Signet Ring Cell Cancer Research Articles

Early onset Colorectal Cancer and its association with its histological subtypes.

There are different clinicopathological features between early and late onset colorectal cancer. We aimed to characterize the histological features of colorectal cancer (CRC) at different age groups in our institution. Total 232 patients with histologically proven colorectal cancer between ages 13-99 were included. This is retrospective study. Data collected from tumour registry Shifa International Hospital from January 1st 2018 to December 31st 2020. Pearson Chi square test was used for significance of categorical variables. P-values less than 0.05 were considered significant. Mean age at diagnosis was 55.49+/-16.43 years. Out of total 232 patients 58.6% were male and 41.3% were females (p value= 0.16). 150 (64.9%) were aged > 50 years and 81 (35.1%) were age < or equal to 50 years (p value = 0.44). Most common histological subtype was adenocarcinoma that was found in 188 (81%) cases. One hundred fifty five (66.8%) patients had Grade-II tumor, 67(28.9%) with Grade-III and 10 (4.3%) with Grade-I tumor. Fifty eight (25%) patients presented with metastatic disease. A significantly higher percentage of patients with signet ring cell cancer presented with a high-grade tumor when compared with patients with adenocarcinoma and mucinous carcinoma (93.7% vs 21.8%, p-value- <0.001%; 93.7% vs 39.2%, p-value <0.001). A significantly higher percentage of patients with mucinous adenocarcinoma and signet ring cell carcinoma presented at age less than 50 as compared to those with adenocarcinoma (60.7%, 56.2% and 30.8% respectively; p-value <0.05). This study signifies that mucinous and signet ring cell type CRC present at an early age and with a higher proportion of patients with high tumour grade. Early diagnosis is key to help improve outcomes in these patients.

KRAS mutations and their prognostic implications in appendiceal cancers.

4177 Background: Despite shared embryonic origin, appendiceal cancers (AC) have distinct clinical and molecular features compared to colorectal cancers (CRC). Detection of mutant KRAS has been associated with worse survival in CRC, whereas in AC the prognostic significance of mutant KRAS (55-65% prevalence) has yet to be characterized. Methods: AC tissues from 852 individual patients that underwent DNA (592, NextSeq, or whole exome sequencing) and whole transcriptome sequencing (NovaSeq) at Caris Life Sciences (Phoenix, AZ) were analyzed. Low-grade appendiceal mucinous neoplasms were excluded. Chi-square, Fishers-exact, and Mann Whitney U tests were used to determine statistical significance and were adjusted for multiple hypothesis testing (p&lt; 0.05). Real-world overall survival (OS) was calculated using insurance claims of AC patients from time of sample collection to last contact. Hazard ratios (HRs) were calculated using the Cox proportional hazards model (log-rank test). Multivariate regression analysis was performed on age, sex, histology, site, comutations and KRASmut vs. KRASwt. Results: AC histological subtypes comprised mucinous adenocarcinoma (37.9%), goblet cell carcinoma (19.6%), signet ring cell carcinoma (12.1%), and adenocarcinoma- not otherwise specified (NOS, 30.4%). Among all AC specimens, KRAS was the most common mutation (49%). KRASmut vs. KRASwt tumors were more frequently associated with TP53mut (51.2% vs. 36.8%, respectively; p&lt; 0.01) and GNASmut (41.1% vs. 5.7%, respectively; p &lt; 0.00001). Most frequent co-mutant gene with KRAS was TP53 (61.2%) in adenocarcinoma-NOS, and GNAS (46.9%) in mucinous adenocarcinomas.Median OS among KRASmut vs. KRASwt was 33.3 vs. 25.1 months, respectively (HR 0.68, 95% CI: 0.58-0.80, p &lt; 0.00001). KRASmut was associated with improved survival in mucinous adenocarcinomas (HR 0.71; 95% CI: 0.52-0.96, p = 0.028) and adenocarcinoma-NOS (HR 0.77; 95% CI: 0.62-0.97, p = 0.025), but not with signet ring cell (HR 1.92; 95% CI: 0.90-4.10, p = 0.087) or goblet cell carcinoma (HR 1.39; 95% CI: 0.50-3.91, p = 0.536). Multivariate analysis showed KRASmut was an independent prognostic factor for improved survival among all AC (HR 0.77, 95% CI: 0.64-0.93, p = 0.007) and mucinous adenocarcinoma (HR 0.60, 95% CI: 0.42-0.84, p&lt;0.0001).Notably, GNASmut was associated with improved survival (HR 0.57, 95% CI: 0.47-0.70, p &lt; 0.00001), while TP53mut was associated with poorer survival (HR 1.58, 95% CI: 1.35-1.86, p &lt; 0.00001) among all AC. Conclusions: KRAS was one of most frequently mutated genes in ACs. In contrast to CRC, KRASmut was associated with significantly improved survival. This observed survival advantage remained consistent in the histologic subgroup of mucinous adenocarcinoma, but not in goblet and signet ring cell cancers. Further studies with population level data understanding the molecular profiles and their survival implications in histologically distinct AC are needed.

Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis.

e14683 Background: Checkpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies. Methods: We retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed. In our study, patients with grade 1 or grade 2 CIPs were defined as low-grade CIPs, and patients with grade 3, grade 4 or grade 5 CIPs were defined as high-grade CIPs. Results: The BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31-78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. Most of the patients were diagnosed with lung cancer (36 patients, 85.7%). There were 3 patients with esophageal squamous cell cancer, 1 patient with hepatic cell cancer, 1 patient with gastric signet ring cell cancer and 1 patient with pericardial malignant mesothelioma. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs. Conclusions: The CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.

Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis.

Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

Эндоскопическая семиотика гастритоподобной формы первичных неходжкинских лимфом желудка

Aim. To characterize the main differentially significant endoscopic features specific to the gastritis-like form of primary gastric non-Hodgkin lymphomas (NHL).&#x0D; Materials &amp; Methods. This prospective study analyzes the results of complex endoscopic diagnosis in 43 patients with primary gastric NHL. They were examined and treated at the NN Blokhin National Medical Cancer Research Center from 2019 to 2023. The patients were 30–70 years of age, those over the age of 50 predominated and accounted for 79 % (n = 34). There were 33 women and 10 men. The control group included 45 patients with gastritis-like malignant gastric tumors: adenocarcinoma and signet-ring cell cancer.&#x0D; Results. The morphological analysis yielded a diagnosis of MALT-lymphoma in 90.7 % (n = 39) and diffuse large B-cell lymphoma in 9.3 % (n = 4) of cases. Sensitivity, specificity, and accuracy of the clarification methods of complex endoscopic diagnosis were considerably higher compared to white-light mode examination. According to the results of complex endoscopic analysis, all patients were stratified into 4 groups with different types of H. pylori-induced atrophic gastritis (n = 10; 23.25 %), erosive gastritis (n = 10; 23.25 %), hyperplastic gastritis (n = 8; 18.6 %), and combined gastritis (n = 15; 34.9 %). The focus was laid on identifying the main differentially significant endoscopic features specific to the gastritis-like form of primary gastric NHL which distinguish it from the lesions in other malignant tumors.&#x0D; Conclusion. The complex examination using 4 concrete clarification methods of endoscopic diagnosis is indispensable to properly interpret the detected changes and timely diagnose the gastritis-like form of primary gastric NHL. These include narrow-band imaging (NBI/BLI and LCI), close-focus and magnification examinations, combined narrow-band imaging and magnification examination, as well as endosonography.

Pelvic exenterations combined with cytoreductions for T4 rectal cancers with peritoneal metastasis: a safety analysis.

Pelvic exenterations and cytoreduction are individually morbid procedures with oncological validity. The combination of these simultaneously in patients with rectal cancers has not been evaluated. The present study aimed to assess the surgical and survival outcomes of the combined procedure. Retrospective, single-centre analysis of consecutive patients that underwent pelvic exenterations and cytoreductions for advanced or recurrent rectal cancers with peritoneal metastasis between 2013 and 2022. The primary outcome measure for safety was major complications (≥Grade IIIA). The threshold for considering the procedure unsafe was set at 50% for the upper confidence limit of major morbidity. Overall and recurrence-free survival were also assessed. Thirty-nine patients underwent the combined procedure that included 24 total pelvic and 15 posterior pelvic exenterations. The median age of the cohort was 35 years, 18 (46.2%) had signet ring cell cancers, and eight patients (21%) had extraperitoneal disease as well. The median PCI was 4 and CC-0 was achieved in 38 patients (97.4%). Hyperthermic intraperitoneal chemotherapy was delivered in 15 patients, and four had placement of an intraperitoneal chemo port. Major complications were experienced by 7 patients (18%; 95% confidence interval: 7.5%-33.5%). Median recurrence-free and overall survivals were 9 and 17 months, respectively. Combined pelvic exenterations and cytoreductions are safe operations in terms of morbidity. Survival, however, remains poor for this group of patients despite aggressive surgery.

ASO Author Reflections: Effect of the Number of Examined Lymph Nodes on Survival in Gastric Signet-Ring Cell Cancer.

ASO Author Reflections: Effect of the Number of Examined Lymph Nodes on Survival in Gastric Signet-Ring Cell Cancer.

Impact of Removal of Lymph Nodes on Survival in Stage I-III Gastric Signet-Ring Cell Cancer: The More, the Better?

There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.

Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis.

Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.

Comparison of survival outcomes and survival prediction in patients with primarycolorectal MANEC and primary colorectal SRCC: a population-based propensity-score matching study.

Primary mixed adeno-neuroendocrine carcinoma (MANEC) and primary signet-ring cell cancer (SRCC) are two rare but highly malignant tumors in colorectal cancer. Therefore, we attempted to compare the tumors' survival outcomes, identify risk factors, and ultimately evaluate the prognosis by developing a nomogram. We identified 755 MANEC and 5836 SRCC patients of colorectal cancer. PSM was used to balance the influence of baseline clinical and pathological differences. Kaplan-Meier method was used to compare the prognosis of different pathological grades and AJCC stages. Cox proportional hazards model was used to identify potential prognostic factors for the two groups. Finally, we developed a nomogram and evaluated the feasibility of the model. After PSM, the median OS and CSS of MANEC patients were significantly better than those of SRCC patients in stage III-IV (P < 0.001) but similar in stage I-II. The median OS and CSS of MANEC patients in each pathological grade were also greater than those of SRCC patients. Patients with MANEC and SRCC who underwent lymph node dissection in more than four areas had longer survival time. MANEC patients benefited from postoperative chemotherapy and radiotherapy; among SRCC patients, those who received preoperative and postoperative comprehensive chemotherapy and radiotherapy had benefits in OS and CSS. Both MANEC and SRCC are often diagnosed in advanced stages, highlighting the importance of early screening. Despite the better prognosis of MANEC compared to SRCC, both types of patients require the formulation of personalized treatment strategies based on different risk factors combined with column charts.

S2124 Shisto or No?: A Rare Case of Signet Ring Cell Carcinoma of the Rectum Mimicking Schistosomiasis

Introduction: Signet ring cell carcinoma (SRCC) of the rectum is a rare type of colorectal cancer with an incidence of less than 2%. SRCC is associated with poor prognosis, and often diagnosed at an advanced stage. While rare in the general population, SRCC occurs in up to 25% of schistosomiasis associated colorectal cancer. We report a case of SRCC in a patient with clinical features that mimicked colorectal and genitourinary schistosomiasis. Case Description/Methods: A 38-year-old male immigrant from rural Cuba presented with a 3 month history of urinary retention, intermittent fevers, and hematuria requiring placement of indwelling foley. Physical exam and vital signs were otherwise normal. Hb was 8.5 G/DL, MCV 85 fl, Creatinine 1.7 mg/dL. CT of the abdomen and pelvis with IV contrast revealed severe bilateral hydroureteronephrosis, concentric bladder wall thickening, splenomegaly, enlarged bilateral inguinal lymph nodes, and concentric submucosal thickening of the distal sigmoid/rectum with extensive calcifications. Colonoscopy revealed severe, diffuse, circumferential inflammation, narrowing, and ulceration from anus to sigmoid. While colitis was suspected, rectosigmoid biopsy showed mucinous adenocarcinoma with signet ring cell features. While we suspected schistosomiasis, Schistosoma IgG Ab was normal. The patient was advised to undergo further workup and chemotherapy, but he declined further treatment (Figure). Discussion: Schistosomiasis is a parasitic disease known to have an association with bladder neoplasia and gastrointestinal manifestations in the form of colitis and rectal calcifications. We suspect that due to his extensive rectosigmoid cancer our patient presented with features mimicking schistosomiasis, namely extrinsic genitourinary compression causing hydroureteronephrosis with hematuria, and cancer appearing like colitis. This case is instructive in that we are reminded of the interesting presentation of schistosomiasis as well as the occasional presence of signet cell cancer in the lower gastrointestinal tract. While the majority of SRCC arise in the stomach, occasionally this entity can present as an isolated primary SRCC of the rectum. Treatment with targeted therapy and chemotherapy have limited effect on improving survival. In conclusion, though SRCC of the rectum is rare, clinicians should consider this in the differential in patients presenting with risk factors for both schistosomiasis and SRCC of the rectum.Figure 1.: A, CT of the pelvis with IV contrast showing concentric submucosal thickening of the distal sigmoid/rectum with calcifications. B, Colonoscopy showing severe circumferential inflammation, narrowing, and ulceration of the sigmoid colon.

Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management.

While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

Novel Endoscopic Polypectomy Surveillance Technique for Fundic Gland Polyps in Familial Adenomatous Polyposis Can Improve Early Detection of Dysplasia and Gastric Cancer.

Fundic gland polyps (FGPs) are commonly found in patients with familial adenomatous polyposis (FAP) and are considered benign. Biopsies are not routinely performed, and conventional forceps may be time-consuming and/or yield nonrepresentative histology. The purpose of this study was to evaluate the role of a novel endoscopic polypectomy surveillance (EPS), a large volume cold-snare polypectomy technique of random FGPs, in the incidence of dysplasia and gastric cancer (GC) in FAP. This is a retrospective longitudinal cohort of patients with FAP referred to a tertiary care center for duodenal adenoma surveillance and who underwent EPS of FGPs between 2001 and 2019. Demographic, endoscopic, and clinicopathologic information was reviewed. Thirty-five patients with FAP were identified at initial endoscopy by the mean age of 43.4 years (±12.8). One hundred thirteen surveillance endoscopies were performed in total using EPS. Dysplasia of FGPs was present on initial esophagogastroduodenoscopy in 7 patients (20%), and 13 additional patients (46.4%) progressed to low-grade dysplasia. Three patients (15%) who subsequently had progression to GC were found to have signet ring cell cancer within the foci of FGPs through EPS. One patient presented as metastatic GC. Progression from nondysplastic FGP to low-grade dysplasia occurred over 63 months (±46.3) with further progression to GC over 34 months (±8.5). Endoscopic risk factors for cancer were polyps &gt;10 mm in size ( P &lt; 0.001) and carpeting of polyps ( P &lt; 0.001). The 5-year cumulative incidence of developing dysplasia was 35.7%. We identified that the incidence of dysplasia and GC is higher than previously reported in patients with FAP. Our study used a novel EPS technique and was able to identify GC within the foci of FGPs. Upper endoscopic guidelines should include a more rigorous sampling method for FGPs, such as EPS, to optimize early detection of dysplasia and GC.

Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes.

Simple SummaryThis study reports the long-term results of total gastrectomy for patients with a family history of gastric cancer and CDH1 gene mutations that predispose to hereditary diffuse gastric cancer (HDGC). Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 had HDGC diagnosed preoperatively. 7 of 8 symptomatic had metastatic lymph nodes with cancer. 21 of 22 asymptomatic patients had gastric cancer localized to the stomach and each was cured. 15 of those patients had 9-year follow-up. Each had significant weight loss (23% body weight) with a normal body mass index, 40% had bile reflux controlled with medication, and each returned to work and said they would do it again. Long-term quality of life following gastrectomy was acceptable.Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable. Methods: We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher’s exact test. Results: In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology (p = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue (p = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again. Conclusions: Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable.

Клинический случай эндоскопической диагностики перстневидноклеточного рака антрального отдела желудка

Signet ring cell cancer (SRC) is a rare form of high-grade adenocarcinoma that produces mucin. This is an epithelial malignant tumor characterized by the histological appearance of cells resembling rings. Primary SRC tumors are most often found in the glandular cells of the stomach (SRC occurs in the stomach in 56% of patients) and less often in the mammary gland, gallbladder, bladder and pancreas. SRC usually does not form in the lungs, although several cases have been reported. Among cases of colorectal cancer, the prevalence of SRC is less than one percent. Although the incidence and mortality from stomach cancer have decreased in many countries over the past 50 years, there has been an increase in the number of cases of stomach cancer of the type of SRC. As a rule, SRC grows in the submucosal layer, which makes diagnostics using standard imaging methods, such as computed tomography and positron emission tomography, less effective. In this clinical case, the possibilities of endoscopic diagnosis of SRC in a patient who has not been able to establish a correct diagnosis for a long time have been demonstrated.

CDH1 germline variants are enriched in patients with colorectal cancer, gastric cancer, and breast cancer

Background and aimsCDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities.MethodsWe evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3).ResultsCDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3.ConclusionWe report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.

Prognostic Significance of Signet Ring Cells in Gastric Cancer: The Higher Proportion, The Better Survival.

BackgroundDue to the fact that the definition of gastric signet ring cell cancer (GSRC) was still controversial in the past decades, the prognosis affected by the proportion of signet ring cells within gastric cancer is uncertain. This study compared the clinicopathological features and prognosis of GSRC with the various proportions of signet ring cells.MethodsWe collected GSRC cases without metastasis who underwent curative (R0) resection between 2011 and 2018. Individuals who were in the low-proportion signet ring cell group (LSRC, <50%) were matched to those who were in the high-proportion signet ring cell group (HSRC, >50%) through propensity score matching (1:1). We used Cox proportional hazard regression to calculate the adjusted hazard ratios (HR) and 95% confidence intervals (CI) and explored interactions with gender and stage.ResultsWe had 1:1 matched individuals including 231 cases from the LSRC group and 231 cases from the HSRC group. Patients with HSRC had a significantly higher overall survival rate in the multivariable model (aHR = 0.56, 95%CI = 0.38, 0.84) compared with those with LSRC. The association of HSRC appeared to be more substantial among individuals at early stage and N0 stage (p-interaction < 0.01).ConclusionsThis study confirms that GSRC with different proportions of signet ring cells could affect the survival of the patient. Further clinical studies should be developed in the future to provide an appropriate treatment strategy for GSRC.

Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum-Is TNT the solution?

The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology. A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS: CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS. SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.

Prognostic Significance of EMVI in Rectal Cancer in a Tertiary Cancer Hospital in India.

Background Presence of extramural venous invasion (EMVI) is a poor prognostic factor for rectal cancer as per literature. However, India-specific data are lacking. Aim The aim of the study is to determine the prognostic significance of EMVI in locally advanced rectal cancer on baseline MRI. Materials and Methods We retrospectively reviewed 117 MRIs of operable non-metastatic locally advanced rectal cancers in a tertiary cancer institute. Three dedicated oncoradiologists determined presence or absence of EMVI, and its length and thickness, in consensus. These patients were treated as per standard institutional protocols and followed up for a median period of 37 months (range: 2–71 months). Kaplan-Meier curves (95% CI) were used to determine disease-free survival (DFS), distant-metastases free survival (DMFS), and overall survival (OS). Univariate analysis was performed by comparing groups with log-rank test. Results EMVI positive cases were 34/114 (29%). More EMVI-positive cases developed distant metastasis compared with EMVI-negative cases (14/34–41% vs. 22/83–26%). The difference, however, was not statistically significant ( p = 0.146). After excluding signet-ring cell cancers ( n = 14), EMVI showed significant correlation with DMFS ( p = 0.046), but not with DFS or OS. The median thickness and length of EMVI was 6 and 14 mm, respectively in patients who developed distant metastasis, as compared with 5 and 11 mm in those who did not, although this difference was not statistically significant. Conclusion EMVI is a predictor of distant metastasis in locally advanced non-metastatic, non-signet ring cell rectal cancers. EMVI can be considered another high-risk feature to predict distant metastasis.

Redox forms of glutathione in malignant lesions of the stomach with varying aggressiveness degrees

Aim. To study the levels of reduced and oxidized glutathione (GSH and GSSG, respectively), as well as the thiol status in gastric cancer (GC) tumors of various histological types and grades. Materials and methods. The indicators were determined by ELISA methods in tumor, peritumoral and visually intact tissues obtained during surgery from 52 patients with GC: 18 patients had a G1-2 adenocarcinoma (AC), 8 with G3 AC, 6 with signet ring cell cancer (SRCC), 14 with combined gastric lesions (CGL) – AC with signet ring cell fragments, 6 with patients with a component of undifferentiated cancer, G4. Results. In the groups of patients with low-differentiated and undifferentiated tumors, the GSH content in the tumor tissue and the peritumoral zone was higher than in the group of patients with well- and moderately-differentiated tumors. Tumor GSH levels in G3 AC and SRCC exceeded the values in visually intact tissues. Moreover, in the visually intact tissue of patients with SRCC, GSH level was reduced relative to G1-2 AC and CGL. GSH in all tissues of patients with CGL was higher than in patients with G1-2 AC. The lowest level of GSSG in the tumor tissue was registered in SRCC: 27.5% lower than in G1-2 AC and 30.3% lower than in G3 AC. Patients with undifferentiated tumors (G4 AC) had the highest GSH content in all studied tissues: by 29.9% in tumor; by 40.7% in peritumoral zone; and in visually intact tissue not only GSH, but also GSSG was increased by 22.5–25.5% in comparison with AC G1-2. G4 AC was also characterized by a sharp increase in the thiol status in tumor tissues by 80.2 and 89.9% higher than in visually intact and peritumoral tissues, and it was statistically higher than in AC G1-2, AC G3, SRCC and CGL. The ratio of GSH and GSSG was the most informative. Conclusion . Poor AC differentiation (in the row G1-2, G3, G4) and a change of histological tumor type (AC, SPL and SRCC), i.e. an increase in tumor aggressiveness, were accompanied by the enhancement of reductive processes in tumor tissue, as evidenced by the statistically significant increase in the GSH/GSSG coefficient and a sharp increase in the thiol status in G4 AC.