The Complexity of Shapes: How the Circularity of Tumor Nodules Affects Prognosis in Colorectal Cancer.

The current stratification of tumor nodules in colorectal cancer (CRC) staging is subjective and leads to high interobserver variability. In this study, the objective assessment of the shape of lymph node metastases (LNMs), extranodal extension (ENE), and tumor deposits (TDs) was correlated with outcomes. A test cohort and a validation cohort were included from 2 different institutions. The test cohort consisted of 190 cases of stage III CRC. Slides with LNMs and TDs were annotated and processed using a segmentation algorithm to determine their shape. The complexity ratio was calculated for every shape and correlated with outcomes. A cohort of 160 stage III CRC cases was used to validate findings. TDs showed significantly more complex shapes than LNMs with ENE, which were more complex than LNMs without ENE (P < .001). In the test cohort, patients with the highest sum of complexity ratios had significantly lower disease-free survival (P < .01). When only the nodule with the highest complexity was considered, this effect was even stronger (P < .001). This maximum complexity ratio per patient was identified as an independent prognostic factor in the multivariate analysis (hazard ratio, 2.47; P < .05). The trends in the validation cohort confirmed the results. More complex nodules in stage III CRC were correlated with significantly worse disease-free survival, even if only based on the most complex nodule. These results suggest that more complex nodules reflect more invasive tumor biology. As most of the more complex nodules were diagnosed as TDs, we suggest providing a more prominent role for TDs in the nodal stage and include an objective complexity measure in their definition.

Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer.

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

Tumour deposits are independently associated with recurrence in colon cancer.

AIM: Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. METHOD: Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. RESULTS: Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. CONCLUSION: Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. PATIENTS AND METHODS: The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. RESULTS: In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. CONCLUSION: TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

Distinguishing mesorectal tumor deposits from metastatic lymph nodes by using diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in rectal cancer.

OBJECTIVES: This study aimed to identify whether apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are helpful in distinguishing mesorectal tumor deposits (TD) from metastatic lymph nodes (MLN) in rectal cancer (RC). METHODS: Thirty patients (59 lesions, including 30 TD and 29 MLN) with RC who underwent pretreatment-MRI between February 2016 and August 2018 were enrolled. The morphological features, ADC values, and semi-quantitative parameters of DCE-MRI, including relative enhancement (RE), maximum enhancement (ME), maximum relative enhancement (MRE), time to peak (TTP), wash-in rates (WIR), wash-out rates (WOR), brevity of enhancement (BRE), and area under the curve (AUC) were measured on lesions (TD or MLN) and RC. The parameters were compared between TD and MLN, tumor with and without TD group by using Fisher's exact test, independent-samples t-test, and Mann-Whitney U test. The ratio (lesion-to-tumor) of the parameters was compared between TD and MLN. Receiver operating characteristic curve analysis and binary logistic regression analysis were used to assess the diagnostic ability of single and combined metrics for distinguishing TD from MLN. RESULTS: The morphological features, including size, shape, and border, were significantly different between TD and MLN. TD exhibited significantly lower RE, MRE, RE-ratio, MRE-ratio, ADCmin-ratio, and ADCmean-ratio than MLN. RE-ratio showed the highest AUC (0.749) and accuracy (77.97%) among single parameters. The combination of DCE-MRI and DWI parameters together showed higher diagnostic efficiency (AUC = 0.825). CONCLUSIONS: Morphological features, ADC values, and DCE-MRI parameters can preoperatively help distinguish TD from MLN in RC. KEY POINTS: • DWI and DCE-MRI can facilitate early detection and distinguishing mesorectal TD (tumor deposits) from MLN (metastatic lymph nodes) in rectal cancer preoperatively. • TD has some specific morphological features, including relatively larger size, lower short- to long-axis ratio, irregular shape, and ill-defined border on T2-weighted MR images in rectal cancer. • The combination of ADC values and semi-quantitative parameters of DCE-MRI (RE, MRE) can help to improve the diagnostic efficiency of TD in rectal cancer.

MRI-detected tumor deposits in cT3 and cT4 rectal cancer following neoadjuvant chemoradiotherapy.

OBJECTIVES: To evaluate the identification of tumor deposits (TDs) and the prognostic significance of an MRI tumor regression grade for TDs in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). METHODS: Ninety-one patients with cT3 or cT4 rectal cancer who underwent surgery following nCRT between August 2014 and June 2020 were retrospectively analyzed. Changes in pre-nCRT MRI-detected TDs (mrTDs) were described as mrTD regression grade. The diagnostic performance of post-nCRT MRI-detected TDs (ymrTDs) was compared with histopathological reference standard. The correlation between ymrTDs, mrTD regression grade, and disease-free survival (DFS) was assessed. RESULTS: The sensitivity and specificity of ymrTDs were 88.00% and 89.39%, respectively. The area under the receiver operating characteristic curve was 0.887 (95% confidence interval [CI]: 0.803-0.944). The 3-year DFS of patients with positive ymrTDs was significantly lower than of the negative group (44.83% vs 82.73%, p < 0.001). The 3-year DFS was 33.33% for patients with poor regression of mrTDs following nCRT and 55.56% for those with moderate regression, compared to 69.23% in good responders and 83.97% in patients without mrTDs (p < 0.001). On multivariable Cox regression, mrTD regression grade was the only independent MRI factor associated with DFS (p = 0.042). CONCLUSIONS: Diagnostic performance of ymrTDs was moderate. The mrTD regression grade was independently correlated with DFS, which may have a prognostic implication for treatment and follow-up. CLINICAL RELEVANCE STATEMENT: Patients with poor regression of MRI-detected tumor deposits may benefit from more aggressive treatments, such as chemoradiation therapy plus induction or consolidation chemotherapy. KEY POINTS: • MRI provides a preoperative and noninvasive way to visualize tumor deposits (TDs) after neoadjuvant chemoradiotherapy (nCRT). • Post-nCRT MRI-detected TDs are a poor prognostic marker in cT3 and cT4 rectal cancer patients. • The regression of MRI-detected TDs after nCRT is associated with an improved disease-free survival.

Tumor deposits are associated with a higher risk of peritoneal disease in non-metastatic colorectal cancer patients.

BACKGROUND AND OBJECTIVES: Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients. METHODS: A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage. RESULTS: A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31). CONCLUSIONS: In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HR counterparts. Alternative strategies for surveillance and treatment should be considered.

Adverse impact of tumor deposits in lymph node negative rectal cancer - a national cohort study.

PURPOSE: This study aimed to investigate the prognostic effect of tumor deposits (TDs) in lymph node negative rectal cancer. METHODS: Patients who had undergone surgery for rectal cancer with curative intention between 2011 and 2014 were extracted from the Swedish Colorectal Cancer Registry. Patients with positive lymph nodes, undisclosed TD status, stage IV disease, non-radical resections, or any outcome (local recurrence (LR), distant metastasis (DM) or mortality) within 90 days after surgery were excluded. TDs status was based on histopathological reports. Cox-regression analyses were used to examine the prognostic impact of TDs on LR, DM, and overall survival (OS) in lymph node-negative rectal cancer. RESULTS: A total of 5455 patients were assessed for inclusion of which 2667 patients were analyzed, with TDs present in 158 patients. TD-positive patients had a lower 5-year DM-free survival (72.8%, p < 0.0001) and 5-year overall survival (75.9%, p = 0.016), but not 5-year LR-free survival (97.6%) compared to TD-negative patients (90.2%, 83.1% and 95.6%, respectively). In multivariable regression analysis, TDs increased the risk of DM [HR 4.06, 95% CI 2.72-6.06, p < 0.001] and reduced the OS [HR 1.83, 95% CI 1.35-2.48, p < 0.001]. For LR, only univariable regression analysis was performed which showed no increased risk of LR [HR 1.88, 95% CI 0.86-4.11, p = 0.11]. CONCLUSION: TDs are a negative predictor of DM and OS in lymph node-negative rectal cancer and could be taken into consideration when planning adjuvant treatment.

Clinical significance of tumor deposits in gastric cancer after radical gastrectomy: a propensity score matching study.

OBJECTIVE: The value of tumor deposits (TDs) in the prognosis and staging of gastric cancer (GC) is still under debate. This study aims to evaluate the prognostic value of TDs and the best ways to incorporate TDs in the TNM classification of GC. METHODS: Patients (n = 3460) undergoing curative gastrectomy for GC in the West China Hospital from 2005 to 2017 were retrospectively reviewed and divided into two groups according to the TD status (positive vs. negative). Later, clinicopathological features and overall survival (OS) between the two groups were compared. Thereafter, the associations between the presence of TD and other clinicopathological factors were evaluated through logistic regression. In addition, univariate and multivariate Cox regression were conducted for determining prognostic factors. The possibility of selection bias was reduced through conducting the 1:1 propensity score matching (PSM) analysis. The modified classification systems proposed previously that incorporated TDs into the TNM staging system were assessed. RESULTS: There were 10.5% of patients (362/3460) diagnosed with TDs. TDs were significantly related to unfavorable factors such as advanced T stage and N stage and independently associated with poor prognosis. The 5-year OS of patients with TDs was significantly lower than that of patients without TDs (31.0% vs. 60.9%, P < 0.001), whereas higher than that of patients with peritoneal metastasis (31.0% vs. 5.0%, P < 0.001). In patients receiving chemotherapy, the 5-year OS of patients with TDs was also significantly lower than that of patients without TDs (42.0% vs. 50.9%, P = 0.026). Moreover, the system incorporating TDs in the TNM classification as metastatic lymph nodes outperformed others. CONCLUSIONS: TDs are related to the aggressive characteristics and are an independent prognostic factor for GC. Incorporating TDs in the TNM classification as the metastatic lymph nodes increases the accuracy in predicting prognosis.

Long-term outcomes of upfront robotic rectal cancer surgery: a single-center, retrospective cohort study in Japan.

PURPOSE: The purpose of this study was to evaluate the long-term outcomes of robotic rectal cancer surgery and to examine the risk factors for recurrence. METHODS: In a high-volume center in Japan, we retrospectively enrolled patients with pStage I-III rectal cancer within 15 cm of the anal verge who underwent robotic surgery from 2011 to 2017. Almost all patients underwent upfront surgery, and lateral lymph-node dissection (LLND) was performed for patients with locally advanced lower rectal cancer. We evaluated the 5-year overall survival (OS), relapse-free survival (RFS), and cumulative local recurrence (LR) rates and examined the risk factors for the RFS. RESULTS: We evaluated 488 patients who underwent robotic rectal cancer surgery, including 5.1% who underwent preoperative chemoradiotherapy to obtain clear resection margins and 33.6% who underwent LLND. There were 203, 87, and 198 patients with pStage I, II, and III, respectively, and the positive resection margin rate was 1.0%. The 5-year OS, RFS, and LR rates were 95.5%, 81.7%, and 2.2%, respectively. The independent risk factors for the RFS were the presence of venous invasion, extramural tumor deposits without lymph-node structure, and pT ≥ 3. CONCLUSION: This study demonstrated the favorable long-term outcomes of robotic rectal cancer surgery.

New Histoprognostic Factors to Consider for the Staging of Colon Cancers: Tumor Deposits, Invasive Tumor Infiltration and High-Grade Budding.

Colorectal cancer is a major public health issue due to its high incidence and mortality. It is, therefore, essential to identify histological markers for prognostic purposes and to optimize the therapeutic management of patients. The main objective of our study was to analyze the impact of new histoprognostic factors, such as tumor deposits, budding, poorly differentiated clusters, mode of infiltration, the intensity of inflammatory infiltrate and the type of tumor stroma, on the survival of patients with colon cancer. Two hundred and twenty-nine resected colon cancers were fully histologically reviewed, and survival and recurrence data were collected. Survival was analyzed using Kaplan-Meier curves. A univariate and multivariate Cox model was constructed to identify prognostic factors for overall survival and recurrence-free survival. The median overall survival of the patients was 60.2 months and the median recurrence-free survival was 46.9 months. Overall survival and recurrence-free survival were significantly worse in the presence of isolated tumor deposits (log rank = 0.003 and 0.001, respectively) and for an infiltrative type of tumor invasion (log rank = 0.008 and 0.02, respectively). High-grade budding was associated with a poor prognosis, with no significant difference. We did not find a significant prognostic impact of the presence of poorly differentiated clusters, the intensity of the inflammatory infiltrate or the stromal type. In conclusion, the analysis of these recent histoprognostic factors, such as tumor deposits, mode of infiltration, and budding, could be integrated into the results of pathological reports of colon cancers. Thus, the therapeutic management of patients could be adjusted by providing more aggressive treatments in the presence of some of these factors.

Tumor Deposits and Perineural Invasion had Comparable Impacts on the Survival of Patients With Non-metastatic Colorectal Adenocarcinoma: A Population-Based Propensity Score Matching and Competing Risk Analysis.

BACKGROUND: Both tumor deposits (TD) and perineural invasion (PNI) have been identified as risk factors for poor survival in patients with non-metastatic colorectal adenocarcinoma (CRC). However, the adverse impacts of TD and PNI on the survival of patients with non-metastatic CRC have not been compared. METHOD: Patients with non-metastatic CRC with known TD and PNI status were selected from the Surveillance, Epidemiology, and End Results (SEER) database. First, bivariate logistic regression analysis was utilized to identify the factors associated with TD and PNI status. Then, patients were divided into four groups, according to TD and PNI status. Propensity score matching (PSM) was performed to balance the baseline covariates. The impact of TD and PNI on survival was assessed by analyzing overall survival (OS) and cancer-specific mortality (CSM) rates. OS was calculated by the Kaplan-Meier method with log-rank analysis. CSM was estimated by competing risk analysis using the Fine and Gray model. RESULTS: A total of 70 689 patients with CRC met the inclusion and exclusion criteria. The positive rates of TD and PNI were 9.37% and 9.91%, respectively. For TD, the most important risk factor was N stage. With respect to PNI, the most significant factor was T stage. Tumor location, tumor size, differentiation grade, and serum CEA level were also correlated with TD and PNI status. After PSM, 1849 pairs were selected. Patients with TD+PNI+ status had the worst 5 year CSM and 5 year OS. In addition, the long-term survival outcomes of patients with TD+PNI- and TD-PNI+ status were comparable. CONCLUSION: The adverse impacts of TD and PNI on the survival of patients with non-metastatic CRC were comparable. CRC patients with both TD and PNI positive had the worst survival outcome.

Significance of tumor deposits combined with lymph node metastasis in stage III colorectal cancer patients: a retrospective multi-center cohort study from China.

PURPOSE: The study aimed to explore the value of tumor deposits in stage III colorectal cancer (CRC) and verify whether patients with more tumor deposit numbers have higher risk of recurrence. METHODS: The retrospective cohort analysis was performed at two cancer centers of China. Stage III CRC patients who underwent radical resection at the center between April 2008 and February 2019 were identified. The Univariate/Multivariate Cox regression, Kaplan-Meier analysis, and PSM were recurrence-free survival (RFS) used. RESULTS: Total 1080 stage III CRC patients (634 [58.7%] men; median [IQR] age, 60 [50-68] years) who underwent radical surgical resection were identified for inclusion in this study. Patients with tumor deposits had a 12.8% lower 3-year RFS (n = 236 [69.9%]) than the patients without tumor deposits (n = 844 [82.7%]) (P ≤ 0.0001). The 3-year RFS of patients with stage N2 (n = 335 [61.2%]) was 18.6% lower (P ≤ 0.0001) than the original cohort of patients with stage N1 (n = 745 [79.8%]), but it was similar to the RFS of patients with 4 or more tumor deposits plus lymph node metastases (n = 58 [61.4%]) (P = 0.91). The RFS for patients with 4 or more tumor deposits plus number of lymph node metastases (n = 58 [61.4%]) was 15.8% lower than the cohort of patients with 1-3 tumor deposits + number of lymph node metastases (n = 687 [77.2%]) (P = 0.001). Multivariate analysis confirmed that patients with 4 or more tumor deposits + the number of lymph node metastases (hazard ratio [HR], 1.88; 95% CI, 1.24-2.87) were independently associated with a shorter RFS. CONCLUSION: The number of tumor deposits is an indicator of poor postoperative prognosis. It is necessary to incorporate the number of tumor deposits combined with the number of lymph node metastases to stratify postoperative stratification of stage III CRC, which may provide a new theoretical basis for adjuvant therapy for patients with N1 stage CRC after surgery.

Association of tumor deposits with tumor-infiltrating lymphocytes and prognosis in gastric cancer.

BACKGROUND: To investigate the relationship between tumor deposits (TDs) with the clinicopathological characteristics tumor-infiltrating lymphocytes (TILs) and prognosis of gastric cancer. Further analysis was done on the relationship between the number and maximum diameter of TDs with the clinicopathological characteristics and prognosis of gastric cancer. METHODS: The pathological findings of 369 patients with gastric cancer were retrospectively analyzed to observe the expression of TDs and the levels of stromal TILs. The relationship between TDs, clinicopathological characteristics, and levels of stromal TILs was compared using the chi-square test. Kaplan-Meier was used for survival analysis, and the log-rank test was used to determine the relationship between TDs and disease-free survival, cancer-specific survival, and overall survival. The prognostic value of TDs was assessed using multivariate Cox proportional hazards regression analysis. For further analysis, the optimal cutoff values for the number and maximum diameter of TDs were selected based on the receiver operating characteristic (ROC) curve. RESULTS: TDs were significantly associated with sex, lymphovascular invasion, perineural invasion, pathological T,N stage, and clinical stage (all P < 0.05). TILs levels are lower in TDs(+) group and higher in TDs(-) group. Compared with TDs(-) groups, TDs(+) group had poor disease-free survival, cancer-specific survival, and overall survival. TDs are negatively correlated with TILs, and TILs levels are lower in TDs(+) group and higher in TDs(-) group (P < 0.05). The samples are divided into the number of TDs (< 4 and ≥ 4) and the maximum diameter of TDs (< 7 mm and ≥ 7 mm). The number of TDs was significantly associated with pathological N stage (P < 0.05). The maximum diameter of TDs was significantly correlated with Lauren classification (P < 0.05) .TDs ≥ 4 had lower DFS, CSS, and OS (P < 0.05). The maximum diameter of TDs was not statistically significant with prognosis (P > 0.05). CONCLUSION: TDs are independent prognosis predictors of gastric cancer. In the tumor microenvironment, TDs and TILs interact with each other to regulate the development of gastric cancer, thus affecting gastric cancer prognosis of patients. The number of TDs ≥ 4 has a worse prognosis compared to the number of TDs < 4.

The value of tumor deposits in evaluating colorectal cancer survival and metastasis: a population-based retrospective cohort study.

BACKGROUND: The role of tumor deposits (TDs) in TNM staging of colorectal cancer is controversial, especially the relationship with distant metastasis. PURPOSE: This study aimed to determine the effect of TDs on the survival of colorectal cancer and the occurrence of distant metastasis and to determine whether TDs (+) patients behaved similarly to stage IV patients. METHODS: A retrospective analysis of CRC patients from two large independent cohorts from the Surveillance Epidemiology and End Results (SEER) database (n = 58775) and the First Affiliated Hospital of Dalian Medical University (n = 742). RESULTS: Univariate logistic analyses revealed that TDs are an independent predictor of liver metastasis [p < 0.001; odds ratio (OR): 5.738; 95% confidence interval (CI): 3.560-9.248] in the First Affiliated Hospital of Dalian Medical University's patients. Meanwhile, TDs are also an independent predictor of isolated organ metastasis [p <0.001; odds ratio (OR): 3.028; 95% confidence interval (CI): 2.414-3.79; multiple organ metastases [p < 0.001; odds ratio (OR): 4.778; 95% confidence interval (CI): 4.109-5.556]; isolated liver metastasis [p < 0.001; odds ratio (OR): 4.395; 95% confidence interval (CI): 4.099-4.713] and isolated lung metastasis [p < 0.001; odds ratio (OR): 5.738; 95% confidence interval (CI): 3.560-9.248] in the SEER database. Multivariate analyses suggested TDs are an independent poor prognostic factor for distant metastasis (p <0.001). CONCLUSIONS: Our results have shown that compared with patients with negative TDs, CRC patients with positive TDs are more likely to develop distant metastasis. Patients categorized as T4aN2bM0 TDs (+) and T4bN2M0 TDs (+) have a similar prognosis as those with stage IV, and hence these patients should be classified as stage IV.

Comparison of model fit and discriminatory ability of the 8th edition of the tumor-node-metastasis classification and the 9th edition of the Japanese classification to identify stage III colorectal cancer.

BACKGROUND: The most widely accepted staging system for colorectal cancer (CRC) is the tumor-node-metastasis (TNM) classification. In Japan, the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC) system is used. The two systems differ mainly in relation to tumor deposits (TD) and metastasis in the regional lymph nodes along the main feeding arteries and lateral pelvic lymph nodes (N3). Here, we investigated the prognostic ability of the two systems for stage III CRC. METHODS: We reviewed 696 consecutive patients who underwent curative resection of stage III CRC at the National Cancer Center Hospital between May 2007 and April 2014. We examined the clinicopathological features of CRC and predicted overall survival (OS) and relapse-free survival (RFS) according to the 8th TNM and 9th JCCRC systems. The systems were compared using Akaike's information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver-operating characteristic (ROC) curves. RESULTS: The 9th JCCRC system was more clinically effective according to AIC (OS, 1199 vs. 1206; RFS, 2047 vs. 2057), showed better discriminatory ability according to the C-index (OS, 0.65 vs. 0.62; RFS, 0.62 vs. 0.58), and its time-dependent ROC curve was superior compared with the 8th TNM system. CONCLUSION: These results suggest that the 9th JCCRC system has superior discriminative ability to the 8th TNM system, because the 9th JCCRC accounts for the presence of TD and N3 disease, which were both significant predictors of poor prognosis. Reconsidering the clinical value of these two factors in the TNM system could improve its clinical significance.

Prognostic value of tumor deposits in locally advanced rectal cancer: a retrospective study with propensity score matching.

BACKGROUND: The actual risks posed by tumor deposits (TDs) in colorectal cancer are still incompletely assessed. We explored the prognostic value of TDs in locally advanced rectal cancer (LARC) patients using propensity score matching (PSM) method. METHODS: Consecutive LARC patients in Peking University First Hospital between 2011 and 2015 were retrospectively analyzed. Kaplan-Meier methods and Cox proportional hazard regression analysis were conducted to explore prognostic values of TDs. PSM method was conducted to minimize selection bias. The correlation between TDs number and prognosis was explored. RESULTS: Four hundred and fifty-one LARC patients were recruited, and 78 (17.3%) patients were with TDs. Multivariate Cox analysis identified that the presence of TDs was an independent prognostic risk factor for overall survival (OS) (P = 0.044). PSM identified 76 matched pairs of LARC patients, and Kaplan-Meier curves revealed that patients with TDs experienced worse  OS (log-rank P = 0.0220) and relapse-free survival (RFS) (log-rank P = 0.0117). Subgroup analysis of 50 pairs extracted by PSM from 246 LARC patients with lymph node metastasis (LNM) further proved that TDs were significantly associated with worse OS (log-rank P = 0.0415), and the association was barely significant for RFS (log-rank P = 0.0527). There were non-significant tendencies towards higher mortality in TDs ≥ 2 than TD = 1 group (log-rank P = 0.348 for OS, log-rank P = 0.087 for RFS). CONCLUSION: Our study manifested that the presence of TDs was an independent risk factor for LARC patients. The prognostic value of TDs for LARC patients with LNM should not be ignored.

Prognostic value of tumor deposits in rectal cancer: A monocentric series of 505 patients.

BACKGROUND AND OBJECTIVES: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer. The aim of this study was to assess TDs prognosis in rectal cancer. METHODS: Patients who underwent total mesorectum excision for rectal adenocarcinoma (2011-2016) were included. A case-matched analysis was performed to assess the accurate impact of TDs for each pN category after exclusion of synchronous metastasis. RESULTS: A total of 505 patients were included. TDs were observed in 99 (19.6%) patients, (pN1c = 37 [7.3%]). TDs were associated with pT3-T4 stage (P = .037), synchronous metastasis (P = .003), lymph node (LN) invasion (P = .041), vascular invasion (P = .001), and perineural invasion (P < .001). TD was associated with a worse 3-year disease-free survival (DFS) among pN0 (51.2% vs 79.8%; P < .001); pN1 patients (35.2% vs 70.1%; P = .004) but not among pN2 patients (37.5% vs 44.7%; P = .499). After matching, pN1c patients had a worse 3-year DFS compared with pN0 patients (58.6% vs 82.4%; P = .035) and a tendency toward a worse DFS among N1 patients (40.1% vs 64.2%; P = .153). DFS was worse when one TD was compared with one invaded LN (40.8% vs 81.3%; P < .001). CONCLUSION: In rectal cancer, TDs have a metastatic risk comparable to a pN2 stage which may lead to changes in adjuvant treatment.

Stage I-III colon cancer patients with tumor deposits behave similarly to stage IV patients. Cross-section analysis of 392 patients.

BACKGROUND AND OBJECTIVES: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colorectal cancer. However, controversy exists regarding their definition, evaluation, and staging categories. This study aimed to determine the survival and recurrence impact of the TD in colon adenocarcinomas; and to determine if TD patients behave similarly to stage IV patients. METHODS: Cross-section study from 392 patients with colon adenocarcinoma from 2005 to 2012. We performed survival analysis and further stratified patients considering TD patients as a "stage IV-TD" to demonstrate if they behave similarly than stage IV patients. RESULTS: From 392 patients, 204 (52%) were men, the mean age was 57.4 ± 13.9 years and 11.5% of cases had TD. In a multivariate analysis, TD failed to predict mortality and recurrence. Considering cases with TD as stage IV-TD, their mean survival was similar to stage IV patients (69.3 and 64.6 months, respectively) and different to those in stage III (110.5 months), II (135.7 months), and I (114.9 months) (P < 0.001). CONCLUSIONS: TD failed to predict mortality and recurrence. Patients with TD in stage I-III shows similar mortality than stage IV patients; then, we suggest putting them into a substage IV category instead of the N1c category.

Prognostic significance of perigastric tumor deposits in patients with primary gastric cancer.

BACKGROUND: The presence and the prognostic significance of perigastric tumor deposits (TDs) in primary gastric cancer have not been extensively studied. The aim of this study was to evaluate the prognostic significance perigastric TDs in primary gastric cancer. METHODS: From 2005 to 2010, 1250 patients underwent R0 gastrectomy at the Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Out of 1250 patients, 132 patients with perigastric TDs were identified. Additionally, 132 patients with staged matched gastric cancer without tumor deposits were selected as a control group. RESULTS: Perigastric TDs were observed in 132 (10.5%) of the 1250 patients with gastric cancer who underwent R0 gastrectomy. There were 94 males (71.21%) and 38 females (28.79%) (2.47:1). The mean age was 57.21 years. Clinicopathologic characteristics between the two groups matched well. There was a significant difference in the overall survival of those with and without TDs by univariate (p<0.05) and multivariate (p < 0.05) survival analysis. The 1-, 3-and 5-year overall survival rates of patients with TDswere69.6%, 39.3%, and 24.2%, respectively, and were significantly poorer than those of the staged matched control group. There was no correlation between the number of TDs and patient survival in patients with gastric cancer (p>0.05); however, when comparing each pT tumor group with the perigastric TD group, the stage T4 survival rate was very similar to that observed in patients with TDs. CONCLUSIONS: Perigastric TDs are an independent predictive prognostic factor for gastric cancer and may be appropriately considered a form of serosal invasion. We suggest that TDs should be included in TNM staging system for better outcomes.