Distal margin distance in radical resection of locally advanced rectal cancer after neoadjuvant therapy

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.

Gastric cancer: Epidemiology, risk factors and prevention strategies

Gastric cancer(GC) is a global health problem, with more than 1 million people newly diagnosed with GC worldwide each year. GC is more prevalent in less developed countries than in more developed countries. About half of all GC cases worldwide occur in East Asia, notably China. Globally, overall incidence rates of GC are declining, which is potentially attributed to a decrease in Helicobacter pylori(H. pylori) infection and the use of refrigeration to preserve foods rather than salt. GC is a multifactorial disease, and its occurrence and development were impacted by environmental and genetic factors. H. pylori infection is the primary risk factor for GC, especially for non-cardia. The prognosis of GC is poor due to stages at the first diagnosis. The 5-year survival rate is less than 10% when patients are diagnosed at an advanced stage, but the rate is as high as 85% if patients are detected at an earlier stage. Endoscopic screening can potentially prevent GC by early diagnosis and early treatment and has been widely adopted in screening programs in East Asian countries, such as Japan and Korea. This review summarizes updated epidemiological aspects, risk factors, and prevention strategies of GC in recent years to help researchers determine the most effective intervention strategies for reducing risk of GC.

HOXC10 up-regulation promotes gastric cancer cell proliferation and metastasis through MAPK pathway

Objective： As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 （HOXC10） has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. Methods： A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXCIO, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction （RT-PCR） and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, wound healing assay, and matrigel invasion assay in vitro, respectively. Results： HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase （MAPK） signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase （JNK）, extracellular signal-regulated kinase （ERK） and P38 but not their total protein levels. Conclusions： This study demonstrated the tight link between HOXC10 and gastric cancer cell proliferation and metastasis via involvement of the MAPK pathway.

Prognostic value and nomograms of proximal margin distance in gastric cancer with radical distal gastrectomy

Objective:The proximal margin(PM)distance for distal gastrectomy(DG)of gastric cancer(GC)remains controversial.This study investigated the prognostic value of PM distance for survival outcomes,and aimed to combine clinicopathologic variables associated with survival outcomes after DG with different PM distance for GC into a prediction nomogram.Methods:Patients who underwent radical DG from June 2004 to June 2014 at Department of General Surgery,Nanfang Hospital,Southern Medical University were included.The first endpoints of the prognostic value of PM distance(assessed in 0.5 cm increments)for disease-free survival(DFS)and overall survival(OS)were assessed.Multivariate analysis by Cox proportional hazards regression was performed using the training set,and the nomogram was constructed,patients were chronologically assigned to the training set for dates from June 1,2004 to January 30,2012(n=493)and to the validation set from February 1,2012 to June 30,2014(n=211).Results:Among 704 patients with p TNM stage I,p TNM stage II,T1-2,T3-4,N0,differentiated type,tumor size≤5.0 cm,a PM of(2.1-5.0)cm vs.PM≤2.0 cm showed a statistically significant difference in DFS and OS,while a PM>5.0 cm was not associated with any further improvement in DFS and OS vs.a PM of 2.1-5.0 cm.In patients with p TNM stage III,N1,N2-3,undifferentiated type,tumor size>5.0 cm,the PM distance was not significantly correlated with DFS and OS between patients with a PM of(2.1-5.0)cm and a PM≤2 cm,or between patients with a PM>5.0 cm and a PM of(2.1-5.0)cm,so there were no significant differences across the three PM groups.In the training set,the C-indexes of DFS and OS,were 0.721 and 0.735,respectively,and in the validation set,the C-indexes of DFS and OS,were 0.752 and 0.751,respectively.Conclusions:It is necessary to obtain not less than 2.0 cm of PM distance in early-stage disease,while PM distance was not associated with long-term survival in later and more aggressive stages of disease because more advanced GC is a systemic disease.Different types of patients should be considered for removal of an individualized PM distance intra-operatively.We developed a universally applicable prediction model for accurately determining the 1-year,3-year and 5-year DFS and OS of GC patients according to their preoperative clinicopathologic characteristics and PM distance.

Prognostic significance of periostin in colorectal cancer

Accumulating evidence suggests that periostin is frequently upregulated in tissue injury, inflammation,fibrosis and tumor progression. Periostin expression in cancer cells can promote metastatic potential of colorectal cancer(CRC)via activating PI3 K/Akt signaling pathway. Moreover, periostin is observed mainly in tumor stroma and cytoplasm of cancer cells, which may facilitate aggressiveness of CRC. In this review, we summarize information regarding periostin to emphasize its role as a prognostic marker of CRC.

Current status and future perspectives on neoadjuvant therapy in gastric cancer

Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.

Tumor pyruvate kinase M2:A promising molecular target of gastrointestinal cancer

Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinase isoform M2(PKM2),a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate(PEP) to pyruvate,confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment.In this review,we have summarized current research on the expression and regulation of PKM2 in tumor cells,and its potential role in GI carcinogenesis and progression.Furthermore,we have also discussed the potential of PKM2 as a diagnostic and screening marker,and a therapeutic target in GI cancer.

Characteristics of cancer susceptibility genes mutations in 282 patients with gastric adenocarcinoma

Objective:To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma,offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions.Methods:A total of 282 patients with gastric adenocarcinoma(182 males and 100 females)were enrolled in this study,with peripheral blood genomic DNA extracted.Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing.Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results:In this study,7.1%(20/282)of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes.The detection rate in male patients(3.8%,7/182)was significantly lower than that in female patients(13%,13/100)(P=0.004).The most recurrent mutations were in AT mutated(ATM)(1.1%,3/282),followed by BRCA1,BRIP1 and RAD51D,all showed a detection rate of 0.7%(2/282).Mutations in three genes associated with hereditary gastric cancer syndromes were detected,namely,PMS2 and EP CAM associated with Lynch syndrome and CDH1 associated with hereditary di ffuse gastric cancer.The detection frequencies were all 0.4%(1/282).Notwithstanding no significant difference observed,the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers(median age:58.5 vs.60.5 years old),while the age of patients with ATM mutations was the youngest overall(median age:49.3 years old).Conclusions:Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes,and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significandy lower than that in female patients.Some known and unidentified mutations were found in gastric cancer,which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.