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.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

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.

Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge

While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.

Signet-ring cell carcinoma arising from a fundic gland polyp in the stomach

Fundic gland polyps(FGPs)are currently the most common type of gastric polyps and are usually benign.However,although rare,gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma.Here we report the first case of a49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach.The tumor was completely excised by endoscopic snare polypectomy.FGPs should therefore be evaluated for malignant changes although they occur rarely,if the FGP has an erosive or irregular surface.

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.

Early-stage primary signet ring cell carcinoma of the colon

Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its progno-sis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the co-lon. Colonoscopic examination revealed a Ⅱa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen re-vealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant me-tastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node me-tastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature

A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H^+/K^+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.

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.

Primary signet ring cell carcinoma of the appendix: A rare case report

Primary adenocarcinoma of the appendix is a rare malignancythat constitutes < 0.5% of all gastroin-testinalneoplasms. Moreover, primary signet ring cell carcinomaof the appendix is an exceedingly rare entity. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastasesand unresectable peritoneal dissemination occurring in a 45-year-old female patient. She was clinically misdiagnosed as torsion of ovarian cyst. She underwent appendicectomy and unilateral salpingooophorectomy.Histopathology revealed signet ring cell carcinoma and a right hemicolectomy was done. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-fluorouracil, and leucovorin(FOLFOX-4). The patient is doing well till today on follow up without progression of disease 10 mo after beginning chemotherapy.

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.

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Objective： To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma （MGC） and signet-ring cell carcinoma （SRCC）. Methods： Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using Z2 test. Survival was analyzed using the Kaplan- Meier method and multivariate analysis of Cox proportional hazards regression model （backward, stepwise）. Results： A total of 181 patients with gastric cancer （74 MGC, 107 SRCC） were included. MGC, when compared with SRCC, was featured by senile patients, stage III and I~, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion （P〈0.05）. The overall 5-year survival rate showed no difference between the two groups （48.8% vs. 44.8%, P〉0.05）. However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age 〈60 years, negative distant metastasis, and tumor localized at upper third stomach （P〈0.05）. Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions： While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.

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.

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.

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.

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.

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.

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.