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.

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.

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.

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.

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.

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.

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.

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.

CHARACTERISTICS OF MUCINS AND CEA IN GLOBOID DYSPLASTIC CELLS OF HUMAN STOMACH AND ITS RELATIONSHIP WITH SIGNET RING CELL CARCINOMA

Fourty-three cases of globoid dysplasia and signet ring cell carcinoma were stained by mucin and CEA (ABC method). It was found that there were three kinds of mucins (neutral, sialo and sulphomucin in both globoid dysplastic cells and signet ring cells. The percentages of the three kinds of mucins seen in the two kinds of cells were not much different. It was indicated that the altered mucins in the gastric epithelial cells must be a sign of dedifferentiation of the cells and the results of malfunction. The globoid dysplasia type I mainly contained neutral mucin, whereas type II, the acid mucin was predominant, especially the sulphomucin. The CEA positive reaction became stronger as the atypia being remarkable, and the characteristics of distribution of CEA positive particles were similar in the two kinds of cells namely, randomly or disorderly in the cells. Based on the analysis of the results, a conclusion can be made that the variety of mucins in globoid dysplastic cells can be used as a reference point in classification and is not much significant in grading, but the amount of CEA positive matter can be a reference point in grading. The globoid dysplasia is such a lesion with special features in morphology and function manifested in the process of de-differentiation towards signet ring cell carcinoma following the successive action of carcinogens upon the cells of gastric epithelium.

Primary signet ring cell carcinoma of prostate (report of 2 cases)

Objective To study the clinical features of primary signet ring cell carcinoma of prostate. Methods 2 cases of primary signet ring cell carcinoma of the prostate were studied and reviewed. Results The age of the 2 patients was 64 and 73. The clinical symptoms were dysuria, vesical irritability and perineum discomfort. Histologically, signet ring cell carcinoma was composed of round cells with abundant clear cytoplasm and crescent-shaped nuclei on one side. Mitosis were frequently observed. Immunohistochemical testing showed the cancer cell was positive for prostate specific antigen (PSA.), prostate acid phosphatase ( PAP ), AR, cytokeratin and negative for caicinoernbryonic antigen (CEA), alcian blue/ periodic arid-schiff (AB/PAS). One case (stage D) died 6 months after bilateral orchiectomy and flutamide therapy because of wide-spead metastasis; the other (stage B2) has been surviving 25 months after radical prostatectomy, bilateral orchiectomy, endocrine therapy and local irradiation ministration.

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.

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.

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.

Signet Ring Cell Carcinoma of Ampulla of Vater: Report of a Rare Malignancy and Literature Review

Introduction: Signet ring cell carcinoma is a rare tumor that generally originates in the gastrointestinal tract. Signet-ring cell carcinoma of the ampulla of Vater is extremely uncommon and a very rare clinical entity, which is infrequently reported in medical literature and only 31 cases have been mentioned. Most tumors affecting Vater’s Ampulla are adenocarcinomas and other histological variants are less frequent. It mainly occurs in elderly patients. Case Presentation: We report a case of signet ring cell carcinoma of Vater’s Ampulla. The tumour had infiltrated the duodenal, but local lymph nodes were clear (T3N0M0). Duodenopancreatectomy with pylorus preservation is the treatment of choice. Conclusions: Etiology and survival are not well-defined in the literature due to the extreme rarity of this disease.