Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Huang's three-step maneuver for laparoscopic spleen-preserving No.10 lymph node dissection for advanced proximal gastric cancer

Due to the complexity of the splenic hilar vessels, their anatomical variation and the narrow and deep space, as well as the bleeding-prone splenic parenchyma and the difficulty to manage splenic or vascular bleeding at the splenic hilum,the procedure remains challenging and technically demanding procedure for the performance of laparoscopic pancreas- and spleen-preserving splenic hilar lymph nodes dissection. Based on our experiences, we gradually explored a set of procednral operation steps called ＂Huang＇s three-step maneuver＂. In this paper, we not only provide the concrete operation steps for the surgeon, but we also provide our recommended technique of pulling and exposure for assistants. This new maneuver simplifies the complicated procedure and improves the efficiency of laparoscopic spleen-preserving splenic hilar lymphadenectomy, making it easier to master and allowing for its widespread adoption.

Serum VEGFR-3 and survival of advanced gastric cancer patients treated with FOLFOX

AIM: To explore if vascular endothelial growth factor receptor-3 (VEGFR-3) and carcinoembryonic antigen (CEA) can predict overall survival in advanced gastric cancer.METHODS: VEGFR-3 level was assessed by enzymelinked immunosorbent assay,and CEA was assessed by chemiluminescence immunoassay in the sera of 81 advanced gastric cancer patients before treatment with oxaliplatin plus 5-fluorouracil and folinic acid.RESULTS: Median survival time in patients with a low serum VEGFR-3 level was significantly longer than in those with a higher VEGFR-3 level (15.4 mo vs 7.7 mo,P < 0.001).Patients with a low CEA level had a longer survival than those with a higher CEA level (15.8 mo vs 8.6 mo,P < 0.001).Thirty-nine patients with low VEGFR-3 and low CEA levels had a median survival of 19.7 mo (P = 0.0006).The hazard ratio for patients with a high VEGFR-3 level was 2.443 (P = 0.002).CONCLUSION: High serum VEGFR-3 level is correlated significantly with poor survival.In patients with a high serum level of VEGFR-3,alternative chemotherapy regimens should be considered.

Optimal proximal resection margin distance for gastrectomy in advanced gastric cancer

BACKGROUND The conventional guidelines to obtain a safe proximal resection margin(PRM)of5-6 cm during advanced gastric cancer(AGC)surgery are still applied by many surgeons across the world.Several recent studies have raised questions regarding the need for such extensive resection,but without reaching consensus.This study was designed to prove that the PRM distance does not affect the prognosis of patients who undergo gastrectomy for AGC.AIM To investigate the influence of the PRM distance on the prognosis of patients who underwent gastrectomy for AGC.METHODS Electronic medical records of 1518 patients who underwent curative gastrectomy for AGC between June 2004 and December 2007 at Asan Medical Center,a tertiary care center in Korea,were reviewed retrospectively for the study.The demographics and clinicopathologic outcomes were compared between patients who underwent surgery with different PRM distances using one-way ANOVA and Fisher’s exact test for continuous and categorical variables,respectively.The influence of PRM on recurrence-free survival and overall survival were analyzed using Kaplan-Meier survival analysis and Cox proportional hazard analysis.RESULTS The median PRM distance was 4.8 cm and 3.5 cm in the distal gastrectomy(DG)and total gastrectomy(TG)groups,respectively.Patient cohorts in the DG and TG groups were subdivided into different groups according to the PRM distance;≤1.0 cm,1.1-3.0 cm,3.1-5.0 cm and>5.0 cm.The DG and TG groups showed nostatistical difference in recurrence rate(23.5%vs 30.6%vs 24.0%vs 24.7%,P=0.765)or local recurrence rate(5.9%vs 6.5%vs 8.4%vs 6.2%,P=0.727)according to the distance of PRM.In both groups,Kalpan-Meier analysis showed no statistical difference in recurrence-free survival(P=0.467 in DG group;P=0.155 in TG group)or overall survival(P=0.503 in DG group;P=0.155 in TG group)according to the PRM distance.Multivariate analysis using Cox proportional hazard model revealed that in both groups,there was no significant difference in recurrence-free survival according to the PRM distance.CONCLUSION The distance of PRM is not a prognostic factor for patients who undergo curative gastrectomy for AGC.

New prognostic model for patients with advanced gastric cancer:Fluoropyrimidine/platinum doublet for first-line chemotherapy

BACKGROUND New prognostic factors have been reported in patients with metastatic or recurrent gastric cancer(MRGC),necessitating modifications to the previous prognostic model.AIM To develop a new model,MRGC patients who received fluoropyrimidines/platinum doublet chemotherapy between 2008 and 2015 were analyzed.METHODS A total of 1883 patients was divided into a training set(n=937)and an independent validation set(n=946).RESULTS Multivariate analysis showed that the following six factors were associated with poor overall survival(OS)in the training set:Eastern Cooperative Oncology Group performance score≥2 and bone metastasis(2 points each),peritoneal metastasis,high alkaline phosphatase level,low albumin level,and high neutrophil-lymphocyte ratio(1 point each).A prognostic model was developed by stratifying patients into good(0-1 point),moderate(2-3 points),and poor(≥4 points)risk groups.In the validation set,the median OS of the three risk groups was 15.8,10.1,and 5.7 mo,respectively,and those differences were significant(P<0.001).CONCLUSION We identified six factors readily measured in clinical practice that are predictive of poor prognosis in patients with MRGC.The new model is simpler than the old and more easily predicts OS.

Laparoscopic splenic hilum lymph node dissection for advanced proximal gastric cancer:A modified approach for pancreasand spleen-preserving total gastrectomy

AIM:To investigate the feasibility and optimal approach for laparoscopic pancreasand spleen-preserving splenic hilum lymph node dissection in advanced proximal gastric cancer.METHODS:Between August 2009 and August 2012,12 patients with advanced proximal gastric cancer treated in Nanfang Hospital,Southern Medical University,Guangzhou,China were enrolled and subsequently underwent laparoscopic total gastrectomy with pancreasand spleen-preserving splenic hilum lymph node(LN)dissection.The clinicopathological characteristics,surgical outcomes,postoperative course and followup data of these patients were retrospectively collected and analyzed in the study.RESULTS:Based on our anatomical understanding of peripancreatic structures,we combined the characteristics of laparoscopic surgery and developed a modified approach(combined supraand infra-pancreatic approaches)for laparoscopic pancreasand spleenpreserving splenic hilum LN dissection.Surgery was completed in all 12 patients laparoscopically without conversion.Only one patient experienced intraoperative bleeding when dissecting LNs along the splenic artery and was handled with laparoscopic hemostasis.The mean operating time was 268.4 min and mean number of retrieved splenic hilum LNs was 4.8.One patient had splenic hilum LN metastasis(8.3%).Neither postoperative morbidity nor mortality was observed.Peritoneal metastasis occurred in one patient and none of the other patients died or experienced recurrent disease during the follow-up period.CONCLUSION:Laparoscopic total gastrectomy with pancreasand spleen-preserving splenic hilum LN dissection using the modified approach for advanced proximal gastric cancer could be safely achieved.

Prognostic impact of D2-plus lymphadenectomy and optimal extent of lymphadenectomy in advanced gastric antral carcinoma: Propensity score matching analysis

Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gastrectomy for advanced gastric antral carcinoma.Methods: A total of 203 patients with advanced gastric cancer(GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index(TVI) was calculate to evaluate the survival benefit of dissecting each LN station.Results: Of 102 patients with D2-plus lymphadenectomy, 21(20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival(OS) was significantly better in the D2-plus than the D2 group(P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy(hazard ratio, 0.516;P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, p N stage [odds ratio(OR), 2.533;95% confidence interval(95% CI), 1.368-4.691;P=0.003] and extent of LNs metastasis(OR, 5.965;95% CI, 1.335-26.650;P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1(No. 8p), 5.7(No. 12p), 5.1(No. 13), and 7.1(both No. 16a2 and No. 16b1), respectively.Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.

Different risk factors for advanced colorectal neoplasm in young adults

AIM: To compare the risk of developing advanced colorectal neoplasm(ACRN) according to age in Koreans.METHODS: A total of 70428 Koreans from an occupational cohort who underwent a colonoscopy between 2003 and 2012 at Kangbuk Samsung Hospital were retrospectively selected. We evaluated and compared odds ratios(OR) for ACRN between the young-adults(YA < 50 years) and in the older-adults(OA ≥ 50 years). ACRN was defined as an adenoma ≥ 10 mm in diameter, adenoma with any component of villous histology, high-grade dysplasia, or invasive cancer.RESULTS: In the YA group, age(OR = 1.08, 95%CI: 1.06-1.09), male sex(OR = 1.26, 95%CI: 1.02-1.55), current smoking(OR = 1.37, 95%CI: 1.15-1.63), family history of colorectal cancer(OR = 1.46, 95%CI: 1.01-2.10), diabetes mellitus related factors(OR = 1.27, 95%CI: 1.06-1.54), obesity(OR = 1.23, 95%CI: 1.03-1.47), CEA(OR = 1.04, 95%CI: 1.01-1.09) and low-density lipoprotein-cholesterol(OR = 1.01, 95%CI: 1.01-1.02) were related with an increased risk of ACRN. However, age(OR = 1.08, 95%CI: 1.06-1.09), male sex(OR = 2.12, 95%CI: 1.68-2.68), current smoking(OR = 1.38, 95%CI: 1.12-1.71), obesity(OR = 1.34, 95%CI: 1.09-1.65) and CEA(OR = 1.05, 95%CI: 1.01-1.09) also increased the risk of ACRN in the OA group.CONCLUSION: The risks of ACRN differed based on age group. Different colonoscopic screening strategies are appropriate for particular subjects with risk factors for ACRN, even in subjects younger than 50 years.

Station 10 lymph node dissections in laparoscopic-assisted spleen-preserving radical gastrectomy for advanced proximal gastric cancer

D2 gastric resection has been increasingly recognized as the optimal surgical treatment for advanced gastric cancer. Dissection of the station 10 splenic lymph nodes is required in the treatment of advanced proximal gastric cancer. Based on vascular anatomy and anatomical plane of fascial space, integrated with our experience in station 10 splenic lymph node dissection in open surgery and proven skills of laparoscopic operation, we have successfully mastered the surgical essentials and technical keypoints in laparoscopic-assisted station 10 lymph node dissection.

Effect of lymphadenectomy extent on advanced gastric cancer located in the cardia and fundus

AIM:To analyze the prognostic impact of lymphade-nectomy extent in advanced gastric cancer located in the cardia and fundus. METHODS: Two hundred and thirty-six patients with advanced gastric cancer located in the cardia and fundus who underwent D2 curative resection were analyzed retrospectively. Relationships between the numbers of lymph nodes (LNs) dissected and survival was analyzed among different clinical stage subgroups. RESULTS: The 5-year overall survival rate of the entire cohort was 37.5%. Multivariate prognostic variables were total LNs dissected (P < 0.0001; or number of negative LNs examined, P < 0.0001), number of positive LNs (P < 0.0001), T category (P < 0.0001) and tumor size (P = 0.015). The greatest survival differences were observed at cutoff values of 20 LNs resected for stage Ⅱ (P = 0.0136), 25 for stage Ⅲ (P < 0.0001), 30 for stage Ⅳ (P = 0.0002), and 15 for all patients (P = 0.0024). Based on the statistically assumed linearity as best fit, linear regression showed a significant survival enhancement based on increasing negative LNs for patients of stages Ⅲ (P = 0.013) and Ⅳ (P = 0.035). CONCLUSION: To improve the long-term survival of patients with advanced gastric cancer located inthe cardia and fundus, removing at least 20 LNs for stage Ⅱ, 25 LNs for stage Ⅲ, and 30 LNs for stage Ⅳ patients during D2 radical dissection is recommended.

Neoadjuvant vs adjuvant pelvic radiotherapy for locally advanced rectal cancer: Which is superior?

The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy, degree of sphincter preservation with neoadjuvant radiotherapy, and short and long term effects of radiotherapy are controversial topics. The MEDLINE, Cochrane Library databases, and meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomized controlled trials and meta-analyses comparing neoadjuvant and adjuvant radiotherapy with surgery to surgery alone for rectal cancer. Neoadjuvant radiotherapy shows superior results in terms of local control compared to adjuvant radiotherapy. Neither adjuvant or neoadjuvant radiotherapy impacts overall survival. Short course versus long course neoadjuvant radiotherapy remains controversial. There is insufficient data to conclude that neoadjuvant therapy improves rates of sphincter preserving surgery. Radiation significantly impacts anorectal and sexual function and includes both acute and long term toxicity. Data demonstrate that neoadjuvant radiation causes less toxicity compared to adjuvant radiotherapy, and specifically short course neoadjuvant radiation results in less toxicity than long course neoadjuvant radiation. Neoadjuvant radiotherapy is the preferred modality for administering radiation in locally advanced rectal cancer. There are significant side effects from radiation, including anorectal and sexual dysfunction, which may be less with short course neoadjuvant radiation.

A multicenter randomized study on Me-CCNU,5-FU and ADM versus ACNU,5-FU and ADM intreatment of advanced gastric cancer

ＡｍｕｌｔｉｃｅｎｔｅｒｒａｎｄｏｍｉｚｅｄｓｔｕｄｙｏｎＭｅＣＣＮＵ，５ＦＵａｎｄＡＤＭｖｅｒｓｕｓＡＣＮＵ，５ＦＵａｎｄＡＤＭｉｎｔｒｅａｔｍｅｎｔｏｆａｄｖａｎｃｅｄｇａｓｔｒｉｃｃａｎｃｅｒＸＩＡＯＳｈｕＤｏｎｇ１，ＬＩＤｅＨｕ...

Effectiveness of integrated nursing interventions for fatigue in patients with advanced cancer:a systematic review of randomized controlled trials

Objective:To evaluate the effectiveness of integrated nursing interventions for fatigue in patients with advanced cancer.Methods:Medline,Pubmed,Embase,CINAHL,Web of Science,and the Cochrane Library were searched systematically till June 2017.A systematic review was conducted to collect randomized controlled trials(RCTs)reporting on the effect of nurse-driven interventions to improve fatigue in patients with advanced cancer.Quality assessment was conducted using the Cochrane Collaboration’s risk of bias tool.Results:Six RCTs involving 736 adult participants were included.The fatigue intensity was improved significantly by nursing interventions.The analyzed results revealed significant improvements in the intervention group:less than 3 months(standard mean difference[SMD]=?0.33,95%confidence interval[CI][?0.48,?0.19],P<0.01)and more than or equal to 3 months(SMD=?0.40,95%CI[?0.57,?0.24],P<0.01).Four studies with a moderate risk of bias were judged,and the remaining studies were at high risk of bias.Conclusions:The results indicate that integrated nursing interventions may relieve fatigue in patients with advanced cancer.However,due to the high risk of bias in most of the included studies and the diversity of interventions,the results and implementation process should be carefully monitored.

Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas

BACKGROUND Early detection of advanced cystic mucinous neoplasms[(A-cMNs),defined as high-grade dysplasia or malignancy]of the pancreas is of great significance.As a simple and feasible detection method,serum tumor markers(STMs)may be used to predict advanced intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms(MCNs).However,there are few studies on the usefulness of STMs other than carbohydrate antigen(CA)19-9 for early detection of A-cMNs.AIM To study the ability of five STMs-CA19-9,carcinoembryonic antigen(CEA),CA125,CA724,and CA242 to predict A-cMNs and distinguish IPMNs and MCNs.METHODS We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs.The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs.A receiver operating characteristic curve with the area under curve(AUC)was also created to identify the performance of the five STMs.RESULTS A total of 187 patients with cMNs were identified and 72 of them showed AcMNs.We found that CA19-9 exhibited the highest sensitivity(SE)(54.2%)and accuracy(76.5%)and a moderate ability(AUC=0.766)to predict A-cMNs.In predicting high-grade dysplasia IPMNs,the SE of CA19-9 decreased to 38.5%.The ability of CEA,CA125,and CA724 to predict A-cMNs was low(AUC=0.651,0.583,and 0.618,respectively).The predictive ability of CA242 was not identified.The combination of STMs improved the SE to 62.5%.CA125 may be specific to the diagnosis of advanced MCNs.CONCLUSION CA19-9 has a moderate ability,and CEA,CA125,and CA724 have a low ability to predict A-cMNs.The combination of STM testing could improve SE in predicting A-cMNs.

Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy:A case report

BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.

Extraskeletal Ewing sarcoma of the stomach:A rare case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

Underwater endoscopic mucosal resection for neoplasms in the pyloric ring of the stomach: Four case reports

BACKGROUND Tumors located in the pylorus are technically more complex to resect by endoscopic resection,as the anatomical characteristics of this region can affect the adequate assessment of margins and performance of the procedure.We reported the results of underwater endoscopic mucosal resection(UEMR)of benign mucosal neoplasms located in the pyloric ring.CASE SUMMARY This case series describes 4 patients with 4 mucosal neoplasms located in the pyloric ring.The diameter of each neoplasm was less than 15 mm.We performed UEMR for the lesions.Water immersion enabled slight floating of the lesions,resulting in easy identification.We achieved en bloc resection with a snare and electrosurgical unit.All procedure were performed within 3 min without adverse events.Pathologic examination showed low-grade dysplasia with clear resection margins in one case and hyperplastic polyps in three cases.CONCLUSION UEMR can be an effective and safe treatment method for neoplasms in the gastric pyloric ring.

Advances in the study of gastric organoids as disease models

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Construction and validation of a risk-prediction model for anastomotic leakage after radical gastrectomy: A cohort study in China

Objectives:Anastomotic leakage(AL)stands out as a prevalent and severe complication following gastric cancer surgery.It frequently precipitates additional serious complications,significantly influencing the overall survival time of patients.This study aims to enhance the risk-assessment strategy for AL following gastrectomy for gastric cancer.Methods:This study included a derivation cohort and validation cohort.The derivation cohort included patients who underwent radical gastrectomy at Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,from January 1,2015 to December 31,2020.An evidence-based predictor questionnaire was crafted through extensive literature review and panel discussions.Based on the questionnaire,inpatient data were collected to form a model-derivation cohort.This cohort underwent both univariate and multivariate analyses to identify factors associated with AL events,and a logistic regression model with stepwise regression was developed.A 5-fold cross-validation ensured model reliability.The validation cohort included patients from August 1,2021 to December 31,2021 at the same hospital.Using the same imputation method,we organized the validation-queue data.We then employed the risk-prediction model constructed in the earlier phase of the study to predict the risk of AL in the subjects included in the validation queue.We compared the predictions with the actual occurrence,and evaluated the external validation performance of the model using model-evaluation indicators such as the area under the receiver operating characteristic curve(AUROC),Brier score,and calibration curve.Results:The derivation cohort included 1377 patients,and the validation cohort included 131 patients.The independent predictors of AL after radical gastrectomy included age65 y,preoperative albumin<35 g/L,resection extent,operative time240 min,and intraoperative blood loss90 mL.The predictive model exhibited a solid AUROC of 0.750(95%CI:0.694e0.806;p<0.001)with a Brier score of 0.049.The 5-fold cross-validation confirmed these findings with a calibrated C-index of 0.749 and an average Brier score of 0.052.External validation showed an AUROC of 0.723(95%CI:0.564e0.882;p?0.006)and a Brier score of 0.055,confirming reliability in different clinical settings.Conclusions:We successfully developed a risk-prediction model for AL following radical gastrectomy.This tool will aid healthcare professionals in anticipating AL,potentially reducing unnecessary interventions.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.