Individualized prediction of conditional survival for colorectal signet-ring cell carcinoma patients.

Background: Conditional survival (CS) considers the time already survived after surgery and may provide additional survival information. The authors sought to construct and validate novel conditional survival nomograms for the prediction of conditional overall survival (OS) and cancer-specific survival (CSS) of colorectal signet-ring cell carcinoma (SRCC) patients. Methods: Patients diagnosed with stage I-III SRCC between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The formula calculating CS was: CS(x|y) = S(x+y)/S(x), where S(x) represents the survival at x years. CS nomograms were then constructed to predict the 5-year conditional OS and CSS, followed by internal validation. Results: A total of 944 colorectal SRCC patients were finally identified in this study. The 5-year OS and CSS improved gradually with additional survival time. Univariate and multivariate Cox regression analysis conducted in training set revealed that age, race, T stage, LNR, and perineural invasion were independent risk factors for both OS and CSS. Two nomograms with considerable predictive ability were successfully constructed [area under the curve (AUC) for OS: 0.788; AUC for CSS: 0.847] and validated (AUC for OS: 0.773; AUC for CSS: 0.799) for the prediction of 5-year OS and CSS, based on the duration of 1-4 years post-surgery survival. Conclusions: The probability of achieving 5-year OS and 5-year CSS in colorectal SRCC patients improved gradually with additional time. Conditional nomograms considering survival time will be more reliable and informative for risk stratification and postoperative follow-up.

Colorectal Signet Ring Cell Carcinoma Presenting as Ulcerating Rectosigmoid Stricture.

Colorectal signet ring cell carcinoma is a rare type of colon cancer. Early diagnosis remains challenging because of nonspecific colonoscopy findings, such as diffuse circumferential thickening, stricture, and ulcerations, and the potential absence of typical pathological features in the initial biopsy sample. In this article, we report a 41-year-old man with ulcerating rectosigmoid stricture in the rectosigmoid colon with inconclusive histology. Subsequently, the patient developed small bowel obstruction and was diagnosed with stage 4 colorectal signet ring cell carcinoma with peritoneal carcinomatosis.

Prognostic value of log odds of positive lymph nodes, lymph node ratio, and N stage in patients with colorectal signet ring cell carcinoma: A retrospective cohort study.

Aim: Little attention has been paid in the prognosis of colorectal signet ring cell carcinoma (SRCC). This study aims to explore the predictive capacity of log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in the prognosis of patients with colorectal SRCC. Methods: A retrospective cohort study was designed, and data were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Data on demographic characteristics, clinicopathological features, and treatment were extracted. Outcomes were overall survival (OS) and cancer-specific survival (CSS). Association of LODDS, LNR, and pN stage with OS and CSS were explored using Cox proportional hazard model and Cox competing risk model, respectively, with results showing as hazard ratio and 95% confidence interval (CI). Predictive performance of LODDS, LNR, and pN stage in OS and CSS was assessed by calculating C-index. Results: A total of 2,198 patients were included in this study. LODDS, LNR, and pN stage were associated with the OS and CSS of colorectal SRCC patients (all P < 0.05). LODDS showed a good performance in the OS (C-index: 0.704, 95% CI: 0.690-0.718), which was superior to LNR (C-index: 0.657, 95% CI: 0.643-0.671) and pN stage (C-index: 0.643, 95% CI: 0.629-0.657). The C-index of LODDS, LNR, and pN stage for CSS was 0.733 (95% CI: 0.719-0.747), 0.713 (95% CI: 0.697-0.729), and 0.667 (95% CI: 0.651-0.683), respectively. Conclusions: LODDS displayed a better predictive capacity in the OS and CSS than LNR and pN stage, indicating that LODDS may be effective to predict the prognosis of colorectal SRCC in the clinic.

Enhanced glutamine utilization mediated by SLC1A5 and GPT2 is an essential metabolic feature of colorectal signet ring cell carcinoma with therapeutic potential.

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is characterized as a rare subset of colorectal cancer with extremely poor prognosis and it is known to have low or negative 18F fluorodeoxyglucose (18F-FDG) uptake. To date, no in-depth study revealing the metabolic features of colorectal SRCC has been conducted for the lack of reliable study model. The aim of this study was to explore the distinct characteristics of energy utilization for colorectal SRCC based on organoid model. METHODS: Three organoids were derived from colorectal SRCC patients with low or negative FDG uptake and three organoids were derived from colorectal adenocarcinoma (AC) patients. Glucose, fatty acid and glutamine uptake assays were performed to reveal the different metabolic features of SRCC organoids. Immunohistochemistry (IHC), western blotting and real-time PCR were used to test the expression of critical transporters and enzymes of energy metabolism. Glutamine deprivation analyses were used to confirm the dependence of colorectal SRCC on glutamine. RESULTS: Glucose, fatty acid and glutamine uptake assays showed that only glutamine uptake was significantly increased in colorectal SRCC organoids compared with paired normal organoids. Comparing SRCC organoids with AC organoids indicated that glucose and fatty acid uptake were strikingly higher in AC organoids while glutamine uptake was notably lower. Gene expression analyses confirmed that the glutamine transporter SLC1A5 and glutaminolysis enzyme GPT2 were significantly unregulated in colorectal SRCC. Silencing of SLC1A5 or GPT2 could suppress the proliferation of SRCC organoids but attenuating the sensitivity of SRCC to glutamine deprivation. Administration of SLC1A5 or GPT2 inhibitor could prohibit SRCC growth and significantly enhance the sensitivity of SRCC to the treatment of 5-fu and L-OHP. CONCLUSIONS: This study highlights enhanced glutamine uptake and glutaminolysis as a metabolic feature of colorectal SRCC and a potential therapeutic target.

Three-Dimensional CT Texture Analysis to Differentiate Colorectal Signet-Ring Cell Carcinoma and Adenocarcinoma.

PURPOSE: The objective of this research was to validate the diagnostic value of three-dimensional texture parameters and clinical characteristics in the differentiation of colorectal signet-ring cell carcinoma (SRCC) and adenocarcinoma (AC). METHODS: We retrospectively analyzed data from 102 patients with SRCC or AC confirmed by pathology, including 51 SRCC (from January 2015 to July 2019) and 51 AC patients (from January 2019 to July 2019). CT findings and clinical data, including age, gender, clinical symptoms, serological biomarkers, tumor size, and tumor location, were compared between SRCC and AC. CT texture features were quantified on portal phase images using three-dimensional analysis. A list of texture parameters was generated with MaZda software for the classification of tumors. The texture features, clinical data and CT findings were statistically analyzed for the discrimination ability of SRCC and AC, and the potential predictive parameters that may be used to differentiate the two groups were subsequently tested using the least absolute shrinkage and selection operator (LASSO) and logistic regression analyses. The receiver operating characteristic curve (ROC) provided a range of values for establishing the cutoff value, as well as the sensitivity and specificity of prediction for each significant variable. RESULTS: SRCC occurred more often in men than AC did (80.39% vs 49.02%, P < 0.01). The patients were younger in the SRCC group than in the AC group, without a statistically significant difference (55.84 vs 59.20 years, P = 0.216). There were no significant differences in the clinical symptoms, tumor size, or tumor location between the two groups (P=0.505, P=0.19, P=0.843, respectively). The elevation of serological biomarker CA724 was more common in SRCC than in AC (P< 0.001). Perc.01%3D, Perc.10%3D and s(1,0,0) SumAverg were lower in the SRCC group than in the AC group during the portal phase, with the areas under curve (AUCs) of 0.892-0.929, sensitivity of 76.5-84.3% and specificity of 88.2-96.1%. In the differentiation between SRCC and AC, the 1-NN minimal classification error (MCR) was 29.41%. CONCLUSION: Three-dimensional texture parameters, including Perc.01%3D, Perc.10%3D and s(1,0,0) SumAverg, exhibited a favorable discriminatory ability to distinguish SRCC from AC.