p27kip1 expression is inversely related to the grade of gastric MALT lymphoma

Background: Decreased or lost expression of the cyclin-dependent kinase inhibitor p27^kip1 protein has been found to be a poor prognostic factor in many cancers, including gastric cancer. Aim: To evaluate p27^kip1 expression in gastric mucosa-associated lymphoid tissue (MALT) and gastric B-cell lymphoma. Methods: Fifty-two cases of gastric lymphoma, mean age 68.7 yr (range 23–90 yr), 11 of chronic Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were studied. Patients were classified into two groups. Stage IE gastric lymphomas were defined as local gastric lymphoma of MALT and more advanced stages as advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67. Results: The proliferative index was higher in gastric DLBL than in low-grade MALT lymphomas, 57.1±31.2 vs 17.3±20.6 (p=0.0001). The mean p27^kip1 expression score for high-grade patients was significantly lower compared with that of low-grade patients, 0.5 ± 0.4 and 1.6±0.8, respectively (p=0.001). Comparative evaluation of p27^kip1 expression in malignant lymphoid cells revealed that B cells of the localized gastric DLBL patients expressed the least p27^kip1, 0.36±0.32. This value was lower than that of malignant lymphoid cells of patients with advanced DLBL, 0.64±0.53, advanced low-grade MALT lymphoma, 1.59±0.79, and localized low-grade MALT lymphoma, 1.59±0.84. In the multivariate model in which all p27^kip1 variables were entered, the expression of p27^kip1 in malignant lymphoid cells was inversely correlated with the grade of the lymphoma irrespective of the stage of the disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07–0.31, p=0.0001. Conclusion: p27^kip1 may be a putative distinct molecular marker to differentiate between low-grade and high-grade gastric lymphoma.     

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

Background

Adiponectin is inversely related to BMI, positively correlates with insulin sensitivity, and has anti-atherogenic effects. In recent years, adiponectin has been well studied in the field of oncology. Adiponectin has been shown to have antiproliferative effects on gastric cancer, and adiponectin expression is inversely correlated with clinical staging of the disease. However, no studies have reported the correlation between serum adiponectin and receptor expression with disease progression.

Methods

In this study, we evaluated expression levels of 2 adiponectin receptors--AdipoR1 and AdipoR2--and attempted to correlate their expression with prognosis in gastric cancer patients. AdipoR1 and AdipoR2 expression in gastric cancer cell lines (MKN45, TMK-1, NUGC3, and NUGC4) was evaluated by western blotting analysis, and the antiproliferative potential of adiponectin was examined in vitro. Serum adiponectin levels were evaluated in 100 gastric cancer patients, and the expression of AdipoR1 and AdipoR2 was assessed by immunohistochemical staining.

Results

MKN45 and NUGC3 expressed higher levels of AdipoR1 compared to NUGC4, even though there was no significance in AdipoR2 expression. The antiproliferative effect of adiponectin was confirmed in MKN45 and NUGC3 at 10 μg/ml. No significant associations were observed between serum adiponectin levels and clinicopathological characteristics, but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative AdipoR1 immunostaining group (24/32, p = 0.013 and 9/32, p = 0.042, respectively) compared to the positive AdipoR1 group (lymphatic metastasis, 33/68; peritoneal dissemination, 8/68). On the other hand, AdipoR2 expression was only associated with histopathological type (p = 0.001). In survival analysis, the AdipoR1 positive staining group had significantly longer survival rates than the negative staining group (p = 0.01). However, multivariate analysis indicated that AdipoR1 was not an independent prognostic factor on patient's survival on gastric cancer.

Conclusions

In gastric cancer, adiponectin has the possibility to be involved in cell growth suppression via AdipoR1. The presence of AdipoR1 could be a novel anticancer therapeutic target in gastric cancer.

     

Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications简

Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.     

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

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 {"type":"clinical-trial","attrs":{"text":"NCT01198392","term_id":"NCT01198392"}}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.     

Pancreaticoduodenectomy for advanced gastric cancer

Background Although pancreaticoduodenectomy has been rarely performed for gastric caner because of frequent morbidity and mortality, some favorable results after this procedure have been reported recently. Our objective was to present our data that might aid in the selection of patients to undergo this procedure.Methods Between 1970 and 2001, 23 patients who had pancreaticoduodenectomy for gastric cancer with tumor invading the pancreatic head were identified, and they were the subjects of this study. Clinical, operative, and pathological data, and morbidity and mortality rates were collected and analyzed. Survival outcome was also calculated and analyzed.Results Five patients underwent this procedure for disease in the gastric remnant, 18 undergoing the procedure for primary tumors. Median operating time was 8h (range, 6–13h), and median blood loss was 1600ml (range, 700–16000ml). Regarding extent of gastrectomy, all patients with primary cancer (n = 18) underwent a distal gastrectomy and patients with disease in the gastric remnant (n = 5) underwent a completion gastrectomy. Incurable factors, including paraaortic lymph node metastasis, positive lavage cytology, or peritoneal dissemination were found in 8 patients. The postoperative morbidity rate was 73.9%; however, operation-related death was zero. The overall 5-year survival rate was 34.3%. The 5-year survival rate of the 8 patients with incurable factors was 0%, while that of the 15 patients without incurable factors was 47.4%.Conclusion If an R0 resection can be achieved by pancreaticoduodenectomy, this procedure should be performed for patients with tumor invading the pancreatic head. Patients with incurable factors should not be considered for pancreaticoduodenectomy.     

Prognostic impact of RING box protein-1 (RBX1) expression in gastric cancer

Background

RING box protein-1 (RBX1) is an essential component of the E3 ubiquitin ligase Skp1/Cullin/RBX1/F-box protein complex. Although an altered expression of RBX1 has been reported in several human cancers, the role of RBX1 in gastric cancer remains unknown.

Methods

We investigated the RBX1 expression in primary gastric cancer tissues from 145 patients by immunohistochemistry, and explored its clinical relevance and prognostic value. Furthermore, the effect of RBX1 expression on cancer cell proliferation was analyzed in vitro using a siRNA silencing technique.

Results

The RBX1 expression was abundant in gastric cancer tissues. There was a significant difference in the expression level of RBX1 in terms of the tumor depth (P = 0.008), presence of distant metastasis (P = 0.016) and venous invasion (P = 0.005). The postoperative overall (P < 0.001) and relapse-free survival (P < 0.001) rates were significantly poorer in patients with RBX1-high tumors than in patients with RBX1-low tumors. There was a significant correlation of the RBX1 status with postoperative hematogenous recurrence (P = 0.013). Importantly, the RBX1 status was identified as an independent prognostic factor for gastric cancer (P = 0.002). Furthermore, RBX1 gene silencing significantly inhibited the proliferation of gastric cancer cells in vitro.

Conclusions

The RBX1 expression has a significant prognostic value in gastric cancer. RBX1 might play an important role in regulating the proliferation of gastric cancer cells and promoting the development of postoperative recurrence. Our data provide a rationale for developing a novel therapy targeting RBX1 for gastric cancer.     

Predictive biomarkers along gastric cancer pathogenetic pathways

Introduction: Gastric cancer is the second leading cause of cancer all over the world. Unfortunately, several gastric cancers are diagnosed in an advanced stage and chemotherapy and/or target therapies remain the only options to treat patients.

Areas covered: Herein we evaluate the new molecular proposal of gastric cancer classification, offering the possibility to recognize different pathogenetic mechanisms and molecular biomarkers potentially useful for target therapies.

Expert commentary: The possibility of introducing new specific tests for identification of molecular biomarkers critical for targeted therapies response represents the new frontier in the selection of gastric cancer patients to improve their survival. Besides HER2, already used in clinical settings as a target biomarker for biological therapy in gastric cancer patients with tissue cancer cells overexpressing HER2, other promising target biomarkers which are deregulated in gastric cancer, such as MET and FGFR, could be identified in tissue and then used for therapeutic purposes. In addition immunotherapy represents the most promising possibility of advanced gastric cancer treatment. In particular, as in other solid tumors, PD-1/PDL1 pathway has emerged in several clinical trials as an interesting therapeutic target.     

Apatinib plus S-1 for previously treated,advanced gastric or gastro-oesophageal junction adenocarcinoma: a phase 2, single-arm,prospective study

BackgroundThe current management of advanced gastric or gastro-oesophageal junction adenocarcinoma remains unsatisfactory. We investigated the efficacy and safety of the combination therapy of apatinib and S-1, considering the potential advantage of home-based treatment without hospital admission, in patients with platinum-refractory gastric or gastro-oesophageal junction adenocarcinoma.MethodsIn this open-label, single-arm, phase 2 trial, in each 21-day cycle, eligible patients received apatinib at an initial dose of 500 mg once daily continuously and S-1 at a dose of 40–60 mg twice daily on days 1–14 until the trail was discontinued disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoints were progression-free survival. The secondary endpoints were objective response rates, disease control rates, and safety, and overall survival. This study was registered at ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT04338438","term_id":"NCT04338438"}}NCT04338438.ResultsBetween April 2015 and May 2019, we included 37 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma refractory to first-line platinum-containing therapy. At the data cutoff, the 6-month progression-free survival was 31.5%, the median progression-free survival and overall survival were 4.2 (95% CI: 3.50–4.90) months and 8.2 (95% CI: 4.69–11.71) months, respectively. Of 37 eligible patients, 8 (21.6%) patients reached objective responses, 31 (83.8%) patients reached disease control. Grade 3 or 4 adverse events occurred in 8 (21.6%) patients, including hand-foot syndrome, hypertension, and diarrhea, etc.ConclusionsThe combination of Apatinib and S-1 showed promising efficacy and manageable toxicity as a home-based, second-line therapy in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, especially for the elder patients with poor performance status.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT04338438","term_id":"NCT04338438"}}NCT04338438.     

Expression of Mcl-1 and p53 proteins predicts the survival of patients with T3 gastric carcinoma

Background The expression of myeloid cell leukemia 1 (Mcl-1) and p53 proteins was investigated for clinicopathological and prognostic significance in patients with gastric carcinoma.Methods Mcl-1 protein was immunohistochemically examined in 182 patients with gastric carcinoma. The overexpression of p53 was also analyzed in T3 gastric carcinomas.Results The expression of Mcl-1 was detected in 127 (69.8%) patients with gastric carcinoma. Mcl-1 was detected significantly more frequently in the undifferentiated type (P 0.05) and in the advanced stage of disease (P 0.05). The prognosis of patients with an Mcl-1-positive tumor was significantly worse than that of those with an Mcl-1-negative tumor (P 0.05). Multivariate analysis revealed that the expression of Mcl-1 was an independent prognostic factor, as were lymph node metastasis and tumor size. There was no significant relationship between the expression of Mcl-1 and p53. In patients with T3 gastric carcinoma who underwent curative surgery; however, Mcl-1(–)/p53 (–) tumor demonstrated the best postoperative survival rate, whereas Mcl-1(+)/p53(+) tumor had the worst.Conclusion The expression of Mcl-1 is an indicator of tumor progression and postoperative recurrence in patients with gastric carcinoma. Combined analysis of Mcl-1 and p53 proteins may accurately predict the survival of patients with T3 gastric carcinoma.     

Notch1 activation is a poor prognostic factor in patients with gastric cancer

Background:

Aberrant Notch1 activation has been studied in many malignant tumours, but its role in gastric cancer remains unknown. This study is aimed to investigate the prognostic significance of Notch1 activation in patients with gastric cancer.

Methods:

In this study, we prospectively enrolled two independent sets of patients with gastric cancer from China and defined the activation of Notch1 by immunohistochemical staining of its active form, intracellular domain of Notch1 (ICN1). The prognostic value of Notch1 activation and clinical outcomes in gastric cancer were evaluated.

Results:

Expression of ICN1 is elevated in gastric cancer tissues and is predominately localised in the cell cytoplasm and/or membrane. High ICN1 expression positively correlates with tumour invasion depth (P=0.032), lymph node metastasis (P<0.001), advanced TNM stage (P=0.003) and reduced overall survival (P=0.0004) in the training set. Multivariate Cox regression analysis identified ICN1 as an independent prognostic factor (P=0.031), which could be incorporated into the TNM system to generate a better predictive model for patient outcomes. The c-index was 0.7375 when assessed with the TNM stage and improved to 0.8037 when ICN1 expression was added in the training set. These results were validated in the validation set.

Conclusions:

Notch1 activation was correlated with gastric cancer progression and defined as a novel independent prognostic factor. Combining ICN1 expression with TNM stage may provide a better predictive model for outcomes of gastric cancer patients.     

A past history of gastric ulcers and Helicobacter pylori infection increase the risk of gastric malignant lymphoma

Helicobacter pylori (H. pylori) is a causative agent for peptic ulcers as well as some types of gastric lymphoma; however, the relationship between a peptic ulcer history in combination with H. pylori infection and the risk of gastric lymphoma has not been fully evaluated. To examine this point, we conducted a case-control study with 645 patients histologically diagnosed as having malignant lymphomas and 3225 non-cancer controls. Plasma H. pylori IgG status was assessed for subgroups for which blood samples were available (116 cases and 114 controls). An association with a history of gastric, but not duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41, 95% confidence interval (CI): 3.12-9.39]. In the examination according to histological subtype, the OR was high for both gastric mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI: 2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95% CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of total gastric lymphoma was associated with H. pylori infection (OR = 5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and DLBCL (8 out of 9: 88.9%). Further, in subgroup analysis of subjects with H. pylori infection, gastric ulcer history, but not duodenal ulcer history was associated with the risk of gastric lymphoma (OR = 4.15, 95% CI: 1.02-16.89). In conclusion, we found a positive association with a past history of gastric ulcer and H. pylori infection for gastric lymphoma, while duodenal ulcer history was no association. These results suggested the risk of gastric lymphoma increased by interaction between H. pylori infection and gastric ulcer history. Further studies are warranted.     

A clinicopathologic study of gastric mucosa-associated lymphoid tissue lymphoma

BACKGROUND: It is still unclear which patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma will benefit from the eradication of Helicobacter pylori. METHODS: The authors studied a total of 34 patients. Twenty-three patients had primary gastric lymphoma and underwent gastric resection as initial treatment. Eleven patients with gastric MALT lymphoma who received antibiotics against H. pylori as initial treatment were also included. In all 34 patients, the presence of H. pylori, endoscopic findings, and pathologic features were evaluated. Immunohistochemical expression of Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) was classified as follows: (-), no reactive cells; (+), scattered positive cells; (2+), nests of positive cells; (3+), diffuse positive cells. RESULTS: Patients with low grade MALT lymphoma (LG) tended to be positive for H. pylori (6 of 9), to localize within the submucosa (7 of 9), not to have lymph node involvement (7 of 8), and to have lower tumor stage compared with patients with high grade MALT components (HG). Bcl-2 protein was expressed with high frequency by LG (7 of 9). Strong expression of p 53 was more common in the HG tumors (4 of 14), and strong expression of PCNA showed a significant difference between LG (1 of 8) and HG patients (12 of 13). Investigation of the patients with long term follow-up (n = 4) revealed that LG remained superficial for a long time and showed gradual progression. Most of these tumors were Bcl-2+/p53-approximately+/-/ PCNA- approximately +. There were two patients whose superficial LG (sm/Bcl-2+/p53-/PCNA- approximately +) regressed after the disappearance of H. pylori. On the other hand, one patient developed ulcerated LG (sm/Bcl-2 /p53+/PCNA3+) after disappearance of H. pylori. The authors found complete regression of MALT lymphoma in 9 of 11 patients after H. pylori eradication. Initial tumors of these 9 patients were superficial/sm/n(-)/low grade/Bcl-2+approximately +/-/p53-approximately+ (n = 9), /PCNA-approximately+(n = 6), /PCNA 2+ (n = 3). Two local recurrence and one non-Hodgkin lymphoma in other sites were observed after initial therapy. CONCLUSIONS: Gastric MALT lymphoma with (H. pylori positive/superficial/sm/low grade/Bcl-2 +/p53- approximately +/PCNA- approximately +) pattern will disappear after a patient is cured of H. pylori infection.     

An assessment of the feasibility of sentinel lymph node-guided surgery for gastric cancer

Background Sentinel node-guided surgery has received increasing attention in tumor surgery. To ascertain whether sentinel lymph node (SLN)-guided surgery is feasible for gastric cancers 4cm or less in size, we conducted a multicenter clinical study.Methods One milliliter of isosulfan blue was injected endoscopically into the gastric wall at four sites around a gastric cancer lesion. Approximately 15min after the injection of the dye, the surgeons resected (picked-up) the stained blue nodes (defined as SLNs) around the stomach.Results SLNs were detected in 140 of 144 patients (97.2%). The average number of SLNs was 3.3. In 99 patients with D2 lymph node dissection, the false-negative rate (FNR) was evaluated. In 14 T1 patients with pathological positive lymph node metastasis (pN(+)), the FNR was 29%. In 9 T2,3 pN(+) patients, the FNR was 44%. In T1 patients with pN(+) but macroscopically normal lymph nodes during surgery (sN0), the FNR was 11% (1/9).Conclusion T1 and sN0 patients may be a target group for the study of SLN-guided surgery. A larger multicenter trial should be performed to clarify the application of sentinel node navigation surgery for gastric cancer.*Members of the EGI group are the First Department of Surgery of Okayama University Hospital; Satoh Hospital; Kaneda Hospital; Hiroshima City Hospital; Fukuyama National Hospital; Onomichi Citizens Hospital; Okayama Saiseikai Hospital; Matsuyama Citizens Hospital; Himeji Central Hospital; Oomoto Hospital; Tsuyama Central Hospital; Kagawa Rohsai Hospital; Matsuda Hospital; and Mihara Red Cross Hospital.     

Surgical management of gastric perforation in the setting of gastric cancer

Background

Gastric perforation is a rare presentation of gastric cancer and is thought to be a predictor of advanced disease and, thus, poor prognosis. Guidelines do not exist for the optimal management strategy. We aimed to identify, review, and summarize the literature pertaining to perforation in the setting of gastric cancer.

Methods

A qualitative, systematic review of the literature was performed from January 1, 1985, to January 1, 2010. Searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were performed using search terms related to gastric cancer surgery. Abstracts were examined by two independent reviewers and a standardized data collection tool was used to extract relevant data points. Summary tables were created.

Results

Nine articles were included. Perforation was reported to occur in fewer than 5% of gastric cancer patients. Preoperative diagnosis of a gastric cancer was rated and occurred in 14–57% of patients in the papers reviewed. Mortality rates for emergency gastrectomy ranged from 0 to 50% and for simple closure procedures the rates ranged from 8 to 100%. Patients able to receive an R0 gastrectomy demonstrated better long-term survival (median 75 months, 50% 5-year) compared with patients who had simple closure procedures.

Conclusions

Gastric cancer patients presenting with a gastric perforation demonstrate improved overall survival with an R0 resection; however, implementation of this management technique is complicated by infrequent preoperative gastric cancer diagnosis, and inability to perform an oncologic resection due to patient instability and intra-abdominal contamination.

     

Assessment of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the preoperative management of patients with gastric cancer

Background

The significance of ¹⁸F-2-deoxy-2-fluoro-glucose positron emission tomography combined with computed tomography imaging (FDG-PET/CT) in the diagnosis of gastric cancer remains controversial. This study aimed to evaluate the efficacy of preoperative FDG-PET/CT in staging of gastric cancer.

Methods

FDG-PET/CT results for 90 patients with gastric cancer were retrospectively examined. For quantitative PET analysis, FDG uptake was assessed based on the maximum standardized uptake values (SUV_max).

Results

FDG-PET/CT detected the primary gastric cancer in 71 of the 90 patients (sensitivity 78.9 %). The median SUV_max was significantly higher in patients with T3/T4 disease than in those with T1/T2 (9.0 vs. 3.8; P < 0.001), in patients with distant metastasis than in those with no metastasis (9.5 vs. 7.7; P = 0.018), and with stage III/IV tumors than in those with stage I/II (9.0 vs. 4.7; P = 0.017). The SUV_max of the primary tumor was significantly correlated with tumor size (r = 0.461, P < 0.001). The sensitivity, specificity, and accuracy of FDG-PET/CT in assessing metastasis to regional lymph nodes were 64.5, 85.7, and 71.1 %, respectively.

Conclusions

FDG-PET/CT results are significantly associated with tumor progression in gastric cancer, and such findings can reliably identify cancer cell populations.     

Prognostic significance of acute presentation with emergency complications of gastric cancer

Background Although acute complications necessitating emergency hospital admission are well documented in patients with carcinoma of the colon, comparable data for patients with gastric carcinoma is thin. The aim of this study, therefore, was to examine the outcomes of patients presenting to hospital as acute admissions with emergency complications of previously undiagnosed gastric cancer.Methods Three hundred consecutive patients with gastric adenocarcinoma were studied prospectively, and subdivided into two groups according to whether the patients were referred as acute emergencies (n = 116) or as outpatients (n = 184).Resuslts The commonest emergency complications were: abdominal pain (57%), vomiting (41%), gastrointestinal bleeding (37%), dysphagia (26%), and a palpable mass (18%). Stages of disease were significantly more advanced in patients presenting acutely (I:II:III:IV = 7:11:27:71) compared with patients referred via outpatients (20:23:50:91, ² = 3.955; DF, 1; P = 0.047). R0 gastrectomy was significantly less likely after acute presentation (23 patients; 20%) compared with patients referred via outpatients (70 patients; 38%; ² = 11.037; DF, 1; P = 0.001). Cumulative 5-year survival for patients referred acutely was 9%, compared with 22% after outpatient referral (² = 9.11; DF, 1; P = 0.0025). Multivariate analysis revealed two factors to be significantly and independently associated with durations of survival: stage of disease (hazard ratio [HR], 1.742; 95% confidence interval [CI], 1.493–2.034; P = 0.0001) and presentation with acute complications (HR, 1.561; 95% CI, 1.151–2.117; P = 0.004).Conclusion Emergency complications of gastric cancer are a significant and independent prognostic marker of poor outcome.Presented at: British Society of Gastroenterology, Birmingham 2003, and 5th International Gastric Cancer Congress, Rome 2003.     

ncRuPAR inhibits gastric cancer progression by down-regulating protease-activated receptor-1

ncRuPAR is a newly discovered long noncoding RNA molecule that can upregulate protease-activated receptor-1 (PAR-1) during embryonic growth; however, its role in cancer has not been elucidated. Here, we conducted a study to investigate the role of ncRuPAR in gastric cancer. Significant downregulation of ncRuPAR was detected in gastric cancer tissues compared with paired adjacent nontumor tissues; however, both PAR-1 and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) levels were significantly higher in cancerous tissues compared with adjacent normal tissues. Additionally, the expression level of ncRuPAR was found to be significantly correlated with tumor invasion depth, lymph node metastasis, distant metastasis, tumor size, and tumor-nodes-metastasis (TNM) stage and inversely associated with the mRNA levels and extent (E) × intensity (I) scores of PAR-1 and VEGF. The protein level of PAR-1 was significantly correlated with tumor size only, while the VEGF protein level was significantly correlated with invasion depth and tumor size. The area under the receiver operating characteristic (ROC) curve of ncRuPAR was 0.84 (95 % CI 0.79–0.88) at a cutoff value of 4.97; ncRuPAR had a sensitivity of 88.41 %, a specificity of 73.91 %, and an accuracy of 81.16 % for the prediction of gastric cancer. These results suggest that ncRuPAR inhibits gastric cancer development, and its underlying mechanism involves the inhibition of PAR-1. In addition, ncRuPAR could be regarded as a marker for gastric cancer in the future.     

18F-FDG PET/CT在胃癌诊断中应用价值

目的氟代脱氧葡萄糖正电子发射计算机断层显像(18F-fluorodeoxyglucose positron emission tomography/computer tomography,18F-FDG PET/CT)检查对胃癌术后肿瘤的复发和转移有着重要作用,但对胃癌患者术前的应用价值一直以来有待明确。本研究探讨18F-FDG PET/CT对于未接受任何治疗的胃癌患者其诊断的应用价值。方法回顾性分析宁夏医科大学总医院2012-05-08-2018-12-24临床初诊为胃部病变的79例患者临床资料,并于治疗前接受18F-FDG PET/CT检查。根据患者相关的病历资料,包括性别、年龄、肿瘤部位、分化程度、病理分期等因素分别进行分组,再对各组患者18F-FDG PET/CT检查结果中的最大标准摄取值(maximum standard uptake value,SUVmax)进行比对,应用相关统计学软件进行数据分析。结果经病理学确诊,79例胃部病变患者中胃腺癌60例,原发性胃淋巴瘤17例,慢性萎缩性胃炎2例。原发性胃淋巴瘤组的SUVmax为18.39±8.85,胃腺癌组的SUVmax为8.31±5.64,两者之间的差异有统计学意义,t=4.45,P<0.05,说明SUVmax在术前鉴别两种疾病时能够提供有效的诊断价值。胃癌患者术后病理,Ⅰ期SUVmax为3.28±1.22,Ⅱ期SUVmax为13.49±9.68,Ⅲ期SUVmax为8.03±3.61,Ⅳ期SUVmax为10.20±1.91,各组之间差异有统计学意义,F=12.56,P<0.05。从而证实了在胃癌术后病理分期方面,治疗前行18F-FDG PET/CT可以为此提供可靠的半定量依据。结论18F-FDG PET/CT能够在胃癌和原发性胃淋巴瘤的鉴别以及胃癌术后病理分期等方面提供重要的诊断价值,从而更好的指导临床治疗。     

Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of lymph node metastasis and gastric corpus cancer

Background

The aim of this study was to determine the clinicopathological features of gastric cancers with loss of imprinting (LOI) of LIT1. Insulin-like growth factor 2 (IGF2) and H19 in Chinese patients.

Methods

DNA and RNA from tumours were amplified and then digested with RsaI, ApaI and HinfI, and RsaI respectively to determine the LOI status. The demographic and clinicopathological characteristics in LOI positive and LOI negative patients were compared and tested with Statistical analysis.

Results

Of the 89 patients enrolled for analysis, 22, 40 and 35 were heterozygous and thus informative for LIT1, IGF2 and H19 LOI analyses respectively. The positive rate of LIT1, IGF2 and H19 LOI of gastric cancer tissues were 54.6% (12/22), 45% (18/40) and 8.6% (3/32) in Chinese patients. Gastric corpus cancer (8/10, 80%) were more likely to have LOI of IGF2 in tumours than antrum cancers (10/30, 33.3%){odds ratio (OR) = 8, 95% confidence intervals (CI) = 1.425-44.920, p = 0.018)}. LOI of IGF2 in tumours was also associated with the lymph node metastasis (LNM) (OR = 4.5, 95% CI = 1.084-18.689, p = 0.038).

Conclusion

IGF2 LOI is present in high frequency in Chinese gastric cancer patients, especially those with gastric corpus cancer.