[Show abstract][Hide abstract] ABSTRACT: MC tended toward worse tumor biological behavior and long-term survival outcome compared to WMDC. Moreover, MC also showed worse clinicopathological features and survival outcome in some selected patients. For these reasons, MC should be deemed as a special histological type of gastric cancer with worse clinicopathological features and survival outcome.
Preview · Article · Feb 2016 · Gastroenterology Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Background:
Massive abdominal arterial bleeding is an uncommon yet life-threatening complication of radical gastrectomy. The exact incidence and standardized management of this lethal morbidity are not known.
Between January 2003 and December 2013, data from 1875 patients undergoing radical gastrectomy with D2 or D2 plus lymphadenectomy were recorded in a prospectively designed database from a single institute. The clinical data and management of both early (within 24 h) and late (beyond 24 h) postoperative abdominal arterial hemorrhages were explored. For late bleeding patients, transcatheter arterial embolization (TAE) and re-laparotomy were compared to determine the better initial treatment option.
The overall prevalence of postoperative abdominal arterial bleeding was 1.92 % (n = 36), and related mortality was 33.3 % (n = 12). Early and late postoperative bleedings were found in 6 and 30 patients, respectively. The onset of massive arterial bleeding occurred on average postoperative day 19. The common hepatic artery and its branches were the most common bleeding source (13/36; 36.1 %). All the early bleeding patients were treated with immediate re-laparotomy. For late bleeding, patients from the TAE group had a significantly lower mortality rate than that of the patients from the surgery group (7.69 vs. 56.25 %, respectively, P = 0.008) as well as a shorter procedure time for bleeding control (2.3 ± 1.1 vs. 4.8 ± 1.7 h, respectively, P < 0.001). Four rescue reoperations were performed for TAE failures; the salvage rate was 50 % (2/4). Ten patients developed massive re-bleeding after initial successful hemostasis by either TAE (5/13) or open surgery (5/16). Three out of the 10 re-bleeding patients died of disseminated intravascular coagulation (DIC), while the other 7 recovered eventually by repeated TAE and/or surgery.
Abdominal arterial bleeding following radical gastrectomy tends to occur during the later phase after surgery, with further complications such as abdominal infection and fistula(s). For late bleeding, TAE can be considered as the first-line treatment when possible.
No preview · Article · Dec 2015 · Journal of Gastrointestinal Surgery
[Show abstract][Hide abstract] ABSTRACT: The preoperative nutritional and immunological statuses have an important impact in predicting the survival outcome of patients with various types of malignant tumors. Our study aimed to explore the clinical significance and predictive prognostic potential of Onodera's prognostic nutritional index (PNI) in patients with colorectal carcinoma. This retrospective study included a total of 1321 patients who were diagnosed with colorectal cancer and who had been surgically treated between January 1994 and December 2007. The PNI level was determined according the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm(3)). The impact of PNI on clinicopathological features and overall survival (OS) was determined. The optimal cutoff value of PNI was set at 45. Patients in the low-PNI group had a greater potential to have aggressive histological features, advanced tumors (T), nodal involvement (N), metastasis (M), and TNM stage than those in the high-PNI group. The low-PNI group had a worse OS than the high-PNI group (5-year survival rate 56.1 vs 64.8 %, respectively; P < 0.05). Furthermore, the PNI value was an independent prognostic factor for colorectal cancer in this study. The OS was significantly lower in the low-PNI group than in the high-PNI group in patients with TNM stage II and III diseases. Preoperative PNI is a simple and useful marker to predict clinicopathological features and long-term survival outcome in patients with colorectal carcinoma. PNI analysis should be included in the routine assessment of patients with locally advanced colorectal cancer.
[Show abstract][Hide abstract] ABSTRACT: XRCC2 has been shown to increase the radioresistance of some cancers. Here, XRCC2 expression was investigated as a predictor of preoperative radiotherapy (PRT) treatment response in locally advanced rectal cancer (LARC). XRCC2 was found to be overexpressed in rectal cancer tissues resected from patients who underwent surgery without PRT. In addition, overall survival for LARC patients was improved in XRCC2-negative patients compared with XRCC2-positive patients after treatment with PRT (P < 0.001). XRCC2 expression was also associated with an increase in LARC radioresistance. Conversely, XRCC2-deficient cancer cells were more sensitive to irradiation in vitro, and a higher proportion of these cells underwent cell death induced by G2/M phase arrest and apoptosis. When XRCC2 was knocked down, the repair of DNA double-strand breaks caused by irradiation was impaired. Therefore, XRCC2 may increases LARC radioresistance by repairing DNA double-strand breaks and preventing cancer cell apoptosis. Moreover, the present data suggest that XRCC2 is a useful predictive biomarker of PRT treatment response in LARC patients. Thus, inhibition of XRCC2 expression or activity represents a potential therapeutic strategy for improving PRT response in LARC patients.
[Show abstract][Hide abstract] ABSTRACT: Transforming acidic coiled coil-containing protein 3 (TACC3) is well understood to regulate mitotic spindle dynamics and centrosome integrity during mitosis. TACC3 has been suggested to be deregulated in a variety of human malignancies and may be involved in the process of cancer progression. The aim of the present study was to determine the status of TACC3 expression in gastric cancer (GC) and to clarify its clinical/prognostic significance. In the present study, we applied quantitative PCR (qPCR) and western blotting to examine TACC3 mRNA/protein expression in paired GC tissues and matched adjacent non-malignant tissues. Immunohistochemistry (IHC) was performed on a large cohort of 186 postoperative GC samples. Chi-square test, Kaplan-Meier analysis and Cox regression modelling were used to analyse the data. Upregulated mRNA and protein expression levels of TACC3 were observed in the majority of the GC tissues based on qPCR and western blotting compared to the adjacent non-cancerous gastric tissues. Specific IHC staining for TACC3 was predominantly identified in the cytoplasm of the cancer cells. A high expression of TACC3 was detected in 102 of the 186 (54.8%) tissue samples and was significantly associated with the extracapsular extension of the tumour (P<0.001), tumour relapse (P<0.001) and shortened overall survival in GC (P<0.001). Further analysis demonstrated that the TACC3 expression level stratified the patient outcome in stage II (P=0.040), stage III (P<0.001), T3/4 (P<0.001), N positive (P<0.001) and poorly differentiated/undifferentiated tumour subgroups (P<0.001). The Cox regression analysis suggested that a high expression of TACC3 was an independent prognostic factor for GC patients. The measurement of TACC3 protein expression may be beneficial for predicting clinical outcomes for GC patients.
No preview · Article · Jun 2015 · Oncology Reports
[Show abstract][Hide abstract] ABSTRACT: Gastric cancer (GC) is known for its lymph node metastasis and outstanding morbidity and mortality. Thus, improvement in the current knowledge regarding the molecular mechanism of GC is urgently needed to discover novel biomarkers involved in its progression and prognosis. Several long, non-coding RNAs (lncRNAs) play important roles in gastric tumorigenesis and metastasis. However, the signature of lncRNA-associated metastasis in GC is not fully clarified.
We determined the lncRNA and mRNA expression profiles correlating to GC with or without lymph node-metastasis based on microarray analysis. Twelve differentially expressed lncRNAs and six differentially expressed mRNAs were validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay.
The relationships between the aberrantly expressed lncRNAs XLOC_010235 or RP11-789C1.1 and lymph node metastasis, pathologic metastasis status, distal metastasis and TNM (tumour, node, and metastasis) stage were found to be significantly different. Via survival analysis, patients who had high-expressed XLOC_010235 or low-expressed RP11-789C1.1 showed significantly worse survival than patients with inverse-expressed XLOC_010235 or RP11-789C1.1.
In summary, this current study highlights some evidence regarding the potential role of lncRNAs in GC and posits that specific lncRNAs can be identified as novel, poor prognostic biomarkers in GC.
Preview · Article · Jun 2015 · Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer.
We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias.
Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively.
PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.
Full-text · Article · May 2015 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: X-ray repair cross-complementing group 1 (XRCC1) plays a key role in DNA repair, genetic instability, and tumorigenesis. The XRCC1 R399Q polymorphism has been reported in some studies to influence the risk of colorectal cancer (CRC), though this remains controversial. We performed a meta-analysis to determine the association of XRCC1 R399Q polymorphisms with CRC risk in the Chinese Han population. A literature search was conducted using PubMed, EMBASE, and the China National Knowledge Infrastructure to identify eligible studies published before June 2014. The pooled odds ratio (OR) and corresponding 95 % confidence interval (CI) were used to estimate the effect of XRCC1 R399Q polymorphisms on CRC risk. Eleven case–control studies with a total of 3194 CRC cases and 4472 controls were identified. No significant association between the XRCC1 R399Q polymorphism and CRC risk was observed in the Chinese Han population (Gln/Gln vs. Arg/Arg, OR = 1.26, 95 % CI = 0.85–1.87, P
OR = 0.242; Arg/Gln vs. Arg/Arg, OR = 0.95, 95 % CI = 0.70–1.18, P
OR = 0.651; dominant model, OR = 1.09, 95 % CI = 0.86–1.38, P
OR = 0.480; and recessive model, OR = 1.24, 95 % CI = 0.91–1.70, P
OR = 0.177). After excluding two studies that deviated from the Hardy–Weinberg equilibrium, there remained no significant association between XRCC1 R399Q and CRC risk. No publication bias was found using the funnel plot and Egger’s test. Our meta-analysis results suggest that the XRCC1 R399Q polymorphism is not associated with increased risk of CRC in the Chinese Han population.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND
The aim of this meta-analysis was to evaluate the necessity of nasogastric or nasojejunal decompression after gastrectomy for gastric cancer.
Medline, Embase and the Cochrane Library were searched. Only prospective randomized controlled trials (RCTs) that compared subjects with and without nasogastric or nasojejunal decompression after gastrectomy were eligible in this meta-analysis. Time to flatus, time to first oral intake, length of hospital stay, reinsertion rate, anastomotic leakage, pulmonary complications, morbidity and mortality were evaluated.
Eight studies finally fulfilled the inclusion criteria. This meta-analysis enrolled 1141 patients, 570 randomized to routine decompression and 571 randomized to no decompression. Time to first oral intake was significantly shorter in the non-decompression group (WMD=0.53, 95% CI: 0.28 to 0.77; p＜0.001). Additionally, subjects with nasogastric or nasojejunal decompression experienced a longer hospital stay (p=0.001). Time to flatus, anastomotic leakage, reinsertion rates, pulmonary complications, morbidity and mortality rates were similar between the two groups.
Nasogastric or nasojejunal decompression does not facilitate the recovery of bowel function or reduce the risk of postoperative complications. Therefore, routine nasogastric or nasojejunal decompression is unnecessary after gastrectomy for gastric cancer.
No preview · Article · Dec 2014 · European Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Aim:
To study the effect of somatostatin in patients with advanced gastric cancer who received D2 lymphadenectomy and vagina vasorum dissection.
Using a prospective, single-blind, placebo-controlled design, patients with advanced gastric cancer were randomized into a study group (n = 61) and a control group (n = 59). Patients in the study group were given somatostatin for 5-7 d starting 6 h after the operation, and patients in the control group were given normal saline. Preoperative and nonoperative complications in the perioperative period, as well as different types of postoperative drainage in the two groups were compared.
There was no significant difference between the study group and the control group for preoperative clinicopathological indicators. We found no significant difference between the two groups for the overall incidence of complications, but a lower percentage of peritoneal effusion was observed in the treatment group (1.6% vs 10.2%, P < 0.05). There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula. However, there were significant differences in the amylase concentration in drainage fluid, volume and duration of drainage, volume and duration of chylous fistula and peritoneal drainage, and volume and duration of gastric tube drainage. The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred.
Postoperative somatostatin reduces volume and duration of surgical drainage and related complications. Somatostatin may improve safety of gastric cancer surgery, reducing postoperative complications and promoting recovery.
Preview · Article · Oct 2014 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children.
This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding.
We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children’s acceptance of PEG-based laxatives appears to be better than non-PEG laxatives.
Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To explore the efficacy of PCI-24781, a broad-spectrum, hydroxamic acid-derived histone deacetylase inhibitor, in the treatment of gastric cancer (GC).
With or without treatment of PCI-24781 and/or cis-diamminedichloroplatinum (CDDP), GC cell lines were subjected to functional analysis, including cell growth, apoptosis and clonogenic assays. Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme. An in vivo study was carried out in GC xenograft mice. Cell culture-based assays were represented as mean ± SD. ANOVA tests were used to assess differences across groups. All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise type I error rates. Significance was set at P < 0.05.
PCI-24781 significantly reduced the growth of the GC cells, enhanced cell apoptosis and suppressed clonogenicity, and these effects synergized with the effects of CDDP. PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51, which is related to homologous recombination. Depletion of RAD51 augmented the biological functions of PCI-24781, CDDP and the combination treatment, whereas overexpressing RAD51 had the opposite effects. Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes. Furthermore, significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment, which synergized with the anticancer effect of CDDP.
These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC.
[Show abstract][Hide abstract] ABSTRACT: Gastric cancer is one of the most common causes of cancer-related death worldwide. Helicobacter pylori infection plays an important role in the development and progression of gastric cancer. The expression of astrocyte-elevated gene-1 (AEG-1) is increased in gastric cancer tissues, thereby contributing to the inflammatory response. We investigated whether and how AEG-1 regulated proinflammatory signaling in gastric cancer cells. We used human gastric cancer cell lines and athymic nude mice to investigate the role of AEG-1 in the regulation of the TLR4/NF-κB signaling pathway and cancer invasion and compared the expression of AEG-1 and related proteins in 93 gastric cancer patients by immunohistochemistry. In human gastric cancer cells, both AEG-1 and TLR4 could be induced by lipopolysaccharide (LPS) stimulation. AEG-1 was upregulated via LPS-TLR4 signaling and in turn promoted nuclear translocation of the NF-κB p65 subunit. At the same time, AEG-1 overexpression decreased the levels of suppressor of cytokine signaling (SOCS) protein SOCS-1, a negative regulator of the TLR4 pathway. Furthermore, nude mice engrafted with AEG-1/TLR4-expressing cells demonstrated larger tumor volumes than control animals. In gastric cancer patients, the expression of AEG-1 correlated with that of TLR4, SOCS-1, and NF-κB, and was higher in tumors compared to non-cancerous adjacent tissues. Overall survival in gastric cancer patients with simultaneous expression of AEG-1 and TLR4 was poor. Our results demonstrate that AEG-1 can promote gastric cancer progression by a positive feedback TLR4/NF-κB signaling-related mechanism, thus providing new mechanistic explanation for the role of inflammation in cancer progression.
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinicopathological features of gastric carcinoma in southern China and disease trends changes over the last 18 years.
We designed a retrospective study in the Department of Gastrointestinal Surgery, the first affiliated hospital, Sun Yat-sen University. A total of 2100 adult patients with definitely diagnosed, histologically proven gastric carcinomas treated with radical gastrectomy from 1994 to 2013 were examined retrospectively. In all cases patient age, gender, tumor location, Borrmann type, histopathological type and grade, and pTNM stage were identified and recorded. The information was obtained from hospital records. The data were analyzed with Stata12.0 software.
In this study, the mean age of patients was 57 years with a range from 19-89 years. A higher incidence was found in patients over 60 years of age. In the study population, 67.38% of patients were male and 32.62% were female. Women had a higher disease incidence than men in patients less than 40 years of age (P < 0.001). No obvious change of patient age and gender was observed in the last 18 years. The rates of disease by location were the following: antrum (44.57%), followed by fundus/ body (24.95%) and cardia/gastroesophageal junction (23.00%). The mean tumor diameter was 5.57 cm, and advanced gross type Borrmann III was most common. Most patients were at advanced stages when first diagnosed, and patients with early stage disease were relatively rare. More early stage patients were detected in recent years, especially after 2000 (P < 0.001). Gastric carcinoma has different features in young and old patients. The young patients had the following features: more frequently female, tumors in the antrum, larger tumor size, poorly differentiated carcinoma, high rate of metastasis to other sites and advanced stages (P < 0.05).
In southern China, gastric carcinoma was more frequent in old men and young women. Young and old patients should be treated differently for having different features.
Preview · Article · Apr 2014 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Reactive nodular fibrous pseudotumor (RNFP), which presents abdominal clinical manifestations and malignant radiographic results, usually requires radical resection as the treatment. However, RNFP has been recently described as an extremely rare benign post-inflammatory lesion of a reactive nature, which typically arises from the sub-serosal layer of the digestive tract or within the surrounding mesentery in association with local injury or inflammation. In addition, a postoperative diagnosis is necessary to differentiate it from the other reactive processes of the abdomen. Furthermore, RNFP shows a good prognosis without signs of recurrence or metastasis. A 16-year-old girl presented with a 3-mo history of epigastric discomfort, and auxiliary examinations suggested a malignant tumor originating from the stomach; postoperative pathology confirmed RNFP, and after a 2-year follow-up period, the patient did not display any signs of recurrence. This case highlights the importance of preoperative pathology for surgeons who may encounter similar cases.
[Show abstract][Hide abstract] ABSTRACT: According to cancer-related microRNA (miRNA) expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. However, the expression and biological role of miR-362 in gastric progression remain unclear.
miR-362 expression levels in gastric cancer tissues and cell lines were determined using real-time PCR. The roles of miR-362, in promoting gastric cancer cell proliferation and apoptosis resistance, were assessed by different biological assays, such as colony assay, flow cytometry and TUNEL assay. The effect of miR-362 on NF-κB activation was investigated using the luciferase reporter assay, fluorescent immunostaining.
MiR-362 overexpression induced cell proliferation, colony formation, and resistance to cisplatin-induced apoptosis in BGC-823 and SGC-7901 gastric cancer cells. MiR-362 increased NF-κB activity and relative mRNA expression of NF-κB-regulated genes, and induced nuclear translocation of p65. Expression of the tumor suppressor CYLD was inhibited by miR-362 in gastric cancer cells; miR-362 levels were inversely correlated with CYLD expression in gastric cancer tissue. MiR-362 downregulated CYLD expression by binding its 3' untranslated region. NF-κB activation was mechanistically associated with siRNA-mediated downregulation of CYLD. MiR-362 inhibitor reversed all the effects of miR-362.
The results suggest that miR-362 plays an important role in repressing the tumor suppressor CYLD and present a novel mechanism of miRNA-mediated NF-κB activation in gastric cancer.
Preview · Article · Feb 2014 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the impact of pre-existing type-2 diabetes on postoperative recovery and prognosis in gastric cancer (GC) patients who underwent radical gastrectomy.
From June 2001 to June 2011, a total of 1,014 eligible patients were enrolled. Among them, 67 patients were diagnosed with type-2 diabetes. The clinicopathologic features and prognostic data were compared between patients with type-2 diabetes (the DM group) and without diabetes (the non-DM group).
Median survival was 68.3 months. The 5-year overall survival in the DM group was similar to that in the non-DM group (52.1 vs. 53.0 %, p = 0.411). Propensity score matching analysis demonstrated that the hazard ratio of death in the DM group was 1.191 (95 % confidential index 0.693-2.072; p = 0.531) compared to the-non DM group. Incidence of postoperative complications was higher in the DM group than in the non-DM group (17.9 vs. 8.1 %, p = 0.006). The DM remission rate was 46 % among patients who received Roux-en-Y reconstruction, and 13 % among patients who received Billroth II anastomosis (p = 0.009). The 5-year overall survival rate was 62.1 % for patients with cured or improved DM and 23.4 % for patients with worse or same DM status (p = 0.003).
Type-2 diabetes can be cured by radical gastrectomy plus Roux-en-Y reconstruction in some GC patients. Pre-existing diabetes is associated with increased postoperative complications and decreased survival when it becomes worse after curative dissection for GC.
No preview · Article · Dec 2013 · Digestive Diseases and Sciences
[Show abstract][Hide abstract] ABSTRACT: To explore the risk factors and prognostic impact of duodenohepatic ligamentous lymph node (No.12 LN) metastasis in cases with curable advanced distal gastric cancer.
The data of 379 cases with advanced distal gastric cancer undergoing radical resection were screened from the Database of Gastric Cancer Center of Sun Yat-sen University from January 1997 to December 2010. According to No.12 LN metastasis, they were divided into negative (n = 339) and positive (n = 40) groups. Their clinicopathological parameters and surgical regimens were compared. And the risk factors and prognostic impact of No.12 LN metastasis were analyzed.
No significant inter-group difference existed in gender, age, infiltration depth or differentiation degree (all P > 0.05). In negative and positive groups, the percent of tumor size ≥ 5 cm was 30.1% (102/339) vs 55.0% (22/40), lymph node metastasis N3 stage 8.3% (28/339) vs 42.5% (17/40), other lymph nodes except for No.12 metastasis 70.2% (238/339) vs 92.5% (37/40), distal metastasis M1 10.9% (37/339) vs 32.5% (13/40), TNM stage IV 18.6% (63/339) vs 65.0% (26/40), infiltration Borrmann type 74.3% (252/339) vs 92.5% (37/40), non-adenocarcinoma 15.9% (54/339) vs 35.0% (14/40) and positive serum-carcinoembryonic antigen (S-CEA) 12.7% (43/339) vs 32.5% (13/40). There were all with significant difference (all P < 0.01). Logistic regression analysis showed tumor size ≥ 5 cm, lymph node (except for No.12) metastasis, distal metastasis and positive S-CEA were independent risk factors of No.12 LN metastasis (OR = 2.144, 3.581, 2.597, 2.552; P = 0.035, 0.042, 0.019, 0.022 respectively). Cox regression analysis showed lymph nodes (except for No.12) and No.12 metastasis, distal metastasis and Borrmann type were independent prognostic factors for all cases. In negative and positive groups, median survival time was 63.0 versus 12.0 months with significant difference (P = 0.000).
For cases with curable advanced distal gastric cancer, No.12 LN metastasis was an independent prognostic factor. No.12 LN should be dissected thoroughly in cases with tumor size ≥ 5 cm, lymph nodes (except No.12) metastasis, distal metastasis and positive S-CEA.
No preview · Article · Dec 2013 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients.
Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients.
Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3-94·4) for the low-risk group, and 60% (46·3-71·0) for the high-risk group (hazard ratio [HR] 4·24, 95% CI 2·13-8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3-91·8) for the low-risk group, and 57% (42·8-68·5) for the high-risk group (HR 3·63, 1·86-7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6-89·0) for the low-risk group and 54% (46·4-61·1) for the high-risk group (HR 3·70, 2·56-5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17-2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer.
Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease.
Natural Science Foundation of China.
No preview · Article · Nov 2013 · The Lancet Oncology