Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review

BACKGROUND Upper gastrointestinal(GI)signet ring cell carcinomas(SRCC)confer a poor prognosis.The benefit of operative intervention for this patient group is contro-versial in terms of overall survival.AIM To investigate factors relating to survival in patients with upper GI SRCC.METHODS A retrospective,tertiary,single-centre review of patients who were diagnosed with oesophageal,gastroesophageal junction and gastric SRCC was performed.The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management.Secon-dary outcomes included assessing the relationship between demographic and histopathological factors,and survival.RESULTS One hundred and thirty-one patients were included.The one-year survival for the operative group was 81%and for the nonoperative group was 19.1%.The five-year survival in the operative group was 28.6%vs 1.5%in the nonoperative group.The difference in overall survival between groups was statistically significant(HR 0.19,95%CI(0.13-0.30),P<0.001).There was no difference in survival when ad-justing for age,smoking status or gender.On multivariate analysis,patients who underwent surgical management,those with a lower stage of disease,and those with a lower Charlson Comorbidity Index(CCI)had significantly improved sur-vival.CONCLUSION Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery.Offering surgery to a carefully selected patient group may improve the outcome for this disease.

Endoscopic submucosal dissection for early signet ring cell gastric cancer:A systematic review and meta-analysis

BACKGROUND The use of endoscopic submucosal dissection(ESD)for treating early signet ring cell carcinoma(SRC)is controversial due to the risk of lymph node metastasis.AIM To carry out a meta-analysis to evaluate ESD for therapeutic efficacy and safety in early signet ring cell gastric cancer.METHODS The PubMed,Web of Science,Cochrane Library,and EMBASE databases were used to search for relevant studies evaluating the therapeutic efficacy and safety of ESD in SRC.The rates of recurrence,complete resection,incomplete resection,curative resection,en bloc resection,and adverse events were extracted and analyzed.The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale.Publication bias was evaluated by the Egger’s test.Institutional review board approval and written consent were not needed for this report.RESULTS This meta-analysis enrolled seven studies with 653 participants undergoing ESD treatment for early SRC.The overall recurrence rate was 0.010[95%confidence interval(CI):0.000-0.040,Z=1.422,P=0.155].The total lymph-ovascular invasion rate was 0.038(95%CI:0.007-0.088,Z=3.026,P=0.002).The total en bloc resection rate was estimated at 0.984(95%CI:0.925-1.000,Z=19.463,P=0.000).The total complete and incomplete resection rates were estimated at 0.785(95%CI:0.596-0.928,Z=9.789,P=0.000)and 0.188(95%CI:0.016-0.468,Z=2.531,P=0.011),respectively.The total procedureassociated gastric hemorrhage and perforation rates were estimated at 0.026(95%CI:0.005-0.061,Z=3.006 P=0.003)and 0.004(95%CI:0.000-0.028,Z=0.938,P=0.348),respectively.The curative resection,vertical margin invasion,and lateral margin invasion rates were 72.1%(145/341),2.3%(8/348),and 34.45%(41/119),respectively.CONCLUSION ESD constitutes a promising therapeutic approach for early undifferentiated SRC gastric cancer.However,further improvements are required for increasing its treatment efficacy and reducing adverse outcomes.

DISTRIBUTION AND ULTRASTRUCTURAL LOCALIZATION OF CARCINOEMBRYONIC ANTIGEN (CEA) IN SIGNET RING CELLS OF GASTRIC CANCER

The distribution and ultrastructural localization of CEA in signet-ring cells of 15 gastric cancer specimens were observed by PAP and immunoelectron microscopic methods. The mechanism of abnormal distribution of CEA in the signet-ring cell and its biological significance are discussed. The results showed that the CEA positive rate in signet-ring cells was 100% with the polarity lost in distribution. Under the light microscope, the CEA stain patterns were of two types: cytoplasmic and membranous types. The former was predominant. Under the electron microscope, most of the CEA was distributed on the cell membrane and cytoplasm. CEA was found in intracellular membranous structure of the cancer cells, especially in protein synthesis and transport organellae (RER, Golgi Complex etc.). The synthesis of CEA in cancer cells increased, yet its elimination was somewhat hampered. The result was that the RER became extended and were full of CEA (+) material. In the free signet-ring cell, there was a small and short contact plane. The tight junction was severed as the cell junction reduced. The antigenic determinant of CEA was glycoprotein. The abnormal distribution of CEA in signet-ring cells might be the morphologic reflection of the glycosylation of surface glycoprotein of tumor cells.

Adenosquamous carcinoma may have an inferior prognosis to signet ring cell carcinoma in patients with stages Ⅰ and Ⅱ gastric cancer

BACKGROUND Primary gastric adenosquamous carcinoma(ASC)is an exceedingly rare histological subtype.Gastric signet ring cell carcinoma(SRC)is a unique subtype with distinct tumor biology and clinical features.The prognosis of gastric ASC vs SRC has not been well established to date.We hypothesized that further knowledge about these distinct cancers would improve the clinical management of such patients.AIM To investigate the clinicopathological characteristics and prognosis of gastric ASC vs SRC.METHODS A cohort of gastric cancer patients was retrospectively collected from the Surveillance,epidemiology,and end results program database.The 1:4 propensity score matching was performed among this cohort.The clinicopathological features and prognosis of gastric ASC were compared with gastric SRC by descriptive statistics.Kaplan-Meier method was utilized to calculate the median survival of the two groups of patients.Cox proportional hazard regression models were used to identify prognostic factors.RESULTS Totally 6063 patients with gastric ASC or SRC were identified.A cohort of 465 patients was recruited to the matched population,including 370 patients with SRC and 95 patients with ASC.Gastric ASC showed an inferior prognosis to SRC after propensity score matching.In the post-matching cohort,the median cancer specific survival was 13.0(9.7-16.3)mo in the ASC group vs 20.0(15.7-24.3)mo in the SRC group,and the median overall survival had a similar trend(P<0.05).ASC and higher tumor-node-metastasis stage were independently associated with a poor survival,while radiotherapy and surgery were independent protective factors for improved prognosis.Subgroup survival analysis revealed that the prognosis of ASC was inferior to SRC only in stages I and II patients.CONCLUSION ASC may have an inferior prognosis to SRC in patients with stages I and II gastric cancer.Our study supports radiotherapy and surgery for the future management of this clinically rare entity.

Prognostic nomograms for predicting overall survival and causespecific survival of signet ring cell carcinoma in colorectal cancer patients

BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.

Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment.Clinical and pathological information were obtained from the medical records.Gene expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA.Tissue microarrays were constructed from 368 gastric cancer patients.Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity.Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer cases.PKM2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones.Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive cells.Importantly,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION:PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas.Its function and potential as a prognostic marker should be further verified in gastric cancer.

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P<0.001).The 3-year CSS rate in the A/P≤0.5 group was significantly greater than that in the A/P>0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

Prognostic significance of preoperative lymphocyte to monocyte ratio in patients with signet ring gastric cancer

BACKGROUND The ratio of lymphocytes to monocytes(LMR)has been shown to be an effective predictor of gastric cancer prognosis.However,its predictive accuracy for signet ring gastric cancer is currently not well understood.AIM To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer.METHODS A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University,Department of Gastrointestinal Surgery,from January 2012 to December 2016 were enrolled in the study.The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic.Factors that significantly affect the survival of patients were identified using single factor analysis,and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis.RESULTS The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors,including tumor invasion(χ^(2)=49.726;P<0.001),lymph node metastasis(χ^(2)=30.269;P<0.001),pTNM stage(χ^(2)=49.322;P<0.001),surgical approach(χ^(2)=8.489;P=0.004),age(t=-2.213;P<0.028),carcinoembryonic antigen(CEA)(Z=-3.265;P=0.001),platelet-to-lymphocyte ratio(Z=-2.196;P=0.028),LMR(Z=-2.226;P=0.026),ALB(t=3.284;P=0.001),prognostic nutritional index(t=-3.789;P<0.001)and FIB(Z=-3.065;P=0.002).Furthermore,the multivariate analysis further demonstrated that age(HR:0.563,95%CI:0.363-0.873),tumor invasion depth(HR:0.226,95%CI:0.098-0.520),pTNM stage(HR:0.444,95%CI:0.255-0.771),preoperative CEA level(HR:0.597,95%CI:0.386-8.790),and preoperative LMR level(HR:1.776,95%CI:1.150-2.741)were independent factors influencing the prognosis of signet ring gastric cancer.CONCLUSION In signet ring gastric cancer patients,a low preoperative LMR level predicts poor prognosis.The death risk ratio of the low LMR group compared to the high LMR group is 1.776.

BRAF mutation in colorectal carcinomas with signet ring cell component

Objective:Signet ring cell carcinoma is a rare subtype of colorectal carcinoma(CRC)with an associated BRAFV600E mutation.We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters.Methods:According to the presence of signet ring cell component,tumors were categorized into groups as follows:0%–9%,10%–24%,25%–49%,and>50%.Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism.Eleven of 28 cases(39.3%)showed BRAFV600E mutation,which was also confirmed by Sanger sequencing.To elucidate the importance of existence of signet ring cell component at the molecular level,we separated cases into two groups with cut-off levels of 10%and 50%,which pertain to percentages of signet ring cells.Results:Seven of 19 cases(36.8%)under the threshold of 50%and four of nine cases(44.4%)over this threshold value demonstrated BRAF mutation.Three of 7 cases(42.8%)featuring<10%signet ring cell component and eight out of 21 cases(38.1%)showing>10%were BRAF mutated.Conclusions:BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.

Microangiopathic Hemolytic Anemia and Diffuse Bone Metastasis by Signet Ring Cell Adenocarcinoma

Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome and is typically associated with gastric adenocarcinoma. We report a 47-year-old woman who presented with asthenia, lower back pain and bleeding. Twelve years ago the patient underwent total gastrectomy due to gastric adenocarcinoma and achieved complete remission. The patient was diagnosed with MAHA and diffuses bone metastasis of signet ring cell adenocarcinoma of unknown origin and was treated successfully with polichemotherapy based on cisplatin and 5-fluorouracil.

Signet ring cell carcinoma hidden beneath large pedunculated colorectal polyp:A case report

BACKGROUND Large pedunculated colorectal polyps are not frequent among colonic polyps.We present a clinical case of a large pedunculated colorectal polyp with signet ring cell cancer infiltrating the submucosa and lymph node invasion in a patient who ultimately underwent additional surgery.Clinicians should attach importance to pedunculated colorectal polyps and choose the most appropriate therapy.CASE SUMMARY A 52-year-old female farmer underwent routine screening colonoscopy and denied constipation,diarrhea,hematochezia,or other gastrointestinal symptoms.Her past medical history and general biochemical examination results were unremarkable.During the colonoscopy,a 25-mm pedunculated polyp in the sigmoid colon was identified.The superficial epithelium was macroscopically congestive,rough,and granular,showing characteristic features of adenoma.We first ligated the root of the pedunculated polyp using nylon loops as well as a titanium clip.Histopathological examination revealed high-grade intraepithelial neoplasia of the tumor surface and a negative margin with signet ring cell adenocarcinoma infiltrating the submucosal layer.The deepest infiltration was approximately 0.9 cm from the tumor surface and 0.55 cm from the stratum basale.We performed radical resection of the left colon with lymph node dissection after two weeks.The lesion was completely resected,and pathological assessment revealed signet ring cell adenocarcinoma infiltrating the submucosal layer as well as lymph node invasion(stage PT1N1M0 and grade IIIA in pathological grading,NRAS-,BRAF V600E-,KRAS-).CONCLUSION This case highlights the importance of paying attention to the malignancy of large pedunculated polyps.Polyps or adenomas removed via endoscopy must be evaluated histologically.Even if adenomas may be fragile,endoscopy doctors should still remove polyps as completely as possible and choose perpendicular sections through the stalk and base to fix by formaldehyde solution.

Diffuse invasive signet ring cell carcinoma in total colorectum caused by ulcerative colitis:A case report and review of literature

BACKGROUND Diffuse invasive signet ring cell carcinoma of the colorectum is extremely rare clinically.This type of colorectal cancer has certain clinical,pathological and biological characteristics that are different from ordinary colorectal cancer.CASE SUMMARY A 31-year-old young woman was admitted to the hospital for nearly 1 wk due to recurrent symptoms of mucopurulent bloody stools and abdominal distension.Preoperative colonoscopy showed a ring-shaped intestinal wall mass 10 cm from the rectum to the anus.Three pieces of tumor tissue were removed for examination.The pathological results showed rectal mucinous adenocarcinoma.The patient underwent laparoscopic exploration under general anesthesia,and then laparoscopic total colorectal resection,ileal pouch–anal anastomosis and ileostomy were performed.The patient was switched to a FOLFOX+cetuximab regimen.After the fifth cycle,the patient was unable to tolerate further treatment due to tumor progression and multiple organ dysfunction,and died at the end of May 2020.Overall survival was 7 mo.CONCLUSION Carcinogenesis of ulcerative colitis is different from sporadic colon cancer,and the overall prognosis is extremely poor.

Diagnosis of small intramucosal signet ring cell carcinoma of the stomach by non-magnifying narrow-band imaging: A pilot study

AIM: To examine the efficacy of non-magnifying narrow-band imaging(NM-NBI) imaging for small signet ring cell carcinoma(SRC).METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection(ESD) and 14 randomly selected whitish gastric ulcer scars(control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging(WLI) were assessed with Image J(NIH, Bethesda).RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index(P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle(C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs(P = 0.001). According to the receiveroperating characteristic analysis, the resulting cut-off value of the circularity index(C-index) for SRC was 0.60(85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar(OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009).CONCLUSION: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.

Neoadjuvant chemotherapy vs upfront surgery for gastric signet ring cell carcinoma:A retrospective,propensity score-matched study

BACKGROUND The benefit of neoadjuvant chemotherapy for patients with signet-ring cell carcinoma of the stomach is controversial.AIM To evaluate the perioperative and long-term outcomes of neoadjuvant chemotherapy for locally advanced gastric signet-ring cell carcinoma.METHODS This retrospective study identified patients with locally advanced signet-ring cell carcinomas of the stomach(cT3/4 and cN any)diagnosed from January 2012 to December 2017 by using the clinical Tumor-Node-Metastasis(cTNM)staging system.We performed 1:1 propensity score matching(PSM)to reduce bias in patient selection.The histologic and prognostic effects of neoadjuvant chemotherapy were assessed.The overall survival rates were used as the outcome measure to compare the efficacy of neoadjuvant chemotherapy vs surgery-first treatment in the selected patients.RESULTS Of the 144 patients eligible for this study,36 received neoadjuvant chemotherapy,and 108 received initial surgery after diagnosis.After adjustment by PSM,36 pairs of patients were generated,and baseline characteristics,including age,sex,American Society of Anesthesiologists score,tumor location,and cTNM stage,were similar between the two groups.The R0 resection rates were 88.9%and 86.1%in the surgery-first and neoadjuvant chemotherapy groups after PSM,respectively(P=1.000).The median follow-up period was 46.4 mo.The 5-year overall survival rates of the neoadjuvant chemotherapy group and surgery-first group were 50.0%and 65.0%(P=0.235),respectively,before PSM and 50%and 64.7%(P=0.192),respectively,after PSM.Multivariate analyses conducted before and after PSM showed that NAC was not a prognostic factor.CONCLUSION Neoadjuvant chemotherapy provides no survival benefit in patients with locally advanced gastric signet-ring cell carcinoma.For resectable gastric signet-ring cell carcinoma,upfront surgery should be the primary therapy.

Development and validation of prognostic nomogram based on log odds of positive lymph nodes for patients with gastric signet ring cell carcinoma

Objective: Our aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma(SRC), for individualized prediction of overall survival(OS) rate and cancer-specific survival(CSS).Methods: We selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results(SEER) database, and then randomly partitioned them into a training cohort and a validation cohort.Independent predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index(C-index), receiver operating characteristics(ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement(IDI), net reclassification improvement(NRI) and decision curve analysis(DCA) were used to assess clinical utility of our nomogram models.Results: Six independent predicted indicators, age, race, log odds of positive lymph nodes(LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer(AJCC) 8 th edition tumor-node-metastasis(TNM) staging system(0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging system.Conclusions: The novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8 th edition TNM staging system alone.

Lymph Node Metastasis in Early Signet Ring Cell Carcinoma:Endoscopic Mucosal Resection

Objective： To identify clinicopathological factors predictive of lymph node metastases （LNM） in early signet ring cell carcinoma （SRC）, and further to expand the possibility of using endoscopic mucosal resection （EMR） for the treatment of early SRC. Methods： Data from 27 surgically treated patients with early SRC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Results： In the univariate analysis, a tumor larger than 3.0 cm, submucosal invasion, and the presence of lymphatic vessel involvement （LVI） were significantly associated with a higher rate of LNM （all P〈0.05）. In the multivariate model, the presence of LVI was found of to be an independent pathological risk factor for LNM. There was no LNM in 14 patients without the three clinicopathological risk factors （a tumor larger than 3.0 cm, submucosal invasion, and the presence of LVI）. Conclusion： EMR alone may be sufficient treatment for intramucosal early SRC if the tumor is less than or equal to 3.0 cm in size, and when LVI is absent upon postoperative histological examination. When specimens show LVI, an additional radical gastrectomy with lymphadenectomy should be recommended.

Clinicopathological characteristics and prognosis of gastric signet ring cell carcinoma

BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma(GSRC)remain controversial,particularly with regard to sensitivity to postoperative adjuvant therapy.AIM To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.METHODS By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance,Epidemiology and End Results,and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University,we analyzed the general pathological characteristics of GSRC by the chi-square test.Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma.The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma.The prognosis model of advanced GSRC was established with R software,and the area under curve(AUC)and C-index were used to assess the accuracy of the model.RESULTS Analysis of pathological features revealed that signet ring-cell carcinoma(SRC)was more frequently seen in younger(<60 years),female,and White patients compared to non-SRC patients.SRC was less commonly associated with early gastric cancer(EGC)(23.60%vs 39.10%),lower N0(38.61%vs 61.03%),and larger tumour sizes>5 cm(31.15%vs 27.10%)compared to the differentiated type,while the opposite was true compared to the undifferentiated type.Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients.In contrast,among advanced gastric cancer(AGC)patients,the prognosis of SRC patients was correlated with age,race,tumour size,AJCC stage,T-stage,and postoperative adjuvant therapy.The predictive model showed that the 3-year AUC was 0.787,5-year AUC was 0.806,and C-index was 0.766.Compared to non-SRC patients,patients with SRC had a better prognosis in EGC[hazard ratio(HR):0.626,95%confidence interval(CI):0.427-0.919,P<0.05]and a worse prognosis in AGC(HR:1.139,95%CI:1.030-1.258,P<0.05).When non-SRC was divided into differentiated and undifferentiated types for comparison,it was found that in EGC,SRC had a better prognosis than differentiated and undifferentiated types,while there was no significant difference between differentiated and undifferentiated types.In AGC,there was no significant difference in prognosis between SRC and undifferentiated types,both of which were worse than differentiated types.A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival(34.6%and 36.2%vs 18.6%,P<0.05).CONCLUSION The prognosis of SRC is better than that of undifferentiated type,especially in EGC,and its prognosis is even better than that of differentiated type.SRC patients can benefit from early detection,surgical resection,and aggressive adjuvant therapy.

Identification of key genes and pathways in gastric signet ring cell carcinoma based on transcriptome analysis

BACKGROUND Gastric signet ring cell carcinoma(GSRCC)is one of the most malignant tumors.It has the features of high invasiveness,rapid progression,and resistance to chemotherapy.However,systematic analyses of mRNAs have not yet been performed for GSRCC.AIM To identify key mRNAs and signaling pathways in GSRCC.METHODS A transcriptome analysis of two GSRCC and two non-GSRCC samples was performed in this study.Differentially expressed mRNAs and pathways were identified based on the KEGG and PANTHER pathway annotations.The interactive relationships among the differential genes were mapped with the STRING database.Quantitative real-time polymerase chain reaction was used to validate the key gene expression in GSRCC.RESULTS About 1162 differential genes(using a 2-fold cutoff,P<0.05)were identified in GSRCC compared with non-GSRCC.The enriched KEGG and PANTHER pathways for the differential genes included immune response pathways,metabolic pathways,and metastasis-associated pathways.Ten genes(MAGEA2,MAGEA2B,MAGEA3,MAGEA4,MAGEA6,MUC13,GUCA2A,FFAR4,REG1A,and REG1B)were identified as hub genes in the protein-protein interaction network.The expression levels of five genes(MAGEA2,MAGEA3,MAGEA4,MAGEA6,and REG1B)showed potential clinical value.CONCLUSION We have identified the potential key genes and pathways in GSRCC,and these hub genes and pathways could be diagnostic markers and therapeutic targets for GSRCC.

Clinical significance of signet ring cells in surgical esophageal and esophagogastric junction adenocarcinoma:A systematic review and meta-analysis

BACKGROUND The clinical significance of signet ring cells(SRCs)in surgical esophageal and esophagogastric junction adenocarcinoma(EEGJA)remains unclear now.AIM To explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies.METHODS The PubMed,Web of Science,and EMBASE electronic databases were searched for the relevant literature up to March 28,2021.The relative risk(RR)with 95%confidence interval(CI)was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients,and the hazard ratio(HR)with 95%CI was calculated to explore the impact of SRC on the prognosis.All statistical analyses were conducted with STATA 12.0 software.RESULTS A total of ten articles were included,involving 30322 EEGJA patients.The pooled results indicated that the presence of SRCs was significantly associated with tumor location(RR:0.76,95%CI:0.61-0.96,P=0.022;I2=49.4%,P=0.160)and tumor-node-metastasis stage(RR:1.30,95%CI:1.02-1.65,P=0.031;I2=73.1%,P=0.002).Meanwhile,the presence of SRCs in surgical EEGJA patients predicted a poor overall survival(HR:1.36,95%CI:1.12-1.65,P=0.002;I2=85.7%,P<0.001)and disease-specific survival(HR:1.86,95%CI:1.55-2.25,P<0.001;I2=63.1%,P=0.043).CONCLUSION The presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients.However,more high-quality studies are still needed to verify the above findings.

Log odds of positive lymph nodes is a better prognostic factor for oesophageal signet ring cell carcinoma than N stage

BACKGROUND Signet ring cell carcinoma is a rare type of oesophageal cancer,and we hypothesized that log odds of positive lymph nodes(LODDS)is a better prognostic factor for oesophageal signet ring cell carcinoma.AIM To explore a novel prognostic factor for oesophageal signet ring cell carcinoma by comparing two lymph node-related prognostic factors,log odds of positive LODDS and N stage.METHODS A total of 259 cases of oesophageal signet ring cell carcinoma after oesophagectomy were obtained from the Surveillance,Epidemiology,and End Results database between 2006 and 2016.The prognostic value of LODDS and N stage for oesophageal signet ring cell carcinoma was evaluated by univariate and multivariate analyses.The Akaike information criterion and Harrell’s C-index were used to assess the value of two prediction models based on lymph nodes.External validation was performed to further confirm the conclusion.RESULTS The 5-year cancer-specific survival(CSS)and 5-year overall survival(OS)rates of all the cases were 41.3%and 27.0%,respectively.The Kaplan-Meier method showed that LODDS had a higher score of log rank chi-squared(OS:46.162,CSS:41.178)than N stage(OS:36.215,CSS:31.583).Univariate analyses showed that insurance,race,T stage,M stage,TNM stage,radiation therapy,N stage,and LODDS were potential prognostic factors for OS(P<0.1).The multivariate Cox regression model showed that LODDS was an significant independent prognostic factor for oesophageal signet ring carcinoma patients after surgical resection(P<0.05),while N stage was not considered to be a significant prognostic factor(P=0.122).Model 2(LODDS)had a higher degree of discrimination and fit than Model 1(N stage)(LODDS vs N stage,Harell’s C-index 0.673 vs 0.656,P<0.001;Akaike information criterion 1688.824 vs 1697.519,P<0.001).The results of external validation were consistent with those in the study cohort.CONCLUSION LODDS is a superior prognostic factor to N stage for patients with oesophageal signet ring cell carcinoma after oesophagectomy.