Efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in treatment of advanced gastric cancer or gastroesophageal junction cancer: A meta-analysis

BACKGROUND Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer(GC/GEJC), researchers have turned toward, with the support of promising clinical trials, anti-PD-1/anti-PD-L1 antibody therapy. But there are also different clinical trial results. To better assess its efficacy and safety, we integrated data from 13 eligible studies for a systematic review and meta-analysis.AIM To comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.METHODS PubMed, Web of Science, Cochrane Library,and EMBASE databases were searched to identify eligible articles with outcomes including objective response rate(ORR), disease control rate(DCR), overall survival(OS), progression-free survival(PFS), and adverse events(AEs) of anti-PD-1/anti-PD-L1 antibody therapy.RESULTS Our study encompassed a total of 13 trials totaling 1618 patients. The outcomes showed a pooled ORR and DCR of 15%(95% confidence interval [CI]: 14%-18%) and 40%(95%CI: 33%-46%), respectively. The pooled 6-mo OS and PFS were 54%(95%CI: 45%-64%) and 26%(95%CI: 20%-32%), respectively, and the 12-mo OS and PFS were 42%(95%CI: 21%-62%) and 11%(95%CI: 8%-13%), respectively. In addition, the incidence of any-grade AEs and grade ≥ 3 AEs was 64%(95%CI: 54%-73%) and 18%(95%CI: 16%-20%), respectively. Most importantly, PD-L1 positive patients exhibited a higher ORR rate than PD-L1 negative patients(odds ratio = 2.54, 95%CI: 1.56-4.15).CONCLUSION Anti-PD-1/anti-PD-L1 antibody therapy has shown promising anti-tumor efficacy with manageable AEs in advanced GC/GEJC patients, with PD-L1 overexpressing patients exhibiting a higher ORR. What is more, the clinical efficacy of anti-PD-1/PD-L1 combined with traditional chemotherapy drugs is even better, although the occurrence of AEs still causes considerate concerns.

Evaluating the use of three-dimensional reconstruction visualization technology for precise laparoscopic resection in gastroesophageal junction cancer

BACKGROUND Laparoscopic gastrectomy for esophagogastric junction(EGJ)carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function,thereby providing patients with better treatment outcomes and quality of life.Nonetheless,this surgical technique also presents some challenges and limitations.Therefore,three-dimensional reconstruction visualization technology(3D RVT)has been introduced into the procedure,providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning,navigation,and outcome evaluation.AIM To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas.METHODS Data were obtained from the electronic or paper-based medical records at The First Affiliated Hospital of Hebei North University from January 2020 to June 2022.A total of 120 patients diagnosed with EGJ carcinoma were included in the study.Of these,68 underwent laparoscopic resection after computed tomography(CT)-enhanced scanning and were categorized into the 2D group,whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group.This study had two outcome measures:the deviation between tumor-related factors(such as maximum tumor diameter and infiltration length)in 3D RVT and clinical reality,and surgical outcome indicators(such as operative time,intraoperative blood loss,number of lymph node dissections,R0 resection rate,postoperative hospital stay,postoperative gas discharge time,drainage tube removal time,and related complications)between the 2D and 3D groups.RESULTS Among patients included in the 3D group,27 had a maximum tumor diameter of less than 3 cm,whereas 25 had a diameter of 3 cm or more.In actual surgical observations,24 had a diameter of less than 3 cm,whereas 28 had a diameter of 3 cm or more.The findings were consistent between the two methods(χ^(2)=0.346,P=0.556),with a kappa consistency coefficient of 0.808.With respect to infiltration length,in the 3D group,23 patients had a length of less than 5 cm,whereas 29 had a length of 5 cm or more.In actual surgical observations,20 cases had a length of less than 5 cm,whereas 32 had a length of 5 cm or more.The findings were consistent between the two methods(χ^(2)=0.357,P=0.550),with a kappa consistency coefficient of 0.486.Pearson correlation analysis showed that the maximum tumor diameter and infiltration length measured using 3D RVT were positively correlated with clinical observations during surgery(r=0.814 and 0.490,both P<0.05).The 3D group had a shorter operative time(157.02±8.38 vs 183.16±23.87),less intraoperative blood loss(83.65±14.22 vs 110.94±22.05),and higher number of lymph node dissections(28.98±2.82 vs 23.56±2.77)and R0 resection rate(80.77%vs 61.64%)than the 2D group.Furthermore,the 3D group had shorter hospital stay[8(8,9)vs 13(14,16)],time to gas passage[3(3,4)vs 4(5,5)],and drainage tube removal time[4(4,5)vs 6(6,7)]than the 2D group.The complication rate was lower in the 3D group(11.54%)than in the 2D group(26.47%)(χ^(2)=4.106,P<0.05).CONCLUSION Using 3D RVT,doctors can gain a more comprehensive and intuitive understanding of the anatomy and related lesions of EGJ carcinomas,thus enabling more accurate surgical planning.

Immune checkpoint inhibitors for treatment of advanced gastric or gastroesophageal junction cancer:Current evidence and future perspectives

Despite the application of conventional therapies,the prognosis of advanced gastric cancer(GC)or gastroesophageal junction cancer(GEJC)is still poor.In recent years,immune checkpoint inhibitors(ICIs)have reshaped the paradigm of cancer therapy.Emerging evidence support the feasibility of programmed cell death-1(PD-1)and its ligand(PD-L1)inhibition in chemo-refractory GC/GEJC.Nivolumab and pembrolizumab have initially been approved in Japan and United States,respectively for the third-line treatment of progressive GC or GEJC.In March 2020,nivolumab has also been licensed in China for treating advanced GC/GEJC who received≥2 lines of systemic therapies.Current studies are moving forward to the first-line application or focusing on combination strategies,though data are insufficient and disputable.In this review,we summarize the recently reported and ongoing clinical trials in ICIs for advanced GC/GEJC.Molecular characteristics and clinical implications of different tumor subtypes are also reviewed.We further discuss the safety profile and biomarkers for predicting the response of ICIs,which has guiding values in clinical practice.

Immune-related adverse events associated with immune checkpoint inhibitors for advanced gastric and gastroesophageal junction cancer:A meta-analysis

BACKGROUND Immune checkpoint inhibitors(ICIs)have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer.However,the inhibitors also cause immune-related adverse events(irAEs).The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs.AIM To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer.METHODS This systematic review was registered with PROSPERO(Reg.number:CRD42020152291).Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs.A systematic literature search was conducted using the PubMed,EMBASE,and Cochrane Library databases.Meta-analysis was carried out using the single sample rate method.Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software.RESULTS The patients enrolled in the present study included 14 patients from 14 case reports,326 patients from 6 case series,and 1249 patients from 8 clinical trials.It was found that the overall incidence of irAEs was 16%[95%confidence interval(CI):11-20]for all grades and 3%(95%CI:2-4)for the severe grade.It was evident that the incidence of irAEs varied with the type of inhibitor and organs.A comparative study of the anti-programmed cell death receptor-1(PD-1)and antiprogrammed death receptor-ligand 1(PD-L1)treatments showed that the antiPD-1 group had a higher overall incidence of irAEs(20%)as compared with that of the anti-PD-L1 group(13%).Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs(7.4%),including hypothyroidism,hyperthyroidism,thyroiditis,diabetes,and adrenal insufficiency,followed by gastroenterology(2.2%),pulmonology(1.8%),neurology(1.4%),dermatology(1.4%),hematology(0.8%),and hepatology(0.7%).In clinical trials,it was found that the incidence of death related to irAEs was 1%(95%CI:0-2.0),whereby colitis and interstitial lung diseases were the leading causes of death.CONCLUSION It was evident that the incidence and nature of irAEs are both organ-and inhibitor-specific.The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs.Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

Nomogram for predicting the overall survival of patients after D2/R0 resection and chemoradiotherapy for stage Ⅲ gastric cancer or gastroesophageal junction cancer

Objective:To explore the independent factors associated with the overall survival(OS)after D2/R0 resection and adjuvant chemoradiotherapy(CRT)for stage Ⅲ gastric cancer(GC)and gastroesophageal junction(GEJ)cancer,and establish and validate a nomogram model to predict the OS in this patient population.Methods:A total of 569 stage Ⅲ GC or GEJ cancer patients who underwent D2/R0 resection and adjuvant CRT at our center from January 2013 to May 2018 were retrospectively enrolled in this study.The patients were randomly divided into training and validation cohorts in a 3:1 ratio.In the training cohort,univariate and multivariate analysis were conducted to identify clinical factors associated with OS,and a nomogram model was established on the basis of the independent factors.The concordance index(C-index)and the calibration curve were used to validate the prediction power of the nomogram.Results:Overall,427 and 142 patients were enrolled in the training and validation cohorts,respectively.In the univariate and multivariate analyses,age,Lauren's classification,TNM stage,and administration of adjuvant CRT were independent factors for OS to construct the nomogram.The C-index values were 0.654 and 0.613 in the training and validation cohorts,respectively.The calibration curves were identical to the actual OS.Risk stratification based on the nomogram model showed good risk stratification for OS in both groups.Conclusion:Our study included adjuvant CRT as a predictive factor and established a nomogram model for predicting the OS in patients with stage III GC or GEJ after D2/R0 resection and adjuvant therapy.This nomogram could facilitate more individualized prediction of OS in clinical practice.

Systematic treatment in gastric cancer patients with overt bleeding:A propensity score matching analysis

BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety of chemotherapy as an initial therapy for GC/GEJC patients with overt bleeding(OB).AIM To investigate the impact of OB on the survival and treatment-related adverse events(TRAEs)of GC/GEJC patients.METHODS Patients with advanced or metastatic GC/GEJC who received systematic treatment at Peking University Third Hospital were enrolled in this study.Propensity score matching(PSM)analysis was performed.RESULTS After 1:2 PSM analysis,93 patients were assessed,including 32 patients with OB before treatment(OBBT)and 61 patients without OBBT.The disease control rate was 90.6%in the group with OBBT and 88.5%in the group without OBBT,and this difference was not statistically significant.There was no difference in the incidence of TRAEs between the group with OBBT and the group without OBBT.The median overall survival(mOS)was 15.2 months for patients with OBBT and 23.7 months for those without OBBT[hazard ratio(HR)=1.101,95%confidence interval(CI):0.672-1.804,log rank P=0.701].The mOS was worse for patients with OB after treatment(OBAT)than for those without OBAT(11.4 months vs 23.7 months,HR=1.787,95%CI:1.006-3.175,log rank P=0.044).CONCLUSION The mOS for GC/GEJC patients with OBBT was similar to that for those without OBBT,but the mOS for patients with OBAT was worse than that for those without OBAT.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Surgical resection of gastric stump cancer following proximal gastrectomy for adenocarcinoma of the esophagogastric junction

BACKGROUND Proximal gastrectomy(PG) is performed widely as a function-preserving operation for early gastric cancer located in the upper third of the stomach and is an important function-preserving approach for esophagogastric junction(EGJ)adenocarcinoma. The incidence of gastric stump cancer(GSC) after PG is increasing. However, little is known about the GSC following PG because very few studies have been conducted on the disease.AIM To clarify clinicopathologic features, perioperative complications, and long-term survival rates after the resection of GSC following PG.METHODS Data for patients with GSC following PG for adenocarcinoma of the EGJ diagnosed between January 1998 and December 2016 were retrospectively reviewed. Multivariate analysis was performed to identify factors associated with overall survival(OS). GSC was defined in accordance with the Japanese Gastric Cancer Association.RESULTS A total of 35 patients were identified. The median interval between the initial PGand resection of GSC was 4.9(range 0.7-12) years. In 21 of the 35 patients, the tumor was located in a nonanastomotic site of the gastric stump. Total gastrectomy was performed in 27 patients; the other 8 underwent partial gastrectomy. Postoperative complications occurred in 6 patients(17.1%). The tumor stage according to the depth of tumor invasion was T1 in 6 patients, T2 in3 patients, T3 in 9 patients, and T4 in 17 patients. Lymph node metastasis was observed in 18 patients. Calculated 1-, 3-, and 5-year OS rates were 86.5%, 62.3%,and 54.2%, respectively. Multivariate analysis showed advanced T stage to be associated with OS.CONCLUSION This study reveals the characteristics of GSC following PG for adenocarcinoma of the EGJ and suggests that a surgical approach can lead to a satisfactory outcome.

Leptomeningeal metastases originated from esophagogastric junction/gastric cancer:A brief report of two cases

Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present two patients; one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer, who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment. Furthermore, a thorough and short review of the literature is carried out.

Trimodality treatment in gastric and gastroesophageal junction cancers:Current approach and future perspectives

Gastric and gastroesophageal junction(GEJ)cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage,with an increasing incidence both in Asia and in Western countries.These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses.Accordingly,the understanding of phenotypic and genotypic correlations/classifications has been improved.Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone,with the incorporation of other treatment modalities,such as radiation and chemotherapy(including biologics).Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival.Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate,which is associated with improved long-term outcomes.Several studies have defined various chemotherapy regimens to accompany radiation(before and after surgery).Recently,addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval.Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results.The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers,highlight the remaining questions and present the current research effort addressing them.

Scaphoid metastasis as the first sign of occult gastroesophageal junction cancer:A case report

BACKGROUND Metastatic tumors of the hand are very rare.They are usually late manifestations of massive advanced malignancies.However,a small portion of acrometastases are indications of occult primary cancer.Here,we report an extremely rare case in which a scaphoid bone lesion was the initial manifestation and was found to be a metastasis from gastroesophageal junction(GEJ)cancer.CASE SUMMARY A 57-year-old male patient presented with ongoing left wrist pain and swelling after trauma.He was initially misdiagnosed with infection of the scaphoid bone and treated with antibiotics and anti-inflammatory drugs.Further radiographic investigations showed a scaphoid pathological fracture,indicating a metastatic tumor derived from the GEJ and/or right lung malignancies.Gastroscopy failed to identify the pathology of the mass at the GEJ,which grew in an exophytic pattern.A lung puncture biopsy was not performed because the patient refused the procedure.To relieve his wrist pain and obtain a definite pathology,we resected the scaphoid lesion.Based on the clinical and pathological results,the patient was finally diagnosed with multiple metastases of advanced GEJ adenocarcinoma.He underwent chemotherapy and died 6 mo after his initial presentation.CONCLUSION Despite the rareness of the disease,orthopedic surgeons should consider the possibility of metastasis to the bones of the hand when patients complain of persistent and progressive pain in the hand.

How does Helicobacter pylori cause gastric cancer through connexins: An opinion review

Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which cause gastrointestinal diseases. Connexins function in gap junctional homeostasis, and their downregulation is closely related to gastric carcinogenesis. Investigations into H. pylori infection and the fine-tuning of connexins in cells or tissues have been reported in previous studies. Therefore, in this review, the potential mechanisms of H. pylori-induced gastric cancer through connexins are summarized in detail.

Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer

AIM To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells(PBMCs) for prognostic circulating tumor cell(CTC) detection in gastroesophageal cancer.METHODS Using 7.5 m L blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the Iso Flux platform. Paired specimens taken during the same blood draw(n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs lasted from 2 wk to 25.2 mo(median 14.6 mo). CTCs isolated from pre-treatment cryopreserved PBMCs(n = 43) were examined for associations with clinicopathological variables and survival outcomes.RESULTS While there was a significant trend to a decrease in CTC numbers associated with cryopreserved specimens(mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in samples with a total CTC count of > 50, with low CTC count samples less affected(P = 0.06). There was no significant association between the duration of cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples prior to treatment, a high CTC count(> 17) was associated with poorer overall survival(OS)(n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate analysis, after controlling for sex, age, stage, ECOG performance status, and primary tumor location, a high CTC count remained significantly associated with a poorer OS(HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). CONCLUSION PBMC cryopreservation for delayed CTC isolation is a valid strategy to assist with sample collection, transporting and processing.

Role of stenting in the palliation of gastroesophageal junction cancer: A brief review

Gastroesophageal junction cancer has an increasing in-cidence in western countries. It is inoperable when firstmanifested in more than 50% of cases. So, palliationis the only therapeutic option for the advanced diseaseto relieve dysphagia and its consequences in weakenedpatients with an estimated mean survival under 6 mo.This article has tried to identify trends focusing on cur-rent information about the best palliative treatment,with an emphasis on the role of stenting. Self-expand-ing stent placement, either metal or plastic, is the mainmanagement option. However, this anatomical loca-tion creates some particular problems for stent safetyand effectiveness which may be overcome by properlydesigned novel stents. The stents ensure a good qual-ity of life and must be preferred over other alterna-tive methods of loco-regional modalities, i.e., externalradiation, laser thermal or photodynamic therapy. Al-though stent placement is generally a simple, safe andeffective method, there are sometimes complications,increasing the morbidity and mortality rate. Bypassoperative procedures have now been abandoned as afirst choice. The stomach instead of the colon must beused for a bypass operation when it is needed. Chemo-therapy, despite the toxicity, and intraluminal radiation(brachytherapy) have a well-defined role.

Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer:A meta-analysis

AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all published randomized controlled trials(RCTs) investigating the efficacy of the flurouracilbased NAC for gastroesophageal and gastric cancer,and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery.Studies that included patients with metastases at enrollment were excluded.Primary endpoint was the odds ratio(OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer.Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gas-troesophageal and gastric cancer.Safety analyses were also performed.The OR was the principal measurement of effect,which was calculated as the treatment group(NAC plus surgery) vs control group(surgery alone) and was presented as a point estimate with 95% confidence intervals(CI).All calculations and statistical tests were performed using RevMan 5.1 software.RESULTS:Seven RCTs were included for the analysis.A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group(n = 620) and control group(n = 629).The quality scores of the RCTs were assessed according to the method of Jadad.The RCT quality scores ranged from 2 to 7(5-point scale),with a mean of 3.75.The median follow-up time in these studies was over 3 years.The meta-analysis showed that NAC improved the overall survival rate(OR 1.40,95%CI 1.11-1.76;P = 0.005),which was statistically significant.The 3-year progression-free survival rate was significantly higher in treatment group than in control group(37.7% vs 27.3%)(OR 1.62,95%CI 1.21-2.15;P = 0.001).The tumor down-stage rate was higher in treatment group than in control group(55.76% vs 41.38%)(OR 1.77,95%CI 1.27-2.49;P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group(75.11% vs 68.56%)(OR 1.38,95%CI 1.03-1.85;P = 0.03),with significant differences.No obvious safety concerns about mortality and complications were raised in these trials.There were no statistically significant differences in perioperative mortality(5.08% vs 4.86%)(OR 1.05,95%CI 0.57-1.94;P = 0.87 fixed-effect model) and in the complication rate between the two groups(13.25% vs 9.66%)(OR 1.40,95%CI 0.91-2.14;P = 0.12 fixed-effect model).Trials showed that patients from Western countries favored NAC compared with those from Asian countries(OR 1.40,95%CI 1.07-1.83).Monotherapy was inferior tomultiple chemotherapy(OR 1.40,95%CI 1.07-1.83).Intravenous administration of NAC was more advantageous than oral route(OR 1.41,95%CI 1.09-1.81).CONCLUSION:Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer.Additionally,NAC can down the tumor stage and improve R0 resection.

Metastatic pattern in esophageal and gastric cancer:Influenced by site and histology

BACKGROUND Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited.Early recognition of metastases is important to avoid futile locoregional treatments.Furthermore,knowledge on metastatic patterns is necessary for further development of personalized treatment modalities.AIM To gain insight into the metastatic pattern of gastroesophageal cancer.METHODS A nationwide retrospective autopsy study of 3876 patients with adenocarcinoma(AC)or squamous cell carcinoma(SCC)of the esophagus or stomach between 1990 and 2017 was performed.Only patient with metastases were included for analysis.The metastatic pattern was analyzed according to the primary tumor location and histological subtype.RESULTS Metastatic disease was found in 268 esophageal and 331 gastric cancer patients.In esophageal cancer,the most common metastatic locations were liver(56%),distant lymph nodes(53%)and lung(50%).Esophageal AC showed more frequently metastases to the peritoneum and bone compared with esophageal SCC.In gastric cancer,the most common metastatic locations were distant lymph nodes(56%),liver(53%)and peritoneum(51%).Intestinal-type AC of the stomach showed metastases to the liver more frequently,whereas metastases to the bone,female reproductive organs and colorectum were observed more frequently in diffuse-type gastric AC.CONCLUSION This study showed differences in metastatic patterns of patients with esophageal and gastric cancer according to the primary tumor location and histological subtype.

Surgical management of esophagogastric junction tumors

Surgical resection with lymphadenectomy is the mainstay of treatment for all resectable esophagogastric junction tumors, prior to systemic generalization of the disease. This makes accurate pre-treatment staging and classification of the tumors most demanding. A well-established and internationally accepted classification for adenocarcinomas of the esophagogastric junction （AEG） helps to choose the appropriate surgical approach and to make results from different institutions comparable. Distal esophageal adenocarcinomas （AEGⅠ） are distinguished from true cardia carcinomas （AEGⅡ） and subcardiac gastric cancers （AEGⅢ）. Substantial advancements in this surgical field during the preceding decades have clearly revealed that individualization of the surgical strategy is the key to successfully approaching these entities. In this review we discuss the surgical management of esophagogastric junction tumors with a tailored surgical strategy.

Advanced gastric cancer:Is there enough evidence to call second-line therapy standard?

Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.

Combination chemotherapy with paclitaxel,cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma:a multicenter prospective study

Objective： To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU （PCF） as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction （EGJ） adenocarcinoma in China. Methods： The patients were treated with paclitaxel 150 mg/m2 on dl; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/（mLd） intravenously on d 1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. Results： Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy （group A） and 34 received the regimen as the second-line therapy （group B） with the median age of 59 years old and Karnofsky performance status （KPS） score 〉80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival （mOS） was 12.0 months （95% CI： 7.9-16.2 months） in group A and 7.3 months （95% CI： 4.3-10.3 months） in group B, respectively. The median progression-free survival （mPFS） was 5.7 months （95% CI： 4.1-7.2 months） and 5.0 months （95% CI： 3.1-6.9 months）, respectively. The response rate （CR^PR） was 40% （16/40; 95% CI： 24.9-56.7%） in group A and 22.6% （7/31; 95% CI： 9.6-41.1%） in group B. Major grade 3 or 4 adverse events include neutropenia （41.3 %）, febrile neutropenia （9.3 %）, nausea/anorexia （10.7%）, and vomiting （5.3 %）. There was no treatment-related death. Conclusions： The combination chemotherapy with PCF is active and tolerable as first-line and second- line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.