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This study aimed to evaluate the protein expression of glutathione peroxidase 4 (GPX4) in resected non-small cell lung cancer (NSCLC). The clinical relevance and prognostic significance of GPX4 expression were analyzed. We reviewed patients with resected NSCLCs at Taipei Veterans General Hospital between September 2002 and January 2018. Available paraffin-embedded specimens were retrieved for immunohistochemistry (IHC) staining to detect GPX4 expression. The cutoff value for defining GPX4 positivity was determined according to the percentage of tumor stained in the microscopic field. The correlation between immune expression, clinicopathologic data, overall survival (OS), and disease-free survival (DFS) were analyzed. A total of 265 NSCLC specimens were retrieved for IHC staining. GPX4 expression positive was in 192 (72.5%) according to a cutoff value of 5%. GPX4 was a significant prognostic factor for OS and DFS on multivariate analysis at both 5% and 25% cutoff values. GPX4 expression was associated with poor OS and DFS, especially in lung adenocarcinoma (p = 0.008, and 0.027, respectively). In conclusions, IHC analysis revealed that GPX4 expression was associated with poor survival outcomes in patients with resected lung adenocarcinoma. Further research is needed to understand the role of GPX4 in tumorigenesis and the underlying mechanism responsible for survival outcomes in patients with resected lung adenocarcinoma., (© 2022. The Author(s).)

Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan-Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44-0.51), 1.22 (95% CI 1.1-1.36), and 3.23 (95% CI 3.01-3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease., (© 2021. The Author(s).)

To date, few reports have investigated the genetic alterations and clinicopathological features in gastric cancer (GC) according to sex. In total, 2673 GC patients receiving curative surgery were enrolled. Among the 2673 GC patients, 1979 (74.0%) patients were male. After propensity-score matching, 846 patients were enrolled for the analysis, including 423 males and 423 females. There was no significant difference in the clinicopathological features between the sexes. Regarding the initial recurrence pattern, the males were more likely to develop tumor recurrence and liver metastasis than the females, especially in stage III GC. Regarding the molecular analysis, the males had higher PD-L1 expression than the females, especially in stage III GC. In addition, the patients aged ≥ 65 years had higher PD-L1 expression than the patients younger than 65 years. The multivariate analysis demonstrated that sex was among the independent prognostic factors affecting overall survival (OS) and disease-free survival (DFS). Among the patients with liver metastases, PD-L1 expression was more common among the aged male patients. The males were associated with more tumor recurrence and higher PD-L1 expression than the females, especially in stage III GC. For GC patients with liver metastases, PD-L1 testing is recommended, especially among aged male patients.

Aims: The aims of this study were to investigate the incidence of BRAF mutations in colorectal cancers (CRCs) in Taiwan and the sensitivity and specificity of VE1 immunohistochemistry in detecting the BRAF(V) (600E) mutation., Methods and Results: A total of 425 resected colorectal adenocarcinoma specimens were recruited into this study. Direct Sanger sequencing of exon 15 of the BRAF gene was performed for all cases. The incidence of BRAF mutation was 5.4% (23 of 425). Tissue microarrays were constructed for VE1 immunohistochemistry, and the staining intensity was scored as negative (0), weak (1+), moderate (2+) and strong (3+). In BRAF-mutated cases, two (8.7%) scored as 0, three (13.0%) as 1+, 13 (56.5%) as 2+ and five (21.7%) as 3+. Among 402 BRAF wild-type cases, five (1.2%) were scored as 1+, while the others were negative. The sensitivity and specificity of VE1 expression in detecting the BRAF mutation was 91.3% and 98.8%, respectively., Conclusions: Immunohistochemistry for VE1 antibody is a sensitive and specific marker for detection of BRAF mutations in CRCs. Incorporation of VE1 immunohistochemistry into Lynch syndrome screening protocol may be a reliable and cost-effective method., (© 2015 John Wiley & Sons Ltd.)

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer., (© 2016 UICC.)

The investigation of prognostic factor for gastric cancer is still desirable because of dismal prognosis in gastric cancer. Lauren's classification is currently a useful histological classification. There are few large series evaluating the prognostic significance of Lauren's classification in gastric cancer. From January 1987 to December 2013, a total of 3071 patients received gastrectomy for gastric cancer. According Lauren's classification, 1423(46.3%) patients were intestinal type, 1000 patients (32.6%) were diffuse type, and 648 patients (21.1%) were mixed type. The clinicopathological characteristics and prognosis in Lauren's classification were analyzed in these patients. Our results showed that patients with intestinal type gastric cancer (57.7%) had a better 5-year overall survival than diffuse type (45.6%) and mixed type (43.4%, P < 0.001). The clinicopathological characteristics showed that gastric cancer patients with intestinal type were older (P < 0.001), male predominant (P < 0.001), smaller tumor size (P < 0.001), distal stomach predominant (P < 0.001), relative well differentiated (P < 0.001), less advanced Borrmann type (P < 0.001), less scirrhous type stromal reaction(P < 0.001), less infiltrating type of Ming's histology type(P < 0.001), less tumor invasion depth and less lymphovascular invasion (P < 0.001). Multivariate analysis with overall survival as an endpoint showed that age (P = 0.005), Borrmann classification (P < 0.001), pathological T category (P = 0.023), pathological N category (P < 0.001) and Lauren's classification (P = 0.003) were significant correlated in gastric cancer. Lauren's classification is an independent prognostic factor in gastric cancer patient undergoing gastrectomy. Lauren's classification can serve as a prognostic marker for gastric cancer patient receiving gastrectomy. The clinicopathological appearance and prognosis of mixed type gastric cancer is similar to diffuse type gastric cancer.

Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is an effective alternative treatment for early gastric cancer. However, a major concern is the likelihood of lymph node metastasis. From December 1987 to December 2006, 391 patients who underwent curative surgery for gastric cancer with mucosal (T1a, n = 265) or submucosal (T1b, n = 126) invasion and a retrieved lymph node number ≧ 15 were enrolled. The frequency and risk factors of lymph node metastasis were analyzed. The frequency of lymph node metastasis was 4.9 % in T1a lesions and 21.4 % in T1b lesions. Although the depth of submucosal tumor invasion was < 2 mm, there was a 28.6 % chance of lymph node metastasis. A T1b lesion, i.e., the width of the submucosal tumor invasion was < 5 mm, resulted in fewer lymph node metastases than lesions > 5 mm in width. Multivariate analysis demonstrated that Lauren's diffuse type and lymphatic invasion were independent risk factors for lymph node metastasis in T1a lesions, while lymphatic invasion was the strongest risk factor for lymph node metastasis in T1b lesions. EMR/ESD is a good alternative for T1a intestinal type adenocarcinoma without lymphatic invasion. Surgical resection is necessary for patients with T1b gastric cancer with lymphatic invasion.

Adenosquamous carcinoma of the stomach is a very rare disease, consisting of less than 0.4 % of all stomach cancer. From 1991 to 2013, a total of 2800 patients received gastrectomy for gastric cancer at Taipei Veterans General hospital. Among them, seven patients (0.25 %) diagnosed as adenosquamous carcinoma were enrolled. The clinicopathologic characteristics and prognosis were analyzed. The mean age of the seven patients was 62.3 years-old. There were 5 males and 2 females. Six patients were stage III disease and one patient was stage IV disease. Four patients finally died of gastric cancer. Only one patient had no recurrence until death. Among the seven patients, adenocarcinoma component comprises the majority of the metastatic lymph node in 6 patients (85.7 %). The only one patient with major squamous cell carcinoma component in metastatic lymph node had no tumor recurrence till death. Adenosquamous carcinoma of stomach is a rare disease and is associated with a poor prognosis. The component of adenocarcinoma and squamous cell carcinoma in the metastatic lymph node may influence the prognosis.

Background: SIRT3-mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-3-plays an important role in regulating cell metabolism and carcinogenesis. The role of SIRT3 in gastric cancer has not yet been investigated., Methods: A total of 221 gastric cancer patients who underwent curative surgery were enrolled at the Department of Surgery, Taipei Veterans General Hospital. SIRT3 expression in gastric tissues and tumors were examined in these patients using immunohistochemical staining. Clinicopathologic characteristics and survival were analyzed and compared in gastric cancer patients with or without SIRT3 expression., Results: The 5-year survival rates of patients with or without SIRT3 expression were 51.2 and 39.1 %, respectively (p = 0.005). The 5-year disease-free survival rates of patients with or without SIRT3 expression were 49.6 and 38.0 %, respectively (p = 0.010). Microscopic features showed that there are more poor cell differentiation (p = 0.001), more diffuse-type Lauren's histology (p = 0.018), and more scirrhous-type stromal reactions (p = 0.027) in gastric cancer without SIRT expression. Multivariate analysis with overall survival as an endpoint showed that age (p < 0.001), Lauren's histology (p = 0.007), stromal reaction (p = 0.035), TNM pathologic N category (p < 0.001), and SIRT3 expression (p < 0.001) were significantly correlated with gastric cancer., Conclusions: Gastric cancer patients with SIRT3 expression have a better prognosis than those without. SIRT3 expression is an independent prognostic marker for overall survival and may act as a tumor suppressor in gastric cancer.

Background: Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial., Methods: Between May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared., Results: The MSI-H tumors accounted for 11.7 % (n = 25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64 % vs. 49.2 %) and were more often the intestinal type (72 % vs. 61.4 %) compared to the MSI-L/S gastric cancers. The MSI-H gastric cancers had a significantly better 5-year overall survival (OS) rate (68 % vs. 47.6 %, p = 0.030) and a trend of a better 3-year disease-free survival rate (71.8 % vs. 55.2 %, p = 0.076) compared to the MSI-L/S gastric cancers. A multivariate analysis revealed that pathologic TNM stage and MSI status were the independent prognostic factors for OS after curative surgery., Conclusions: Compared to MSI-L/S tumors, MSI-H tumors are associated with a better OS rate for gastric cancer patients after R0 resection.

Background: Robotic gastrectomy has become more popular in the treatment of gastric cancer, especially in Asian countries. Until now, few studies have compared robotic surgery with open or laparoscopic surgery for gastric cancer patients., Methods: Data were prospectively collected between January 2006 and February 2012. A total of 689 patients underwent curative resection of adenocarcinoma of the stomach. Patients were separated into three groups according to the different surgical approaches used (586 open, 64 laparoscopic, and 39 robotic). The clinicopathological characteristics and surgical outcomes of the three groups were compared., Results: The open group was associated with a larger tumor size, more D2 dissection, more advanced tumor stage, and more blood loss than the groups treated with laparoscopic and robotic methods. Robotic gastrectomy was associated with female predominance, less blood loss, shorter hospital stay, and longer operative time than open and laparoscopic gastrectomy. The retrieved lymph node numbers were similar between the open and robotic groups. Postoperative morbidity rates were similar among the three groups. In terms of the learning curve of robotic gastrectomy, operative time and docking time were significantly reduced in the recent robotic group (n=14) compared to the initial robotic group (n=25)., Conclusion: Robotic gastrectomy could achieve extended lymph node dissection similar to open surgery. Our results showed a significant learning curve effect in the initial 25 cases of the robotic group.

Purpose: The cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer., Methods: A tissue microarray consisting of 167 colon cancer specimens was investigated. The association between CIP2A and clinicopathological parameters was analyzed using the χ(2) test. Survival was analyzed using the Kaplan-Meier method. The impact of CIP2A on proliferation and drug resistance was evaluated using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide test. An anchorage-independent colony formation assay was also performed., Results: CIP2A was an independent prognostic factor in colon cancer after controlling for other clinical confounding factors, such as stage and lymphovascular invasion, particularly in stages III and IV (hazard ratio = 2.974, P < 0.001). The knockdown of CIP2A reduced the proliferation and anchorage-independent colony formation of colon cancer cells. Knockdown of CIP2A decreased the resistance of the cells to 5-fluorouracil, oxaliplatin, and SN38 (an active metabolite of irinotecan). Treatment with 5-fluorouracil, oxaliplatin, and SN38 decreased CIP2A expression., Conclusions: CIP2A is a prognostic factor in colon cancer. The knockdown of CIP2A reduced proliferation and anchorage-independent colony formation and increased 5-fluorouracil, oxaliplatin, and SN38 efficacy in colon cancer cell lines.

Purpose: The seventh edition of the American Joint Committee on Cancer (AJCC) staging system has new substages for colon cancer. We used survival data from a single medical center to analyze this new AJCC edition., Methods: The colon cancer database of Taipei Veterans General Hospital provided 1,865 patient records covering from 1999 to 2005. Survival rates were evaluated using the Kaplan-Meier method., Results: There were 268, 607, 561, and 421 patients in stages I, II, III, and IV disease with 5-year observed survival rates of 86.3%, 79.2%, 65.4%, and 12.8%, respectively. Survival rates were not significantly different between those with T4a and T4b disease (P = 0.806). The outcome of N1c disease was similar to N1a and N1b but worse than N0 (P = 0.004). Survival rates for M1a and M1b disease became different after reclassifying solely peritoneal seeding as M1a (P < 0.001). No discrepancy of outcomes between stage IIIA and stage IIB/IIC remained in the seventh edition., Conclusions: Evolution from the fifth to seventh edition of the AJCC staging system is successful in separating prognostic groups by substaging. But some issues remain unresolved, including the subdivision of T4, N1, and M1.

Background: The AJCC 7th edition changes the classification of T- and N-factors and the TNM stage of gastric cancer. We evaluated its prognostic impact., Methods: From December 1987 to December 2006, a total of 1,380 patients underwent curative surgery for gastric cancer at the Department of Surgery, Taipei Veterans General Hospital, with a retrieved lymph node number ≥ 15. Survival was compared for disease classified according to the AJCC 6th and 7th editions., Results: There is a significant difference in 5-year survival between T2 and T3 gastric cancer classified according to the AJCC 7th edition (75.2 vs. 54.9%, p < 0.001), as well as between N1 and N2 (71.4 vs. 44.1%, p < 0.001). Although patients with N3a had a better 5-year survival than did those with N3b (27.6 vs. 11.3%, p < 0.001), the N3 categories were combined and not applied in the TNM stage in the 7th edition. Multivariate analysis using Cox's proportional hazards model with a forward logistics regression stepwise procedure demonstrates that age, N category of 6th edition, and T and N categories of 7th edition are independent prognostic factors; however, T category of 6th edition is no longer significant. Furthermore, the discriminative power of survival difference between each TNM stage seems to be comparable between the 6th and 7th editions., Conclusions: The AJCC 7th edition provides a more stratified survival difference in staging of gastric cancer. Future division of N3a and N3b in the classification of the TNM stage is recommended.

Background: Despite curative surgery for gastric cancer, many patients die of recurrent cancer. Few studies have investigated the time to recurrence after curative resection for gastric cancer., Methods: Data were collected prospectively between December 1987 and December 2006. A total of 1,549 patients underwent curative resection of adenocarcinoma of the stomach at Taipei Veterans General Hospital. Among them, 419 patients had recurrence; they were divided into early recurrence (<2 years) and late recurrence (≥2 years). The clinicopathological characteristics, survival time after recurrence, and recurrence patterns were compared between the two groups., Results: Multivariate analysis showed that stage III gastric cancer patients with early recurrence had larger tumors and more lymph node metastasis than patients with late recurrence, while no difference between early and late recurrence was observed in stage I and II patients. Early recurrence was associated with more distant metastasis than was late recurrence. Patients with advanced TNM stage tended to die within 2 years after recurrence., Conclusions: Gastric cancer patients with larger tumors and more lymph node metastasis tended to have early recurrence, especially stage III patients. Advanced TNM stage was associated with early cancer death after recurrence.

Background/aims: The rate of recurrence increases in proportion to the degree of tumor depth, even after curative resection for gastric adenocarcinoma. Serosal exposure is considered as an important risk factor of peritoneal recurrence. However, some patients with serosa-negative cancer were found to have peritoneal recurrence. There are few reports concerning risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma. The aim of this study is to evaluate the incidence and risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma after curative resection., Methodology: Total 1128 serosa-negative gastric cancer patients (574 pT1, 251 pT2, 303 pT3) diagnosed as gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were enrolled., Results: Peritoneal recurrence was observed in 50 (4.4%) patients, including 3 pT1, 3 pT2 and 44 pT3 patients. The incidence of peritoneal recurrence increased significantly with tumor invading subserosa (pT3). Multivariate analysis showed that the independent risk factor of peritoneal recurrence was tumor depth., Conclusions: The incidence of peritoneal recurrence in serosa-negative cancer is low, and tumor depth is a significant risk factor. We should be aware of peritoneal recurrence during follow-up, especially for patients with subserosal tumor invasion.

Anti-cancer activities of resveratrol (3,4',5-trihydroxylstilbene) have attracted extensive research attention. Suppression of pulmonary metastasis of BALB/c mice challenged with CT26 colorectal adenocarcinoma cells achieved by oral administration of resveratrol was assessed in three separate experiments. Each mouse was challenged by tail vein injection with CT26 cells. Prior to challenge, 8-wk-old mice were fed with a basal diet and orally administered with resveratrol (30 mg/kg/2 days) eight or twelve times. After challenge, oral administration of resveratrol was continued until mice were sacrificed on day 20. As integrated from three experiments, 3.7% of the control mice (n=27) and 68.7% of the resveratrol-treated mice (n=26) exhibited free of metastasis. In a second study, 8-wk-old BALB/c mice were orally administered with resveratrol 12 times and challenged with CT26 cells for 100 days. All control mice died but 50% of the resveratrol-treated mice survived. The surviving mice were challenged with CT26 cells by hypodermic injection, fed with a basal diet for an additional 30 days, and sacrificed. Tumor lumps or nodules were not detected at the injection sites or in the lungs. This reveals that intrinsic vaccination-like defense has resulted from administration of resveratrol and challenge of tumor cells.

Gastric cancer is one of the most common malignancies in the world. The routes of metastasis include direct extension, lymphatics, and peritoneal or hematogenous spread. Testicular metastasis is rare. We present here a 23-year-old gastric cancer patient who first presented with right-side testis swelling and pain. Diagnosis of metastatic adenocarcinoma was made after right-side orchiectomy. Gastric adenocarcinoma with ascites and peritoneal seeding was found after esophagogastroscopy and abdominal computed tomography. The patient received chemotherapy consisting of docetaxel 36 mg/m(2) and cisplatin 30 mg/m(2) on day 1 and day 8, plus oral tegafur/uracil 300 mg/m(2)/day and leucovorin 90 mg/day on day 1 to day 14 in a 21-day cycle, and he had a partial response to the chemotherapy. Metastatic tumors, especially gastric adenocarcinoma, should be considered in the differential diagnosis of patients presenting with testicular mass and they may respond well to chemotherapy., (Copyright 2010 Elsevier. Published by Elsevier B.V. All rights reserved.)

Members of the suppressor of cytokine-induced signaling (SOCS) family are negative regulators of cytokine signaling pathways. By mRNA differential display, we showed that SOCS6 was frequently down-regulated in gastric cancer (GC). Our data showed that allelic loss and promoter hypermethylation may account for the major mechanisms leading to SOCS6 inactivation. Ectopic expression of SOCS6 suppressed cell growth and colony formation, in part through eliciting intrinsic apoptotic pathway, accompanied with decreased mitochondrial membrane potential. Taken together, this study provides molecular and functional data supporting the importance of loss-of-function of SOCS6 as a frequent event in gastric tumorigenesis., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rapidly increasing. We evaluated the clinicopathological difference and outcomes of Taiwanese patients with AEG according to the Siewert classification., Methods: Data were prospectively collected between December 1987 and July 2007. Two hundred thirty-one patients underwent curative resection of AEG at Taipei Veterans General Hospital and were divided into different Siewert types. The clinicopathological characteristics, operative morbidity, survival, and initial recurrence pattern were compared between the different types., Results: Fifty-one type II and 180 type III cancer patients were studied. Subtotal esophagectomy via a left thoracotomy (19.6% vs 2.8%), smaller tumor size (4.43 +/- 2.04 vs. 5.35 +/- 2.03 cm), and more combined organ resection (60% vs. 43.1%) were more common in type II than type III cancer. Multivariate analysis showed that three independent risk factors for death were gender, tumor size, and lymphovascular invasion. There were long-term survivors among the patients with lesser curvature site lymph node metastasis, whereas metastasis to the lymph nodes of the distal stomach and along the greater curvature site was associated with poor prognosis. The 5-year survival was similar between type II and type III cancer (59.6% vs. 63.5%, P = 0.947)., Conclusions: Lymphovascular invasion, tumor size, and gender were determined to be three independent factors of survival after curative resection for AEG, and Siewert type was not associated with differences in survival.

Background and Aim: Prognostic factors of lymph node-negative gastric adenocarcinoma after curative resection have been discussed. Recurrent pattern of advanced lymph node-negative gastric cancer after curative resection has rarely been described., Methods: Recurrent sites and correlated clinicopathological factors of 372 patients with lymph node-negative advanced gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were analyzed., Results: Recurrence was noted in 51 (13.7%) patients. Recurrent rates according to site of recurrence were 26 peritoneal seeding (51.0%), 26 locoregional (51.0%), 17 hematogenous (33.3%), and 4 lymph node metastasis (7.8%). Clinicopathological factors to predict peritoneal seeding were serosal exposure, lymphovascular invasion, Lauren's diffuse type differentiation and scirrhous stromal reaction. Serosal exposure, tumor size, microscopic infiltrating growth type predicts locoregional recurrence. Tumor had only lymphovascular invasion predict hematogenous spreading., Conclusion: Node-negative advanced gastric cancer has more peritoneal seeding and locoregional recurrence. Aggressive cell behavior predicted the route of tumor cell spreading.

Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E(2) or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2.

Background: Presence or absence of nodal metastasis influences outcome of gastric cancer patients. This study gives insight into survival predictors and clinicopathological features of node-negative gastric adenocarcinoma., Methods: Between 1988 and 1999, 689 gastric cancer patients without other cancer or gastrectomy for benign disease who underwent curative resection were enrolled in this study. Clinicopathological data in patients with node metastasis were compared with those without., Results: The survival rate at 5 and 10 years for node-negative cases was 91.7% and 89.7%, respectively. On univariate analysis, node-negative patients were characterized by frequent location in the lower two-thirds of the stomach (84.9%), tumor size less than 4 cm (63.5%), grossly superficial type (71.6%), more medullary stromal reaction (50.5%) and intestinal type (67.7%), tumor invasion confined to serosa (78.4%), less poorly differentiated cell type (43.2%), and less lymphovascular invasion (33.4%). Multivariate analysis demonstrated that lymphovascular invasion (relative risk: 5.036) and depth of cancer invasion (relative risk: 4.404) were independent poor prognostic factors. However, lymphovascular invasion and serosal invasion were also correlated (P < 0.001)., Conclusion: Patients with node-negative gastric adenocarcinoma had less disease progression and a favorable survival. Lymphovascular invasion and depth of cancer invasion were two independent but correlated survival predictors.

Background: Degenerated PCR primers, designed according to the consensus tyrosine phosphatase catalytic motifs, were used in order to amplify expressed protein-tyrosine phosphatase molecules from human gastric cancer-derived cells. From such profiles, more than twenty different types of tyrosine phosphatase were identified from gastric cancer tissue. A non-receptor tyrosine phosphatase, PTPN4, was found to be expressed in a tumor-tissue profile with only low frequency. The most closely-related gene to tyrosine phosphatase, PTPN3, has been shown to be mutated in cases of human colorectal cancer, but its expression is cases of gastric cancer is not known., Materials and Methods: The mRNA expression of PTPN3 and PTPN4 by RT-PCR was investigated, and the protein expression status of PTPN3 was examined, using immunohistochemistry, to elucidate clinicopathological associations of the PTPN3 and PTPN4 family within human stomach cancer., Results: PTPN3 and PTPN4 were expressed in all gastric cancer cell lines and clinical cancer tissue specimens examined. Following the examination of 92 gastric cancer patients' pathological specimens, PTPN3 expression showed no statistical significance with respect to the patients' survival. A statistically significant correlation between PTPN3 staining and the differentiation status of gastric cancer tissue was, however, observed., Conclusion: This finding indicates that both PTPN3 and PTPN4 are expressed within human gastric cancer cells and that PTPN3 seems to play an important role in gastric cancer differentiation and the progression of malignancy.

Background/aims: The significance of tumor volume and its change after concurrent chemoradiotherapy (CCRT) was evaluated., Methodology: Standard-dose external radiation and oral UFUR plus leucovorin were used to treat 30 middle and lower rectal adenocarcinoma patients. Volume of tumor calculated from images obtained by dynamic MRI of the rectum before and after CCRT was compared to pathological results after definite resection and other clinical data., Results: The T-stage in 15 patients (50%), the N-stage in 13 (72.2%), and overall, the TNM stage in 18 (60%), were downstaged, including 7 (23.3%) with complete responses (CR). Volume of tumor before CCRT (Vpre) and after CCRT (VPost) was 10.3+/-6.1cm3 and 4.2+/-2.2cm3, respectively, and VPre correlated with initial T stage, N stage, age, and location. The net decrease ratio (NDR) of tumor volume was related to Vpre and initial T stage. As to the downstaging effect, VPre was related to incidence of CR; NDR was related to the downstaging of the N stage., Conclusions: All tumors showed volume reduction after CCRT, but the downstaging benefits were not in proportion to the size change. Initially larger tumors had higher ratios of volume reduction, and smaller tumors had higher chance of CR.

Background and Aims: The aim of this study was to identify the occurrence and analyze the characteristics of metachronous colorectal cancers, and to compare the characteristics of these cases (index tumor) with the control group to find any predicting factor that may influence the occurrence of metachronous cancer., Patients and Methods: The database of colorectal cancer in the Veterans General Hospital-Taipei, from January 1981 to September 2001 was reviewed. In total, 3,846 cases of adenocarcinoma of the colon and rectum, which received curative resection during this period, were found. The criteria of metachronous cancer were: occurrence more than 12 months after curative surgery; with pre-operative complete colonoscopy or one negative post-operative colonoscopic follow-up to rule out synchronous tumor; tumor arising from mucosa at a site other than anastomosis. The age, gender of the patients, the location, pathological characteristics of the metachronous tumors, occurrence of associated adenomas, the number of lesions, and the tumor stage were analyzed and compared with the control group., Results: In total, 43 cases of metachronous cancer were identified, giving an annual incidence of 0.18%. The distribution of the location of the index tumor of metachronous cases was predominantly left-sided, which was not different from that of the control group. The mean duration of occurrence of metachronous cancer after the primary operation was 71+/-46.6 months. The association of adenomas had no relationship with the occurrence of the metachronous cancer. No significant predicting factors for the development of metachronous tumors were found., Conclusion: Lifelong regular post-operative colonoscopic surveillance is essential for colorectal cancer patients.

Background: This study evaluated the relationship between DNA aneuploidy and loss of heterozygosity (LOH) at different genetic loci in colorectal adenocarcinoma., Methods: A total of 112 patients with surgically removed colorectal adenocarcinoma in Taipei Veterans General Hospital from January 1999 to July 2001 were included in this study. The pattern of DNA ploidy was determined with DNA flow cytometry, and the LOH of various genetic loci was determined with fluorescence polymerase chain reaction and denaturing gradient gel electrophoresis. The relationship between DNA ploidy, LOH of various genetic loci, and clinicopathologic variables was analyzed with the chi(2) test with Yates' correction as well as by multivariate binary logistic regression analysis., Results: Seventy-one (63.4%) of the 112 carcinomas had DNA aneuploidy. The DNA aneuploidy was not associated with any clinicopathologic variable. Ninety-one tumors (81.3%) exhibited LOH in at least one genetic locus. In the univariate analysis, the DNA aneuploidy was associated with LOH of Tp53-penta, D8S254, D5S346, and high-frequency LOH (P =.001, P =.016, P =.041, and P <.001, respectively). In the multivariate analysis, the most significant factor influencing DNA aneuploidy was D8S254, followed by Tp53-penta, high-frequency LOH, and D5S346., Conclusions: DNA aneuploidy is strongly associated with LOH at specific genetic loci.

Background/aims: Death from gastric carcinoma after curative resection is mostly due to recurrence. The most common recurrence is peritoneal dissemination, which represents 33 to 50% of total recurrence after curative gastrectomy. Since survival after peritoneal dissemination is very poor, selection of high-risk patients for further management after resection may contribute to better survival., Methodology: Based on a prospective database, a total of 1,092 patients with gastric carcinoma who underwent curative resection were included in this study. The incidence of peritoneal recurrence, disease-free interval and survival after peritoneal recurrence were determined. The clinicopathological factors including sex, age, tumor location, size, gross appearance, histological findings, depth of tumor invasion, lymph node status, tumor cell infiltration pattern were analyzed to see if there is any relationship with peritoneal dissemination., Results: The incidence of peritoneal recurrence after curative resection was 13.46%. The mean disease-free interval was 14.2 months and the survival after peritoneal recurrence was 4.9 months in average. Almost all the clinicopathological factors were related with peritoneal recurrence, but only depth of tumor invasion, gross appearance and tumor infiltration pattern are closely associated with peritoneal tumor dissemination after multivariate analyses., Conclusions: Since the prognosis after peritoneal recurrence is so poor, selection of high-risk patients for further management after gastrectomy may be based on these three factors.

Background: Gastric cancer is one of the prevalent cancer types in the Far East region. In order to discover new prognostic and diagnostic biomarkers for gastric cancer progression, we have used degenerated PCR primers designed to amplify all expressed protein tyrosine kinase molecules from human cancer tissues. In previous studies, we have shown the clinical significance of arg tyrosine kinases in a colorectal cancer progression model., Materials and Methods: We further investigated the protein expression of arg tyrosine kinase by immunohistochemistry and analyzed the clinicopathological association with human cancers., Results and Conclusion: Specimens from 79 patients were examined and this demonstrated that the expression of arg kinase showed no statistically significant correlation with the patients' overall survival. However, higher levels of arg kinase immunoreactivity did show a statistically significant association with vessel invasion in gastric cancer tissues examined. This indicates a potential involvement of arg in gastric cancer invasion and progression.

Background: Signet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate.Methods: From January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients.Results: The overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017).Conclusion: The clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection. [ABSTRACT FROM AUTHOR]

Background: Adenosqamous carcinoma (ASC) is a rare disease involving various organs, yet there are no large-scale population-based comparative studies on ASC among different organs. Methods: The incidence and overall survival of ASC among various organs in cases diagnosed in Taiwan from January 1, 2003 to December 31, 2010 were calculated and compared using data from the Taiwan Cancer Registry (TCR). The various organs were classified and divided into three different systems: the female reproductive, respiratory, and alimentary systems. Survival analysis were also compared among 30,850 patients diagnosed as ASC, adenocarcinoma (AC) or squamous cell carcinoma (SCC) in organs with frequent ASC. Results: During the study period, a total of 576 ASC cases were diagnosed in Taiwan. The most common primary system was respiratory (73.8%), followed by alimentary (16.2%) and female reproductive (10%). The overall survival were significantly higher for cases involving the female reproductive system, followed by the respiratory and alimentary systems (P = 0.016). The median overall survival were worse in males than females for cases involving the respiratory system (22.4 vs. 31.8 months, P = 0.044). Multivariate analysis showed that age≧65, more advanced T and N categories were independent unfavorable prognostic factors of overall survival in ASC. ASC histology is an independent unfavorable prognostic factor compared with AC and SCC. Conclusions: ASC at an old age and more advanced T and N categories were found to be associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the impact of a family history (FH) of colorectal cancer (CRC) in first-degree relatives on the outcome of patients with CRC in a veterans’ hospital in Taiwan. Patients ( N = 3,383) with colorectal adenocarcinoma were studied; pedigrees were collected prospectively. Associations between FH and clinicopathologic variables were analyzed using linear-by-linear association. Survival was examined with Kaplan–Meier curves and the log-rank test. Two hundred ninety-seven patients (8.78%) had a first-degree relative with CRC. The average age of onset of CRC was 68.3 years in patients without a FH. This was significantly higher than the age of onset in patients with a FH (66.4 years—one first-degree relative with CRC; 48.8 years—two or more first-degree relatives, P < 0.001). Patients with more affected family members had a higher incidence of right-sided tumor ( P = 0.004), metachronous cancer ( P = 0.034), and less-advanced disease ( P = 0.044). The 5-year overall survival was 83% for patients with two or more first-degree relatives with CRC, 57% for those with one first-degree relative, and 55% for those without a FH ( P = 0.001). The 5-year DFS was 91% for patients with two or more first-degree relatives, 66% for those with one first-degree relative, and 64% for those without a FH of CRC ( P = 0.002). In the multivariate analysis, TNM stage played the most independent prognostic factor, followed by FH ( P < 0.001, hazard ratio = 1.52; 95% confidence interval, 1.24–1.85). CRC patients with a family history of CRC had better survival than did those without a family history of CRC. [ABSTRACT FROM AUTHOR]

Background and Aim: Prognostic factors of lymph node-negative gastric adenocarcinoma after curative resection have been discussed. Recurrent pattern of advanced lymph node-negative gastric cancer after curative resection has rarely been described. Methods: Recurrent sites and correlated clinicopathological factors of 372 patients with lymph node-negative advanced gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were analyzed. Results: Recurrence was noted in 51 (13.7%) patients. Recurrent rates according to site of recurrence were 26 peritoneal seeding (51.0%), 26 locoregional (51.0%), 17 hematogenous (33.3%), and 4 lymph node metastasis (7.8%). Clinicopathological factors to predict peritoneal seeding were serosal exposure, lymphovascular invasion, Lauren's diffuse type differentiation and scirrhous stromal reaction. Serosal exposure, tumor size, microscopic infiltrating growth type predicts locoregional recurrence. Tumor had only lymphovascular invasion predict hematogenous spreading. Conclusion: Node-negative advanced gastric cancer has more peritoneal seeding and locoregional recurrence. Aggressive cell behavior predicted the route of tumor cell spreading. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy is approved in selected cases of gastric cancer, and durable responses have been observed in exceptional responders. Several potential predictive biomarkers have been identified in gastric cancer, such as microsatellite instability-high (MSI-H), Epstein–Barr virus (EBV), and programmed death ligand 1 (PD-L1). We explored the real-world evidence of these biomarkers and their outcomes. When only combined positive score (CPS) ≥ 1 was used as the biomarker, the overall response rate (ORR) and progression-free survival (PFS) were not statistically significant. CPS ≥ 1 was commonly combined with MSI-H (75%) and Epstein–Barr encoding region (EBER) (80%). MSI-H and CPS ≥ 5 were prognostic biomarkers associated with better ORR and PFS. In patients with EBER, better ORR and PFS were observed only in patients with CPS ≥ 1. These results could transform clinical practice and can be used to formulate more precise treatment suggestions for patients with gastric cancer. Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers—microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein–Barr encoding region (EBER)—were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

This study aims to determine prognostic indicators among patient-, tumor-, and treatment-related factors of gastric cancer patients. A total of 510 patients who underwent curative gastric resection were studied. Univariate analysis of patient-related factors showed a significantly lower survival in patients with a history of obstruction, hypoalbuminemia, and anemia. Tumor-related factors including gross appearance, location, and size of tumor; depth of cancer invasion; level, number, and frequency of lymph node metastasis; stromal reaction and tumor growth pattern; and histological classification all significantly affected survival. Surgical treatment related factors such as total or distal subtotal gastrectomy, extent of lymphadenectomy, and combined resection of adjacent organ(s) showed a statistically significant adverse influence on survival. Multivariate analysis identified only four tumor-related factors-number of metastatic lymph nodes, depth of cancer invasion, stromal reaction, and gross appearance of the tumor-as independently affecting survival. These findings suggest that only four tumor-related factors were prognostic indicators in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients. [ABSTRACT FROM AUTHOR]