Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).

Percutaneous transhepatic biliary drainage for obstructive jaundice caused by metastatic gastric cancer： efficacy and complications

Objective： The aim of our study was to evaluate the efficacy and incidence of complications of percutaneous transhepatic biliary drainage （PTBD） as palliative treatment of obstructive jaundice caused by metastatic gastric cancer. Methods： Hospital records were reviewed for 32 consecutive patients with biliary obstruction caused by metastatic gastric cancer who underwent PTBD at our institution between October 2004 and April 2010. Patients （23 males and 9 females） age ranged from 35 to 72 years. The indexes of hepatic function before PTBD and within one month after PTBD were compared. The incidence of complications and corresponding treatments were also documented. Results： The level of obstruction was defined as the distal bile duct （beyond the level of the liver hilum） in 22 patients （group 1） and the liver hilum in 10 patients （group 2）. Successful decompression of the biliary system after PTBD was defined by a total bilirubin decrease of more than 30% of the baseline value. Success rates were 100% （22/22） for group 1, 70% （7/10） for group 2, and 90.6% （29/32） for all patients. Differences in success rates between group 1 and group 2 were significant （P = 0.024）. Serum TBIL, ALT, and AST significantly decreased from （292.8 ± 179.9） μmol/L, （174.5 ± 107.4） IU/L, （159.9 ± 103.9） IU/L before PTBD to （111.5 ± 92.5） μmol/L, （58.5 ± 46.3） IU/L, （59.6 ± 48.9） IU/L, respectively within one month after PTBD （P 0.05）. Complications associated with PTBD included cholangitis in 13 patients （40.5%）, drainage tube displacement in 6 patients （18.8%）, hemobilia in 4 patients （12.5%）, tube occlusion in 2 patients （6.3%）, and pancreatitis in 1 patient （3.1%）. All complications were successfully treated with appropriate measures. Conclusion： Hepatic function can be improved by PTBD without serious complications in patients with obstructive jaundice caused by metastatic gastric cancer.

Neoadjuvant Combination Chemotherapy with Pegylated Liposomal Doxorubicin and Vinorelbine for Locally Advanced Breast Cancer

OBJECTIVE In China, vinorelbine plus an anthracycline is a common neoadjuvant regimen for locally-advanced breast cancer （LABC）. Pegylated liposomal doxorubicin （PLD） is an alternate anthracycline formulation with a more favorable safety profile compared with conventional anthracyclines. METHODS In this open-label trial, 61 women with LABC received up to 6 cycles of PLD 30 mg/m2 on Day 1 and vinorelbine 25 mg/m2 on Days 1 and 8 every 21 days. Hormone receptor and/or HER2 status was not routinely available. RESULTS The overall clinical response rate （primary efficacy endpoint） was 80% （95% CI： 68%-89%）. Two patients achieved a pathological complete response （3%）, with 75% having their tumor down-staged, and 89% proceeding to tumor resection. The most frequent nonhematologic adverse events were stomatitis, fever, rash, and palmar-plantar erythrodysesthesia, with none considered serious. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 10% and 2% of patients, respectively. CONCLUSION PLD plus vinorelbine demonstrated comparable efficacy to conventional anthracyclines plus vinorelbine in the neoadjuvant treatment of LABC, but may offer safety advantages.

Recombinant adenovirus-p53(Gendicine) sensitizes a pancreatic carcinoma cell line to radiation

Objective： In this study, we examine the effects of recombinant adenovirus-p53 （rAd-p53） on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. Methods： Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions （SF） were calculated. Dose survival cttrves were constructed and modeled for comparison. Results： Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation （Do for the experimental and control groups was 2.199 and 2.462, respectively）. Conclusions： Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial.

The initial results of Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) for screening nasopharyngeal carcinoma (NPC)

Objective: Early diagnosis of nasopharyngeal carcinoma (NPC) is an important method to improve the survival rate.However,the sensitivity and specificity of the screening protocols which was widely used in clinic now are considered to be unsatisfactory.Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) is one of the proteins that have been suggested to be a classic oncogene with transformation properties.The current study set out to discuss the clinical significance of LMP-1 on the screening of NPC.Methods: Three hundred patients who visited our institution (Department of Radiation Oncology,Fujian Provincial Cancer Hospital,Fuzhou,China) with ENT symptoms between 2007 and 2008 were involved in this study,and all of them were agreed to be involved in this investigation.Not only did they undergo nasopharyngeal swab to obtain cells for the LMP-1 polymerase chain reaction (PCR) analysis,but also nasopharyngeal biopsy were taken to identify the diagnosis.Results: An amount of DNA that was sufficient for PCR was extracted from 243 (81%) swab samples,the positive rate of LMP-1 of those with non-nasopharyngeal carcinoma was 3.85% (4/108),which was much lower than those with nasopharyngeal carcinoma (P < 0.05).By detecting LMP-1 in nasopharyngeal swabs,NPC was diagnosed with a sensitivity of 88.15% (119 of 135 patients),specificity of 96.30% (104 of 108 patients),a positive predictive value of 95.2% (119 of 123 patients),a negative predictive value of 86.67% (104 of 120 patients),accuracy of 91.77%,and Youden index of 84.45%.Conclusion: The nasopharyngeal swab coupled with PCR-based EBV LMP-1 detection have high sensitivity and specificity,and also good repeatability,it could serve as part of the screening program for high-risk populations.

Laparoscopic segmental colectomy for colonic lymphangiomas: A definitive, minimally invasive surgical option

Colonic lymphangioma is an unusual benign malformation.We herein describe two cases.A 36-year-old woman was admitted with one year of intermittent abdominal pain;colonoscopy,abdominopelvic computed tomography and endoscopic ultrasonography(EUS)revealed enlarged cystic masses at the ascending colon.In another 40-year-old man,colonoscopy and EUS revealed an asymptomatic lobulated cystic mass with four small sessile polyps at the sigmoid colon.Both patients underwent laparoscopic segmental colectomy.Both masses were histologically confirmed as cystic lymphangiomas,and the patients were discharged without complications.The management of colonic lymphangioma depends on the individual situation;close surveillance or endoscopic therapy may be appropriate for asymptomatic lesions smaller than 2.5 cm in diameter.Surgical intervention can be considered for larger lesions or in patients who develop complication risks.Laparoscopic segmental colon resection may be recommended to excise relatively large submucosal lesions because it is a definitive,minimally invasive intervention with a fast postoperative recovery.

Optimization on cationic liposome-mediated cell transfection of plasmid DNA

Objective:The development of gene carriers for efficient gene delivery into cells has attracted growing attention in recent years.The aim of this study was to achieve a better outcome of AAV-293 cells transfection by plasmid DNA.Methods:We studied the optimal condition for higher efficiency of cationic lipid-mediated cell transfection.Four experimental groups were set.Plasmid DNA and liposome were mixed in each groups at different ratios(μg:μL),1:2.5,1:3.5,1:4.0 and 1:5.0,respectively.LacZ gene functioned as reporter gene,measuring the transfection efficiency of the four groups using the method of X-gal staining.Results:When the ratio was 1:3.5,the cell transfection rate was the highest.While the ratio of 1:2.5 recommended by product manual achieve the lowest transfection rate.Their difference had statistical significance.Conclusion:In order to obtain a higher transfection efficiency,optimization on conditions of the ratio of plasmid DNA to liposome is necessary in cell transfection.

A new prognostic histopathologic classification of nasopharyngeal carcinoma

Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.

Diagnosis and Treatment of Cholangiocarcinoma: A Consensus from Surgical Specialists of China

Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.

Percutaneous transgastric endoscopic tube ileostomy in a porcine survival model

AIM To introduce natural orifice transgastric endoscopic surgery(NOTES) tube ileostomy using pelvis-directed submucosal tunneling endoscopic gastrostomy and endoscopic tube ileostomy.METHODS Six live pigs(three each in the non-survival and survival groups) were used. A double-channeled therapeutic endoscope was introduced perorally into the stomach. A gastrostomy was made using a 2-cmtransversal mucosal incision following the creation of a 5-cm longitudinal pelvis-directed submucosal tunnel. The pneumoperitoneum was established via the endoscope. In the initial three operations of the series, a laparoscope was transumbilically inserted for guiding the tunnel direction, intraperitoneal spatial orientation and distal ileum identification. Endoscopic tube ileostomy was conducted by adopting an introducer method and using a Percutaneous Endoscopic Gastrostomy Catheter Kit equipped with the Loop Fixture. The distal tip of the 15 Fr catheter was placed toward the proximal limb of the ileum to optimize intestinal content drainage. Finally, the tunnel entrance of the gastrostomy was closed using nylon endoloops with the aid of a twin grasper. The gross and histopathological integrity of gastrostomy closure and the abdominal wall-ileum stoma tract formation were assessed 1 wk after the operation.RESULTS Transgastric endoscopic tube ileostomy was successful in all six pigs, without major bleeding. The mean operating time was 71 min(range: 60-110 min). There were no intraoperative complications or hemodynamic instability. The post-mortem, which was conducted 1-wk postoperatively, showed complete healing of the gastrostomy and adequate stoma tract formation of ileostomy.CONCLUSION Transgastric endoscopic tube ileostomy is technically feasible and reproducible in an animal model, and this technique is worthy of further improvement.

Anatomical variation of infra-pyloric artery origination： A prospective multicenter observational study (IPA-Origin)

Objective： Infra-pyloric artery （IPA） is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA. Methods： We did this prospective, multicenter, open-label, observational study at gastric surgery departments of 34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ2 tests and Fisher＇s tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov （No. NCT03071237）. Results： Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419 （97.7%） patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398 （95.0%） patients, including gastroduodenal artery （GDA） in 154 （36.8%） patients, anterior superior pancreaticoduodenal artery （ASPDA） in 130 （31.0%） patients, and right gastroepiploic artery （RGEA） in 114 （27.2%） patients. Fifteen （3.6%） patients were identified with multiple IPA and 6 （1.4%） patients were identified as IPA absence. The differences in the distribution of surgical approach （P=0.003） and geographic area （P=0.030） were statistically significant. No difference was shown in sex, age, gastrectomy type, tumor location, and clinical T, N and M stage. Conclusions： Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions. Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.

Adjuvant and neo‐adjuvant immunotherapy in resectable non‐small cell lung cancer (NSCLC): Current status and perspectives

Surgery followed by adjuvant chemotherapy is the standard of care for selectedpatients with early‐stage or locally advanced non‐small cell lung cancer(NSCLC). However, many of these patients still experience postoperativerecurrence at 5 years. At present, peri‐operative treatment methods areemerging to prevent early relapse, such as targeted therapy and immunotherapy.Investigation on predictive biomarkers of responses to adjuvant andneoadjuvant therapies is also continuously ongoing. Immunotherapy representedby immune checkpoint inhibitors (ICIs), either by monotherapy or incombination with chemotherapy, has shown benefit in promoting pathologicalresponses and prolonging survival for patients with NSCLC without oncogenicmutations. Exploratory studies have also provided evidence regarding theselection of patients who benefit from ICI‐based perioperative treatment. Thisreview focuses on the existing data of current clinical trials of adjuvant andneoadjuvant strategies with ICIs in resectable NSCLC, the exploration ofpredictive biomarkers, and the perspectives and urgent challenges in thefuture.

Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study

Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ study.Methods:In this study,180 patients received 225 mg of ensartinib orally once daily until disease progression,death or withdrawal.OS was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib.Circulating tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical management.Results:At the data cut-off date(August 31,2022),with a median follow-up time of 53.2 months,97 of 180(53.9%)patients had died.The median OS was 42.8 months(95%CI:29.3-53.2 months).A total of 333 plasma samples from 168 patients were included for ctDNA analysis.An inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(TP53)mutation.In addition,patients with concurrent TP53 mutations had shorter OS than those without con-current TP53 mutations.High ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor OS.Additionally,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,respectively.Furthermore,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer OS.Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 weeks.Conclusion:Ensartinib led to a favorable OS in patients with advanced,crizotinib-resistant,and ALK-positive NSCLC.Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients:promising findings from a prospective,open-label,randomized,phase III trial

Background:The 5-fluorouracil/leucovorin plus oxaliplatin(FOLFOX)regimen is the standard first-line treatment for metastatic colorectal cancer(mCRC),however,the optimal second-line regimen for KRAS wild-type mCRC patients is still investigational.In this study,we aimed to determine the clinical efficacy and safety of CMAB009 plus irinotecan compared to irinotecan-only as a second-line regimen for treating KRAS wild-type mCRC patients.Methods:Patients with KRAS wild-type mCRC who had previously failed to respond to FOLFOX treatment were ran-domly assigned in a 2:1 ratio,to receive CMAB009 plus irinotecan or irinotecan-only.Patients receiving irinotecan-only were permitted to switch to CMAB009 therapy on disease progression and were grouped as the sequential-CMAB009 arm.The primary endpoints were overall response rate(ORR)and median progression-free survival(PFS).The second-ary endpoints were median overall survival(OS),disease control rate(DCR),clinical benefit rate(CBR),and duration of response(DOR).Results:The CMAB009 plus irinotecan arm demonstrated significantly improved ORR(33.2%vs.12.8%;P<0.001)and longer median PFS(169 days vs.95 days;P<0.001)as compared to the irinotecan-only arm.Patients receiv-ing CMAB009 plus irinotecan also demonstrated improved DCR(80.1%vs.65.2%,P<0.001),CBR(30.0%vs.14.6%,P<0.001),and DOR(210 days vs.109 days;P<0.001)as compared to irinotecan-only.However,patients treated with CMAB009 had an increased risk of skin rash(66.9%vs.5.5%,P<0.001)and paronychia(9.8%vs.0.0%,P<0.001).Anti-drug antibodies(ADA)were detected in 3.6%of patients,and only 0.9%of patients who received CMAB009 experienced hypersensitivity reactions.In patients receiving sequential-CMAB009 therapy after failure with irinotecan,their median PFS was 84 days (95% CI 65 to 113 days). The median OS was 425 days for patients receiving CMAB009 plus irinotecan and 401 days for those with sequential-CMAB009 (P = 0.940). Conclusions: Treatment with CMAB009 plus irinotecan was found to be a superior second-line regimen in com-parison to irinotecan-only in KRAS wild-type mCRC patients. Further, switching to CMAB009 can be considered as an efficient third-line of treatment after treatment failure with second-line irinotecan-only. Trial registration ClinicalTrials.gov: NCT01550055, retrospectively registered on March 9, 2012.

Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study

Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.

The synergy of Helicobacter pylori and lipid metabolic disorders in induction of Th17-related cytokines in human gastric cancer

Aim:To study the impact of Helicobacter pylori(H.pylori)and lipid metabolic disorder on the expression of Th17-related cytokines in gastric cancer(GC).Methods:GC specimens were randomly collected from 42 patients,of whom 15 had H.pylori infection and 27 were without.Tumor RNA was extracted for reverse transcription quantitative polymerase chain reaction quantification of gene expression.Results:The mRNA levels of interleukin(IL)-6 and leptin,which are known to regulate Th17 differentiation,were upregulated by 20 and 6 folds,respectively,in H.pylori-infected compared to uninfected patients.IL-17A and granulocyte-macrophage colony-stimulating factor,two cytokines produced by Th17 cells,were 5-and 6-fold higher in tumors with H.pylori infection,respectively.Consistently,RORγt,a transcription factor regulating Th17 differentiation,was increased 6-fold in H.pylori-positive vs.negative tumors.Further elevation of RORγt was seen in advanced H.pylori-associated tumors.In addition,H.pylori infection was also associated with enhanced expression of CXCL1(5 folds),chemotactic factor capable of driving bone marrow-derived immature myeloid cells.Interestingly,we observed that H.pylori-associated increase of IL-17A was enhanced in the group with higher plasma triglycerides.Conclusion:The findings demonstrate a cross-talk and synergistic role of H.pylori infection and abnormal lipid metabolism in GC development,at least partly via cooperative induction of Th17 differentiation and activation.

Infrapyloric lymph node metastasis pattern in middle/lower gastric cancer:an exploratory analysis of a multicenter prospective observational study(IPA-ORIGIN)

To the Editor:Gastric cancer is one of the most common cancers in China.It is mainly found in the middle/lower part of the stomach,[1]where it commonly metastasizes from the infrapyloric lymph node(No.6).Previous studies reported that the risk of No.6 lymph node metastasis was different based on tumor locations.In lower gastric cancer patients,the metastatic rate of No.6 lymph node can reach up to 18.7%,and in upper gastric cancer,the rate is merely 1.9%.[2]The distance between the primary tumor and the pylorus was proved to be related to No.6 lymph node metastasis.However,most of the studies were retrospective and their lymph nodes dissection’s quality control was controversial.

Esophageal mycobiome landscape and interkingdom interactions in esophageal squamous cell carcinoma

Background The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma(ESCC).Methods Patients with primary ESCC were recruited from two central hospitals.We performed internal transcribed spacer 1(ITS1)ribosomal DNA sequencing analysis.We compared differential fungi and explored the ecology of fungi and the interaction of bacteria and fungi.Results The mycobiota diversity was significantly different between tumors and tumor-adjacent samples.We further analysed the differences between the two groups,at the species level,confirming that Rhodotorula toruloides,Malassezia dermatis,Hanseniaspora lachancei,and Spegazzinia tessarthra were excessively colonized in the tumor samples,whereas Preussia persica,Fusarium solani,Nigrospora oryzae,Acremonium furcatum,Golovinomyces artemisiae,and Tausonia pullulans were significantlymore abundant in tumor-adjacent samples.The fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in tumors.Similarly,themore complex bacterial–fungal interactions in tumor-adjacent samples were also detected.The expression ofmechanistic target of rapamycin kinase was positively correlated with the abundance of N.oryzae and T.pullulans in tumor-adjacent samples.In tumors,the expression ofMET proto-oncogene,receptor tyrosine kinase(MET)had a negative correlation and a positive correlation with the abundance of R.toruloides and S.tessarthra,respectively.Conclusion This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC.

Effect of CO2 pneumoperitoneum on the expression of the chemokine receptors CXCR4 and CCR7 in colorectal carcinoma cells in vitro

Background The ability of pneumoperitoneum in laparoscopic surgery to promote proliferation and metastasis of colorectal cancer has become a focus of research in the field of minimally invasive surgery. The aim of this research was to investigate the effect of CO~ pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells. Methods We constructed an in vitro pneumoperitoneum model. SW480 colon carcinoma cells were exposed to CO2 pneumoperitoneum under different pressures （6, 9, 12, and 15 mmHg） for 1, 2, and 4 hours. These cells were then cultivated under the same conditions as normal SW480 colon carcinoma cells without CO= pneumoperitoneum （control group）, treated at 37℃, and 5% CO2. The expression of the chemokine receptors CXC receptor 4 （CXCR4） and chemokine C receptor 7 （CCR7） was detected by immunocytochemistry and reverse transcriptase polymerase chain reaction after being cultivated for 0, 24, 48, and 72 hours. Results Immunocytochemistry showed that CXCR4 expression in SW480 cells was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups for the same exposure times compared with controls （P 〈0.05）. CCR7 expression in SW480 cells was significantly decreased in the 12 and 15 mmHg CO2 pneumoperitoneum- treated groups compared with controls （P 〈0.05）. CXCR4 and CCR7 expression increased up to the level of the control group after 24 and 48 hours （P 〉0.05）. If the CO2 pneumoperitoneum pressure increased, CXCR4 and CCR7 expression decreased at all exposure times. If the CO2 pneumoperitoneum exposure time prolonged, there were no significant differences in CXCR4 and CCR7 expression under the same pressure. Under all exposure times, CXCR4 and CCR7 mRNA expression was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups （P 〈0.05） compared with controls, and it increased up to the level of controls after being cultivated for 48 hours （P 〉0.05）. If the CO2 pneumoperitoneum pressure increased （with all exposure times） and exposure time prolonged （under the same pressure）, there were no significant differences in CXCR4 and CCR7 expression. Conclusions CXCR4 and CCR7 expression is temporarily affected after continuous CO2 pneumoperitoneum treatment. The high pressure of CO2 pneumoperitoneum plays an important role in suppressing the expression of these chemokine receptors. Different lengths of time of exposure to a CO2 pneumoperitoneum-like environment do not change CXCR4 and CCR7 expression.

Comparison of Volumetric and Dosimetric Variations in Nasopharyngeal Carcinoma during Intensity-modulated Radiation Therapy with and without Neoadjuvant Chemotherapy

Objective Patients with nasopharyngeal carcinoma(NPC)undergoing intensity-modulated radiation therapy(IMRT)may experience significant volumetric and dosimetric variations throughout the treatment course.However,neoadjuvant chemotherapy may reduce the extent of these variations.This study was carried out to evaluate volumetric and dosimetric changes in target volumes and organs at risk(OARs)during IMRT in patients with locally advanced NPC who received concurrent chemoradiotherapy(CCRT)alone or in combination with neoadjuvant chemotherapy(NACT).Methods 35 NPC patients were recruited for this study and divided into the NACT(n=15)and CCRT(n=20)groups.Computed tomography(CT)scans were performed before neoadjuvant chemotherapy,before IMRT,before the 24 th fraction of IMRT,and after treatment.The original plan(plan 0)was based on CT images collected before IMRT.Hybrid plan 1(plan 1)and hybrid plan 2(plan 2)were generated by applying the beam configurations of plan0 to the CT scans collected before the 24 th fraction of IMRT and after treatment.Volumetric and dosimetric variations were assessed by comparing the results of plan 0 with those of plan 1 and plan 2.Results In the NACT group,compared with that in plan 0,the primary gross tumor volume(GTVnx)decreased by 33.2%±18.4%and 50.5%±12.6%in plan1 and plan 2,respectively.In the CCRT group,the corresponding reduction rates in plan 1 and plan 2 were 49.4%±8.0%and 77.8%±28.1%,respectively.The volume decrease rates in the NACT group were less than those in the CCRT group(P<0.001).In the NACT group,compared with that of plan0,the dose to 95%of the volume(D95)for the planning target volume of the primary tumor(PTVnx)decreased by 1.0%±0.7%and 0.6%±0.6%in plan 1 and plan 2,respectively.In the CCRT group,the corresponding decrease rates in plan 1 and plan 2 were 4.2%±3.8%and 6.1%±6.3%,respectively.The decrease rate of D95 for PTVnx in the NACT group was less than that in the CCRT group(P<0.001).Similar results among the plans were found in terms of D99,Dmean,V93 for PTVnxand PTVnd,and Dmeanfor the parotid glands.Conclusion Neoadjuvant chemotherapy reduces the extent of volumetric and dosimetric variations in target volumes and OARs during IMRT and,thus,helps achieve better target volume coverage,protects adjacent important structures,and minimizes unnecessary replanning during radiotherapy.