Prognostic factors of primary gastrointestinal stromal tumors： a cohort study based on high-volume centers

Objective： We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors（GISTs）.Methods： Data from 2,570 consecutive GIST patients from four medical centers in China（January2001–December 2015） were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors.Results： Of the included patients, 1,375（53.5%） were male, and the patient age range was 18 to 95（median, 58）years. The tumors were mostly found in the stomach（64.5%）, small intestine（25.1%） and colorectal region（5.1%）.At the time of diagnosis, the median tumor size was 4.0（range： 0.1–55.0） cm, and the median mitotic index per 50 high power fields（HPFs） was 3（range： 0–254）. Of the 2,168 resected patients, 2,009（92.7%） received curative resection. According to the modified National Institutes of Health（NIH） classification, 21.9%, 28.9%, 14.1% and35.1% were very low-, low-, intermediate-and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1（DOG-1）, 8.0% for S-100, 31.0% for smooth muscle actin（SMA） and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib（P〈0.001）, whereas intermediate-risk patients did not（P=0.954）.Conclusions： Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

The apoptosis induction effect of siRNA recombinant expression vector targeting Livin gene in human colon cancer cells

Objective:To construct siRNA recombinant expression vector targeting Livin gene and observe the apoptosis induction effect of it in human colon cancer cells. Methods:SiRNA recombinant expression vector targeting Livin gene was constructed and transfected into human colon cancer cell. The effect of siRNA recombinant expression vector was detected by RT-PCR, Western blot, MTT reduction assay and flow cytometry. Results: It was confirmed by restriction endonuclease and sequence analysis that siRNA recombinant expression vector targeting Livin gene was constructed successfully. Inhibition ra-tio of Livin siRNA at mRNA and protein levels were 30.18% and 28.88%. The growth of cancer cells was inhibited significantly and the apoptotic ratio was 13.36 ± 1.45%. Conclusion: The siRNA recombinant expression vector targeting Livin gene has been constructed successfully. It not only can inhibit the expression of Livin gene but also can induce apoptosis in human colon cancer cells remarkably.

Protective effects of IRG1/itaconate on acute colitis through the inhibition of gasdermins-mediated pyroptosis and inflammation response

Inflammatory bowel disease(IBD)is a chronic relapsing gastrointestinal disorder,while the treatment effect is not satisfactory.Immune responsive gene 1(IRG1)is a highly ex-pressed gene in macrophage in response to inflammatory response and catalyzes the production of itaconate.Studies have reported that IRG1/itaconate has a significant antioxidant effect.This study aimed to investigate the effect and mechanism of IRG1/itaconate on dextran sulfate so-dium(DSS)-induced colitis in vivo and in vitro.In vivo experiments,we found IRG1/itaconate ex-erted protective effects against acute colitis by increasing mice weight,the length of colon,reducing disease activity index and colonic inflammation.Meanwhile,IRG1 deletion aggravated the macrophages/CD4+/CD8+T-cell accumulation,and increased the release of interleukin(IL)-1b,tumor necrosis factor-a(TNF-a),IL-6,the activation of nuclear factor-kB(NF-kB)/mitogen-activated protein kinase(MAPK)signaling pathway,and gasdermin D(GSDMD)mediated pyrop-tosis.Four-octyl itaconate(4-OI),a derivative of itaconate,attenuated these changes,therefore relieved DSS-induced colitis.In vitro experiment,we found 4-OI inhibited the reactive oxygen species production,thereby inhibiting the activation of MAPK/NF-kB signaling pathway in RAW264.7 and murine bone-marrow-derived macrophages.Simultaneously,we found 4-OI inhib-ited caspase1/GSDMD-mediated pyroptosis to reduce the release of cytokines.Finally,we found anti-TNF-a agent reduced the severity of DSS-induced colitis and inhibited gasdermin E(GSDME)-mediated pyroptosis in vivo.Meanwhile,our study revealed that 4-OI inhibited caspase3/GSDME-mediated pyroptosis induced by TNF-a in vitro.Taken together,IRG1/itaconate exerted a pro-tective role in DSS-induced colitis by inhibiting inflammatory response and GSDMD/GSDME-medi-ated pyroptosis,which could be a promising candidate for IBD therapy.

Evaluation of early liquid drinking after radical gastrectomy in gastric cancer:a Chinese multicenter propensity score matching analysis

Background:Enhanced recovery after surgery is used in gastrointestinal surgery.This study aimed to access the effects of early liquid drinking(ELD)on gastrointestinal function recovery in patients with gastric cancer(GC)who underwent radical gastrectomy,as high-quality evidence on the outcomes of ELD after gastrectomy is currently lacking.Methods:Clinicopathological data of patients with GC from 11 centers were retrospectively analysed.Clinical outcomes were investigated in 555 patients,including 225 who started drinking liquid within 48 h(ELD group)of surgery and 330 who started drinking liquid after flatus resumption(traditional liquid drinking[TLD]group).Propensity score matching(PSM)analysis was performed using a match ratio of 1:1 and 201 patients were selected from each group for the analysis.Primary outcome was time to first passage of flatus.Secondary outcomes included time to first defecation,post-operative hospitalization days,occurrence of short-term post-operative complications,and hospitalization costs.Results:After PSM,baseline characteristics were not significantly different between the two groups.The time to first flatus(2.7261.08 vs 3.3661.39 days),first defecation(4.3461.85 vs 4.7761.61 days),and post-operative hospital stay(8.2764.02 vs 12.9464.43 days)were shorter in the ELD group than in the TLD group(all P<0.05).The ELD group had lower hospitalization costs than the TLD group([7.8362.44 vs 8.7863.41]104 RMB,P=0.041).No significant differences were observed in the incidence of post-operative complications.Conclusions:Compared with TLD,post-operative ELD could promote rapid recovery of gastrointestinal function and reduce hospitalization costs;moreover,ELD does not increase the risk of post-operative complications.

Examined lymph node numbers influence prognosis in rectal cancer treated with neoadjuvant therapy

Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy.Methods:Data were collected from seven prospective hospital databases in China from July 2002 to May 2018.Binary logistic regression models were used to predict lymph node metastasis.The cut-off value for LNe was determined using X-tile 3.6.1.Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model.Results:A total of 482 patients were included,of whom 459 had complete overall survival(OS)information.Using the percentile method,the total number of lymph nodes examined(TLNe)was 14-16(40th-60th percentile),and the proportion of patients with lymph node metastasis reached a maximum of 48.1%.Cox multivariate analysis showed that the odds ratio(OR)remained the highest when TLNe was 14-16(OR=3.379,P=0.003).The 3-year and 5-year OS were 85.4% and 77.8%,respectively.Negative lymph nodes examined(NLNe)of≤6 was an independent risk factor for 3-year and 5-year OS(3-year OS 71.1%vs.85.9%,P=0.004;5-year OS 66.3%vs.74.3%,P=0.035).Subgroup analysis for patients with ypN+showed that higher 3-year and 5-year OS were achieved when the TLNe was>10,78.8%vs.54.0%(P=0.005),and 60.8%vs.36.0%(P=0.012),respectively.Patients with ypN0M0 had a higher 5-year OS when the TLNe was>19(P=0.055).Conclusion:The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.

Laparoscopic sigmoid vaginoplasty in women withMayer-Rokitansky-Kuster-Hauser syndrome

The feasibility and clinical therapeutic effects of laparoscopic sigmoid vaginoplasty in women with Mayer-Rokitansky-Kuster-Hauser syndrome(MRKHs)were explored.The records of 11 MRKHs patients who underwent laparoscopic sigmoid vaginoplasty from 2003 to 2005 were reviewed,and long-term results were evaluated by follow-up.The mean operating time was 234 min(range,130–300 min),the mean hospital stay was 9.4 days(range,7–15 days),and the mean hemoglobin drop was 1.91 g/dL(range,1.6–3.2 g/dL).A functional neovagina was created measuring 11 to 14 cm in length and twofingers in breadth in all patients.No introitus stenosis was observed.No intra-operative or postoperative bowel complication occurred.At the 3rd postoperative month,thefirst intercourse began.One patient was lost to follow-up.One had no intercourse and was required to wear vaginal mold occasionally.None of the other nine women(100%)complained of local irritation or dyspar-eunia.They were satisfied with their sexual life.The cosmetic results were excellent.The laparoscopic sigmoid vaginoplasty realizes to make a functional neovagina.The main advantage is its minimal invasiveness.It is an ideal procedure for MRKHs patients.

CACA guidelines for holistic integrative management of rectal cancer

Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.