Research status and hotspots of tight junctions and colorectal cancer:A bibliometric and visualization analysis

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide and the second leading cause of cancer-related death.Over the past two decades,numerous researchers have provided important evidence regarding the role of tight junction(TJ)proteins in the occurrence and progression of CRC.The causal relationship between the presence of specific TJ proteins and the development of CRC has also been confirmed.Despite the large number of publications in this field,a bibliometric study to review the current state of research and highlight the research trends and hotspots in this field has not yet been performed.AIM To analyze research on TJs and CRC,summarize the field’s history and current status,and predict future research directions.METHODS We searched the Science Citation Index Expanded database for all literature on CRC and TJs from 2001-2023.We used bibliometrics to analyze the data of these papers,such as the authors,countries,institutions,and references.Co-authorship,co-citation,and co-occurrence analyses were the main methods of analysis.CiteSpace and VOSviewer were used to visualize the results.RESULTS A total of 205 studies were ultimately identified.The number of publications on this topic has steadily increased since 2007.China and the United States have made the largest contributions to this field.Anticancer Research was the most prolific journal,publishing 8 articles,while the journal Oncogene had the highest average citation rate(68.33).Professor Dhawan P was the most prolific and cited author in this field.Co-occurrence analysis of keywords revealed that“tight junction protein expression”,“colorectal cancer”,“intestinal microbiota”,and“inflammatory bowel disease”had the highest frequency of occurrence,revealing the research hotspots and trends in this field.CONCLUSION This bibliometric analysis evaluated the scope and trends of TJ proteins in CRC,providing valuable research perspectives and future directions for studying the connection between the two.It is recommended to focus on emerging research hotspots,such as the correlations among intestinal microbiota,inflammatory bowel disease,TJ protein expression,and CRC.

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.

Uncharted Territory: Frequent Relapsing, Steroid Sensitive Secondary Minimal Change Nephrotic Syndrome Cause by Solid Tumor of the Gastro-Esophageal Junction —(Case Presentation and Review of the Literature)

We reported a biopsy proved case of minimal change nephrotic syndrome in a 72-year-old patient. The minimal change nephrotic syndrome has been steroid sensitive, but the patient had 7 relapses over a span of 5 years. Each time the dose of steroid is tapered, a relapse of the nephrotic syndrome occurred. Eventually, the patient was complaining of dysphagia and difficulty swallowing. Hospital work-up with barium swallow, endoscopy, and CT of the chest, abdomen and pelvis, revealed a focal stenotic lesion with mild to moderate esophageal dysmotility 7/15/2022. A diagnosis of an ulcerating lesion with biopsy confirmed a neuro-endocrine carcinoma of the gastro-esophageal junction was entertained. The CT of the chest/abdomen/pelvis, 7/19/2022, has shown, an esophageal mass of 5.1 × 5.6 × 7 cm of the gastro-esophageal junction with ulceration. No evidence of spread beyond the esophagus and stomach. The histology revealed a poorly differentiated neuroendocrine tumor of the gastro-esophageal junction. The patient underwent several rounds of chemotherapy, radiation, and surgery culminating in tumor control. His nephrotic syndrome was resolved after the tumor has been controlled by surgery and chemotherapy.

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.

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.

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.

Evaluation of routine biopsies in endoscopic screening for esophagogastric junction cancer

AIM: To explore whether routine biopsies at the high incidence spot of esophagogastric junction (EGJ) cancer are justified in endoscopic screening.

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.

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.

Current status and future perspectives for the treatment of resectable locally advanced esophagogastric junction cancer:A narrative review

Incidence rates for esophagogastric junction cancer are rising rapidly worldwide possibly due to the economic development and demographic changes.Therefore,increased attention has been paid to the prevention,diagnosis,and the treatment of esophagogastric junction cancer.Although there are discrepancies in the treatment strategy between Asian and Western countries,surgery remains the mainstay of treatment for esophagogastric junction cancer.Recent developments of perioperative multidisciplinary treatment may lead to better therapeutic effect,higher complete resection rate,and better control of the residual diseases,thus result in prolonged prognosis.In this review,we will focus on the treatment of locally advanced resectable esophagogastric junction cancer,and discuss the current status and future perspectives of the perioperative treatment including chemotherapy,radiation therapy,and immunotherapy,as well as the surgical strategy.Better understanding of the latest treatment strategy and future overlook may enable to standardize and individualize the treatment for esophagogastric junction cancer,thus leading to better prognosis for those patients.

Targeting tight junctions during epithelial to mesenchymal transition in human pancreatic cancer

Pancreatic cancer continues to be a leading cause of cancer-related death worldwide and there is an urgent need to develop novel diagnostic and therapeutic strategies to reduce the mortality of patients with this disease. In pancreatic cancer, some tight junction proteins, including claudins, are abnormally regulated and therefore are promising molecular targets for diagnosis, prognosis and therapy. Claudin-4 and-18 are overexpressed in human pancreatic cancer and its precursor lesions. Claudin-4 is a high affinity receptor of Clostridium perfringens enterotoxin(CPE). The cytotoxic effects of CPE and monoclonal antibodies against claudin-4 are useful as novel therapeutic tools for pancreatic cancer. Claudin-18 could be a putative marker and therapeutic target with prognostic implications for patients with pancreatic cancer. Claudin-1,-7, tricellulin and marvelD3 are involved in epithelial to mesenchymal transition(EMT) of pancreatic cancer cells and thus might be useful as biomarkers during disease. Protein kinase C is closely related to EMT of pancreatic cancer and regulates tight junctions of normal human pancreatic duct epithelial cells and the cancer cells. This review focuses on the regulation of tight junctions via protein kinase C during EMT in human pancreatic cancer for the purpose of developing new diagnostic and therapeutic modalities for pancreatic cancer.

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.

Association of anastomotic leakage with long-term oncologic outcomes of patients with esophagogastric junction cancer

BACKGROUND Despite improvements in surgical procedures and peri-operative patients management,the postoperative complications in esophagogastric junction(EGJ)cancer remain high because of technical aspects.Several studies have indicated the negative influence of postoperative infectious complications on long-term survival after gastrointestinal surgery.However,no study has shown the association between postoperative complications and long-term survival of patients with EGJ cancer.AIM To elucidate influence of postoperative complications on the long-term outcomes of patients with EGJ cancer.METHODS A total of 122 patients who underwent surgery for EGJ cancer at the Keio University were included in this study.We examined the association between complications and long-term oncologic outcomes.RESULTS In all patients,the 3-year overall survival(OS)rate was 71.9%,and the recurrencefree survival(RFS)rate was 67.5%.Compared with patients without anastomotic leakage,those with anastomotic leakage had poor median OS(8 mo vs not reached,P=0.028)and median RFS(5 mo vs not reached,P=0.055).Among patients with cervical anastomosis,there were not significant differences between patients with and without anastomotic leakage.However,among patients who underwent intrathoracic anastomosis,patients with anastomotic leakage had significantly worse OS(P=0.002)and RFS(P=0.005).CONCLUSION Anastomotic leakage was significantly associated with long-term oncologic outcomes of patients with EGJ cancer,especially those who underwent intrathoracic anastomosis.Cervical anastomosis with subtotal esophagectomy may be an option for the patients who are at high risk for anastomotic leakage.

Non-junctional Cx32 mediates anti-apoptotic and pro-tumor effects via epidermal growth factor receptor in human cervical cancer cells

OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.

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.

Transthoracic vs transhiatal surgery for cancer of the esophagogastric junction:A meta-analysis

AIM:To compare the efficacy and safety of the transthoracic and transhiatal approaches for cancer of the esophagogastric junction.METHODS:An electronic and manual search of the literature was conducted in PubMed,EmBase and the Cochrane Library for articles published between March1998 and January 2013.The pooled data included the following parameters:duration of surgical time,blood loss,dissected lymph nodes,hospital stay time,anastomotic leakage,pulmonary complications,cardiovascular complications,30-d hospital mortality,and long-term survival.Sensitivity analysis was performed by excluding single studies.RESULTS:Eight studies including 1155 patients with cancer of the esophagogastric junction,with 639 patients in the transthoracic group and 516 in the transhiatal group,were pooled for this study.There were no significant differences between two groups concerning surgical time,blood loss,anastomotic leakage,or cardiovascular complications.Dissected lymph nodes also showed no significant differences between two groups in randomized controlled trials(RCTs)and nonRCTs.However,we did observe a shorter hospital stay(WMD=1.92,95%CI:1.63-2.22,P<0.00001),lower30-d hospital mortality(OR=3.21,95%CI:1.13-9.12,P=0.03),and decreased pulmonary complications(OR=2.95,95%CI:1.95-4.45,P<0.00001)in the transhiatal group.For overall survival,a potential survival benefit was achieved for typeⅢtumors with the transhiatal approach.CONCLUSION:The transhiatal approach for cancers of the esophagogastric junction,especially typesⅢ,should be recommended,and its long-term outcome benefits should be further evaluated.

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.

Total esophagogastrectomy plus extended lymphadenectomy with transverse colon interposition:A treatment for extensive esophagogastric junction cancer

AIM:To review the post-operative morbidity and mortality of total esophagogastrectomy(TEG) with second barrier lymphadenectomy(D2) with interposition of a transverse colon and to determine the oncological outcomes of TEG D2 with interposition of a transverse colon.METHODS:This study consisted of a retrospective review of patients with a cancer diagnosis who underwent TEG between 1997 and 2013. Demographic data,surgeryprotocols,complications according to Clavien-Dindo classifications,final pathological reports,oncological follow-ups and causes of death were recorded. We used the TNM 2010 and Japanese classifications for nodal dissection of gastric cancer. We used descriptive statistical analysis and Kaplan-Meier survival curves. A P-value of less than 0.05 was considered statistically significant.RESULTS:The series consisted of 21 patients(80.9% men). The median age was 60 years. The 2 main surgical indications were extensive esophagogastric junction cancers(85.7%) and double cancers(14.2%). The mean total surgery time was 405 min(352-465 min). Interposition of a transverse colon through the posterior mediastinum was used for replacement in all cases. Splenectomy was required in 13 patients(61.9%),distal pancreatectomy was required in 2 patients(9.5%) and resection of the left adrenal gland was required in 1 patient(4.7%). No residual cancer surgery was achieved in 75.1% of patients. A total of 71.4% of patients had a postoperative complication. Respiratory complications were the most frequently observed complication. Postoperative mortality was 5.8%. Median follow-up was 13.4 mo. Surgery specific survival at 5 years of follow-up was 32.8%; for patients with curative surgery,it was 39.5% at 5 years.CONCLUSION:TEG for cancer with interposition of a transverse colon is a very complex surgery,and it presents high post-operative morbidity and adequate oncological outcomes.

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.

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.