skin metastasis from gastric adenocarcinoma. Complete excision of the skin lesion and additional chemotherapy were performed. Herein, we report a case of nodular tumor-like scalp metastasis from early gastric cancer with a brief review of the literature. PMID:27443622

  8. [A Case of Unresectable Local Recurrence of Gastric Cancer Successfully Resected after Pre-Operative Chemotherapy with Trastuzumab].

    PubMed

    Okubo, Satoshi; Takahashi, Tsuyoshi; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Yamazaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2015-11-01

    A 69-year-old man was diagnosed with advanced gastric cancer and underwent total gastrectomy (tubular adenocarcinoma, tub2, pT3N0M0, stageⅡA). Eight months after the surgery, recurrence on the anastomosis was observed. Tumor invasion of the aortic artery was suspected, and the patient was considered inoperable. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy regimen. After 4 courses of the chemotherapy, significant tumor reduction was observed, and the patient underwent anastomosis resection. Chemotherapy with trastuzumab appears to be an effective NAC treatment for HER2-positive, advanced gastric cancer. PMID:26805275

  9. Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

    PubMed Central

    Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

    2015-01-01

    AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

  10. Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer

    PubMed Central

    Zhang, Yong; Ma, Bing; Huang, Xiao-Tian; Li, Yan-Song; Wang, Yu; Liu, Zhou-Lu

    2016-01-01

    Abstract The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC). A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0). Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78–0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72–0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27–1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups. In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens. PMID:26937908

  11. [Urachal adenocarcinoma].

    PubMed

    Dakir, M; Dahami, Z; Sarf, I; Tahri, A; Elmrini, M; Benjelloun, S

    2001-09-01

    Cancer of the urachus is very unusual. The lesion is a mucosecretory adenocarcinoma. The diagnosis is usually established late, and has a serious prognosis because of a long clinical latency. We report a case of metastatic adenocarcinoma of the urachus revealed by hematuria. A review of the literature allows us to demonstrate the rarity of this tumour and to demonstrate its various clinical, histological, radiological and therapeutical aspects. PMID:11761694

  12. Identification of differentially expressed serum proteins in gastric adenocarcinoma☆

    PubMed Central

    Subbannayya, Yashwanth; Mir, Sartaj Ahmad; Renuse, Santosh; Manda, Srikanth S.; Pinto, Sneha M.; Puttamallesh, Vinuth N.; Solanki, Hitendra Singh; Manju, H.C.; Syed, Nazia; Sharma, Rakesh; Christopher, Rita; Vijayakumar, M.; Kumar, K.V. Veerendra; Prasad, T.S. Keshava; Ramaswamy, Girija; Kumar, Rekha V.; Chatterjee, Aditi; Pandey, Akhilesh; Gowda, Harsha

    2015-01-01

    Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based biomarkers of gastric cancer have the potential to improve diagnosis and monitoring of these tumors. Proteins that show altered levels in the circulation of gastric cancer patients could prove useful as putative biomarkers. We used an iTRAQ-based quantitative proteomic approach to identify proteins that show altered levels in the sera of patients with gastric cancer. Our study resulted in identification of 643 proteins, of which 48 proteins showed increased levels and 11 proteins showed decreased levels in serum from gastric cancer patients compared to age and sex matched healthy controls. Proteins that showed increased expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu–Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients. Biological significance Gastric cancer is a highly aggressive cancer associated with high mortality. Serum-based biomarkers are of considerable interest in diagnosis and monitoring of various diseases including cancers. Gastric cancer is often diagnosed at advanced stages resulting in poor prognosis and high mortality. Pathological diagnosis using biopsy specimens remains the gold standard for diagnosis of gastric cancer. Serum-based biomarkers are of considerable importance as they are minimally invasive. In this study, we carried out quantitative proteomic profiling of serum from gastric cancer patients to identify proteins that show altered levels in gastric cancer patients. We identified more than 50 proteins that showed altered levels in gastric cancer patient sera. Validation in a large cohort of well

  13. Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: A meta-analysis

    PubMed Central

    Ge, Lei; Wang, Hai-Jiang; Yin, Dong; Lei, Cheng; Zhu, Jin-Feng; Cai, Xiao-Hui; Zhang, Guo-Qing

    2012-01-01

    AIM: To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis. METHODS: MEDLINE and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the flurouracil-based NAC for gastroesophageal and gastric cancer, and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery. Studies that included patients with metastases at enrollment were excluded. Primary endpoint was the odds ratio (OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer. Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gastroesophageal and gastric cancer. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as the treatment group (NAC plus surgery) vs control group (surgery alone) and was presented as a point estimate with 95% confidence intervals (CI). All calculations and statistical tests were performed using RevMan 5.1 software. RESULTS: Seven RCTs were included for the analysis. A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group (n = 620) and control group (n = 629). The quality scores of the RCTs were assessed according to the method of Jadad. The RCT quality scores ranged from 2 to 7 (5-point scale), with a mean of 3.75. The median follow-up time in these studies was over 3 years. The meta-analysis showed that NAC improved the overall survival rate (OR 1.40, 95%CI 1.11-1.76; P = 0.005), which was statistically significant. The 3-year progression-free survival rate was significantly higher in treatment group than in control group (37.7% vs 27.3%) (OR 1.62, 95%CI 1.21-2.15; P = 0.001). The tumor down-stage rate was higher in treatment group than in control group (55.76% vs 41

  14. Comparison of laparoscopy-assisted and open radical gastrectomy for advanced gastric cancer

    PubMed Central

    Hao, Yingxue; Yu, Peiwu; Qian, Feng; Zhao, Yongliang; Shi, Yan; Tang, Bo; Zeng, Dongzhu; Zhang, Chao

    2016-01-01

    Abstract Laparoscopy-assisted gastrectomy (LAG) has gained international acceptance for the treatment of early gastric cancer (EGC). However, the use of laparoscopic surgery in the management of advanced gastric cancer (AGC) has not attained widespread acceptance. This retrospective large-scale patient study in a single center for minimally invasive surgery assessed the feasibility and safety of LAG for T2 and T3 stage AGC. A total of 628 patients underwent LAG and 579 patients underwent open gastrectomy (OG) from Jan 2004 to Dec 2011. All cases underwent radical lymph node (LN) dissection from D1 to D2+. This study compared short- and long-term results between the 2 groups after stratifying by pTNM stages, including the mean operation time, volume of blood loss, number of harvested LNs, average days of postoperative hospital stay, mean gastrointestinal function recovery time, intra- and post-operative complications, recurrence rate, recurrence site, and 5-year survival curve. Thirty-five patients (5.57%) converted to open procedures in the LAG group. There were no significant differences in retrieved LN number (30.4 ± 13.4 vs 28.1 ± 17.2, P = 0.43), proximal resection margin (PRM) (6.15 ± 1.63 vs 6.09 ± 1.91, P = 0.56), or distal resection margin (DRM) (5.46 ± 1.74 vs 5.40 ± 1.95, P = 0.57) between the LAG and OG groups, respectively. The mean volume of blood loss (154.5 ± 102.6 vs 311.2 ± 118.9 mL, P < 0.001), mean postoperative hospital stay (7.6 ± 2.5 vs 10.7 ± 3.6 days, P < 0.001), mean time for gastrointestinal function recovery (3.3 ± 1.4 vs 3.9 ± 1.5 days, P < 0.001), and postoperative complications rate (6.4% vs 10.5%, P = 0.01) were clearly lower in the LAG group compared to the OG group. However, the recurrence pattern and site were not different between the 2 groups, even they were stratified by the TNM stage. The 5-year overall survival (OS) rates were 85.38%, 79

  15. Neoadjuvant chemoradiotherapy followed by D2 gastrectomy in locally advanced gastric cancer

    PubMed Central

    Kim, Mi Sun; Lim, Joon Seok; Hyung, Woo Jin; Lee, Yong Chan; Rha, Sun Young; Keum, Ki Chang; Koom, Woong Sub

    2015-01-01

    AIM: To investigate the efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectability of locally advanced gastric cancer (LAGC). METHODS: Between November 2007 and January 2014, 29 patients with LAGC (clinically T3 with distal esophagus invasion/T4 or bulky regional node metastasis) that were treated with NACRT followed by D2 gastrectomy were included in this study. Resectability was evaluated with radiologic and endoscopic exams before and after NACRT. Using three-dimensional conformal radiotherapy, patients received 45 Gy, with a daily dose of 1.8 Gy. The entire tumor extent and the regional metastatic lymph nodes were included in the gross tumor volume. Patients presenting with a resectable tumor after NACRT received a total or subtotal gastrectomy with D2 dissection. The pathologic tumor response was evaluated using Japanese Gastric Cancer Association histologic evaluation criteria. Postoperative morbidity was evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and progression-free survival (PFS) rates were estimated using a Kaplan-Meier analysis and compared using the log-rank test. RESULTS: All patients were assessed as unresectable cases. Twenty-four patients (24/29; 82.8%) showed LAGC on positron emission tomography-computed tomography (CT) and contrast-enhanced CT, whereas four patients (4/29; 13.8%) with vague invasion or abutment to an adjacent organ underwent diagnostic laparoscopy. One patient (1/29; 3.4%), initially assessed as a resectable case, underwent an “open and closure” after the tumor was found to be unresectable. Abutment to an adjacent organ (34.5%) was the most common reason for NACRT. The clinical response rate one month after NACRT was 44.8%. After NACRT, 69% (20/29) of patients had a resectable tumor. Of the 20 patients with a resectable tumor, 18 patients (62.1%) underwent a D2 gastrectomy. The R0 resection rate was 94.4% and two patients (2/18; 11

  16. Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

    PubMed Central

    NAMIKAWA, TSUTOMU; MUNEKAGE, ERI; MUNEKAGE, MASAYA; MAEDA, HIROMICHI; YATABE, TOMOAKI; KITAGAWA, HIROYUKI; SAKAMOTO, KOUICHI; OBATAKE, MASAYUKI; KOBAYASHI, MICHIYA; HANAZAKI, KAZUHIRO

    2016-01-01

    The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3–4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically. PMID:27330770

  17. Gastric metastasis from salivary duct carcinoma mimicking primary gastric cancer

    PubMed Central

    Yamashita, Kanefumi; Takeno, Shinsuke; Nimura, Satoshi; Sugiyama, Yoshikazu; Sueta, Takayuki; Maki, Kenji; Kayashima, Yoshiyuki; Shiwaku, Hironari; Kato, Daisuke; Hashimoto, Tatsuya; Sasaki, Takamitsu; Yamashita, Yuichi

    2016-01-01

    Introduction We present a very rare case of gastric metastasis mimicking primary gastric cancer in a patient who had undergone surgery for salivary duct carcinoma. Presentation of case A 67-year-old man had been diagnosed as having right parotid cancer and had undergone a right parotidectomy and lymph node dissection. The histological diagnosis was salivary duct carcinoma. One year after the surgery, a positron emission tomography–computed tomography scan using fluorodeoxyglucose (FDG) revealed an abnormal uptake of FDG in the left cervical, mediastinal, paraaortic, and cardiac lymph nodes; stomach; and pancreas. On gastroduodenoscopy, there was a huge, easily bleeding ulcer mimicking primary gastric cancer at the upper body of the stomach. Biopsy revealed poorly differentiated adenocarcinoma. Therefore, we were unable to differentiate between the primary gastric cancer and the metastatic tumor using gastroduodenoscopy and biopsy. Because of the uncontrollable bleeding from the gastric cancer, we performed an emergency palliative total gastrectomy. On histological examination, the gastric lesion was found to be metastatic carcinoma originating from the salivary duct carcinoma. Discussion In the presented case, we could not diagnose the gastric metastasis originating from the salivary duct carcinoma even by endoscopic biopsy. This is because the histological appearance of salivary duct carcinoma is similar to that of high-grade adenocarcinoma, thus, resembling primary gastric cancer. Conclusion When we perform endoscopic examination of patients with malignant neoplasias, a possibility of metastatic gastric cancer should be taken into consideration. PMID:27085106

  18. [A Case of Advanced Gastric Cancer with Long-Term Survival after Chemotherapy with Combined S-1 and CPT-11].

    PubMed

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

    2015-11-01

    Here, we report a 54-year-old man diagnosed with type 3 advanced gastric cancer who underwent a total gastrectomy and splenectomy plus D2 lymphadenectomy. The pathologic diagnosis was Stage Ⅳ (T3N0H0P0CY1M1). Sixteen courses of combined S-1/CPT-11 chemotherapy were completed, at which time the CPT-11 was discontinued because of malaise, and S-1 alone was continued for a year. The patient is well and has been recurrence-free for 7 years. Thus, he is considered a long- term survivor who was treated with combination S-1/CPT-11 chemotherapy. PMID:26805264

  19. The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells

    PubMed Central

    Zhang, Ye; Mu, Xiao-Dong; Li, En-Zhe; Luo, Ying; Song, Na; Qu, Xiu-Juan; Hu, Xue-Jun; Liu, Yun-Peng

    2013-01-01

    Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in both K562/DNR and SGC7901/ADR cells and significantly inhibited the expression of P-gp. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c-Cbl and Cbl-b. Importantly, β-elemene significantly enhanced the anti-tumor activity of DOX in nude mice bearing SGC7901/ADR xenografts. Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment. PMID:23665906

  20. Hepatoid adenocarcinoma of the stomach: a report of three cases.

    PubMed

    Ye, Min-Feng; Tao, Feng; Liu, Fang; Sun, Ai-Jing

    2013-07-21

    Hepatoid adenocarcinoma of the stomach (HAS) is a rare form of gastric cancer that has unique clinicopathological features and an extremely poor prognosis. Here, we report on three patients with suspected gastric cancer who were referred to our hospital. Gastrointestinal fiberscopy on the three patients revealed two lesions in the antrum and a third lesion in the gastroesophageal junction. The alpha fetoprotein (AFP) serum levels were markedly elevated in all cases. At the time of diagnosis, two cases were advanced stages with lymph nodes and/or liver metastases. Two patients underwent exploratory laparotomy. A total gastrectomy was performed on the operable lesion, and an expanded gastrectomy was completed in the case with hepatic metastases. Histopathological analysis revealed that the tumors displayed two pathological changes: hepatoid-like foci and adenocarcinomatous. Furthermore, the tumor cells were immunohistochemically positive for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. All three patients received chemotherapy. The follow-up duration ranged from 8-36 mo. Our experience and previous published studies have suggested that HAS is an aggressive type of adenocarcinoma. However, radical surgery and chemotherapy may positively impact clinical outcomes. PMID:23885160

  1. New utility of an old marker: serum low-density lipoprotein predicts histopathological response of neoadjuvant chemotherapy in locally advanced gastric cancer

    PubMed Central

    Zhou, Ji-Chun; Guo, Ju-Feng; Teng, Rong-Yue; Wang, Qin-Chuan; Wang, Ji; Wei, Qun; Li, Zi-Duo; Shen, Jian-Guo; Wang, Lin-Bo

    2016-01-01

    Background Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. Patients and methods A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker’s tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. Results Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. Conclusion In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice. PMID:27574445

  2. Histopathological study using computer database of 10 000 consecutive gastric specimens: (2) malignant lesions.

    PubMed

    Terada, Tadashi

    2016-02-01

    Using a computer database, the author investigated the histopathology of 10 000 consecutive gastric specimens collected in the last 12 years 2002-2013 at his pathology laboratory in a relatively large hospital in Japan. Examination of histological sections was done when appropriate. The gastric specimens were made up of 8579 benign conditions and 1421 malignant lesions. The latter comprised gastric carcinoma in 1342 cases (94.4%), gastrointestinal stromal tumor (GIST) in 34 (2.4%), mucosal-associated lymphoid tissue (MALT) lymphoma in 25 (1.8%), non-Hodgkin's malignant lymphoma in 19 (1.3%), and metastatic carcinoma in 1 case (0.1%). Of the 1342 cases of gastric carcinoma, the histological type was as follows: tubular adenocarcinoma in 755 cases, papillary adenocarcinoma in 176, mucinous adenocarcinoma in 147, signet ring cell carcinoma in 145, poorly differentiated adenocarcinoma in 114, adenosquamous carcinoma in 4, and metastatic small cell carcinoma from the lung in 1. In surgically resected cases, the number of early gastric carcinomas was 258 and of advanced carcinoma, 521 cases. In GIST (n = 34), there were 2 cases of the epithelioid type and 32 of the spindle cell type. The size of GIST ranged from 1-15 cm, with a mean of 5.6 cm. KIT (CD117) was positive in 34/34 cases, CD34 in 31/34, desmin 2/34, and S100 4/34. A genetic analysis was performed in 6 cases of GIST, all of which showed point mutation of KIT and/or PDGFRA genes. In MALT lymphoma (n = 25), centrocyte-like cells and lymphoepithelial lesions were seen in every case. Helicobactor pylori infection was noted in 92%. In non-Hodgkin's lymphoma (n = 19), 17 cases were of diffuse large B-cell lymphoma, and 1 was peripheral T-cell lymphoma, while 1 was NK-cell lymphoma. PMID:25667235

  3. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives.

    PubMed

    Biondi, Alberto; Lirosi, Maria C; D'Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando Cm; Persiani, Roberto

    2015-12-15

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  4. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

    PubMed Central

    Biondi, Alberto; Lirosi, Maria C; D’Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando CM; Persiani, Roberto

    2015-01-01

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  5. Gastric Cancer Presenting as a Krukenberg Tumor at 22 Weeks' Gestation

    PubMed Central

    Gupta, Ashutosh; Attar, Bashar M; Demetria, Melchor

    2014-01-01

    Gastric cancer is rare during pregnancy, and often advanced upon presentation. A Krukenberg tumor presents a diagnostic and therapeutic challenge in the pregnant patient. We present a case of a 38-year-old woman at 22 weeks' gestation who presented with worsening epigastric pain, and was found to have a left pelvic mass on ultrasound, which was confirmed by magnetic resonance imaging. She went into active labor and delivered a viable infant via vaginal delivery. An exploratory laparotomy revealed a large mass originating from her left ovary and diffuse thickening of the lesser curvature of the stomach. Frozen section investigation revealed the presence of signet cell adenocarcinoma. Subsequent upper endoscopy showed linitis plastica, while biopsy confirmed the presence of adenocarcinoma. In conclusion, the occurrence of gastric cancer in pregnancy is rare despite extremely common symptoms. The management poses a challenge because of the need for early treatment, and the continuation of the pregnancy. PMID:25580361

  6. Laparoscopic gastric cancer surgery: Current evidence and future perspectives

    PubMed Central

    Son, Taeil; Hyung, Woo Jin

    2016-01-01

    Laparoscopic gastrectomy has been widely accepted as a standard alternative for the treatment of early-stage gastric adenocarcinoma because of its favorable short-term outcomes. Although controversies exist, such as establishing clear indications, proper preoperative staging, and oncologic safety, experienced surgeons and institutions have applied this approach, along with various types of function-preserving surgery, for the treatment of advanced gastric cancer. With technical advancement and the advent of state-of-the-art instruments, indications for laparoscopic gastrectomy are expected to expand as far as locally advanced gastric cancer. Laparoscopic gastrectomy appears to be promising; however, scientific evidence necessary to generalize this approach to a standard treatment for all relevant patients and care providers remains to be gathered. Several multicenter, prospective randomized trials in high-incidence countries are ongoing, and results from these trials will highlight the short- and long-term outcomes of the approach. In this review, we describe up-to-date findings and critical issues regarding laparoscopic gastrectomy for gastric cancer. PMID:26811620

  7. Effectiveness of Magnifying Narrow-Band Imaging Endoscopy for Differential Diagnosis between the High-Risk Mixed-Type and Low-Risk Simple-Type of Low-Grade, Well-Differentiated Gastric Tubular Adenocarcinoma

    PubMed Central

    Takamura, Asako; Watanabe, Gen; Sugitani, Suzuko; Ajioka, Yoichi

    2016-01-01

    Backgrounds. Magnifying endoscopy with narrow-band imaging (NBI-ME) is useful for diagnosing differentiated early gastric cancer (D-EGC). D-EGC is classified as high- or low-grade based on its glandular architectural and cytological atypia. Low-grade, well-differentiated tubular adenocarcinoma (LG-tub1) mixed with high-grade tub1 (HG-tub1) and/or other histological types (M-LG-tub1) may indicate a primitive high-risk malignant lesion compared to histologically simple-type LG-tub1 (S-LG-tub1). Because LG-tub1 is occasionally difficult to diagnose due to its unclear demarcation under conventional white light endoscopy, early precise diagnoses are important. Methods. We compared NBI-ME and postendoscopic submucosal dissection histological findings for 30 S-LG-tub1 and 15 M-LG-tub1 lesions. We classified the NBI-ME findings of S-LG-tub1 (and not D-EGC) into four patterns. The differential diagnosis between M-LG-tub1 and S-LG-tub1 depended on the presence of more than one of these patterns without or with other patterns (referred to as “limited-to-four-pattern [LFP] sign-positive” and “sign-negative”, resp.). Result. The sensitivity, specificity, accuracy, positive and negative predictive values, and intraobserver and interobserver agreement, using the “LFP sign” for the differential diagnosis between M-LG-tub1 and S-LG-tub1, were 87.9%, 91.7%, 88.9%, 96.7%, 73.3%, and k = 0.842 and k = 0.737, respectively. Conclusion. NBI-ME may be useful in differentiating between high-risk M-LG-tub1 and low-risk S-LG-tub1. PMID:27127502

  8. Effectiveness of Magnifying Narrow-Band Imaging Endoscopy for Differential Diagnosis between the High-Risk Mixed-Type and Low-Risk Simple-Type of Low-Grade, Well-Differentiated Gastric Tubular Adenocarcinoma.

    PubMed

    Saitoh, Takashi; Takamura, Asako; Watanabe, Gen; Sugitani, Suzuko; Ajioka, Yoichi

    2016-01-01

    Backgrounds. Magnifying endoscopy with narrow-band imaging (NBI-ME) is useful for diagnosing differentiated early gastric cancer (D-EGC). D-EGC is classified as high- or low-grade based on its glandular architectural and cytological atypia. Low-grade, well-differentiated tubular adenocarcinoma (LG-tub1) mixed with high-grade tub1 (HG-tub1) and/or other histological types (M-LG-tub1) may indicate a primitive high-risk malignant lesion compared to histologically simple-type LG-tub1 (S-LG-tub1). Because LG-tub1 is occasionally difficult to diagnose due to its unclear demarcation under conventional white light endoscopy, early precise diagnoses are important. Methods. We compared NBI-ME and postendoscopic submucosal dissection histological findings for 30 S-LG-tub1 and 15 M-LG-tub1 lesions. We classified the NBI-ME findings of S-LG-tub1 (and not D-EGC) into four patterns. The differential diagnosis between M-LG-tub1 and S-LG-tub1 depended on the presence of more than one of these patterns without or with other patterns (referred to as "limited-to-four-pattern [LFP] sign-positive" and "sign-negative", resp.). Result. The sensitivity, specificity, accuracy, positive and negative predictive values, and intraobserver and interobserver agreement, using the "LFP sign" for the differential diagnosis between M-LG-tub1 and S-LG-tub1, were 87.9%, 91.7%, 88.9%, 96.7%, 73.3%, and k = 0.842 and k = 0.737, respectively. Conclusion. NBI-ME may be useful in differentiating between high-risk M-LG-tub1 and low-risk S-LG-tub1. PMID:27127502

  9. Adenocarcinoma

    Cancer.gov

    Compared to adenomas, adenocarcinomas show greater cytological atypia, increased frequency of mitoses, regional variation in growth pattern, more papillary structures, have size over 5 mm in diameter, show invasion of vessels, large airways or pleura, as well as lymphatic and hematogenous metastases.

  10. Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid

    PubMed Central

    Koizumi, Noriaki; Harada, Yoshinori; Minamikawa, Takeo; Tanaka, Hideo; Otsuji, Eigo; Takamatsu, Tetsuro

    2016-01-01

    Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma. PMID:26811665

  11. Unanswered questions in the management of gastroesophageal junction adenocarcinoma: an overview from the medical oncologist's perspective.

    PubMed

    Shah, Manish A

    2013-01-01

    Patients with gastroesophageal junction (GEJ) adenocarcinoma have multiple treatment options; however, are victims of lack of consensus and wide variation in treatment, sometimes within the same hospital. While there is a consensus that surgery alone is inadequate for locally advanced disease, locoregional treatment has become the point for debate. Only in 2010 was the reclassification of GEJ cancers as esophageal cancers. Treatment options remain as varied as the classification of GEJ cancers: preoperative chemoradiotherapy, definitive chemoradiation, perioperative chemotherapy, and resection followed by postoperative chemoradiation. Several studies have examined the varying treatment paradigms; however, many fall short due to methodology or sample size. The MAGIC study determined perioperative chemotherapy to be an acceptable standard treatment option for patients with gastric cancer, althouth a significant portion of enrolled patients had distal esophageal and GEJ adenocarcinoma. The CROSS study concluded combination chemotherapy and radiation before resection beneficial. Preoperative therapy in cases of GEJ is beneficial for survival, but not as much impact is seen as in esophageal SCC, which exhibits an increased sensitivity to CRT. There is concurrence with two phase III studies from Japan and Korea on the role of adjuvant chemotherapy for gastric cancer. However, the applicability of these studies to GEJ adenocarcinoma remains a question, especially with the significantly different epidemiology of increased proximal and GEJ tumors in the West compared to Asia. To move forward with this increasingly prevalent disease, we will need to do more than understand the multiple treatment paradigms-we will need to select a strategy and examine it. PMID:23714486

  12. The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

    PubMed

    Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

    2014-02-15

    Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. PMID:23907728

  13. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  14. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

    PubMed

    Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-02-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  15. Asian gastric cancer patients at a southern California comprehensive cancer center are diagnosed with less advanced disease and have superior stage-stratified survival.

    PubMed

    Theuer, C P

    2000-09-01

    The 5-year overall survival after curative gastrectomy for gastric cancer is markedly different in the West from that in the Far East. Japanese surgeons feel that extended lymphadenectomy contributes to this superior survival, although survival differences may reflect improved staging or less aggressive tumor biology. We analyzed consecutive cases of gastric adenocarcinoma diagnosed and treated at the University of California, Irvine Medical Center from 1989 through 1998 to determine whether patients of Asian descent diagnosed with gastric cancer in Southern California have improved outcome. Fifty-two cases (36%) occurred in patients of Asian descent (39% Vietnamese, 31% Chinese, 13% Korean, 6% Filipino, and 2% Japanese). Only one Asian patient was born in the United States. Non-Asian patients (67% white, 30% Latino, and 3% black) were younger (59 years vs 64 years; P < 0.05) and more likely to have tumors of the gastroesophageal junction (33% vs 4%; P < 0.001). Asian patients were less likely to have distant metastases (24% vs 39%; P = 0.08), were more likely to undergo formal gastrectomy (71% vs 45%; P < 0.01), and were more likely to undergo a curative resection (40% vs 18%; P < 0.01). The overall survival of Asian patients at 3 years was significantly higher than the overall survival of non-Asians (39.4% vs 19.6%, P < 0.05). Asians with regional (node-positive) disease had superior survival (40.2% vs 14.8%, P < 0.05), which can be largely attributed to greater rates of resectability. We conclude that the clinical behavior of gastric cancer in Asians in Southern California differs from that in non-Asians. The increased proportion of resectable disease and improved survival of patients of Asian descent likely reflects less aggressive tumor biology. PMID:10993608

  16. Successful laparoscopic distal gastrectomy with D2 lymph node dissection preserving the common hepatic artery branched from the left gastric artery for advanced gastric cancer with an Adachi type VI (group 26) vascular anomaly.

    PubMed

    Goto, Hironobu; Yasuda, Takashi; Oshikiri, Taro; Imanishi, Tatsuya; Yamashita, Hironori; Oyama, Masato; Kakinoki, Keitaro; Ohara, Tadayuki; Sendo, Hiroyoshi; Fujino, Yasuhiro; Tominaga, Masahiro; Kakeji, Yoshihiro

    2016-12-01

    We report a case of successful laparoscopic distal gastrectomy with D2 lymph node dissection preserving the common hepatic artery branched from the left gastric artery for advanced gastric cancer with an Adachi type VI (group 26) vascular anomaly. A 76-year-old female patient was admitted with a diagnosis of advanced gastric cancer at the anterior wall to the lesser curvature of the antrum (cT3N0M0 cStage IIA). Dynamic computed tomography showed the ectopia of the common hepatic artery branched from the left gastric artery. We made a diagnosis of an Adachi type VI (group 26) vascular anomaly and performed the abovementioned operation. In this anomaly pattern, scrupulous attention is required to remove the suprapancreatic lymph nodes because the portal vein is located immediately dorsal to those lymph nodes and is at increased risk for the injury in this situation. The common hepatic artery is branched from the left gastric artery, and the hepatic perfusion from the superior mesenteric artery is not present in group 26. Planning to preserve the artery will improve safety when it is possible oncologically. There were no postoperative complications, and the patient was discharged 9 days after the operation. To our knowledge, the present case is the first reported case of a laparoscopic distal gastrectomy with D2 lymph node dissection with an Adachi type VI (group 26) vascular anomaly. Preoperative diagnostic imaging is very important to prevent surgical complications because the reliable identification of vascular anomaly during an operation is very difficult. PMID:27259578

  17. [A Patient with Stage IV Advanced Gastric Cancer with Multiple Liver Metastases Living for More Than 6 Years after Treatment with TS-1 Alone].

    PubMed

    Hara, Ryosuke; Yoshida, Kazuya; Fujii, Toshiyuki; Ikeda, Akihiko; Hashiyata, Hiroshi; Nakamoto, Kenbu; Takeshige, Motohiro

    2016-07-01

    The patient was a 58-year-old man with advanced gastric cancer with multiple liver metastases. He received TXL/TS-1 therapy during February 2009, but treatment was stopped immediately when he developed anorexia, diarrhea, and numbness in his fingers. Therefore, only TS-1 was administered. Following treatment initiation, tumor marker levels promptly dropped. The gastric lesion disappeared and, to date, only a slight scar remains since April 2010. Similarly, liver metastases have not been detected since August 2011. There has been no lesion progression for 6 years since the start of the chemotherapy. PMID:27431636

  18. Phase II Study of Chemoradiotherapy With S-1 and Low-Dose Cisplatin for Inoperable Advanced Gastric Cancer

    SciTech Connect

    Saikawa, Yoshiro Kubota, Tetsuro; Kumagai, Koshi; Nakamura, Rieko; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki; Kitagawa, Yuko

    2008-05-01

    Purpose: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. Patients and Methods: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. Results: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. Conclusion: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.

  19. Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer

    PubMed Central

    Oh, Do-Youn; Doi, Toshihiko; Shirao, Kuniaki; Lee, Keun-Wook; Park, Sook Ryun; Chen, Ying; Yang, Liqiang; Valota, Olga; Bang, Yung-Jue

    2015-01-01

    Purpose This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination. Materials and Methods Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data. Results Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months. Conclusion In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable. PMID:25687867

  20. Early gastric stump cancer following distal gastrectomy

    PubMed Central

    Kaneko, K; Kondo, H; Saito, D; Shirao, K; Yamaguchi, H; Yokota, T; Yamao, G; Sano, T; Sasako, M; Yoshida, S

    1998-01-01

    Background—Gastric stump cancer (GSC) is usually diagnosed at an advanced stage, and consequently the prognosis is poor. 
Aims—To investigate the clinicopathological characteristics of GSC at an early stage to assist in its identification, and thereby improve its prognosis. 
Methods—Forty three patients with resected early GSC were compared with 156 patients with resected primary early cancer in the upper third of the stomach. 
Results—Sixty five per cent (28/43) of the early GSC patients showed the elevated type endoscopically, although the frequency of the depressed type in GSC has tended to increase in the past five years. This occurred in less than 26% (40/156) of the primary early cancers. Half of the early GSCs were located on the lesser curvature (47%), and revealed differentiated adenocarcinoma (81%) histologically. The male:female ratio of early GSC cases was about 6:1, which was much higher than that in patients with primary early cancer. The five year survival rates of patients with early GSCs and early primary cancers were 84% and 95%, respectively. GSC had a favourable prognosis, if it was detected at an early stage. 
Conclusion—To detect early GSC, our results suggest that special attention should be given to elevated as well as depressed lesions on the lesser curvature of the stomach, particularly in men, during endoscopic examinations. 

 Keywords: gastric stump cancer; early gastric cancer; prognosis; endoscopy PMID:9863478

  1. The JAK/STAT signaling cascade in gastric carcinoma (Review).

    PubMed

    Khanna, Puja; Chua, Pei Jou; Bay, Boon Huat; Baeg, Gyeong Hun

    2015-11-01

    Gastric carcinoma remains one of the most prevalent forms of cancer worldwide, despite the decline in incidence rates, increased awareness of the disease and advancement in treatment strategies. Helicobacter pylori infection, dietary factors, lifestyle influences and various genetic aberrations have been shown to contribute to the development and progression of gastric cancer. Recent studies on the genomic landscape of gastric adenocarcinoma have identified several key signaling molecules, including epidermal growth factor receptor family (ErbB) members, vascular endothelial growth factor receptor family (VEGFR) members and PI3K/Akt/mTOR pathway components, that have been implicated in the molecular pathogenesis of gastric cancers. However, clinical trials with compounds that target these molecules have failed to show a significant improvement in overall survival rates when supplemented with conventional therapies. Therefore, it is essential to identify effective prognostic and/or diagnostic biomarkers and develop molecular targeted therapies. The JAK/STAT cascade is a principal signal transduction pathway in cytokine and growth factor signaling, regulating various cellular processes such as cell proliferation, differentiation, migration and survival. Numerous in vivo and in vitro studies have shown that dysregulated JAK/STAT signaling is a driving force in the pathogenesis of various solid cancers as well as hematopoietic malignancies. Hence, a large number of preclinical and clinical studies of drugs targeting this pathway are currently underway. Notably, aberrant JAK/STAT signaling has also been implicated in gastric cancers. In this review, we focus on the ongoing research on the JAK/STAT cascade in gastric carcinoma and discuss the therapeutic potential of targeting JAK/STAT signaling for the treatment of gastric cancer. PMID:26398764

  2. Diagnostic accuracy of 18F-FDG PET/CT for detecting synchronous advanced colorectal neoplasia in patients with gastric cancer.

    PubMed

    Choi, Byung Wook; Kim, Hae Won; Won, Kyoung Sook; Song, Bong-Il; Cho, Kwang Bum; Bae, Sung Uk

    2016-09-01

    Preoperative screening for synchronous colorectal neoplasia (CRN) has been recommended in patients with gastric cancer because patients with gastric cancer are at increased risk for synchronous CRN. The aim of this study was to investigate the diagnostic accuracy of F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting synchronous advanced CRN in patients with gastric cancer.A total of 256 patients who underwent colonoscopy and F-FDG PET/CT for preoperative staging were enrolled in this study. The diagnosis of focal colonic F-FDG uptake on F-FDG PET/CT image was made based on histopathologic results from the colonoscopic biopsy. The F-FDG PET/CT result was considered as true positive for advanced CRN when focal F-FDG uptake matched colorectal carcinoma or adenoma with high-grade dysplasia in the same location on colonoscopy.Synchronous advanced CRN was detected in 21 of the 256 patients (4.7%). Sensitivity, specificity, and accuracy of F-FDG PET/CT were 76.2%, 96.2%, and 94.5%. The size of CRN with a true positive result was significantly larger than that with a false negative result.F-FDG PET/CT demonstrated high diagnostic accuracy for detecting synchronous advanced CRN in patients with gastric cancer. Colonoscopy is recommended as the next diagnostic step for further evaluation of a positive F-FDG PET/CT result in patients with gastric cancer. PMID:27603371

  3. Food group intake and risk of subtypes of esophageal and gastric cancer

    PubMed Central

    SA, Navarro Silvera; ST, Mayne; H, Risch; MD, Gammon; T, Vaughan; W-H, Chow; R, Dubrow; J, Schoenberg; JL, Stanford; AB, West; H, Rotterdam; WJ, Blot; JF, Fraumeni

    2010-01-01

    Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multi-center, population-based case-control study in Connecticut, New Jersey, and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73), and non-cardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and non-cardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma. PMID:18537156

  4. [A Case of Double Cancer of Initially Unresectable Sigmoid Colon Cancer and Advanced Gastric Cancer Treated with Curative Resection after mFOLFOX6 Therapy].

    PubMed

    Yoshikawa, Toru; Aoki, Kazunori; Mitsuhashi, Yuto; Tomiura, Satoko; Suto, Akiko; Miura, Takuya; Ikenaga, Shojirokazunori; Shibasaki, Itaru; Endo, Masaaki

    2016-03-01

    A 61-year-old man was admitted to our hospital because of a complaint of blood in stool. He was diagnosed with advanced colon and gastric cancers. Computed tomography (CT) revealed a sigmoid tumor with invasion to the bladder, a metastatic tumor in the lateral segmental branch of the left hepatic lobe, and ascites. He was diagnosed with initially unresectable double cancer. Ileostomy was performed immediately, and he was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). After 6 courses of the mFOLFOX6 regimen, CT revealed that the primary lesion of the sigmoid colon and liver metastasis had reduced in size, and the ascites had disappeared. Gastroscopy revealed that the gastric cancer had disappeared. Biopsy results were negative. Accordingly, his gastric cancer was diagnosed as treatment effect Grade 3. After 8 courses of mFOLFOX6 therapy, sigmoidectomy, partial resection of the bladder, and partial resection of the liver were performed. Gastric cancer was not resected in accordance with his will. Although 40 months has passed after the radical resection, neither the sigmoid colon cancer nor the gastric cancer recurred. PMID:27067857

  5. Risk of advanced gastric precancerous lesions in Helicobacter pylori infected subjects is influenced by ABO blood group and cagA status

    PubMed Central

    Rizzato, Cosmeri; Kato, Ikuko; Plummer, Martyn; Muñoz, Nubia; Stein, Angelika; van Doorn, Leen Jan; Franceschi, Silvia; Canzian, Federico

    2013-01-01

    A higher incidence of stomach cancer in ABO blood type A individuals than in those with blood type O has been known for a long time. We studied this association in relation to Helicobacter pylori (Hp) of different cagA status. For this study we used baseline gastric histopathology data and DNAs from frozen gastric biopsies of 2077 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela. We analyzed 6 single nucleotide polymorphisms in the ABO gene and we assessed the presence of the Hp cagA gene. Odds ratios for risk of advanced precancerous gastric lesions were calculated using individuals with normal gastric epithelium or non-atrophic gastritis as a reference. Among individuals carrying a cagA negative Hp infection or no Hp infection, those with blood type A had a lower risk of intestinal metaplasia and dysplasia than those with blood type O (OR=0.60; 95% CI 0.38-0.94). In carriers of cagA positive Hp strains, individuals with blood type A had a higher risk of intestinal metaplasia or dysplasia than those with blood type O (OR=1.42, 95% CI 1.09-1.86) and a higher risk if compared with subjects carrying cagA− strain and non-A blood group (OR=3.82, 95%CI=2.80-5.20). The interaction between Hp cagA status and blood type was statistically significant (P=0.0006). We showed that SNPs in the ABO gene, predictive of ABO blood groups, are associated with risk of advanced precancerous gastric lesions in individuals infected with Hp, but the assessment of the risk is strictly dependent on cagA status. PMID:23319424

  6. Imaging Characteristics of Driver Mutations in EGFR, KRAS, and ALK among Treatment-Naïve Patients with Advanced Lung Adenocarcinoma

    PubMed Central

    Park, Jangchul; Kobayashi, Yoshihisa; Urayama, Kevin Y.; Yamaura, Hidekazu; Yatabe, Yasushi; Hida, Toyoaki

    2016-01-01

    This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB–IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups’ characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB–IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal

  7. 18F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value

    PubMed Central

    Kim, Jin Suk; Young Park, Shin

    2014-01-01

    Objective(s): Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. Methods: We analyzed the 18F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The 18F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. Results: Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). Conclusion: An association exists between high SUV and HER2 overexpression and 18F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma.

  8. Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication)

    PubMed Central

    Oinuma, Takeshi

    2014-01-01

    Background and aims: In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin®) for a case of inoperable gastric cancer. Material and methods: The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011. Results: The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011. Conclusion: Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer. PMID

  9. Laparoscopic lymphadenectomy around the left renal vein (16a2lat) by tunneling under the pancreas for advanced Siewert type II adenocarcinoma.

    PubMed

    Takiguchi, Shuji; Miyazaki, Yasuhiro; Murakami, Kohei; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Nakajima, Kiyokazu; Miyata, Hiroshi; Mori, Masaki; Doki, Yuichiro

    2016-09-01

    The para-aortic lymph nodes around the left renal vein (16a2lat) are now considered important to target in the treatment of advanced adenocarcinoma of the esophagogastric junction. We describe a laparoscopic approach for resecting these nodes. This new tunneling approach starts from the ligament of Treitz and then enters the retroperitoneal space. The left renal vein and left adrenal vein are dissected to identify the anatomy of the 16a2lat area. After this dissection, the 16a2lat nodes are retrieved through the suprapancreatic area. Six patients with advanced type II junctional cancer underwent laparoscopic 16a2lat lymph node dissection. The median operative time and estimated blood loss were 479 (390-750) min and 250 (130-500) ml, respectively. The median hospital stay was 22 (17-54) days and there were no deaths or serious complications. Although this series was relatively small, our technique proved effective and feasible. PMID:26482844

  10. Gastric inverted hyperplastic polyp: A rare cause of iron deficiency anemia

    PubMed Central

    Yun, Jin Tak; Lee, Seung Woo; Kim, Dong Pil; Choi, Seung Hwa; Kim, Seok-Hwan; Park, Jun Kyu; Jang, Sun Hee; Park, Yun Jung; Sung, Ye Gyu; Sul, Hae Jung

    2016-01-01

    Gastric inverted hyperplastic polyp (IHP) is a rare gastric polyp characterized by the downward growth of hyperplastic mucosal components into the submucosal layer. Macroscopically, a gastric IHP resembles a subepithelial tumor (SET); as a result, accurately diagnosing gastric IHP is difficult. This issue has clinical significance because gastric IHP can be misdiagnosed as SET or as malignant neoplasm In addition, adenocarcinoma can accompany benign gastric IHP. Although in most cases, gastric IHPs are asymptomatic and are found incidentally, these polyps may cause anemia secondary to chronic bleeding. Here, we report one case involving gastric IHP accompanied by chronic iron deficiency anemia that was successfully managed using endoscopic submucosal dissection. PMID:27099452

  11. Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer

    PubMed Central

    Li, Kai; Chen, Fuchao; Xie, Huijuan

    2016-01-01

    Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in advanced GC and their correlation with prognosis were evaluated. The infiltration of FOXP3+ and GARP+ Tregs in 102 patients with advanced GC who were treated with or without NACT was measured using immunohistochemical method. The infiltration of FOXP3+ and GARP+ Tregs was significantly decreased in the NACT group than in the non-NACT group (P=0.023 and P=0.012, respectively) and significantly associated with tumor, node, metastasis stage (P=0.019 and P=0.011, respectively). There was no significant difference in patient’s overall survival between the NACT and non-NACT groups (P=0.166); however, patients in the NACT group with decreased infiltration of FOXP3+ and GARP+ Tregs had longer overall survival (P=0.002 and P<0.001, respectively). Univariate and multivariate analyses indicated that the infiltration of GARP+ Tregs and lymph node metastasis were independent prognostic factors (P=0.038 and P=0.013, respectively). The results demonstrated that NACT could decrease the infiltration of FOXP3+ and GARP+ Tregs, and that the infiltration of GARP+ Tregs may serve as a new prognostic factor of human GC response to NACT. PMID:27366089

  12. Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.

    PubMed

    Li, Kai; Chen, Fuchao; Xie, Huijuan

    2016-01-01

    Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in advanced GC and their correlation with prognosis were evaluated. The infiltration of FOXP3+ and GARP+ Tregs in 102 patients with advanced GC who were treated with or without NACT was measured using immunohistochemical method. The infiltration of FOXP3+ and GARP+ Tregs was significantly decreased in the NACT group than in the non-NACT group (P=0.023 and P=0.012, respectively) and significantly associated with tumor, node, metastasis stage (P=0.019 and P=0.011, respectively). There was no significant difference in patient's overall survival between the NACT and non-NACT groups (P=0.166); however, patients in the NACT group with decreased infiltration of FOXP3+ and GARP+ Tregs had longer overall survival (P=0.002 and P<0.001, respectively). Univariate and multivariate analyses indicated that the infiltration of GARP+ Tregs and lymph node metastasis were independent prognostic factors (P=0.038 and P=0.013, respectively). The results demonstrated that NACT could decrease the infiltration of FOXP3+ and GARP+ Tregs, and that the infiltration of GARP+ Tregs may serve as a new prognostic factor of human GC response to NACT. PMID:27366089

  13. Isolated Splenic Metastases of Her2+++ Gastroesophageal Junction Adenocarcinoma

    PubMed Central

    Sigrand, Julie; Bazin, Camille; Ewald, Jacques; Dermeche, Slimane; Ries, Pauline; Poizat, Flora; Guiramand, Jerome; Raoul, Jean-Luc

    2016-01-01

    Isolated metastases from gastric adenocarcinoma to the spleen are very infrequent. Usually, there are multiple metastases from gastric cancer, and isolated splenic metastases are very rare [Lam and Tang: Arch Pathol Lab Med 2000;124:526–530] because of certain anatomical and physiological characteristics (e.g., angulation between the splenic artery and celiac trunk, paucity of afferent lymph flow toward the spleen, contractility of the spleen and major immune content). Here, we report 2 cases of isolated splenic metastases from an adenocarcinoma of the gastroesophageal junction, both with long-term survival outcome and overexpression of Her2. PMID:27065846

  14. Isolated Splenic Metastases of Her2+++ Gastroesophageal Junction Adenocarcinoma.

    PubMed

    Sigrand, Julie; Bazin, Camille; Ewald, Jacques; Dermeche, Slimane; Ries, Pauline; Poizat, Flora; Guiramand, Jerome; Raoul, Jean-Luc

    2016-01-01

    Isolated metastases from gastric adenocarcinoma to the spleen are very infrequent. Usually, there are multiple metastases from gastric cancer, and isolated splenic metastases are very rare [Lam and Tang: Arch Pathol Lab Med 2000;124:526-530] because of certain anatomical and physiological characteristics (e.g., angulation between the splenic artery and celiac trunk, paucity of afferent lymph flow toward the spleen, contractility of the spleen and major immune content). Here, we report 2 cases of isolated splenic metastases from an adenocarcinoma of the gastroesophageal junction, both with long-term survival outcome and overexpression of Her2. PMID:27065846

  15. Tumor Heterogeneity in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer Assessed by CT Texture Analysis: Association with Survival after Trastuzumab Treatment

    PubMed Central

    Yoon, Sung Hyun; Lee, Yoon Jin; Park, Jihoon; Kim, Jin Won; Lee, Hye Seung; Kim, Bohyoung

    2016-01-01

    Background Image texture analysis is a noninvasive technique for quantifying intratumoral heterogeneity, with derived texture features reported to be closely related to the treatment outcome of tumors. Gastric cancer is one of the most common tumors and the third leading cause of cancer-related deaths worldwide. Although trastuzumab is associated with a survival gain among patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, optimal patient selection is challenging. The purpose of this study was to determine whether CT texture features of HER2-positive gastric cancer were related to the survival rate after trastuzumab treatment. Methods and Findings Patients diagnosed with HER2-positive advanced gastric cancer from February 2007 to August 2014 were retrospectively selected. Using in-house built software, histogram features (kurtosis and skewness) and gray-level co-occurrence matrices (GLCM) features (angular second moment [ASM], contrast, entropy, variance, and correlation) were derived from the CT images of HER2-positive advanced gastric cancer in 26 patients. All the patients were followed up for more than 6 months, with no confirmed deaths. The patients were dichotomized into a good and poor survival group based on cutoff points of overall survival of 12 months. A receiver-operating characteristics (ROC) analysis was performed to test the ability of each texture parameter to identify the good survival group. Kaplan–Meier curves for patients above and below each threshold were constructed. Using a threshold of >265.8480 for contrast, >488.3150 for variance, and ≤0.1319×10−3. for correlation, all of the area under the ROC curves showed fair accuracy (>0.7). Kaplan–Meier analysis showed statistically significant survival difference between two groups according to optimal cutoff values of contrast, variance, correlation and ASM. However, as this study had a small number of patients, a further study with a larger

  16. Potential predictive role of chemotherapy-induced changes of soluble CD40 ligand in untreated advanced pancreatic ductal adenocarcinoma

    PubMed Central

    Azzariti, Amalia; Brunetti, Oronzo; Porcelli, Letizia; Graziano, Giusi; Iacobazzi, Rosa Maria; Signorile, Michele; Scarpa, Aldo; Lorusso, Vito; Silvestris, Nicola

    2016-01-01

    Pancreas ductal adenocarcinoma lacks predictive biomarkers. CD40 is a member of the tumor necrosis factor superfamily. CD40–sCD40L interaction is considered to contribute to the promotion of tumor cell growth and angiogenesis. The aim of the present study was to investigate the role of serum sCD40L as a predictor in metastatic pancreatic cancer. We evaluated 27 consecutive pancreatic cancer patients treated with FOLFIRINOX (21 patients) or gemcitabine plus nab-paclitaxel combination (six patients). The sCD40L level was measured in serum by enzyme-linked immunosorbent assay at baseline, at first evaluation (all patients), and at time to progression (18 patients). The radiological response was evaluated according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. The Wilcoxon signed-rank test was used to compare pre–post treatment sCD40L levels with respect to clinical response, while Pearson’s correlation coefficient was used for the correlation between sCD40L and CA19.9 pre- and post-treatment. The Kruskal–Wallis test was also conducted for further comparisons. We observed a statistically significant reduction in the sCD40L level after 3 months of treatment in patients with partial response (11,718.05±7,097.13 pg/mL vs 4,689.42±5,409.96 pg/mL; P<0.01). Conversely, in patients with progressive disease, the biomarker statistically increased in the same time (9,351.51±7,356.91 pg/mL vs 22,282.92±11,629.35 pg/mL; P<0.01). This trend of sCD40L was confirmed in 18 patients at time to progression after the first evaluation. No differences were recorded within the stable disease group. Moreover, there was a positive correlation between the sCD40L and CA19.9 pre–post treatment variation percentage (Pearson’s correlation coefficient =0.52; P<0.05). Our data suggest a possible predictive role of sCD40L in pancreatic cancer patients, similar to CA19.9. PMID:27555786

  17. Potential predictive role of chemotherapy-induced changes of soluble CD40 ligand in untreated advanced pancreatic ductal adenocarcinoma.

    PubMed

    Azzariti, Amalia; Brunetti, Oronzo; Porcelli, Letizia; Graziano, Giusi; Iacobazzi, Rosa Maria; Signorile, Michele; Scarpa, Aldo; Lorusso, Vito; Silvestris, Nicola

    2016-01-01

    Pancreas ductal adenocarcinoma lacks predictive biomarkers. CD40 is a member of the tumor necrosis factor superfamily. CD40-sCD40L interaction is considered to contribute to the promotion of tumor cell growth and angiogenesis. The aim of the present study was to investigate the role of serum sCD40L as a predictor in metastatic pancreatic cancer. We evaluated 27 consecutive pancreatic cancer patients treated with FOLFIRINOX (21 patients) or gemcitabine plus nab-paclitaxel combination (six patients). The sCD40L level was measured in serum by enzyme-linked immunosorbent assay at baseline, at first evaluation (all patients), and at time to progression (18 patients). The radiological response was evaluated according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. The Wilcoxon signed-rank test was used to compare pre-post treatment sCD40L levels with respect to clinical response, while Pearson's correlation coefficient was used for the correlation between sCD40L and CA19.9 pre- and post-treatment. The Kruskal-Wallis test was also conducted for further comparisons. We observed a statistically significant reduction in the sCD40L level after 3 months of treatment in patients with partial response (11,718.05±7,097.13 pg/mL vs 4,689.42±5,409.96 pg/mL; P<0.01). Conversely, in patients with progressive disease, the biomarker statistically increased in the same time (9,351.51±7,356.91 pg/mL vs 22,282.92±11,629.35 pg/mL; P<0.01). This trend of sCD40L was confirmed in 18 patients at time to progression after the first evaluation. No differences were recorded within the stable disease group. Moreover, there was a positive correlation between the sCD40L and CA19.9 pre-post treatment variation percentage (Pearson's correlation coefficient =0.52; P<0.05). Our data suggest a possible predictive role of sCD40L in pancreatic cancer patients, similar to CA19.9. PMID:27555786

  18. Identification of potential erythrocyte phospholipid fatty acid biomarkers of advanced lung adenocarcinoma, squamous cell lung carcinoma, and small cell lung cancer.

    PubMed

    Sánchez-Rodríguez, Patricia; Rodríguez, Marina C; Sánchez-Yagüe, Jesús

    2015-07-01

    New biomarkers for lung cancer would be valuable. Our aim was to analyze the fatty acid profiles of the main phospholipid species in erythrocytes from patients with advanced squamous cell lung carcinoma (SCC), lung adenocarcinoma (ADC), and small cell lung cancer (SCLC) and benign lung diseases (chronic obstructive pulmonary disease (COPD) and asthma) to determine the fatty acids that could be use as lung cancer markers. Twenty-eight, 18, 14, 16, and 15 patients with, respectively, SCC, ADC, SCLC, asthma, and COPD and 50 healthy subjects were enrolled in the study. Fatty acid profiles were investigated using gas chromatography/mass spectrometry followed by receiver operating characteristic (ROC) curve analysis. The fatty acid profiles changed significantly in the different pathologies analyzed. Based on the diagnostic yields and operating characteristics, the most significant fatty acids that might be used as biomarkers were as follows: ADC--arachidonic acid (20:4n6) in phosphatidylcholine and oleic acid (18:1n9) in phosphatidylethanolamine (PE); SCC--eicosapentaenoic acid (20:5n3) in PE and palmitic acid (16:0) in phosphatidylserine + phosphatidylinositol (PS+PI); SCLC--eicosadienoic acid (20:2n6) in PS+PI and lignoceric acid (24:0) in sphingomyelin. In conclusion, fatty acids from erythrocyte phospholipid species might serve as biomarkers in the diagnosis, and probably in other aspects related to clinical disease management, of ADC, SCC, and SCLC. PMID:25702090

  19. Oncologic value of laparoscopy-assisted distal gastrectomy for advanced gastric cancer: A systematic review and meta-analysis

    PubMed Central

    Aurello, Paolo; Sagnotta, Andrea; Terrenato, Irene; Berardi, Giammauro; Nigri, Giuseppe; D'Angelo, Francesco; Ramacciato, Giovanni

    2016-01-01

    BACKGROUND: The oncologic validity of laparoscopic-assisted distal gastrectomy (LADG) in the treatment of advanced gastric cancer (AGC) remains controversial. This study is a systematic review and meta-analysis of the available evidence. MATERIALS AND METHODS: A comprehensive search was performed between 2008 and 2014 to identify comparative studies evaluating morbidity/mortality, oncologic surgery-related outcomes, recurrence and survival rates. Data synthesis and statistical analysis were carried out using RevMan 5.2 software. RESULTS: Eight studies with a total of 1456 patients were included in this analysis. The complication rate was lower in LADG [odds ratio (OR) 0.59; 95% confidence interval (CI) = 0.42-0.83; P < 0.002]. The in-hospital mortality rate was comparable (OR 1.22; 95% CI = 0.28-5-29, P = 0.79). There was no significant difference in the number of harvested lymph nodes, resection margins, cancer recurrence rate, cancer-related mortality or overall and disease-free survival (OS and DFS, respectively) rates between the laparoscopic and the open groups (P > 0.05). CONCLUSION: The current study supports the view that LADG for AGC is a feasible, safe and effective procedure in selected patients. Adequate lymphadenectomy, resection margins, recurrence, cancer-related mortality and long-term outcomes appear equivalent to open distal gastrectomy (ODG). PMID:27279389

  20. Theranostic, pH-Responsive, Doxorubicin-Loaded Nanoparticles Inducing Active Targeting and Apoptosis for Advanced Gastric Cancer.

    PubMed

    Ma, Huanrong; Liu, Yuqing; Shi, Min; Shao, Xuebing; Zhong, Wen; Liao, Wangjun; Xing, Malcolm M Q

    2015-12-14

    This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(β-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F-P-DOX). Confocal microscopy illustrated that F-P-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F-P-DOX. The better efficacy of F-P-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F-P-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F-P-DOX could be a promising theranostic candidate for AGC treatment. PMID:26477267

  1. Phenytoin toxicity in a patient receiving concomitant use of phenytoin and S-1 plus cisplatin chemotherapy for advanced gastric cancer.

    PubMed

    Mimatsu, Kenji; Oida, Takatsugu; Kawasaki, Atsushi; Kida, Kazutoshi; Fukino, Nobutada; Kuboi, Youichi; Kano, Hisao; Amano, Sadao

    2011-06-01

    A 61-year-old man had been receiving phenytoin(225mg/day)and valproate(600mg/day)for several years as the treatment for seizures. He was diagnosed with advanced gastric cancer,and S-1 plus cisplatin treatment was administered as neoadjuvant chemotherapy because bulky lymph node metastases were found at the time of the initial diagnosis. He complained of weakness of the lower extremities,light -headedness,and trembling of the upper extremities 2 months after the start of concomitant treatment with S-1 plus cisplatin. The serum phenytoin concentration increased to 21. 2mg/mL. Head computed tomography and magnetic resonance imaging did not reveal any intracranial lesion such as brain metastasis. Therefore, we diagnosed phenytoin toxicity due to concomitant use of S-1 and phenytoin,and the dose of phenytoin was then decreased to 150 mg. Although the weakness of the lower extremities improved,light -headedness remained. Phenytoin and valproate treatments were stopped,and he was able to walk 7 days after the termination of therapy. It is important to predict the timing of phenytoin toxicity due to S-1,and therapeutic drug monitoring should be performed in patients receiving S-1 plus cisplatin and phenytoin. PMID:21677496

  2. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

  3. Clinical Efficacy of Endoscopic Submucosal Dissection for Adenocarcinomas of the Esophagogastric Junction

    PubMed Central

    Nagami, Yasuaki; Machida, Hirohisa; Shiba, Masatsugu; Obayashi, Tomoko; Ominami, Masaki; Fukunaga, Shusei; Sugimori, Satoshi; Yamagami, Hirokazu; Tanigawa, Tetsuya; Watanabe, Kenji; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2014-01-01

    Background and Study Aims There are a few reports about the efficacy of endoscopic submucosal dissection (ESD) for adenocarcinomas of the esophagogastric junction (EGJ). However, there is no detailed analysis that divides EGJ cancers into Barrett’s adenocarcinoma and gastric cardia adenocarcinoma. The aim of this study was to analyze the efficacy of ESD for EGJ cancers, comparing these two adenocarcinomas. Patients and Methods This study included 43 patients who underwent ESD for type II EGJ cancers between 2004 and 2011. Pathological examination of resected specimens confirmed 14 cases of Barrett’s adenocarcinoma and 29 cases of gastric cardia adenocarcinoma. Cutting margins on the oral side were placed 1 cm from the squamocolumnar junction, or 1 cm away from the slight elevation that is an endoscopic sign of subsquamous carcinoma extension. Clinical outcomes, prevalence and length of subsquamous carcinoma extension, and long-term outcomes were compared between these two types of adenocarcinoma. Results No significant differences in clinical outcomes were found between these two types of adenocarcinoma (en bloc, 100 % versus 100 %; complete, 100 % versus 89.7 %; curative, 85.7 % versus 75.9 %). No serious adverse events were encountered. The prevalence of subsquamous carcinoma extension was significantly higher in Barrett’s adenocarcinoma compared with gastric cardia adenocarcinoma. Local and distant recurrence were not observed in any cases with curative resection during the follow-up period (1.6 – 87.6 months). Conclusion ESD for EGJ cancers, including both Barrett’s adenocarcinoma and gastric cardia adenocarcinoma, was efficient and useful. ESD with a 1 cm safety margin may be acceptable for EGJ cancers. PMID:26134607

  4. Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis

    PubMed Central

    zur Hausen, A; van Rees, B P; van Beek, J; Craanen, M E; Bloemena, E; Offerhaus, G J A; Meijer, C J L M; van den Brule, A J C

    2004-01-01

    Background: To determine at what stage during gastric carcinogenesis Epstein-Barr virus (EBV) enters the gastric epithelial cells, the presence of EBV was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomach—gastric carcinoma of the intact stomach (GCIS) and gastric stump carcinoma (GSC)—and their presumed precursor lesions. Patients and methods: Eleven patients with EBV positive GCIS and eight patients with EBV positive GSC, demonstrated by the highly sensitive EBV encoded RNA 1/2 (EBER1/2) RNA in situ hybridisation (RISH) technique, were studied. Paraffin wax embedded tissue available from preoperative gastric biopsies and tumour adjacent tissue from the resection specimens containing normal gastric mucosa, inflamed gastric mucosa, and preneoplastic lesions (intestinal metaplasia and dysplasia) was investigated by EBER1/2 RISH, in addition to EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1 (LMP-1) immunohistochemistry (IHC). Results: In both GCIS and GSC and their precursor lesions EBER1/2 transcripts were restricted to the carcinoma cells. In addition, positivity of EBNA-1 IHC was also restricted to the tumour cells. IHC for LMP-1 was negative in all cases tested. Conclusions: The absence of EBER1/2 transcripts in preneoplastic gastric lesions (intestinal metaplasia and dysplasia) and their presence in two distinct types of gastric carcinoma strongly suggest that EBV can only infect neoplastic gastric cells and thus is a late event in gastric carcinogenesis. PMID:15113855

  5. New Insights in Histogenetic Pathways of Gastric Cancer

    PubMed Central

    Gurzu, Simona; Sugimura, Haruhiko; Orlowska, Janina; Szentirmay, Zoltan; Jung, Ioan

    2015-01-01

    Abstract The aim of this paper was to describe 3 possible histogenetic pathways for poorly cohesive (diffuse) carcinomas and 2 for intestinal-type gastric carcinomas (GCs), which might influence the behavior of GC. In the present observational study, 102 patients with early (n = 50) and advanced GCs (n = 52) were evaluated, and the histogenetic background was analyzed. All of the cases were sporadic GCs. For particular aspects, Maspin, E-cadherin, and SLUG immunostains were performed. For our final conclusions, the results were correlated with literature data. In early stages, poorly cohesive carcinomas can display 3 histogenetic pathways, with particular molecular behaviors: “carcinoma with intraepithelial pagetoid onset” (with or without a switch from E-cadherin to SLUG positivity), “carcinoma with early lymphatic invasion” (carcinoma limited to mucosa but with carcinomatosis of the lymph vessels from subjacent layers), and “microglandular-type poorly cohesive carcinoma” (the onset is similar with adenocarcinoma but abrupt dedifferentiation can be seen in the submucosa, with persistence of a dual component in the deep layers). The intestinal type carcinoma can be developed on the background of superficially located dysplasia (“classic adenocarcinoma”) or in the submucosal heterotopic mucosa (“adenocarcinoma arising from the mucosal infolding in the submucosa”). Based on personal observations correlated with literature data, 5 histopathogenetic pathways are proposed with specific denominations. Each of them can partially explain the aberrant behavior of early gastric cancer. PMID:26496316

  6. [A Case of Resected Advanced Gastric Cancer Exhibiting Pathological Complete Response after Neoadjuvant Che-motherapy(DTX/CDDP/S-1:DCS)].

    PubMed

    Suzuki, Yoshihiro; Kunisaki, Chikara; Tsuburaya, Akira; Ohshima, Takashi; Yukawa, Norio; Rino, Yasushi; Masuda, Munetaka

    2015-11-01

    A 71-year-old man was diagnosed with gastric cancer (LM, Less, type 2, T4aN2M0, cStageⅢb). A diagnostic laparoscopic surgery revealed serosal invasion without peritoneal dissemination. Two courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer using DCS (DTX: 20 mg/m2 on day 1, CDDP: 50 mg/m2 on day 1, S-1: 120 mg/day, twice a day on days 1-14) was performed, which resulted in a clinical partial response. Consequently, distal gastrectomy with D2 lymph node dissection, and BillrothⅠreconstruction were carried out. Histopathological examination revealed no residual cancer cells both in the primary lesion and in the lymph nodes, indicating a pathological complete response (grade 3). Six courses of S-1 (120 mg/day on days 1-28, followed by 2 weeks of rest) were administered as adjuvant chemotherapy. At the 2 years 10 months follow-up after adjuvant therapy, the patient has had no recurrence. Combination chemotherapy with NAC-DCS can be a safe and effective regimen for locally advanced gastric cancer. PMID:26805259

  7. Progression-Free Survival as a Surrogate for Overall Survival in Advanced/Recurrent Gastric Cancer Trials: A Meta-Analysis

    PubMed Central

    Oba, Koji; Bang, Yung-Jue; Bleiberg, Harry; Boku, Narikazu; Bouché, Olivier; Catalano, Paul; Fuse, Nozomu; Michiels, Stefan; Moehler, Markus; Morita, Satoshi; Ohashi, Yasuo; Ohtsu, Atsushi; Roth, Arnaud; Rougier, Philippe; Sakamoto, Junichi; Sargent, Daniel; Sasako, Mitsuru; Shitara, Kohei; Thuss-Patience, Peter; Van Cutsem, Eric; Burzykowski, Tomasz; Buyse, Marc

    2013-01-01

    The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R 2 between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer. PMID:24108811

  8. [New WHO classification of lung adenocarcinoma and preneoplasia].

    PubMed

    Lantuejoul, Sylvie; Rouquette, Isabelle; Brambilla, Elisabeth; Travis, William D

    2016-01-01

    The 2015 WHO classification of tumors of the lung, pleura, thymus and heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes involve (1) use of immunohistochemistry throughout the classification, (2) integration of molecular testing for personalized strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology, (4) a new classification of lung adenocarcinoma as proposed by the 2011 IASLC/ATS/ERS, (5) restriction of the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation. Regarding adenocarcinoma, the terms bronchioloalveolar carcinoma (BAC) and mixed subtype adenocarcinoma have been suppressed and replaced for the former by the term adenocarcinoma in situ (AIS) as a preinvasive lesion to join atypical adenomatous hyperplasia (AAH). A new category has been defined, the minimally invasive adenocarcinoma (MIA), and invasive adenocarcinomas are now classified according to the predominant subtype after subtyping by semi-quantitatively percentage of various subtypes present in 5% increments. The term "lepidic" is restricted to a non-invasive component (previously classified as BAC) present as part of an invasive adenocarcinoma. "Invasive mucinous adenocarcinoma" is used for formerly adenocarcinomas classified as mucinous BAC, excluding tumors that meet criteria for AIS or MIA. The subtypes of clear cell and signet ring adenocarcinoma are discontinued, as well the term of mucinous cystadenocarcinoma, included in the category of colloid adenocarcinoma. Thus new classification of lung adenocarcinoma is sustained by genetics and has clinical impact for therapeutic strategies. PMID:26791238

  9. Helicobacter pylori infection in patients with early gastric cancer by the endoscopic phenol red test

    PubMed Central

    Iseki, K; Tatsuta, M; Iishi, H; Baba, M; Ishiguro, S

    1998-01-01

    Background—An endoscopic procedure that uses a pH indicator called phenol red to assess Helicobacter pylori infected gastric mucosa has recently been developed. This test makes it possible to take biopsy specimens from H pylori infected areas. 
Aim—This test was applied to patients with early gastric cancers to clarify the role of H pylori in gastric carcinogenesis. 
Subjects—Sixty five patients with early gastric cancer (50 with differentiated adenocarcinoma and 15 with undifferentiated adenocarcinoma). 
Methods—Patients with early gastric cancer underwent the endoscopic phenol red test before their operation. In this test, areas infected with H pylori can be observed as "coloured" areas where phenol red was turned from yellow to red. 
Results—H pylori infection was significantly (p<0.001) more frequent in patients with differentiated adenocarcinomas than in those with undifferentiated adenocarcinomas. Differentiated adenocarcinomas were usually located in areas of mucosa infected with H pylori, but undifferentiated adenocarcinomas were frequently located in non-infected areas. 
Conclusion—H pylori may be a strong risk factor for differentiated early gastric cancer. 

 Keywords: endoscopic phenol red test; Helicobacter pylori; gastric cancer; differentiated adenocarcinoma; high risk factor PMID:9505880

  10. S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

    PubMed Central

    Yang, Jian; Zhou, Yan; Min, Ke; Yao, Qiang; Xu, Chun-Ni

    2014-01-01

    AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC). METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values. RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens. CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use. PMID:25206296

  11. Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis.

    PubMed

    Oba, Koji; Paoletti, Xavier; Bang, Yung-Jue; Bleiberg, Harry; Burzykowski, Tomasz; Fuse, Nozomu; Michiels, Stefan; Morita, Satoshi; Ohashi, Yasuo; Pignon, Jean-Pierre; Rougier, Philippe; Sakamoto, Junichi; Sargent, Daniel; Sasako, Mitsuru; Shitara, Kohei; Tsuburaya, Akira; Van Cutsem, Eric; Buyse, Marc

    2013-05-01

    We conducted an individual-patient-data meta-analysis of the efficacy of chemotherapy on overall survival (OS) and progression-free survival (PFS) in advanced/recurrent gastric cancer (AGC). Our primary research question was whether the experimental arms of the trials included in the meta-analysis showed a benefit as compared with their corresponding control arms. MEDLINE (up to 2010), Cochrane Central Register of Controlled Trials, National Institutes of Health (NIH) trial registry and proceedings of major oncologic and gastrointestinal cancer meetings were searched. Randomised controlled trials for AGC closed to patient accrual before the end of 2006 were eligible. As of December 2010, individual patient data were available from 22 trials (4245 patients, representing 47% of the targeted data) of 55 eligible trials. The overall comparison of experimental arms with the corresponding control arms showed statistically significant differences in terms of both OS and PFS. Hazard ratio was 0.88 (95% confidence interval 0.82-0.94, P<0.0001) for OS and 0.81 (0.76-0.88, P<0.0001) for PFS. The results of the sub-analysis of adding a given chemotherapeutic agent to any chemotherapy confirm the results of the overall analysis, with a hazard reduction of 11% for OS (P<0.01) and 26% for PFS (P<0.0001). This meta-analysis of individual patient data shows that the additions of experimental chemotherapeutic agents to pre-existing control or standard regimens have produced a modest improvement in OS and PFS. Median survival remained below 1 year for all investigated chemotherapy regimens and none emerged as a clear standard. PMID:23352439

  12. In vitro-activated tumor-specific T lymphocytes prolong the survival of patients with advanced gastric cancer: a retrospective cohort study

    PubMed Central

    Kuai, Jun; Yang, Fang; Li, Guang-Jun; Fang, Xiang-Jie; Gao, Bao-Qin

    2016-01-01

    Background Conventional tumor managements have limited survival benefits and cause severely impaired immune function in patients with advanced gastric cancer (GC) whereas immunotherapies could restore antitumor immunity. This prospective cohort study was aimed at investigating the efficacy of in vitro-activated tumor-specific T lymphocytes combined with chemotherapy on the survival of patients with advanced GC. Patients and methods Two hundred and seventy-four postoperative patients were enrolled in this study to receive either activated T lymphocytes immunotherapy combining chemotherapy (71 patients) or only receive postoperative chemotherapy (203 patients). Overall survival was analyzed by the Kaplan–Meier with log-rank test and Cox’s regression methods. Results The immunotherapy prolonged 9.8-month median survival for advanced gastric cancer (29.70 vs 19.70 months, P=0.036). Furthermore, immunotherapy significantly benefited the survival of patients who underwent radical, palliative resection, and stage III malignancy. No serious adverse effect was observed in the immunotherapy group. Conclusion In vitro-activated tumor-specific T lymphocytes prolonged survival in patients with advanced GC. PMID:27382313

  13. Adenoma-Like Adenocarcinoma

    PubMed Central

    Gonzalez, Raul S.; Cates, Justin M.M.; Washington, M. Kay; Beauchamp, R. Daniel; Coffey, Robert J.; Shi, Chanjuan

    2015-01-01

    Aims A subset of colorectal carcinomas (CRCs) architecturally and cytologically resembles adenomatous change, making them difficult to diagnose on biopsy. This subset has not been well-characterized to date. Methods and results For 35 carcinomas with adenomatous-like areas (cytologic and surface architectural appearance that would be insufficient to warrant a diagnosis of adenocarcinoma if evaluated on biopsy), we recorded staging information, molecular data, clinical outcome, whether precursor adenoma was present, and whether prior biopsy had been diagnosed as malignant. Despite advanced T-category in 23 (66%) tumors, only 7 (20%) had nodal metastases, and only 5 patients (15%) developed distant metastases. Fifteen cases (43%) had been diagnosed as adenoma on biopsy. Twenty-one resections (60%) showed no residual associated adenoma, including 9 called adenoma on biopsy. Median follow-up was 44 months. Four patients (12%) died of disease; 22 were alive at last follow-up. KRAS mutation was seen in 14/24 (58%), and 4/17 (24%) were microsatellite-unstable. Patients had significantly improved survival compared to a cohort of patients with conventional well-differentiated CRC after controlling for age and stage (p=0.011). Conclusions Adenoma-like adenocarcinoma is an uncommon variant of CRC with a low rate of metastasis and good prognosis. Biopsy diagnosis of this lesion may be challenging. PMID:25913616

  14. A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

    PubMed Central

    Rigg, A.; Cunningham, D.; Gore, M.; Hill, M.; O'Brien, M.; Nicolson, M.; Chang, J.; Watson, M.; Norman, A.; Hill, A.; Oates, J.; Moore, H.; Ross, P.

    1997-01-01

    Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5). PMID:9000605

  15. Impact of Smoking and Brain Metastasis on Outcomes of Advanced EGFR Mutation Lung Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

    PubMed Central

    Jain, Amit; Lim, Cindy; Gan, Eugene MingJin; Ng, David Zhihao; Ng, Quan Sing; Ang, Mei Kim; Takano, Angela; Chan, Kian Sing; Tan, Wu Meng; Kanesvaran, Ravindran; Toh, Chee Keong; Loo, Chian Min; Hsu, Anne Ann Ling; Devanand, Anantham; Lim, Chong Hee; Koong, Heng Nung; Koh, Tina; Fong, Kam Weng; Yap, Swee Peng; Kim, Su Woon; Chowbay, Balram; Oon, Lynette; Lim, Kiat Hon; Lim, Wan Teck; Tan, Eng Huat; Tan, Daniel Shao Weng

    2015-01-01

    Objectives This purpose of this study was to examine clinical-pathologic factors – particularly smoking and brain metastases – in EGFR mutation positive (M+) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI. Methods A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M+ ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival. Results 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M+. Amongst never-smokers (n=468), EGFR M+ were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson’s chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival. Conclusions The high prevalence of EGFR M+ in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival. PMID:25955322

  16. Difference in distant failure site between locally advanced squamous cell carcinoma and adenocarcinoma of the uterine cervix after C-ion RT

    PubMed Central

    Wakatsuki, Masaru; Kato, Shingo; Ohno, Tatsuya; Kiyohara, Hiroki; Karasawa, Kumiko; Tamaki, Tomoaki; Ando, Ken; Irie, Daisuke; Shiba, Shintaro; Tsujii, Hirohiko; Nakano, Takashi; Kamada, Tadashi; Shozu, Makio

    2015-01-01

    We investigated the first site of distant failure after carbon ion radiotherapy (C-ion RT) for locally advanced cervical cancer in three clinical trials. A total of 91 cases were enrolled in the three trials (Protocol 9702, 9704 and 9902). Histologically, 36 cases had squamous cell carcinoma (SqCC) and 55 cases had adenocarcinoma (AC), including 13 with adenosquamous cell carcinoma. The number of cases with Stage IIB, IIIB and IVA disease was 21, 59 and 11, respectively. Of the 91 cases, 42 had positive pelvic lymph nodes (PLNs). The median tumor size was 6.0 cm (range, 3.0–12.0 cm). The median follow-up duration for all cases was 40 months (range, 7–181 months). A total of 40 cases developed distant failure as the first site of failure: 13 of 36 (36.1%) SqCC cases had distant failure, with 9 of them with para-aortic lymph node (PALN) failure; 27 of 55 (44.0%) AC cases had distant failure, and 23 of them had distant failure excluding PALN metastasis. Distant failure rates of SqCC cases who had positive and negative PLNs before C-ion RT were 61.1% and 11.1%, respectively (P = 0.0045). Those of AC cases were 54.2% and 45.2%, respectively (P = 0.507). In conclusion, there were high rates of distant failure after C-ion RT in AC cases regardless of PLN status, and there were high rates of distant failure after C-ion RT, especially PALN failure, in SqCC cases with positive PLNs. PMID:25589503

  17. The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Wild, Aaron T.; Ye, Xiaobu; Ellsworth, Susannah G.; Smith, Jessica A.; Narang, Amol K.; Garg, Tanu; Campian, Jian; Laheru, Daniel A.; Zheng, Lei; Wolfgang, Christopher L.; Tran, Phuoc T.; Grossman, Stuart A.; Herman, Joseph M.

    2014-01-01

    Objectives Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affects clinical outcomes. Methods A retrospective analysis of patients with LAPC treated with chemoradiation at a single institution from 1997 to 2011 was performed. Total lymphocyte counts (TLCs) were recorded at baseline and then monthly during and after chemoradiation. The correlation between treatment-induced lymphopenia, established prognostic factors, and overall survival was analyzed using univariate Cox regression analysis. Important factors identified by univariate analysis were selected as covariates to construct a multivariate proportional hazards model for survival. Results A total of 101 patients met eligibility criteria. TLCs were normal in 86% before chemoradiation. The mean reduction in TLC per patient was 50.6% (SD, 40.6%) 2 months after starting chemoradiation (P< 0.00001), and 46% had TLC< 500 cells/mm3. Patients with TLC < 500 cells/mm3 2 months after starting chemoradiation had inferior median survival (8.7 vs. 13.3mo, P= 0.03) and PFS (4.9 vs. 9.0mo, P = 0.15). Multivariate analysis revealed TLC< 500 cells/mm3 to be an independent predictor of inferior survival (HR= 2.879, P= 0.001) along with baseline serum albumin (HR= 3.584, P = 0.0002), BUN (HR = 1.060, P= 0.02), platelet count (HR= 1.004, P = 0.005), and radiation planning target volume (HR= 1.003, P= 0.0006). Conclusions Severe treatment-related lymphopenia occurs frequently after chemoradiation for LAPC and is an independent predictor of inferior survival. PMID:23648440

  18. Current Status on Stem Cells and Cancers of the Gastric Epithelium

    PubMed Central

    Hoffmann, Werner

    2015-01-01

    Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells. PMID:26287172

  19. Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2014-03-28

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  20. S-1 combined with cisplatin versus cisplatin alone for the treatment of advanced gastric cancer: a pilot randomized-controlled trial.

    PubMed

    Wu, Di; Li, Xin; Tong, Jinxue; Sun, Lingyu; Zheng, Hongqun; Gao, Changlu; Yang, Dongdong; Liu, Dongzhe; Zhang, Qifan

    2015-08-01

    We aimed to assess the efficacy and safety of S-1 combined with cisplatin (SC) over cisplatin alone (C) for the treatment of advanced gastric cancer in China. Between July 2009 and June 2011, 72 eligible patients with advanced gastric cancer were selected and divided randomly into two groups. Thirty-six patients received SC, with S-1 on days 1 through 14 of a 21-day cycle and cisplatin (60 mg/m on day 1) every 4 weeks for two cycles. The other 36 patients were administered only cisplatin (in the same manner as SC). The primary outcome was overall survival. The secondary outcomes were progression-free survival and adverse events. The 2-year overall response rate was 51.5 and 42.3% for the SC and C groups, respectively, and the difference was statistically significant, whereas the median overall survival was 9.4 months (range, 1.9-24.4 months) and 7.6 months (range, 1.7-21.4 months), respectively (P=0.039). The median progression-free survival was 7.7 months for SC (range, 1.8-19.4 months), whereas it was 6.5 months (range, 1.5-16.4 months) for C (P=0.047). The toxicity profile was similar in both groups. In summary, we have shown that S-1 combined with cisplatin is more effective, with acceptable toxicity in comparison with cisplatin alone in Chinese patients with advanced gastric cancer. Chinese Clinical Trials Register: ChiCTR-TRC-13003993. PMID:25933246

  1. [A Case of Advanced Gastric Cancer Responding to Neoadjuvant Docetaxel/CDDP/S-1 Therapy with Metallic Stent Placement, Leading to Curative Surgery].

    PubMed

    Yazawa, Keiichi; Kunisaki, Chikara; Kimura, Jun; Takagawa, Ryo; Minami, Yuta; Makino, Hirochika; Suzuki, Yoshihiro; Tsuburaya, Akira; Akiyama, Hirotoshi; Endo, Itaru

    2015-11-01

    A 59-year-old man presented with epigastralgia. A diagnosis of advanced gastric cancer MLU, Circ, Type 3, 160 mm, tub2, cT4b (SI: panc), cN1, cM0, cH0, cP0, cCY0, cStage ⅢB was made. Because of difficulty with oral intake due to malignant outlet obstruction and tumor bleeding, endoscopic self-expanding metallic stent placement was performed. We administered chemotherapy involving docetaxel, cisplatin, and S-1(DCS). After 2 courses of chemotherapy, the primary lesion and regional lymph nodes had reduced in size. His response was judged as SD according to the RECIST criteria. The patient elected to undergo explorative laparotomy for assessment of the gastric cancer. The intraoperative findings showed that there was no pancreatic invasion, peritoneal dissemination, or distal metastasis, so a total gastrectomy and D2 lymph node dissection was performed. The pathological findings showed that there were very few cancer cells in the primary lesion, and a lymph node metastasis was found. The final stage was gastric cancer MLU, Circ, Type 3, 100 mm, muc, ypT4a(SE), ypN3a (13/51), ypM0, ypH0, ypP0, ypCY0, ypStage ⅢC. The therapy evaluation was Grade 1b. In summary, we encountered a patient with gastric cancer in whom curative surgery was made possible by undergoing chemotherapy and metallic stent placement. PMID:26805260

  2. Somatic DNA Hypomethylation in H. pylori-Associated High-Risk Gastritis and Gastric Cancer: Enhanced Somatic Hypomethylation Associates with Advanced Stage Cancer

    PubMed Central

    Leodolter, Andreas; Alonso, Sergio; González, Beatriz; Ebert, Matthias P; Vieth, Michael; Röcken, Christoph; Wex, Thomas; Peitz, Ullrich; Malfertheiner, Peter; Perucho, Manuel

    2015-01-01

    Objectives: Helicobacter pylori-related high-risk gastritis (HRG) is a severe risk factor for gastric cancer (GC). The link between HRG and long-term risk for GC may involve genetic and epigenetic alterations underlying a field defect, i.e. a region of the mucosa prone to cancer development. Global DNA hypomethylation is a pervasive alteration in GC that associates with chromosomal instability and poor prognosis. The aim of this study was to determine the chronology of this alteration along the progression of HRG to GC, to test the hypothesis that it occurs early in the chronology of this pathway and plays a mechanistic role in the long-term cancer risk. Methods: We comparatively measured the genomic methylation level in gastric biopsies from 94 GC patients and 16 of their cancer-free relatives, 38 HRG patients, and 17 GERD patients, using a quantitative enzymatic method. Results: GC biopsies were hypomethylated compared to their matching non-tumor mucosa (P=9.4 × 10−12), irrespective of the tumor location or patients' country of origin. Genome-wide hypomethylation was also found in gastric mucosa of GC (P=1.5 × 10−5) and HRG (P=0.004) patients compared with healthy donors and GC relatives, regardless of the biopsy location within the stomach or previous H. pylori eradication therapy. An enhanced hypomethylation, distinguished by a bi-slope distribution of the differences in methylation between tumor and normal tissues, associated with a more invasive (P=0.005) and advanced stage (P=0.017) type of GC. Conclusions: Universal DNA demethylation in normal gastric mucosa in GC patients appears sporadic rather than familial. Genomic hypomethylation in HRG possibly contributes to a field defect for cancerization that is not reversed by bacterial eradication. Enhanced somatic hypomethylation may stratify GC for prognostic purposes. PMID:25928808

  3. Diagnosis and therapies for gastric non-invasive neoplasia

    PubMed Central

    Kato, Motohiko

    2015-01-01

    There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia (NIN) were divided into low grade and high grade (including intra-mucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection (ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future. PMID:26640329

  4. Pattern-Recognition Receptors and Gastric Cancer

    PubMed Central

    Castaño-Rodríguez, Natalia; Kaakoush, Nadeem O.; Mitchell, Hazel M.

    2014-01-01

    Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy

  5. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    2016-01-01

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer. PMID:27573782

  6. A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer.

    PubMed

    Wu, Fang-Lan; Lu, De-Cheng; Ying, Yan-Ping; Huang, Jin-Jiao; Zhou, Ai-Min; Jiang, Dun-Ke; Chen, Mao-Wei; Yang, Xi; Zhou, Jia; Huang, Hui-Qiao; Zeng, Hong-Yan

    2015-04-01

    The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy. PMID:25906091

  7. Dose-Volume Analysis of Predictors for Gastrointestinal Toxicity After Concurrent Full-Dose Gemcitabine and Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma

    SciTech Connect

    Huang Jiayi; Robertson, John M.; Ye Hong; Margolis, Jeffrey; Nadeau, Laura; Yan Di

    2012-07-15

    Purpose: To identify dosimetric predictors for the development of gastrointestinal (GI) toxicity in patients with locally advanced pancreatic adenocarcinoma (LAPC) treated with concurrent full-dose gemcitabine and radiotherapy (GemRT). Methods and Materials: From June 2002 to June 2009, 46 LAPC patients treated with definitive GemRT were retrospectively analyzed. The stomach and duodenum were retrospectively contoured separately to determine their dose-volume histogram (DVH) parameters. GI toxicity was defined as Grade 3 or higher GI toxicity. The follow-up time was calculated from the start of RT to the date of death or last contact. Univariate analysis (UVA) and multivariate analysis (MVA) using Kaplan-Meier and Cox regression models were performed to identify risk factors associated with GI toxicity. The receiver operating characteristic curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best DVH parameter to predict for GI toxicity. Results: Of the patients, 28 (61%) received concurrent gemcitabine alone, and 18 (39%) had concurrent gemcitabine with daily erlotinib. On UVA, only the V{sub 20Gy} to V{sub 35Gy} of duodenum were significantly associated with GI toxicity (all p {<=} 0.05). On MVA, the V{sub 25Gy} of duodenum and the use of erlotinib were independent risk factors for GI toxicity (p = 0.006 and 0.02, respectively). For the entire cohort, the V{sub 25Gy} of duodenum is the best predictor for GI toxicity (AUC = 0.717), and the 12-month GI toxicity rate was 8% vs. 48% for V{sub 25Gy} {<=} 45% and V{sub 25Gy} > 45%, respectively (p = 0.03). However, excluding the erlotinib group, the V{sub 35Gy} is the best predictor (AUC = 0.725), and the 12-month GI toxicity rate was 0% vs. 41% for V{sub 35Gy} {<=} 20% and V{sub 35Gy} > 20%, respectively (p = 0.04). Conclusions: DVH parameters of duodenum may predict Grade 3 GI toxicity after GemRT for LAPC. Concurrent use of erlotinib during GemRT may increase GI

  8. Gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation: case report and review of the literature.

    PubMed

    Pericleous, Marinos; Toumpanakis, Christos; Lumgair, Heather; Caplin, Martyn E; Morgan-Rowe, Luke; Clark, Ian; Luong, Tu Vinh

    2012-05-01

    Most gastric neuroendocrine tumours are well differentiated and considered as neuroendocrine neoplasms, whilst poorly differentiated lesions are considered as neuroendocrine carcinomas and account for only 6-16% of gastric neuroendocrine tumours. Gastric mixed adenoneuroendocrine carcinomas are rare malignancies usually composed of a neuroendocrine carcinoma and an adenocarcinoma with a variable grade of differentiation. Here, we report an unusual and rare gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation including a neuroendocrine carcinoma, an adenocarcinoma and a squamous cell carcinoma. A brief discussion of the histopathological features, biological behaviour and treatment of this rare tumour type is presented. PMID:22740822

  9. Gastric Mixed Adenoneuroendocrine Carcinoma with a Trilineage Cell Differentiation: Case Report and Review of the Literature

    PubMed Central

    Pericleous, Marinos; Toumpanakis, Christos; Lumgair, Heather; Caplin, Martyn E.; Morgan-Rowe, Luke; Clark, Ian; Luong, Tu Vinh

    2012-01-01

    Most gastric neuroendocrine tumours are well differentiated and considered as neuroendocrine neoplasms, whilst poorly differentiated lesions are considered as neuroendocrine carcinomas and account for only 6–16% of gastric neuroendocrine tumours. Gastric mixed adenoneuroendocrine carcinomas are rare malignancies usually composed of a neuroendocrine carcinoma and an adenocarcinoma with a variable grade of differentiation. Here, we report an unusual and rare gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation including a neuroendocrine carcinoma, an adenocarcinoma and a squamous cell carcinoma. A brief discussion of the histopathological features, biological behaviour and treatment of this rare tumour type is presented. PMID:22740822

  10. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

    PubMed

    Ciliberto, Domenico; Staropoli, Nicoletta; Caglioti, Francesca; Gualtieri, Simona; Fiorillo, Lucia; Chiellino, Silvia; De Angelis, Antonina Maria; Mendicino, Francesco; Botta, Cirino; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2015-01-01

    It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005-2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655-0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847-1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722-0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents. PMID:26061272

  11. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

    PubMed Central

    Ciliberto, Domenico; Staropoli, Nicoletta; Caglioti, Francesca; Gualtieri, Simona; Fiorillo, Lucia; Chiellino, Silvia; De Angelis, Antonina Maria; Mendicino, Francesco; Botta, Cirino; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2015-01-01

    Summary It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005–2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655–0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847–1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722–0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents. PMID:26061272

  12. Expression of p53β and Δ133p53 isoforms in different gastric tissues

    PubMed Central

    Ji, Wansheng; Zhang, Na; Zhang, Hongmei; Ma, Jingrong; Zhong, Hua; Jiao, Jianxin; Gao, Zhixing

    2015-01-01

    This study aims to detect the mRNA of p53β and Δ133p53 isoforms in three gastric carcinoma cell lines and tissues of superficial gastritis, atrophic gastritis, gastric carcinoma, or paracancerous area. Nested reverse transcription PCR was used to detect the mRNA of p53β and Δ133p53 isoforms in tissues of superficial gastritis, chronic atrophic gastritis, gastric cancer cell lines (SGC-7901, MKN45, KATO III), gastric adenocarcinoma, and paracancerous lesion. The amplified products were shown by agarose gel electrophoresis. The expression difference among various tissues was analyzed by x2 tests. The positive rates of ∆133p53 mRNA were 73.3% (11/15) in gastric adenocarcinoma and 20% (3/15) in paracancerous tissue, whereas the positive rates of p53β mRNA were 20% (3/15) in gastric adenocarcinoma and 66.7% (10/15) in paracancerous tissue. The difference between adenocarcinoma and paracancerous tissues was significant (P<0.05). The positive rates of ∆133p53 mRNA were 25% (5/20), 50% (15/30), and 75% (15/20), respectively, in superficial gastritis, atrophic gastritis, and gastric adenocarcinoma; the positive rates of p53β mRNA were 65% (13/20), 33.3% (10/30), and 25% (5/20), respectively, in superficial gastritis, atrophic gastritis, and gastric adenocarcinoma. The difference between adenocarcinoma and superficial gastritis samples was significant (P<0.05). Both p53β and ∆133p53 mRNAs were positive in MKN45; only p53β mRNA was detected in SGC7901; neither p53β nor ∆133p53 mRNA was detected in KATO III. ∆133p53 and p53β, which are possible indicators for the diagnosis and biological therapy of gastric carcinoma, were expressed differentially in different gastric tissues. PMID:26617756

  13. Hepatoid adenocarcinoma of the stomach – proper identification and treatment remain a challenge

    PubMed Central

    Søreide, Jon Arne; Greve, Ole Jacob; Gudlaugsson, Einar; Størset, Svein

    2016-01-01

    ABSTRACT Objective The term hepatoid adenocarcinoma (HAC) of the stomach was introduced three decades ago with the observation of high serum α-fetoprotein (AFP) levels in some gastric adenocarcinoma patients. This very rare gastric cancer patient subgroup is likely frequently misdiagnosed. Material Two patients who were recently diagnosed with HAC of the stomach at our institution are presented. We also performed a structured literature search and reviewed pertinent articles to provide knowledge to improve the proper identification, diagnosis and management of patients with gastric HAC. Results HAC is a rare subgroup of gastric carcinoma with poor prognosis. Clinical management of this population may be challenging. The scientific literature is largely based on very small patient series or case reports, and the evidence for proper decision making and management is considered weak. Conclusion All physicians involved in the diagnosis and treatment of patients with gastric cancer should pay attention to this rare subgroup to improve identification. PMID:26728165

  14. Hepatoid adenocarcinoma of the stomach - proper identification and treatment remain a challenge.

    PubMed

    Søreide, Jon Arne; Greve, Ole Jacob; Gudlaugsson, Einar; Størset, Svein

    2016-06-01

    Objective The term hepatoid adenocarcinoma (HAC) of the stomach was introduced three decades ago with the observation of high serum α-fetoprotein (AFP) levels in some gastric adenocarcinoma patients. This very rare gastric cancer patient subgroup is likely frequently misdiagnosed. Material Two patients who were recently diagnosed with HAC of the stomach at our institution are presented. We also performed a structured literature search and reviewed pertinent articles to provide knowledge to improve the proper identification, diagnosis and management of patients with gastric HAC. Results HAC is a rare subgroup of gastric carcinoma with poor prognosis. Clinical management of this population may be challenging. The scientific literature is largely based on very small patient series or case reports, and the evidence for proper decision making and management is considered weak. Conclusion All physicians involved in the diagnosis and treatment of patients with gastric cancer should pay attention to this rare subgroup to improve identification. PMID:26728165

  15. Concomitant intraarterial cisplatin, intravenous 5-flourouracil, and split-course radiation therapy for locally advanced unresectable pancreatic adenocarcinoma: a phase II study of the Puget Sound Oncology Consortium (PSOC-703).

    PubMed

    Thomas, C R; Weiden, P L; Traverso, L W; Thompson, T

    1997-04-01

    A Gastrointestinal Tumor Study Group (GITSG) protocol showed a survival benefit for patients with locally advanced unresectable pancreatic adenocarcinoma when treated with split-course radiation therapy and bolus intravenous (i.v.) 5-fluorouracil (5-FU) as compared with survival achieved with radiation alone. In an attempt to improve these results, a phase II trial using intraarterial (i.a.) cisplatin, systemic-infusional 5-FU, and concomitant split-course radiation therapy was conducted. Sixteen previously untreated patients with unresectable pancreatic adenocarcinoma (5 with American Joint Committee on Cancer [AJCC] stage I-II, 11 with stage III) disease were treated with i.a. cisplatin 100 mg/m2 by selective celiac arteriography followed by i.v. infusional 5-FU 1,000 mg/m2/day for 4 days, and concomitant split-course external beam photon radiation therapy at 2.0 Gy for 10 days in a 12-day period. After a planned 14-day interval, the identical chemoradiation treatment was repeated; finally, after a second 2-week interval, a third cycle of chemotherapy with a final 10 Gy radiation was administered. All 16 patients were evaluable for response; there were two partial responses (PR: 12%) and five minor responses (31%). Median follow-up period was 77 months. Median time to progression was 6 months (range 1-12 months), and median survival was 9 months (range 4-94 months). Nausea/vomiting was the major toxicity. There were no treatment-related fatalities. This regimen of concomitant i.a. cisplatin, i.v. infusional 5-FU, and split-course external beam photon radiation is well tolerated but has minimal activity in the treatment of locally advanced unresectable pancreatic adenocarcinoma. Future combined-modality protocols for this disease should explore alternative chemoradiation schemes. PMID:9124192

  16. Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach.

    PubMed

    Park, Jason; Schulz, Stephanie; Haaf, Janis; Kairys, John C; Waldman, Scott A

    2002-08-01

    Guanylyl cyclase C (GC-C), a receptor specifically expressed in cells originating from differentiated intestinal epithelium, is a marker and therapeutic target for colorectal cancer metastases. Intestinal metaplasia, in which epithelial cells assume histological and molecular characteristics of differentiated intestinal enterocytes, is a common precursor to adenocarcinomas of the esophagus and stomach. Thus, those tumors, tissues adjacent to them, and their associated regional lymph nodes were assessed for GC-C expression by reverse transcription coupled with the PCR. GC-C mRNA was detected in five of five and eight of nine esophageal and gastric adenocarcinomas, respectively. Also, GC-C mRNA was detected in three of five and six of seven tissues adjacent to, but not histologically involved in, esophageal and gastric adenocarcinomas, respectively, reflecting molecular changes associated with neoplastic transformation preceding histopathological changes. In contrast, three normal gastric specimens did not express GC-C. Furthermore, GC-C mRNA was detected in 1 of 1 lymph node containing tumor cells by histopathology from a patient with gastric adenocarcinoma and in 3 of 11 lymph nodes, all of which were free of tumor cells by histopathology, from a patient with a gastroesophageal junction tumor. This is the first demonstration that GC-C is ectopically expressed by primary and metastatic adenocarcinomas of the esophagus and stomach and suggests that GC-C may be a sensitive and specific clinical marker and target for adenocarcinomas of the upper gastrointestinal tract. PMID:12163327

  17. The relationship between pathologic nodal disease and residual tumor viability after induction chemotherapy in patients with locally advanced esophageal adenocarcinoma receiving a tri-modality regimen

    PubMed Central

    Rybicki, Lisa A.; Sohal, Davendra; Allende, Daniela S.; Videtic, Gregory M. M.; Rodriguez, Cristina P.; Stephans, Kevin L.; Murthy, Sudish C.; Raja, Siva; Raymond, Daniel; Ives, Denise I.; Bodmann, Joanna W.; Adelstein, David J.

    2016-01-01

    Background A complete pathologic response to induction chemo-radiotherapy (CRT) has been identified as a favorable prognostic factor for patients with loco-regionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastro-esophageal junction (E/GEJ). Nodal involvement at the time of surgery has been found to be prognostically unfavorable. Less is known, however, about the prognostic import of less than complete pathologic regression and its relationship to residual nodal disease after induction chemotherapy. Methods Between February 2008 and January 2012, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3-T4 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50 mg/m2 d1, oxaliplatin 130 mg/m2 d1, and fluorouracil 200 mg/m2/day continuous infusion for 3 weeks, was given every 21 days for three courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy at 1.8-2.0 Gy/d and two courses of cisplatin (20 mg/m2/d) and fluorouracil (1,000 mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. Residual viability (RV) was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier projected 3-year overall survival (OS) for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (P<0.001). The Kaplan-Meier projected 3-year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) residual tumor viability was 67%, 42%, and 17% respectively (P=0.004). On multivariable analysis (MVA), both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3-year OS 85% (0-25% viable) vs. 51

  18. Pure intramedullary spinal cord metastasis secondary to gastric cancer.

    PubMed

    Gazzeri, Roberto; Galarza, Marcelo; Faiola, Andrea; Gazzeri, Giovanni

    2006-04-01

    Pure intramedullary spinal-cord metastases (ISCM) are a rare manifestation of cancer. We report a case of ISCM from gastric cancer. A 68-year-old man, treated with total gastrectomy for a gastric cancer, presented 9 months later with paresis of the left arm, pain and dissociated sensory loss. Magnetic resonance imaging revealed a pure intramedullary lesion at the C3-C5 level. After surgical resection, pathological findings revealed an undifferentiated adenocarcinoma of gastric origin. To our knowledge, this is only the second report of ISCM from gastric cancer in the literature. PMID:16465555

  19. Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis.

    PubMed

    Chen, Xiao-Dong; He, Fu-Qian; Chen, Mi; Tang, Ling-Chao; Tang, Xiao-Li

    2016-06-01

    It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83-1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70-1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56-0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1-4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3-4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1-4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3-4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1-4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [-0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = -0.02, 95% CI [-0.05, -0.00], P = 0.04), as well as less all grade 1-4 and grade 3-4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non

  20. PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis

    PubMed Central

    Kwon, Chae Hwa; Park, Hye Ji; Choi, Yu Ri; Kim, Ahrong; Kim, Hye Won; Choi, Jin Hwa; Hwang, Chung Su; Lee, So Jung; Choi, Chang In; Jeon, Tae Yong; Kim, Dae Hwan; Kim, Gwang Ha; Park, Do Youn

    2016-01-01

    Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers. PMID:26894977

  1. [HER2-Positive Advanced Gastric Cancer with Disseminated Intravascular Coagulation and Diffuse Bone Marrow Carcinomatosis Successfully Treated with S-1/Trastuzumab Chemotherapy--A Case Report].

    PubMed

    Senoo, Satoru; Mannami, Tomohiko; Tamura, Tomoki; Fujiwara, Nobukiyo; Ikeda, Genyo; Komoda, Minori; Ohtawa, Yasuyuki; Fujimoto, Yoshimi; Sato, Naohiro; Kambara, Takeshi; Waku, Toshihiko; Kenmotsu, Masaichi; Kurimoto, Etsuko; Okada, Toshiaki; Harita, Shingo; Sonobe, Hiroshi

    2015-12-01

    Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab. PMID:26809307

  2. Elevated serum CA72-4 levels predict poor prognosis in pancreatic adenocarcinoma after intensity-modulated radiation therapy.

    PubMed

    Liu, Peng; Zhu, Yuan; Liu, Luying

    2015-04-20

    Carbohydrate antigen 72-4 (CA72-4) is a human tumor-associated glycoprotein, commonly used as a tumor marker for diagnosing and predicting outcome in gastric and ovarian cancers. However, the relationship between serum CA72-4 levels and prognosis of pancreatic adenocarcinoma has not been fully elucidated. A total of 113 consecutive locally advanced pancreatic adenocarcinoma patients who underwent intensity-modulated radiation therapy (IMRT) with or without chemotherapy were enrolled in this study. Serum CA72-4 levels were analyzed using immunoenzymometric assays. The association between serum CA72-4 levels and prognosis was evaluated. Serum CA72-4 levels was related with lymph node metastasis (P<0.001). The median overall survival time was 14.0 months for patients with serum CA72-4 normal levels and 10.0 months for the elevated levels (P<0.001). Multivariate analysis identified that Serum CA72-4 concentration was a significant prognostic factor (P<0.001). The hazard ratio (HR) of elevated serum CA72-4 levels compared with normal serum CA72-4 levels was 2.34 (95% confidence interval [CI]: 1.46-3.73), after adjusted for gender and age. Based on this finding, Serum CA72-4 is a potential marker to predict lymph node metastasis and prognosis in pancreatic adenocarcinoma. PMID:25860937

  3. An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach

    SciTech Connect

    Kim, Sung; Lim, Do Hoon; Lee, Jeeyun; Kang, Won Ki . E-mail: wkkang@smc.samsung.co.kr; MacDonald, John S.; Park, Chan Hyung; Park, Se Hoon; Lee, Se-Hoon; Kim, Kihyun; Park, Joon Oh; Kim, Won Seog; Jung, Chul Won; Park, Young Suk; Im, Young-Hyuck; Sohn, Tae Sung; Noh, Jae Hyung; Heo, Jin Seok; Kim, Yong Il; Park, Chul Keun; Park, Keunchil

    2005-12-01

    Purpose: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer. Methods and Materials: From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m{sup 2} of fluorouracil plus 20 mg/m{sup 2} of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. Results: The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160). Conclusion: Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence.

  4. EBV-Infection in Cardiac and Non-Cardiac Gastric Adenocarcinomas is Associated with Promoter Methylation of p16, p14 and APC, but not hMLH1

    PubMed Central

    Geddert, Helene; zur Hausen, Axel; Gabbert, Helmut E.; Sarbia, Mario

    2010-01-01

    Background: Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) constitute a distinct clinicopathological entity of gastric cancer. In order to determine underlying distinct aberrant promoter methylation we tested cardiac and non-cardiac GC with regard to the presence of EBV. Methods: One hundred GC were tested by RNA-in situ hybridization for the presence of EBV by EBV-encoded small RNA (EBER). Aberrant promoter methylation was investigated by methylation-specific real-time PCR for p16, p14, APC and hMLH1. P16 protein expression was assessed by immunohistochemistry. Results: In our selected study cohort, EBER-transcripts were detected in 19.6% (18/92) of GC. EBV-positive GC revealed significantly more often gene hypermethylation of p16, p14 and APC (p < 0.0001, p < 0.0001 and p = 0.02, respectively) than EBV-negative GC. The majority of GC with p16 hypermethylation showed a p16 protein loss (22/28). In contrast, no correlation between the presence of EBV and hMLH1 hypermethylation was found (p = 0.7). EBV-positive GC showed a trend towards non-cardiac location (p = 0.06) and lower stages (I/II) according to the WHO (p = 0.05). Conclusion: Hypermethylation of tumor suppressor genes is significantly more frequent in EBV-associated GC compared to EBV-negative GC. Our data add new insights to the role of EBV in gastric carcinogenesis and underline that EBV-associated GC comprise a distinct molecular-pathologic as well as a distinct clinicopathological entity of GC. PMID:20978327

  5. Clinical epidemiology of gastric cancer in Hehuang valley of China: A 10-year epidemiological study of gastric cancer

    PubMed Central

    Yan, Su; Li, Bin; Bai, Zhen-Zhong; Wu, Jun-Qi; Xie, Da-Wei; Ma, Ying-Cai; Ma, Xu-Xiang; Zhao, Jun-Hui; Guo, Xin-Jian

    2014-01-01

    AIM: To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. METHODS: Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient’s characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. RESULTS: The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. CONCLUSION: Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer. PMID:25132766

  6. Gastric cancer with pregnancy: two case reports

    PubMed Central

    Mohamed, Sahar; Chakravarti, Seema

    2011-01-01

    Gastric cancer with pregnancy is quite rare, and is often diagnosed at advanced stages with poor prognosis. This highlights the need to improve diagnosis by means of early endoscopy. We herein report two cases of advanced gastric cancer during pregnancy who sadly died within five weeks of diagnosis, to alert clinicians to this rare disease.

  7. Serum biomarker panels for diagnosis of gastric cancer

    PubMed Central

    Tong, Weihua; Ye, Fei; He, Liang; Cui, Lifeng; Cui, Miao; Hu, Yuan; Li, Wei; Jiang, Jing; Zhang, David Y; Suo, Jian

    2016-01-01

    Purpose Currently, serum biomarkers that are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinomas are not known. In this study, ten serum markers were assessed using the Luminex system and enzyme-linked immunosorbent assay for the diagnosis of gastric cancer and analysis of the relation between prognosis and metastases. Patients and methods A training set consisting of 228 gastric adenocarcinoma and 190 control samples was examined. A Luminex multiplex panel with nine biomarkers, consisting of three proteins discovered through our previous studies and six proteins previously reported to be cancer-associated, was constructed. One additional biomarker was detected using a commercial kit containing EDTA. Logistic regression, random forest (RF), and support vector machine (SVM) were used to identify the panel of discriminatory biomarkers in the training set. After selecting five proteins as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 57 gastric adenocarcinoma and 48 control samples. Results Serum pepsinogen I, serum pepsinogen II, A Disintegrin And Metalloproteinase domain-containing protein 8 (ADAM8), vascular endothelial growth factor (VEGF), and serum IgG to Helicobacter pylori were selected as classifiers in the three algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (RF 79.0%, SVM 83.8%, logistic regression 76.2%). These algorithms also differentiated the samples in the validation set (accuracy: RF 82.5%, SVM 86.1%, logistic regression 78.7%). Conclusion A panel of combinatorial biomarkers comprising VEGF, ADAM8, IgG to H. pylori, serum pepsinogen I, and pepsinogen II were developed. The use of biomarkers is a less invasive method for the diagnosis of

  8. Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in locally advanced gastric cancer (GC) patients after surgery with curative intent

    PubMed Central

    Wakatsuki, Takeru; Stintzing, Sebastian; Zhang, Wu; Yang, Dongyun; Azuma, Mizutomo; Ning, Yan; Yamauchi, Shinichi; Matsusaka, Satoshi; Volz, Nico B.; Sunakawa, Yu; Koizumi, Wasaburo; Watanabe, Masahiko; Barzi, Afsaneh; El Khoueiry, Anthony B; Shah, Manish A; Lenz, Heinz-Josef

    2014-01-01

    Objective Amphiregulin (AREG) and epiregulin (EREG) are important ligands to the epithelial growth factor receptor (EGFR) which is involved in the regulation of progression and stemness in gastric cancer (GC). This study investigated whether frequent single nucleotide polymorphisms (SNPs) in genes of AREG and EREG are associated with recurrence-free survival and overall survival in patients with locally advanced gastric cancer (GC). Methods SNPs with a minor allele frequency of ≥10% were analyzed using direct DNA sequencing in two independent study populations. Results The minor allele of AREG rs1615111 was associated with a significant higher 3-year recurrence rate and lower 3-year survival rate (HR= 2.21 and 2.35 respectively) when compared to patients homozygous for the dominant allele G. The value for overall survival could be validated with a HR of 2.54 (P= 0.018) in an independent cohort. Patients homozygous for the minor allele A of EREG rs12641042 had a significant higher 3-year survival rate than patients having allele C (HR 0.48; P=0.034), but significance was lost in multivariable analysis (P=0.066). Value of rs12641042 could not be validated (P=0.98). Exploratory multivariable subgroup analysis revealed the strongest prognostic value for rs1615111 in tumors with a diffuse histology (Pfor interaction = 0.004). Conclusions AREG rs1615111, located in the AREG genomic region is able to significantly define different prognostic cohorts in locally advanced GC. This value is most evident in GC patients with diffuse histology which might be relevant as none of the trials testing EGFR-inhibitors has been enriched for diffuse histology or a molecularly defined population. PMID:25203737

  9. Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

    PubMed Central

    Liu, Liya; Yu, Hao; Huang, Lihong; Shao, Fang; Bai, Jianling; Lou, Donghua; Chen, Feng

    2015-01-01

    Background The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy. Methods A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model. Results The median OS was 3.37 months (95% confidence interval 2.63–3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83–6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79–6.41; P<0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74–0.90). Similar results were found in the testing data set. Conclusion These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone third-line or later-line chemotherapy. These observations require prospective validation. PMID:25960663

  10. Gastric mixed adenoneuroendocrine carcinoma with a good prognosis.

    PubMed

    Fukuba, Nobuhiko; Yuki, Takafumi; Ishihara, Shunji; Sonoyama, Hiroki; Tada, Yasumasa; Kusunoki, Ryusaku; Oka, Akihiko; Oshima, Naoki; Moriyama, Ichiro; Kawashima, Kousaku; Kinoshita, Yoshikazu

    2014-01-01

    A flat, elevated lesion measuring 5 mm in diameter was found in the gastric body of an 80-year-old man. A biopsy showed moderately differentiated adenocarcinoma, and endoscopic ultrasonography revealed a hypoechoic mass located in the submucosa. Endoscopic submucosal dissection was subsequently performed, and a pathological examination revealed a tumor composed of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration. The pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma (MANEC). An additional gastrectomy procedure was performed, and no recurrence was noted for at least three years. This case is interesting with respect to the carcinogenesis of endocrine cell carcinoma and MANEC. PMID:25400179

  11. Epirubicin-based compared with docetaxel-based chemotherapy for advanced gastric carcinoma: A systematic review and meta-analysis.

    PubMed

    Petrioli, Roberto; Roviello, Giandomenico; Zanotti, Laura; Roviello, Franco; Polom, Karol; Bottini, Alberto; Marano, Luigi; Francini, Edoardo; Marrelli, Daniele; Generali, Daniele

    2016-06-01

    Docetaxel or Epirubicin-based regimens are both approved for the treatment of metastatic gastric cancer. We perform a systemic review with metanalysis to evaluate the efficacy and toxicities of docetaxel-based chemotherapy compared with epirubicin-containing regimens. A metaanalysis of randomized studies in accordance with the preference guidelines for reported items in systematic reviews and meta-analyses is performed in which the databases of PubMed, the Cochrane Library, and the ASCO University Meeting were searched for relevant publications. The primary outcome was efficacy, the secondary toxicities. A total of 553 cases were included in the meta-analysis; 278 received epirubicin-based treatment and 313 received docetaxel. The pooled risk ratio to achieve an objective response and a disease control rate were 1.08 (95% CI 0.85-1.37; P=0.52) and 0.90 (95% CI 0.75-1.08; P=0.27) respectively. EPI arm showed a decrease in the risk of neutropenia, anemia, fatigue, asthenia and diarrhea, paraesthesia; docetaxel arm showed a decrease in the risk of leucopenia, thrombocytopenia, anorexia, nausea, nausea-vomiting, stomatitis and neutropenic fever. The results of our study suggest a similar activity of docetaxel and epirubicin-based chemotherapeutic regimens in metastatic gastric cancer. Other parameters as, comorbidity, concomitant diseases and prior therapies should be taken into account to address the clinician's choice in selecting the best therapeutical approach for any single patient. PMID:27083592

  12. Immunotherapy in gastric cancer

    PubMed Central

    Matsueda, Satoko; Graham, David Y

    2014-01-01

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright. PMID:24587645

  13. MYC Deregulation in Gastric Cancer and Its Clinicopathological Implications

    PubMed Central

    de Souza, Carolina Rosal Teixeira; Leal, Mariana Ferreira; Calcagno, Danielle Queiroz; Costa Sozinho, Eliana Kelly; Borges, Bárbara do Nascimento; Montenegro, Raquel Carvalho; dos Santos, Ândrea Kely Campos Ribeiro; dos Santos, Sidney Emanuel Batista; Ribeiro, Helem Ferreira; Assumpção, Paulo Pimentel; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2013-01-01

    Our study investigated the relationship between MYC alterations and clinicopathological features in gastric cancers. We evaluated the effect of MYC mRNA expression and its protein immunoreactivity, as well as copy number variation, promoter DNA methylation, and point mutations, in 125 gastric adenocarcinoma and 67 paried non-neoplastic tissues. We observed that 77% of the tumors presented MYC immunoreactivity which was significantly associated with increased mRNA expression (p<0.05). These observations were associated with deeper tumor extension and the presence of metastasis (p<0.05). MYC protein expression was also more frequently observed in intestinal-type than in diffuse-type tumors (p<0.001). Additionally, MYC mRNA and protein expression were significantly associated with its copy number (p<0.05). The gain of MYC copies was associated with late-onset, intestinal-type, advanced tumor stage, and the presence of distant metastasis (p<0.05). A hypomethylated MYC promoter was detected in 86.4% of tumor samples. MYC hypomethylation was associated with diffuse-type, advanced tumor stage, deeper tumor extension, and the presence of lymph node metastasis (p<0.05). Moreover, eighteen tumor samples presented at least one known mutation. The presence of MYC mutations was associated with diffuse-type tumor (p<0.001). Our results showed that MYC deregulation was mainly associated with poor prognostic features and also reinforced the presence of different pathways involved in intestinal-type and diffuse-type gastric carcinogenesis. Thus, our findings suggest that MYC may be a useful marker for clinical stratification and prognosis. PMID:23717612

  14. Adeno-carcinoma of the pharyngo-oesophageal junction and cervical oesophagus in a patient with an oesophagus lined entirely by columnar epithelium report of a case treated by photodynamic therapy (PDT).

    PubMed

    Moghissi, K; Dixon, Kate; Campbell, Anne

    2008-09-01

    A case of adenocarcinoma in the pharyngo oesophageal junction extending to the upper cervical oesophagus is described. In this case the neo-plastic changes had occurred from columnar epithelium of gastric and intestinal type: Barrett's oesophagus. The Barrett's mucosa involved the whole length of the oesophagus. Because of the general condition of the patient and advanced stage of the tumour surgical treatment was considered inappropriate. Endoscopic Photofrin Photodynamic Therapy was used with good palliation of dysphagia. The patient survived for 9 months, dying form carcinomatosis and oesophago-airway fistula. As far as can be documented only one such case has been previously reported in the literature. PMID:19356659

  15. Lymphoepithelioma-like gastric carcinoma: A case report and review of the literature.

    PubMed

    Wang, Zhao-Hui; Zhao, Jun-Jun; Yuan, Zhao

    2016-03-14

    Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with Epstein-Barr virus (EBV) infection, concomitant occurrence with differentiated adenocarcinoma is relatively rare. The clinical manifestations of lymphoepithelioma-like gastric carcinoma (including EBV-positive and -negative forms) are similar to those of gastric cancer, and the diagnosis is based on pathologic, histologic, and immunohistochemical findings. This report describes the case of a 55-year-old female patient who presented with a 10-year history of recurrent and worsening abdominal pain and melena that had been occurring for 2 mo. An ulcerative lesion was detected in the stomach by endoscopic examination, which raised suspicion of early gastric cancer. A subsequent preoperative endoscopic biopsy showed adenocarcinoma, but the postoperative pathologic, histologic, and immunohistochemical analyses of the resected specimen revealed a final diagnosis of lymphoepithelioma-like gastric carcinoma. PMID:26973402

  16. Lymphoepithelioma-like gastric carcinoma: A case report and review of the literature

    PubMed Central

    Wang, Zhao-Hui; Zhao, Jun-Jun; Yuan, Zhao

    2016-01-01

    Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with Epstein-Barr virus (EBV) infection, concomitant occurrence with differentiated adenocarcinoma is relatively rare. The clinical manifestations of lymphoepithelioma-like gastric carcinoma (including EBV-positive and -negative forms) are similar to those of gastric cancer, and the diagnosis is based on pathologic, histologic, and immunohistochemical findings. This report describes the case of a 55-year-old female patient who presented with a 10-year history of recurrent and worsening abdominal pain and melena that had been occurring for 2 mo. An ulcerative lesion was detected in the stomach by endoscopic examination, which raised suspicion of early gastric cancer. A subsequent preoperative endoscopic biopsy showed adenocarcinoma, but the postoperative pathologic, histologic, and immunohistochemical analyses of the resected specimen revealed a final diagnosis of lymphoepithelioma-like gastric carcinoma. PMID:26973402

  17. FDA Approval Summary: Ramucirumab for Gastric Cancer.

    PubMed

    Casak, Sandra J; Fashoyin-Aje, Ibilola; Lemery, Steven J; Zhang, Lillian; Jin, Runyan; Li, Hongshan; Zhao, Liang; Zhao, Hong; Zhang, Hui; Chen, Huanyu; He, Kun; Dougherty, Michele; Novak, Rachel; Kennett, Sarah; Khasar, Sachia; Helms, Whitney; Keegan, Patricia; Pazdur, Richard

    2015-08-01

    The FDA approved ramucirumab (CYRAMZA; Eli Lilly and Company) for previously treated patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma initially as monotherapy (April 21, 2014) and subsequently as combination therapy with paclitaxel (November 5, 2014). In the monotherapy trial, 355 patients in the indicated population were randomly allocated (2:1) to receive ramucirumab or placebo, 8 mg/kg intravenously every 2 weeks. In the combination trial, 665 patients were randomly allocated (1:1) to receive ramucirumab or placebo, 8 mg/kg intravenously every 2 weeks, in combination with paclitaxel, 80 mg/m(2) on days 1, 8, and 15 of 28-day cycles. Overall survival (OS) was increased in patients who received ramucirumab in both the monotherapy [HR, 0.78; 95% confidence interval (CI), 0.60-0.998; log rank P = 0.047] and combination trials (HR, 0.81; 95% CI, 0.68-0.96; P = 0.017). The most common adverse reactions were hypertension and diarrhea in the monotherapy trial and fatigue, neutropenia, diarrhea, and epistaxis in the combination trial. Because of concerns about the robustness of the monotherapy trial results, FDA approved the original application after receiving the results of the combination trial confirming the OS effect. Based on exploratory exposure-response analyses, there is residual uncertainty regarding the optimal dose of ramucirumab. PMID:26048277

  18. Syndromic Gastric Polyps: At the Crossroads of Genetic and Environmental Cancer Predisposition.

    PubMed

    Brosens, Lodewijk A A; Giardiello, Francis M; Offerhaus, G Johan; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare not primarily gastrointestinal syndromes. In addition, Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a recently described heritable syndrome characterized by isolated gastric polyposis and risk of gastric cancer.Some of these syndromes are associated with an increased risk of gastric cancer, whereas others are not. However, the neoplastic potential and the precursor status of these gastric polyps are not always clear, even in syndromes with a well-established risk of gastric cancer. For instance, the neoplastic potential of Peutz-Jeghers polyps is debatable, despite the well-established risk of gastric cancer in this syndrome. Also fundic gland polyps and gastric foveolar-type adenomas in FAP carry a low risk of malignant transformation. In contrast, gastric juvenile polyps are precursor lesions of gastric cancer in juvenile polyposis syndrome through neoplastic progression of juvenile polyps in these patients.Although these hereditary syndromes with gastric polyps are rare, recognition is important for individual patient management. Furthermore, the initiation and progression of these lesions can be influenced by environmental factors such as Helicobacter Pylori infection. This makes these rare lesions an appropriate model for understanding the clonal evolution of early gastric cancer in the wider population. PMID:27573780

  19. Learning Curve of the Application of Huang Three-Step Maneuver in a Laparoscopic Spleen-Preserving Splenic Hilar Lymphadenectomy for Advanced Gastric Cancer

    PubMed Central

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

    2016-01-01

    Abstract To investigate the learning curve of the application of Huang 3-step maneuver, which was summarized and proposed by our center for the treatment of advanced upper gastric cancer. From April 2012 to March 2013, 130 consecutive patients who underwent a laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL) by a single surgeon who performed Huang 3-step maneuver were retrospectively analyzed. The learning curve was analyzed based on the moving average (MA) method and the cumulative sum method (CUSUM). Surgical outcomes, short-term outcomes, and follow-up results before and after learning curve were contrastively analyzed. A stepwise multivariate logistic regression was used for a multivariable analysis to determine the factors that affect the operative time using Huang 3-step maneuver. Based on the CUSUM, the learning curve for Huang 3-step maneuver was divided into phase 1 (cases 1–40) and phase 2 (cases 41–130). The dissection time (DT) (P < 0.001), blood loss (BL) (P < 0.001), and number of vessels injured in phase 2 were significantly less than those in phase 1. There were no significant differences in the clinicopathological characteristics, short-term outcomes, or major postoperative complications between the learning curve phases. Univariate and multivariate analyses revealed that body mass index (BMI), short gastric vessels (SGVs), splenic hilar artery (SpA) type, and learning curve phase were significantly associated with DT. In the entire group, 124 patients were followed for a median time of 23.0 months (range, 3–30 months). There was no significant difference in the survival curve between phases. AUGC patients with a BMI less than 25 kg/m2, a small number of SGVs, and a concentrated type of SpA are ideal candidates for surgeons who are in phase 1 of the learning curve. PMID:27043698

  20. Association between Polymorphisms in XRCC1 Gene and Treatment Outcomes of Patients with Advanced Gastric Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Cao, Zhuo; Song, Jia; Wang, Jun; Guo, Xufeng; Yu, Shijie; Dong, Weiguo

    2014-01-01

    Background Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene and platinum-based chemotherapeutic efficacy. This meta-analysis aimed to summarize published data about the association between two SNPs of XRCC1 (Arg194Trp and Arg399Gln) and treatment outcomes of patients with advanced gastric cancer. Methodology/Principal Findings We retrieved the relevant articles from MEDLINE, Web of Knowledge, and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected according to specific inclusion and exclusion criteria. Study quality was assessed according to the guidelines outlined by Hayden, et al. and PRISMA guidelines. We estimated the odds ratio (OR) for response rate versus no response after platinum-based chemotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated by pooled Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs). We found that none of the XRCC1 Arg194Trp and Arg399Gln polymorphisms was significantly associated with tumor response. Stratified analysis by ethnicity or sensitivity analysis also showed that XRCC1 SNPs were not related with chemotherapy response. Patients with minor variant A allele were likely to have poorer 2-year survival rate than those with G/G genotype. However, in the group of 5-year follow up, there was no significant association between the A allele and OS yet. Conclusions/Significance There is no evidence to support the use of XRCC1 Arg194Trp and Arg399Gln polymorphisms as prognostic predictors of TR and PFS in gastric patients treated with platinum-based chemotherapy. The relationship between minor variant A allele and OS requires further verification. PMID:24465544

  1. Targeted therapy in gastric cancer.

    PubMed

    Thiel, Alexandra; Ristimäki, Ari

    2015-05-01

    Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer. PMID:25706252

  2. Decreased intratumoral Foxp3 Tregs and increased dendritic cell density by neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer

    PubMed Central

    Hu, Min; Li, Kai; Maskey, Ninu; Xu, Zhigao; Peng, Chunwei; Wang, Bicheng; Li, Yan; Yang, Guifang

    2014-01-01

    Although neoadjuvant chemotherapy (NACT) has been increasingly used to improve the outcome of advanced gastric cancer (GC) for decades, its precise efficacy has been difficult to evaluate yet. Abundant studies have investigated the predictive factors that represent the effect of NACT on advanced GC. In the present study, the intratumoral infiltration of regulatory T cells (Tregs) and dendritic cells (DCs) response to NACT in advanced GC and their correlation with prognosis were evaluated. Infiltration of Tregs (marked by Foxp3) and DCs (marked by S-100) in 102 advanced GC specimens with or without NACT was measured using immunohistochemical method. Intratumoral infiltration of Foxp3 Tregs was significantly lower and DC density was significantly higher in NACT group than that in nNACT group (P=0.007, P=0.002, respectively). Infiltration of Foxp3 Tregs was significantly associated with tumor invasion depth (P<0.001). The DC density was significantly correlated with histopathologic type (P=0.035), invasion depth (P=0.002), TNM stage (P=0.018), and lymph node metastasis (P<0.001). There was no significant difference of patient’s OS between NACT and nNACT groups (P=0.452); however, patients treated with NACT had longer OS with lower infiltration of Foxp3 Tregs (P<0.001) and higher infiltration of DCs (P=0.010). Univariate and multivariate analyses indicated that infiltration of Foxp3 Tregs and DCs were independent prognostic factors (P=0.002, P=0.003, respectively). The results demonstrated that NACT could decrease intratumoral Foxp3 Tregs infiltration and increase DCs density, and that infiltration of Foxp3 Tregs and DCs may serve as novel prognostic biomarkers of human GC. PMID:25197340

  3. Gastric suction

    MedlinePlus

    ... al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila) . 2013;51(3); 140-146. ... 2012:chap 49. Zeringe M, Fowler GC. Gastrointesinal decontamination. In: Pfenninger JL, Fowler GC, eds. Pfenninger & Fowler's ...

  4. Gastric Banding

    MedlinePlus

    ... gastric banding before deciding to have the procedure. Advertisements for a device or procedure may not include ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  5. Gastric culture

    MedlinePlus

    ... test or procedure preparation (3 to 6 years) School age test or procedure preparation (6 to 12 ... immune system. The final results of the gastric culture test may take several weeks. Your provider will ...

  6. Prognostic factors of intraperitoneal chemotherapy for peritoneal carcinomatosis of gastric cancer: A retrospective study from a single center

    PubMed Central

    MEN, HAI-TAO; GOU, HONG-FENG; LIU, JI-YAN; LI, QIU; LUO, DE-YUN; BI, FENG; QIU, MENG

    2016-01-01

    Peritoneal carcinomatosis (PC) of gastric origin is currently recognized as a terminal disease with a poor prognosis. Advancements in novel therapeutic approaches, including intraperitoneal chemotherapy (IPC), have recently been made and it is believed that this may have contributed to the improved survival observed in patients with PC. The present study aimed to investigate overall survival (OS) and the associated prognostic factors in patients with PC of gastric origin who underwent IPC. A total of 57 patients were studied, with a median age of 51 years. The median follow-up time was 12.4 months. PC was diagnosed in all patients with gastric cancer. The median survival time of all patients was 10.1 months, whilst the OS rate at 1, 2 and 3 years was observed to be 46, 19 and 12%, respectively. Symptomatic ascites and a signet ring cell (SRC) histopathological type were demonstrated to signify a poor prognosis. Complete resection of all gross disease (CCR-0) and an increased number of cycles of systemic chemotherapy were independent factors that were observed to correlate with increased OS. The most common morbidities of grade 3/4 adverse effects were bone marrow suppression, nausea or vomiting, and diarrhea. In conclusion, IPC is an important treatment option for patients with PC that has originated from gastric cancer. Symptomatic ascites and SRC adenocarcinoma serve as negative clinicopathological prognostic factors, whilst CCR-0 and increased systemic chemotherapy cycles (≥4 cycles) may prove to be an important therapeutic option for PC patients. PMID:27123142

  7. Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A.

    PubMed

    Wisnieski, Fernanda; Calcagno, Danielle Queiroz; Leal, Mariana Ferreira; Chen, Elizabeth Suchi; Gigek, Carolina Oliveira; Santos, Leonardo Caires; Pontes, Thaís Brilhante; Rasmussen, Lucas Trevizani; Payão, Spencer Luiz Marques; Assumpção, Paulo Pimentel; Lourenço, Laércio Gomes; Demachki, Sâmia; Artigiani, Ricardo; Burbano, Rommel Rodríguez; Smith, Marília Cardoso

    2014-07-01

    Gastric cancer is still the second leading cause of cancer-related death worldwide, even though its incidence and mortality have declined over the recent few decades. Epigenetic control using histone deacetylase inhibitors, such as trichostatin A (TSA), is a promising cancer therapy. This study aimed to assess the messenger RNA (mRNA) levels of three histone deacetylases (HDAC1, HDAC2, and HDAC3), two histone acetyltransferases (GCN5 and PCAF), and two possible targets of these histone modifiers (MYC and CDKN1A) in 50 matched pairs of gastric tumors and corresponding adjacent nontumors samples from patients with gastric adenocarcinoma, as well as their correlations and their possible associations with clinicopathological features. Additionally, we evaluated whether these genes are sensitive to TSA in gastric cancer cell lines. Our results demonstrated downregulation of HDAC1, PCAF, and CDKN1A in gastric tumors compared with adjacent nontumors (P < 0.05). On the other hand, upregulation of HDAC2, GCN5, and MYC was observed in gastric tumors compared with adjacent nontumors (P < 0.05). The mRNA level of MYC was correlated to HDAC3 and GCN5 (P < 0.05), whereas CDKN1A was correlated to HDAC1 and GCN5 (P < 0.05 and P < 0.01, respectively). In addition, the reduced expression of PCAF was associated with intestinal-type gastric cancer (P = 0.03) and TNM stages I/II (P = 0.01). The increased expression of GCN5 was associated with advanced stage gastric cancer (P = 0.02) and tumor invasion (P = 0.03). The gastric cell lines treated with TSA showed different patterns of histone deacetylase and acetyltransferase mRNA expression, downregulation of MYC, and upregulation of CDKN1A. Our findings suggest that alteration of histone modifier genes play an important role in gastric carcinogenesis, contributing to MYC and CDKN1A deregulation. In addition, all genes studied here are modulated by TSA, although this modulation appears to be dependent of the genetic background of the cell

  8. Delayed gastric emptying in Parkinson's disease.

    PubMed

    Marrinan, Sarah; Emmanuel, Anton V; Burn, David J

    2014-01-01

    Gastrointestinal symptoms are evident in all stages of Parkinson's disease (PD). Most of the gastrointestinal abnormalities associated with PD are attributable to impaired motility. At the level of the stomach, this results in delayed gastric emptying. The etiology of delayed gastric emptying in PD is probably multifactorial but is at least partly related to Lewy pathology in the enteric nervous system and discrete brainstem nuclei. Delayed gastric emptying occurs in both early and advanced PD but is underdetected in routine clinical practice. Recognition of delayed gastric emptying is important because it can cause an array of upper gastrointestinal symptoms, but additionally it has important implications for the absorption and action of levodopa. Delayed gastric emptying contributes significantly to response fluctuations seen in people on long-term l-dopa therapy. Neurohormonal aspects of the brain-gut axis are pertinent to discussions regarding the pathophysiology of delayed gastric emptying in PD and are also hypothesized to contribute to the pathogenesis of PD itself. Ghrelin is a gastric-derived hormone with potential as a therapeutic agent for delayed gastric emptying and also as a novel neuroprotective agent in PD. Recent findings relating to ghrelin in the context of PD and gastric emptying are considered. This article highlights the pathological abnormalities that may account for delayed gastric emptying in PD. It also considers the wider relevance of abnormal gastric pathology to our current understanding of the etiology of PD. PMID:24151126

  9. P53 expression in invasive pancreatic adenocarcinoma and precursor lesions.

    PubMed

    Norfadzilah, M Y; Pailoor, Jayalakshmi; Retneswari, M; Chinna, K; Noor, Laili M M

    2011-12-01

    Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma. PMID:22299208

  10. H. Pylori in a gastric schwannoma: a case report.

    PubMed

    Lavy, Daniel S; Paulin, Ethan T; Parker, Mitchell I; Zhang, Bin; Parker, Glenn S; Schwartz, Mark R

    2016-04-01

    Schwannomas are benign, often asymptomatic, slow-growing tumors that originate from Schwann cells of the neural sheath. Although H. Pylori has been associated with gastric adenocarcinoma, there has never been a recorded association with schwannoma formation. We present a 64-year-old woman who underwent a laparoscopic partial wedge gastrectomy for an incidentally discovered gastric mass. Histologic examination was consistent with schwannoma; however, chronic inflammation with microorganisms morphologically consistent with H. Pylori was also present. This case suggests the first recorded case of H. Pylori in an immunohistochemically confirmed gastric schwannoma. PMID:27162787

  11. H. Pylori in a gastric schwannoma: a case report

    PubMed Central

    Paulin, Ethan T.; Parker, Mitchell I.; Zhang, Bin; Parker, Glenn S.; Schwartz, Mark R.

    2016-01-01

    Schwannomas are benign, often asymptomatic, slow-growing tumors that originate from Schwann cells of the neural sheath. Although H. Pylori has been associated with gastric adenocarcinoma, there has never been a recorded association with schwannoma formation. We present a 64-year-old woman who underwent a laparoscopic partial wedge gastrectomy for an incidentally discovered gastric mass. Histologic examination was consistent with schwannoma; however, chronic inflammation with microorganisms morphologically consistent with H. Pylori was also present. This case suggests the first recorded case of H. Pylori in an immunohistochemically confirmed gastric schwannoma. PMID:27162787

  12. The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy.

    PubMed

    Mangia, Anita; Caldarola, Lucia; Dell'Endice, Stefania; Scarpi, Emanuela; Saragoni, Luca; Monti, Manlio; Santini, Daniele; Brunetti, Oronzo; Simone, Giovanni; Silvestris, Nicola

    2015-01-01

    Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na(+)/H(+) exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1α MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1α (nHIF-1α) expression (68.8% versus 31.3% respectively, P = 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1α and sorcin expression (P = 0.011; P = 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7% of patients with high nNHERF1 expression had a disease control rate, while 84.6% of subjects with negative nuclear expression of the protein showed progressive disease (P = 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P = 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor. PMID:26126066

  13. The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy

    PubMed Central

    Mangia, Anita; Caldarola, Lucia; Dell'Endice, Stefania; Scarpi, Emanuela; Saragoni, Luca; Monti, Manlio; Santini, Daniele; Brunetti, Oronzo; Simone, Giovanni; Silvestris, Nicola

    2015-01-01

    Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na+/H+ exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1α MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1α (nHIF-1α) expression (68.8% versus 31.3% respectively, P = 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1α and sorcin expression (P = 0.011; P = 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7% of patients with high nNHERF1 expression had a disease control rate, while 84.6% of subjects with negative nuclear expression of the protein showed progressive disease (P = 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P = 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor. PMID:26126066

  14. Endoscopic evaluation of gastric conduit perfusion in minimally invasive Ivor Lewis esophagectomy

    PubMed Central

    Fikfak, Vid; Gaur, Puja; Kim, Min P.

    2015-01-01

    Introduction Laser-assisted indocyanine green (ICG) fluorescent dye angiography has been used in esophageal reconstructive surgery where it has been shown to significantly decrease the anastomotic leak rate. Recent advances in technology have made this possible in minimally invasive esophagectomy. Presentation of case We present a 69-year-old male with a cuT2N0M0 adenocarcinoma of the esophagus at the gastroesophageal junction who presented to our clinic after chemoradiation and underwent a minimally invasive Ivor Lewis esophagectomy. The perfusion of the gastric conduit was assessed intraoperatively using endoscopic ICG fluorescent imaging system. The anastomosis was created at the well-perfused site identified on the fluorescent imaging. The patient tolerated the procedure well, had an uneventful recovery going home on postoperative day 6 and tolerating a regular diet 2 weeks after the surgery. Discussion Combination of minimally invasive surgery and endoscopic evaluation of perfusion of gastric conduit provide improved outcomes for surgical treatment for patients with esophageal cancer. Conclusion The gastric conduit during minimally invasive Ivor Lewis esophagectomy can be evaluated using endoscopic ICG fluorescent imaging. PMID:26745315

  15. Synchronous Gastric Carcinoma and Nodal Malignant Lymphoma: A Rare Case Report and Literature Review.

    PubMed

    Xue, Li-Jun; Yang, Ji-Hong; Su, Quan-Sheng; Wang, Hai; Liu, Chang

    2010-01-01

    Synchronous double malignancies of gastric carcinoma (GC) and malignant lymphoma (ML) are rare and very difficult to treat. We report a case of synchronous GC and nodal ML, regarding which clinical and pathological features and treatment are discussed. A 68-year-old woman with a history of inguinal hernia was admitted for abdominal pain and high fever and subsequently underwent herniorrhaphy, but the fever remained. Computerized tomography showed a stomach mass and multiple enlarged lymph nodes in the abdominal cavity and inguinal regions. Gastric adenocarcinoma coexistent with advanced in situ follicular lymphoma was confirmed by endoscopy, biopsy of inguinal lymph nodes and bone marrow examination. Two chemotherapy regimens, R-CHOP (rituximab, cyclophosphamide, perarubicin, vincristine and prednisone) and systemic therapy (5-fluorouracil and calcium folinate) combined with regional perfusion (oxaliplatin and etoposide) through the left gastric artery were performed at intervals against ML and GC, respectively. Partial remission in both tumors was achieved after 4 courses of treatment, but the patient finally died of heart failure. Scrupulous biopsy of non-draining lymph nodes in patients with gastrointestinal carcinomas is supposed to improve the diagnostic rate of simultaneous nodal ML. The interval chemotherapy strategy with two independent regimens is beneficial for such patients, especially for those unable to tolerate major surgery. PMID:20740201

  16. Efficacy and safety of cord blood-derived dendritic cells plus cytokine-induced killer cells combined with chemotherapy in the treatment of patients with advanced gastric cancer: a randomized Phase II study

    PubMed Central

    Mu, Ying; Wang, Wei-hua; Xie, Jia-ping; Zhang, Ying-xin; Yang, Ya-pei; Zhou, Chang-hui

    2016-01-01

    Background Cellular immunotherapy has been widely used in the treatment of solid tumors. However, the clinical application of cord blood-derived dendritic cells and cytokine-induced killer cells (CB-DC-CIK) for the treatment of gastric cancer has not been frequently reported. In this study, the efficacy and safety of CB-DC-CIK for the treatment of gastric cancer were evaluated both in vitro and in vivo. Methods The phenotypes, cytokines, and cytotoxicity of CB-DC-CIK were detected in vitro. Patients with advanced gastric cancer were divided into the following two groups: the experimental group (CB-DC-CIK combined with chemotherapy) and the control group (chemotherapy alone). The curative effects and immune function were compared between the two groups. Results First, the results showed that combination therapy significantly increased the overall disease-free survival rate (P=0.0448) compared with chemotherapy alone. The overall survival rate (P=0.0646), overall response rate (P=0.410), and disease control rate (P=0.396) were improved in the experimental group, but these changes did not reach statistical significance. Second, the percentage of T-cell subsets (CD4+, CD3−CD56+, and CD3+CD56+) and the levels of IFN-γ, TNF-α, and IL-2, which reflect immune function, were significantly increased (P<0.05) after immunotherapy. Finally, no serious side effects appeared in patients with gastric cancer after the application of cellular immunotherapy based on CB-DC-CIK. Conclusion CB-DC-CIK combined with chemotherapy is effective and safe for the treatment of patients with advanced gastric cancer. PMID:27524915

  17. Sentinel node biopsy using blue dye and technetium99 in advanced gastric cancer: anatomical drainage and clinical application

    PubMed Central

    Santos, F.A.V.; Drummond-Lage, A.P.; Rodrigues, M.A.; Cabral, M.A.; Pedrosa, M.S.; Braga, H.; Wainstein, A.J.A.

    2016-01-01

    Lymph node metastases are an independent prognosis factor in gastric carcinoma (GC) patients. Radical lymphadenectomy can improve survival but it can also increase surgical morbidity. As a principle, sentinel node (SN) navigation surgery can avoid unnecessary lymphadenectomy without compromising prognosis. In this pilot study, 24 patients with untreated GC were initially screened for SN navigation surgery, of which 12 were eligible. Five patients had T2 tumors, 5 had T3 tumors and 2 had T1 tumors. In 33% of cases, tumor diameter was greater than 5.0 cm. Three hundred and eighty-seven lymph nodes were excised with a median of 32.3 per patient. The SN navigation surgery was feasible in all patients, with a median of 4.5 SNs per patient. The detection success rate was 100%. All the SNs were located in N1 and N2 nodal level. In 70.9% of cases, the SNs were located at lymphatic chains 6 and 7. The SN sensitivity for nodal staging was 91.6%, with 8.3% of false negative. In 4 patients who were initially staged as N0, the SNs were submitted to multisection analyses and immunohistochemistry, confirming the N0 stage, without micrometastases. In one case initially staged as negative for nodal metastases based on SN analyses, metastases in lymph nodes other than SN were found, resulting in a 20% skip metastases incidence. This surgery is a reproducible procedure with 100% detection rate of SN. Tumor size, GC location and obesity were factors that imposed some limitations regarding SN identification. Results from nodal multisection histology and immunohistochemistry analysis did not change initial nodal staging. PMID:27409337

  18. DNA profiles in mitotic cells from gastric adenomas.

    PubMed Central

    Rubio, C. A.; Kato, Y.

    1988-01-01

    Quantitative DNA measurements were done in mitotic figures from 17 gastric adenomas having slight (3 cases), moderate (8 cases), or severe dysplasia (3 cases) or foci of invasive adenocarcinoma (3 cases). Values higher than for normal diploid control cells (2c) or their estimated tetraploid values (4c) were found to increase gradually from slight dysplasia to invasive adenocarcinoma through moderate and severe dysplasia. While none of the adenomas having slight or moderate dysplasia demonstrated aneuploid mitoses (ie, values higher than 5c), 1% of the mitoses in severe dysplasia and 27% of those with invasive adenocarcinoma had values higher than 5c. The present results thus suggest that aneuploid mitotic figures may help to recognize those gastric adenomas having invasive growth. Images Figure 1 PMID:3348355

  19. Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF)

    PubMed Central

    Sadighi, Sanambar; Mohagheghi, Mohammad Ali; Montazeri, Ali; Sadighi, Zahra

    2006-01-01

    Background Health related quality of life (HRQOL) is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC) receiving either a standard or an experimental treatment. Methods Seventy-one patients have been treated in Cancer Institute (Tehran, Iran) with docetaxel, cisplatin, 5 FU (TCF) or epirubicin, cisplatin, 5-FU (ECF) and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy. Results The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001). Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups. Conclusion Docetaxel based treatment (TCF) showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF). However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients. PMID:17147808

  20. Neoadjuvant Chemotherapy with FOLFOX4 Regimen to Treat Advanced Gastric Cancer Improves Survival without Increasing Adverse Events: A Retrospective Cohort Study from a Chinese Center

    PubMed Central

    Zhu, Rui-Juan; Yang, Gui-Fang; Li, Yan

    2014-01-01

    Background/Aim. To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). Patients and Methods. Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. Results. The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0–49) versus 13 (3–40)) between the two groups (P > 0.05). The number of lymph node metastases in the neoadjuvant group (3 (0–14)) was significantly fewer than that in the adjuvant group (6 (0–27)) (P = 0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P = 0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P = 0.015). Conclusion. The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC. PMID:25136668

  1. Metabolic changes in cimetidine treatment for scald injury on the peritoneo-serosal surface in far-advanced gastric cancer patients treated by intraperitoneal hyperthermic perfusion.

    PubMed

    Fujimoto, S; Takahashi, M; Kobayashi, K; Kokubun, M; Shrestha, R D; Kiuchi, S; Konno, C

    1993-01-01

    Since pretreatment with cimetidine results in the prevention of scald injury on the peritoneo-serosal surface caused by intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, the diverse influence of IPHP on patients who were either given or not given cimetidine was studied both during and after IPHP treatment. Cimetidine 50 mg/kg was injected intravenously into 12 patients immediately prior to IPHP. There were no statistical background differences between the cimetidine and control groups (those not given cimetidine). The inflow and outflow temperatures of the hyperthermic perfusate in the control and cimetidine groups were 46.1 +/- 0.1 degree C and 44.1 +/- 0.1 degree C and 46.3 +/- 0.1 degree C and 44.2 +/- 0.04 degree C, respectively. Either the pre-IPHP hypothermia or IPHP in the control group resulted in a considerable increase in serum noradrenaline and adrenaline. The intravenous administration of cimetidine led to a stransient but moderate drop in the mean blood pressure as well as a delayed appearance of high concentrations of noradrenaline and adrenaline, induced by high concentrations of circulating histamine released with cimetidine. These results suggest that the sympathetic nervous responses were activated either by hypothermia or hyperthermia. The transient hypotension and delayed increases of both serum catecholamines were attributed to a marked increase in circulating histamine, released with the intravenous cimetidine. PMID:8324332

  2. Gastric Mixed Adenoneuroendocrine Carcinoma Occurring 50 Years after a Gastroenterostomy with Braun Anastomosis

    PubMed Central

    Nemoto, Hiroshi; Tate, Genshu; Yokomizo, Kazuaki; Umemoto, Takahiro; Matsubara, Taketo; Mizukami, Hiroki; Kigawa, Gaku; Matsumiya, Akihiko; Tanaka, Junichi

    2014-01-01

    A 75-year-old man was diagnosed with gastric cancer. Fifty years previously, he had undergone gastroenterostomy with a Braun enteroenterostomy. At present, a distal gastrectomy and small intestinal partial resection were performed. Intraoperatively, the tumor was localized to the previous stomal site. HE staining showed that the tumor comprised two elements: a tubular adenocarcinoma on the gastric side and a neuroendocrine carcinoma (NEC) on the jejunal side. The final pathologic diagnosis was mixed adenoneuroendocrine carcinoma based on an immunohistochemical analysis of endocrine markers and an elevated Ki-67 labeling index. The risk of later cancer development cancer recurrence near the gastrojejunostomy site is well known. Potentially, chronic enterogastric bile reflux may irritate the gastric mucosa and act as a promoter. Gastric NEC has a strong malignant potential. We suspect that, in the present case, the constant exposure to secondary bile may have induced a gastric mucosal adenocarcinoma, which finally differentiated into a NEC. PMID:24987352

  3. Testicular metastasis from gastric carcinoma: A case report

    PubMed Central

    Li, Bo; Cai, Hui; Kang, Zheng-Chun; Wu, Hao; Hou, Jian-Guo; Ma, Li-Ye

    2015-01-01

    Gastric cancer (GC) is the most prevalent malignancy in the world, especially in China. GC has been postulated to spread via several different routes, including through hematogenous channels, lymphatic vessels, the seeding of peritoneal surfaces, direct extension through the gastric wall, and retrograde extension through the vas deferens or lymphatics. Testicular metastasis is rare. We show here a 53-year-old patient with GC who underwent a radical total gastrectomy approximately 22 mo ago after he presented with a sensation of heaviness and swelling of the right hemiscrotum. The diagnosis of metastatic adenocarcinoma was made after a right-side orchiectomy. We report the first case of testicular metastasis from gastric adenocarcinoma in mainland China and summarize the clinicopathologic features of the disease based on previously published papers. PMID:26074716

  4. Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zamfir, Alina D.; Serb, Alina; Vukeli, Željka; Flangea, Corina; Schiopu, Catalin; Fabris, Dragana; Kalanj-Bognar, Svjetlana; Capitan, Florina; Sisu, Eugen

    2011-12-01

    Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di- O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.

  5. Solid adenocarcinoma

    Cancer.gov

    Uniformly solid character of the lesions is usually indicative of a well differentiated tumor. No solid adenocarcinomas have observed in our series. However, rare cases have been described by others. In human pathology this diagnosis is usually based on detection of mucin after periodic acid-Schiff reaction with diastase (α-amylase) digestion.

  6. Safety and application of laparoscopic gastrectomy for benign gastric disease and gastric cancer

    PubMed Central

    Zia, MK; Morris-Stiff, G; Luhmann, A; Jeffries, R; Ehsan, O; Hassn, A

    2010-01-01

    INTRODUCTION Laparoscopic gastrectomy is rapidly expanding despite reservations by some surgeons regarding its safety and radicality. The aim of this study was to evaluate patients undergoing laparoscopic gastrectomy for both benign and malignant disease with particular emphasis on technical feasibility, safety, effectiveness and complications. PATIENTS AND METHODS Review of prospectively collected data of patients who underwent laparoscopic gastrectomy from May 2005 to September 2009 under the care of one consultant surgeon. RESULTS A total of 61 laparoscopic gastrectomies were performed (35 men and 26 women) with a median age of 68 years (range, 41–90 years). There were 39 distal gastrectomies (19 adenocarcinoma, 6 gastrointestinal stromal tumour [GIST], 4 benign gastric outlet obstruction, 4 high-grade dysplasia in gastric adenomas, 4 non-healing ulcers, 2 gastric antral vascular ectasia [GAVE]); 15 sub-total gastrectomies (13 adenocarcinomas, 2 GIST); and 7 total gastrectomies (5 adenocarcinomas, 1 GIST, 1 carcinoid). Median follow-up was for 48 months (range, 1–72 months). There was one death, two major and six minor complications. All patients with complications made a satisfactory recovery. CONCLUSIONS Laparoscopic gastrectomy is associated with a low mortality (1.75%) and major morbidity (3.50%). Although technically demanding, especially when a D2 lymphadenectomy is performed, our results have shown that tailored laparoscopic resection based on tumour characteristics with either D1 or D2 lymphadenectomy results in good surgical and oncological outcomes. PMID:20810021

  7. Gene methylation in gastric cancer.

    PubMed

    Qu, Yiping; Dang, Siwen; Hou, Peng

    2013-09-23

    Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. PMID:23669186

  8. [Gastric Acid].

    PubMed

    Ruíz Chávez, R

    1996-01-01

    Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms. PMID:12165790

  9. Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

    PubMed Central

    Graham, David Y.

    2015-01-01

    Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections. PMID:25655557

  10. Efficacy of cisplatin/pemetrexed with bevacizumab to treat advanced lung adenocarcinoma with different drive genes: case report and literature review

    PubMed Central

    Wang, Haiyong; Zhu, Hui; Kong, Li; Yu, Jinming

    2016-01-01

    Background Bevacizumab combined with chemotherapy has become the first-line therapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). However, few studies have focused on cisplatin/pemetrexed with bevacizumab as the first-line therapy to treat advanced nonsquamous NSCLC. Importantly, whether the epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements can influence the efficacy of bevacizumab in combination with chemotherapy is very interesting. Herein, we report three cases with different types of gene drives in advanced nonsquamous NSCLC. Case presentation In the first case, a patient presented with wild-type EGFR and negative ALK rearrangement. In the second case, a patient presented with wild-type EGFR and positive ALK rearrangement. In the third case, a patient presented with negative ALK rearrangement and mutated EGFR in exon 19. Conclusion We speculate that bevacizumab in combination with cisplatin/pemetrexed as the first-line therapy is well tolerated and results in a clinically meaningful treatment benefit, irrespective of the gene drive type in advanced nonsquamous NSCLC. However, more data are needed to confirm the relationship. PMID:27555784

  11. Symptomatic subserosal gastric lipoma successfully treated with enucleation

    PubMed Central

    Krasniqi, Avdyl Selmon; Hoxha, Faton Tatil; Bicaj, Besnik Xhafer; Hashani, Shemsedin Isuf; Hasimja, Shpresa Mehmet; Kelmendi, Sadik Mal; Gashi-Luci, Lumturije Hasan

    2008-01-01

    Gastric lipomas are rare tumors, accounting for 2%-3% of all benign gastric tumors. They are of submucosal or extremely rare subserosal origin. Although most gastric lipomas are usually detected incidentally, they can cause abdominal pain, dyspeptic disorders, obstruction, invagination, and hemorrhages. Subserosal gastric lipomas are rarely symptomatic. There is no report on treatment of subserosal gastric lipomas in the English literature. We present a case of a 50-year-old male with symptomatic subserosal gastric lipoma which was successfully managed with removal, enucleation of lipoma, explorative gastrotomy and edge resection for histology check of gastric wall. The incidence of gastric lipoma, advanced diagnostic possibilities and their role in treatment modalities are discussed. PMID:18855998

  12. Prospective phase II trial of pazopanib plus CapeOX (capecitabine and oxaliplatin) in previously untreated patients with advanced gastric cancer.

    PubMed

    Kim, Seung Tae; Lee, Jeeyun; Lee, Su Jin; Park, Se Hoon; Jung, Sin-Ho; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Park, Joon Oh

    2016-04-26

    We designed a single-arm, open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx (capecitabine and oxaliplatin) in metastatic /recurrent advanced gastric cancer (AGC) patients. Previously untreated AGC patients received capecitabine (850 mg/m2 bid, day 1-14) plus oxaliplatin (130 mg/m2, day 1) in combination with pazopanib (800 mg, day 1-21) every three weeks. Treatment was continued until progression of the disease or intolerable toxicity was observed. In all, 66 patients were treated with pazopanib plus CapeOx. The median age of the patients was 51.5 years (range, 23.0-77), and the median ECOG performance status was 1 (0-1). Among all 66 patients, one complete response and 37 partial responses were observed (overall response rate, 62.4%; 95% confidence interval (CI), 45.7-73.5% accounting for the 2-stage design of this trial). Stable disease was observed in 23 patients (34.8%), revealing a 92.4% disease control rate. The median progression free survival and overall survival were 6.5 months (95% CI, 5.6-7.4) and 10.5 months (95% CI, 8.1-12.9), respectively. Thirty-four patients (51.5%) experienced a treatment-related toxicity of grade 3 or more. The most common toxicities of grade 3 or more were neutropenia (15.1%), anemia (10.6%), thrombocytopenia (10.6%), anorexia (7.6%), nausea (3.0%), and vomiting (3.0%). There were no treatment-related deaths. The combination of pazopanib and CapeOx showed moderate activity and an acceptable toxicity profile as a first-line treatment in metastatic / recurrent AGC patients (ClinicalTrials.gov NCT01130805). PMID:27003363

  13. HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients: a prospective cohort observation.

    PubMed

    Qiu, Miao-Zhen; Li, Qian; Wang, Zhi-Qiang; Liu, Tian-Shu; Liu, Qing; Wei, Xiao-Li; Jin, Ying; Wang, De-Shen; Ren, Chao; Bai, Long; Zhang, Dong-Sheng; Wang, Feng-Hua; Li, Yu-Hong; Xu, Rui-Hua

    2014-05-15

    The monoclonal antibody trastuzumab has brought survival benefit to patients with advanced gastric cancer (AGC) that have human epidermal growth factor receptor 2 (HER2) over expression or amplification. This study was designed to compare the clinical outcomes of HER2-negative and HER2-positive AGC patients with or without trastuzumab treatment. There were three groups of patients enrolled for analysis. Group A was 51 HER2-positive AGC patients treated with trastuzumab and chemotherapy; group B was a matched control group of 47 HER2-positive patients who received chemotherapy only; group C was a matched group of 251 HER2-negative patients who received chemotherapy. All the patients were enrolled at Sun Yat-sen University Cancer Center or Zhongshan Hospital, Fudan University between January 2010 and December 2012. The primary endpoint was overall survival (OS). The Kaplan-Meier method and log-rank test were used for survival analysis. The median duration of follow-up was 13.5 months (range 5-18.6 months). The median OS of these three groups of patients was 14.8 months, 11.3 months and 14.4 months respectively (p < 0.001). The survival difference between group A and B was significant, p < 0.001. Similarly, there was significant difference between group B and C, p < 0.001. Moreover the survival between group A and C was comparable, p = 0.281. The median progression-free survival for these three groups was 7.4, 6.0 and 7.2 months. Multivariate analysis confirmed that trastuzumab treatment was an independent prognostic factor in group A and B patients (p = 0.017). HER2 positive was an independent adverse prognostic factor in group B and C patients (p = 0.013). PMID:24155030

  14. Mitomycin C plus S-1 as second-line therapy in patients with advanced gastric cancer: a noncomparative phase II study.

    PubMed

    Park, Se Hoon; Kim, Young Saing; Hong, Junshik; Park, Jinny; Nam, Eunmi; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon; Lee, Woon Kee; Chung, Min

    2008-03-01

    S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status. PMID:18510177

  15. Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer: A Meta-Analysis of 10 Randomized Controlled Trials.

    PubMed

    Zhang, Yong; Ma, Bing; Huang, Xiao-Tian; Li, Yan-Song; Wang, Yu; Liu, Zhou-Lu

    2016-02-01

    The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC).A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0).Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78-0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72-0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27-1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups.In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens. PMID:26937908

  16. Polymorphisms of ERCC1 and XRCC1 predict the overall survival of advanced gastric cancer patients receiving oxaliplatin-based chemotherapy

    PubMed Central

    Zhang, Lijian; Yao, Ruyong; Fang, Shibao; Wang, Xiuwen; Li, Xin

    2015-01-01

    The aim of the present study was to evaluate the clinical outcome of excision repair cross-complementing protein 1 (ERCC1) and X-ray repair cross-complementing protein 1 (XRCC1) gene polymorphisms in 89 patients receiving oxaliplatin/5-fluorouracil-based chemotherapy as a first-line treatment regimen for advanced gastric cancer. ERCC1 codon 118C/T and XRCC1 codon 399A/G polymorphisms were identified using quantitative polymerase chain reactions, and the associations between disease control rate (DCR), median overall survival (mOS) and gene polymorphisms were analyzed. Following two cycles of chemotherapy, a complete response was observed in two patients, a partial response in 18 patients, stable disease in 38 patients and progressive disease in 31 patients. It was determined that ERCC1 and XRCC1 polymorphisms are not associated with DCR (P=0.662 and P=0.631, respectively). The mOS of patients exhibiting ERCC1 and XRCC1 polymorphisms was eight months, and although no significant association was identified between ERCC1 codon 118 genotypes and mOS (P>0.05), the combination of ERCC1 and XRCC1 polymorphisms, as well as the specific presence of the XRCC1 codon 399A/G polymorphism, was associated with mOS (P<0.05). Thus, the present study indicated that the XRCC1 polymorphism and the combination of XRCC1 and ERCC1 polymorphisms were independent predictors for mOS; however, the XRCC1 and ERCC1 genes were not able to predict the DCR. PMID:26770441

  17. A Case of Gastric Cancer with Neuroendocrine Carcinoma, Signet Ring Cell Carcinoma Components, and Intramural Metastases

    PubMed Central

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2016-01-01

    Patient: Male, 67 Final Diagnosis: Gastric cancer with neuroendocrine carcinoma Symptoms: — Medication: — Clinical Procedure: Total gastrectomy • splenectomy with D2 lymph node dissection Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Many neuroendocrine carcinomas exhibit medullary infiltration and expanded proliferation. Differentiated tubular adenocarcinoma is frequently seen in the superficial region in many neuroendocrine carcinoma cases. However, the present case showed non-medullary infiltration and signet ring cell carcinoma in the superficial region, with intramural metastases distributed throughout the whole of the stomach. Case Report: A 67-year-old man was referred to our institution for treatment of gastric cancer. Type IIc-like advanced gastric cancer was detected in the greater curvature of the middle body of the stomach. The patient underwent total gastrectomy, splenectomy with D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a large-cell endocrine carcinoma of the stomach. A solid growth of signet ring cells was seen in the mucosa and submucosa. Intramural metastases were observed in many other depressed lesions. Large-cell carcinoma invaded the submucosa, mainly in the intramural metastatic site. Metastasis to one lesser curvature lymph node was also seen on histological examination. The final diagnosis was a gastric cancer of type 0–IIc (T4a) [M] (with intramural metastases) at T4aN1H0P0M0 Stage IIIA. This patient has remained alive without recurrence for 72 months after surgery. Conclusions: We recommend close preoperative examination of neuroendocrine carcinoma, taking intramural metastases into consideration. PMID:27102318

  18. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  19. Gastric Carcinoids

    PubMed Central

    Borch, Kurt; Ahrén, Bo; Ahlman, Håkan; Falkmer, Sture; Granérus, Göran; Grimelius, Lars

    2005-01-01

    Objective: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. Background: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. Methods: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. Results: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. Conclusion: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids. PMID:15973103

  20. Cutaneous metastasis in anorectal adenocarcinoma.

    PubMed

    Varma, Krishnendra; Singh, Ujjwal Kumar; Jain, Mansi; Dhand, P L

    2015-01-01

    Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum) of a metastatic adenocarcinoma. PMID:26009722

  1. Cutaneous metastasis in anorectal adenocarcinoma

    PubMed Central

    Varma, Krishnendra; Singh, Ujjwal Kumar; Jain, Mansi; Dhand, P. L.

    2015-01-01

    Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum) of a metastatic adenocarcinoma. PMID:26009722

  2. Comparison of laparoscopy-assisted and open radical gastrectomy for advanced gastric cancer: A retrospective study in a single minimally invasive surgery center.

    PubMed

    Hao, Yingxue; Yu, Peiwu; Qian, Feng; Zhao, Yongliang; Shi, Yan; Tang, Bo; Zeng, Dongzhu; Zhang, Chao

    2016-06-01

    Laparoscopy-assisted gastrectomy (LAG) has gained international acceptance for the treatment of early gastric cancer (EGC). However, the use of laparoscopic surgery in the management of advanced gastric cancer (AGC) has not attained widespread acceptance. This retrospective large-scale patient study in a single center for minimally invasive surgery assessed the feasibility and safety of LAG for T2 and T3 stage AGC. A total of 628 patients underwent LAG and 579 patients underwent open gastrectomy (OG) from Jan 2004 to Dec 2011. All cases underwent radical lymph node (LN) dissection from D1 to D2+. This study compared short- and long-term results between the 2 groups after stratifying by pTNM stages, including the mean operation time, volume of blood loss, number of harvested LNs, average days of postoperative hospital stay, mean gastrointestinal function recovery time, intra- and post-operative complications, recurrence rate, recurrence site, and 5-year survival curve. Thirty-five patients (5.57%) converted to open procedures in the LAG group. There were no significant differences in retrieved LN number (30.4 ± 13.4 vs 28.1 ± 17.2, P = 0.43), proximal resection margin (PRM) (6.15 ± 1.63 vs 6.09 ± 1.91, P = 0.56), or distal resection margin (DRM) (5.46 ± 1.74 vs 5.40 ± 1.95, P = 0.57) between the LAG and OG groups, respectively. The mean volume of blood loss (154.5 ± 102.6 vs 311.2 ± 118.9 mL, P < 0.001), mean postoperative hospital stay (7.6 ± 2.5 vs 10.7 ± 3.6 days, P < 0.001), mean time for gastrointestinal function recovery (3.3 ± 1.4 vs 3.9 ± 1.5 days, P < 0.001), and postoperative complications rate (6.4% vs 10.5%, P = 0.01) were clearly lower in the LAG group compared to the OG group. However, the recurrence pattern and site were not different between the 2 groups, even they were stratified by the TNM stage. The 5-year overall survival (OS) rates were 85.38%, 79.70%, 57

  3. Challenges of deciphering gastric cancer heterogeneity

    PubMed Central

    Hudler, Petra

    2015-01-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  4. Challenges of deciphering gastric cancer heterogeneity.

    PubMed

    Hudler, Petra

    2015-10-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  5. How Is Small Intestine Adenocarcinoma Staged?

    MedlinePlus

    ... small intestine adenocarcinoma, by stage How is small intestine adenocarcinoma staged? Staging is a process that tells ... distant m etastasis (M). T categories for small intestine adenocarcinoma T categories of small intestine cancer describe ...

  6. Intramucosal gastric mixed adenoneuroendocrine carcinoma completely resected with endoscopic submucosal dissection.

    PubMed

    Yamasaki, Yasushi; Nasu, Junichiro; Miura, Kou; Kono, Yoshiyasu; Kanzaki, Hiromitsu; Hori, Keisuke; Tanaka, Takehiro; Kita, Masahide; Tsuzuki, Takao; Matsubara, Minoru; Kawano, Seiji; Kawahara, Yoshiro; Tabata, Masahiro; Okada, Hiroyuki; Yamamoto, Kazuhide

    2015-01-01

    Composite tumors in the stomach composed of adenocarcinoma and neuroendocrine carcinoma are rare. We herein report a case of intramucosal gastric mixed adenoneuroendocrine carcinoma (MANEC) that was treated with endoscopic submucosal dissection (ESD). A 77-year-old man who had previously received ESD for early gastric adenocarcinoma underwent esophagogastroduodenoscopy for screening, which showed a depressed lesion on the lesser curvature of the antrum. The tumor was removed en bloc via ESD and pathologically diagnosed as MANEC. The tumor was located within the mucosal layer, and no lymphovascular invasion was evident. Seven months after the ESD procedure, the patient is currently feeling well without recurrence or metastasis. PMID:25876572

  7. A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series

    PubMed Central

    Chen, Jiezhong; Kaley, Kristin; Garcon, Marie Carmel; Rodriguez, Teresa; Saif, Muhammad Wasif

    2016-01-01

    Background: The objective of this study was to report a case series on the efficacy and safety of capecitabine 7/7 schedule combined with erlotinib (CAP-ERL) in patients with advanced pancreatic cancer (APC) who have failed prior therapies. Methods: We retrospectively evaluated 13 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine or oxaliplatin–irinotecan-based first-line regimens. Treatment consisted of capecitabine (Xeloda) at a flat dose of 1000 mg orally twice daily on days 1–7 out of 14 days (7/7 schedule) and erlotinib (Tarceva) 100 mg orally once daily until unacceptable toxicity or disease progression. Tumor assessments were repeated every two cycles (8 weeks) and serum tumor markers were measured every 4 weeks. Results: All patients (median age: 63 years; 7 female/3 male) had various previous lines of treatments of chemotherapies. Median number of cycles with CAP-ERL was 4 (range 2–12). The overall response rate was 20%. CA19-9 was reduced more than 25% in 40% patients. The median overall survival and progression-free survival from the start of CAP-ERL were 4.5 months (range 3–7.5) and 2 months (range 1.5–4), respectively. The most common grade 3 toxicities included hand–foot syndrome, nausea, vomiting, diarrhea, rash, and fatigue. Conclusions: Our result suggests that the combination of a fixed low dose of CAP-ERL 7/7 schedule was tolerated with manageable toxicity and showed encouraging activity as salvage treatment in patients with refractory APC with ECOG performance status 0–2. Further prospective studies are warranted to evaluate this combination. PMID:26929778

  8. Gastric infarction following gastric bypass surgery

    PubMed Central

    Do, Patrick H; Kang, Young S; Cahill, Peter

    2016-01-01

    Gastric infarction is an extremely rare occurrence owing to the stomach’s extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition. PMID:27200168

  9. [A case of chronic pancreatitis occurring in gastric aberrant pancreas poorly distinguishable from gastric aberrant pancreas ductal carcinoma].

    PubMed

    Ogawa, Sayaka; Miyaoka, Youichi; Fujiwara, Aya; Tsukano, Kousuke; Kotani, Satoshi; Yamanouchi, Satoshi; Kusunoki, Ryusaku; Ito, Satoko; Fujishiro, Hirofumi; Kohge, Nariaki; Onuma, Hideyuki

    2015-11-01

    A man in his 40s was referred to our hospital with abdominal pain. A gastric submucosal tumor (SMT) was diagnosed nine years previously, but the patient was lost to follow-up. Upon our evaluation, the SMT had enlarged, as demonstrated by esophagogastroduodenoscopy and abdominal computed tomography. Endoscopic ultrasonography revealed a hypoechoic and isoechoic mosaic mass, which primarily occupied the third and fourth layers of the gastric wall. Aspiration cytodiagnosis was performed, the results of which led to a suspicion of adenocarcinoma arising from gastric ectopic pancreas. Next, we conducted segmental gastrectomy. Pathological examination showed adiponecrosis, a pancreatic stone, chronic inflammatory cell infiltration, and fibrosis. Thus, the patient was diagnosed with chronic pancreatitis occurring in a gastric aberrant pancreas. PMID:26537325

  10. Protective effect of ascorbic acid in experimental gastric cancer: reduction of oxidative stress

    PubMed Central

    P.M.S.Oliveira, Claudia; Kassab, Paulo; Lopasso, Fabio P.; Souza, Heraldo P.; Janiszewski, Mariano; Laurindo, Francisco R. M.; Iriya, Kioshi; Laudanna, Antonio A.

    2003-01-01

    AIM: Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations. Our aim was to assess whether ascorbic acid, an antioxidant, could have a role in preventing ROS (Reactive Oxygen Species) generation in experimental gastric carcinoma in a rat model. METHODS: Experimental gastric cancer was induced in twelve Wistar male rats (weighting 250-350 g) by profound duodeno-gastric reflux throught split gastrojenunostomy. The rats were allocated to the following groups: Group I (n = 6) was the control; Group II (n = 6) which was mantained with daily intake of tape water with Vitamin C (30 mg/Kg). After 6 or 12 months, samples of gastric tumor or non tumor mucosa were taken from the anastomosis of both groups. Oxidative stress was measured by superoxide quantification through lucigenin-amplified chemiluminescence base and by staining with Nitrobluetetrazolium. The histopathologic confirmation of adenocarcinoma was made by eosin-hemathoxilin method. RESULTS: The intestinal type of gastric adenocarcinoma was microscopically identified in all animals of group I whereas only 3 rats of group II showed an adenocarcinoma without macroscopic evidence of them. The cancers were located in the anastomosis in all cases. Basal luminescence from tumor gastric tissue generated 38.4 ± 6.8 count per minute/mg/x106 (mean ± SD) and 14.9 ± 4.0 count per minute/mg/x106, respectively, in group I and II animals (P < 0.05). The Nitrobluetetrazolium method showed intense staining in tumor tissues but not in non neoplasic mucosa. CONCLUSION: Experimental gastric tumors seem to produce more reactive oxygen species than non neoplasic gastric tissue. The reduction of oxidative stress and gastric tumor incidence in rats were induced by the intake of ascorbic acid. Therefore, it may have a role in the prevention of gastric carcinoma. PMID:12632494

  11. Hyperthermic intraperitoneal chemotherapy (HIPEC) and neoadjuvant chemotherapy as prophylaxis of peritoneal carcinosis from advanced gastric cancer—effects on overall and disease free survival

    PubMed Central

    Celotti, Andrea; Ceresoli, Marco; Montori, Giulia; Marini, Michele; Catena, Fausto; Ansaloni, Luca

    2016-01-01

    Background The possibility to enlarge criteria for intra-peritoneal chemotherapy (IPC) to all patients at high-risk to develop peritoneal carcinosis (i.e., with serosal invasion) is still discussed. Methods Retrospective case-control study. Three-groups: advanced-gastric-cancer (AGC) (pT4) without proven carcinosis: prophylactic group (PG), those with PC: treatment group (TG), AGC (pT3–pT4) operated without hyperthermic intraperitoneal chemotherapy (HIPEC), surgery alone group (SG T3, SG T4). Results Forty four patients. 26 (59.1%) were male. Sixteen (36%) patients underwent 16 HIPEC: 6 (38%) had AGC (pT4) without PC (PG), 10 (62%) had carcinosis (TG), 28 were operated without HIPEC (SG T3, SG T4). The mean disease free survival (DFS): TG: 7.7 months, SG T4: 21.6 months, SG T3: 27.7 months, PG: 34.5 months. DFS was significantly different for TG (P=0.03, P=0.021, P=0.013 respectively). The mean OS TG: 10 months, SG T4: 27.1 months, SG T3: 28.2 months, PG: 34.6 months. OS was significantly different for TG (P=0.04, P=0.04, P=0.045 respectively). Severe complication rate: TG: 60%, PG: 16.7%, SG T3: 7.7% and SG T4: 25% (P=0.035). Length-of-stay differs significantly (P=0.003); overall length-of-stay: 19.41 days [standard deviation (SD) ±15.03]; TG: 33.01 (SD ±23.08), PG: 20.17 (SD ±6.21), SG T3: 11.33 (SD ±3.22), SG T4: 15.36 (SD ±5.48). Conclusions Prophylactic intraperitoneal chemotherapy associated to neoadjuvant chemotherapy increases the DFS and OS in patients with AGC without carcinosis. More data are needed in order to confirm these results.

  12. The journey of personalizing gastric cancer treatment.

    PubMed

    Yan, Li

    2016-01-01

    Gastric cancer ranks the fourth most prevalent malignancy yet it is the second leading cause of cancer-related death. Every year, gastric cancer adds nearly 1 million new cancer cases, and 723,000 or 10% of cancer deaths to the global cancer burden. Approximately, 405,000 or 43% of the new cases and 325,000 or 45% of the deaths are in China, making gastric cancer a particularly challenging malignancy. This thematic series discusses the molecular classifications of gastric cancer by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) as well as the implications in personalized therapeutic choices; discusses the evolution of gastric surgery and presents perspectives on surgical techniques in treating gastric cancer; and reviews current and emerging targeted agents as well as immunotherapies in treating gastric cancer. With these advancements in molecular characterization, surgical intervention, and targeted and immunotherapies, gastric cancer will enter a personalized medicine era in the next 5 years. PMID:27581614

  13. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits.

    PubMed

    Graham, David Y

    2015-04-01

    Helicobacter pylori infection contributes to the development of diverse gastric and extragastric diseases. The infection is necessary but not sufficient for the development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, therefore there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to the development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk-these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma. When tested, these hypotheses have not been confirmed and are therefore most likely false. PMID:25655557

  14. Modeling Murine Gastric Metaplasia Through Tamoxifen-Induced Acute Parietal Cell Loss.

    PubMed

    Saenz, Jose B; Burclaff, Joseph; Mills, Jason C

    2016-01-01

    Parietal cell loss represents the initial step in the sequential progression toward gastric adenocarcinoma. In the setting of chronic inflammation, the expansion of the mucosal response to parietal cell loss characterizes a crucial transition en route to gastric dysplasia. Here, we detail methods for using the selective estrogen receptor modulator tamoxifen as a novel tool to rapidly and reversibly induce parietal cell loss in mice in order to study the mechanisms that underlie these pre-neoplastic events. PMID:27246044

  15. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas

    PubMed Central

    Attia, Steven; Kolesar, Jill; Mahoney, Michelle R.; Pitot, Henry C.; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles

    2015-01-01

    Summary 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m2 intravenously days 1–4 and 15–18 of a 28-day cycle in both chemotherapy-nai