Improving the management of early colorectal cancers (eCRC) by using quantitative markers to predict lymph node involvement and thus the need for major resection of pT1 cancers

2021 ◽  
pp. jclinpath-2021-207482
Author(s):  
Scarlet Brockmoeller ◽  
Eu-Wing Toh ◽  
Katerina Kouvidi ◽  
Sarah Hepworth ◽  
Eva Morris ◽  
...  

BackgroundSince implementing the NHS bowel cancer screening programme, the rate of early colorectal cancer (eCRC; pT1) has increased threefold to 17%, but how these lesions should be managed is currently unclear.AimTo improve risk stratification of eCRC by developing reproducible quantitative markers to build a multivariate model to predict lymph node metastasis (LNM).MethodsOur retrospective cohort of 207 symptomatic pT1 eCRC was assessed for quantitative markers. Associations between categorical data and LNM were performed using χ2 test and Fisher’s exact test. Multivariable modelling was performed using logistic regression. Youden’s rule gave the cut-point for LNM.ResultsAll significant parameters in the univariate analysis were included in a multivariate model; tumour stroma (95% CI 2.3 to 41.0; p=0.002), area of submucosal invasion (95% CI 2.1 to 284.6; p=0.011), poor tumour differentiation (95% CI 2.0 to 358.3; p=0.003) and lymphatic invasion (95% CI 1.3 to 192.6; p=0.028) were predictive of LNM. Youden’s rule gave a cut-off of p>5%, capturing 18/19 LNM (94.7%) cases and leading to a resection recommendation for 34% of cases. The model that only included quantitative factors were also significant, capturing 17/19 LNM cases (90%) and leading to resection rate of 35% of cases (72/206).ConclusionsIn this study, we were able to reduce the potential resection rate of pT1 with the multivariate qualitative and/or quantitative model to 34% or 35% while detecting 95% or 90% of all LNM cases, respectively. While these findings need to be validated, this model could lead to a reduction of the major resection rate in eCRC.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5049-5049 ◽  
Author(s):  
G. B. Kristensen ◽  
H. Lyng ◽  
D. H. Svendsrud ◽  
R. Holm ◽  
K. Knutstad ◽  
...  

5049 Background: Lymph node involvement is the first indication of cervical cancer spread and a strong prognostic factor. The aims of the present study were to identify genes associated with lymph node involvement. Methods: The nodal status and tumor volume were determined from MR images in 48 patients with FIGO stage 2a to 4a at the time of diagnosis. cDNA microarray technique was used to identify genes that differed in expression between node positive and negative tumors. Biopsies enriched for carcinoma tissue were co-hybridized with a common reference sample in a dye-swap design. Quantitative real time PCR (qRT PCR) and immunohistochemistry were used to validate microarray results and determine protein expression of selected genes. Results: Pathologic lymph nodes were seen in 29 patients and normal nodes in 19. We identified 16 genes with higher and 15 with lower expression in node positive tumors as compared to the negative ones. QRT PCR data of 4 genes were consistent with these findings. CKS2, MRPS23, MRPL11, LSM3 and PDK2 were upregulated in node positive tumors suggesting high proliferation activity and oxygen consumption. MSN, KLF3 and TBX3 were downregulated. CKS2, MRPS23, MRPL11, PDK2, LSM3, TBX3, KLF3 and MSN were significantly related to progression free survival in univariate analysis. Protein expression, determined for CKS2 and MSN, was significantly correlated to survival, consistent with these results. In multivariate analysis including only gene variables, MRPL11, PDK2 and TBX3 were significant. Including also clinical and MRI variables, tumor volume, KLF3 and TBX3 were significant. NEK1, CSTA, ANX4 and DDOST were upregulated indicating activated DNA damage repair (NEK1) and resistance to apoptosis (CSTA, ANX4, DDOST). NTN4 and HYAL1, which are involved in cell-matrix interactions, were downregulated, suggesting mechanisms for increased cell migration and invasive growth. Conclusions: Our findings are consistent with known phenotypic characteristics of node positive cervical tumors, such as hypoxia and high lactate content. They point to molecular mechanisms for development of hypoxia, deregulation of glucose metabolism, activation of survival strategies and interactions between carcinoma cells and tumor stroma that may promote metastasis formation. No significant financial relationships to disclose.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4133-4133
Author(s):  
C. Dreyer ◽  
C. Le Tourneau ◽  
S. Faivre ◽  
V. Paradis ◽  
Q. Zhan ◽  
...  

4133 Background: Cholangiocarcinoma remains an orphan disease for which prospective studies are missing to evaluate the impact of systemic chemotherapy on survival. Methods: Univariate and multivariate analysis of parameters that might impact survival were analyzed in a cohort of 242 consecutive patients with cholangiocarcinoma treated in a single institution between 2000 and 2004. Variables were WHO performance status (PS), age, symptoms, tumor size, extent of the disease, lymph node involvement, site of metastasis, tumor markers, pathology, and type of treatment including surgery, chemotherapy and radiotherapy. Results: Statistically significant prognostic factors of survival in univariate analysis are displayed in the table : In multivariate analysis, PS, tumor size and surgery were independent prognostic factors. Subgroup analysis demonstrated that in patients with advanced diseases (lymph node involvement, peritoneal carcinomatosis and/or distant metastasis), patients who had no surgery benefited of chemotherapy (median survival 13.1 versus 7.4 months in patients with/without chemotherapy, p = 0.006). Moreover, survival was further improved when patients could benefit of chemotherapy following total and/or partial resection (median survival 22.9 versus 13.0 months in patients with/without chemotherapy, p = 0.03). Conclusions: This study strongly suggests the positive impact on survival of multimodality approaches including surgery and chemotherapy in patients with advanced cholangiocarcinoma. [Table: see text] No significant financial relationships to disclose.


2020 ◽  
Vol 9 (1) ◽  
pp. 250
Author(s):  
Yohann Dabi ◽  
Marie Gosset ◽  
Sylvie Bastuji-Garin ◽  
Rana Mitri-Frangieh ◽  
Sofiane Bendifallah ◽  
...  

The most important prognostic factor in vulvar cancer is inguinal lymph node status at the time of diagnosis, even in locally advanced vulvar tumors. The aim of our study was to identify the risk factors of lymph node involvement in these women, especially the impact of lichen sclerosis (LS). We conducted a retrospective population-based cross-sectional study in two French referral gynecologic oncology institutions. We included all women diagnosed with a primary invasive vulvar cancer. Epithelial alteration adjacent to the invasive carcinoma was found in 96.8% (n = 395). The most frequently associated was LS in 27.7% (n = 113). In univariate analysis, LS (p = 0.009); usual type VIN (p = 0.04); tumor size >2 cm and/or local extension to vagina, urethra or anus (p < 0.01), positive margins (p < 0.01), thickness (p < 0.01) and lymphovascular space invasion (LVSI) (p < 0.01) were significantly associated with lymph node involvement. In multivariate analysis, only LS (OR 2.3, 95% CI [1.2–4.3]) and LVSI (OR 5.6, 95% CI [1.7–18.6]) remained significantly associated with positive lymph node. LS was significantly associated with older patients (p = 0.005), anterior localization (p = 0.017) and local extension (tumor size > 2 cm: p = 0.001). LS surrounding vulvar cancer is an independent factor of lymph node involvement, with local extension and LVSI.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15180-e15180
Author(s):  
Jorge Leon ◽  
Fernando Namuche ◽  
Paola Catherine Montenegro ◽  
Claudio J. Flores

e15180 Background: The incidence of colorectal cancer (CRC) in Peru has increased in the last decades. In our population more than 80% of patients are stage I-III. Recurrence is one of the most important factors to consider in the survival of CRC patients. The aim of this study was to identify which factors influence in the recurrence of CRC in our population. Methods: We retrospectively reviewed the electronic medical records of 506 patients with stage I-III CRC from one specialized Peruvian cancer center between 2006 and 2016. Survival analysis (with recurrence as the event to evaluate) was performed with Kaplan Meier curves and Long-rank test. We use a preliminary univariate analysis to do the multivariate analysis with Cox regression. We performed a ROC curve analysis to determine an appropriate cut-off value for the tumor size (≥4.2). Results: In the univariate analysis we found that sidedness, tumor size (cut-off ≥4.2), CEA, lymph node involvement, stage, histological grade, LVI, PNI, and chemotherapy were statistically significant. In the multivariate model, tumor size [HR, 1.462; 95% CI, 1.065-2.217; p<0.05], lymph node involvement [HR, 0.136; 95% CI,0.41-0.447; p<0.001], and stage III [HR, 0.003; 95% CI, 0.263-0.758; p<0.05] retained a significant association and were independent factors with relapse disease. Conclusions: In stage I-III CRC pts it is important to evaluate tumor size, lymph node involvement and clinical stage as they are possible prognostic factors that will help our diagnosis and treatment along with other standard features.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 93-94
Author(s):  
Shaohua Wang ◽  
Xiaofeng Chen ◽  
An Wang

Abstract Background The pattern of lymph node metastasis and surgical method in superficial esophageal squamous cell carcinoma (sESCC) remains to be established. Methods Clinical data of all patients from 2003 to 2015 who underwent curative esophagectomy for thoracic sESCC were collected based on a prospectively-maintained database. The pattern of lymph node metastasis was analyzed based on depth of tumor invasion and tumor location. Results The involved lymph node region was associated to the tumor location, however, upper mediastinal and perigastric region was the most vulnerable region. As for the depth of tumor invasion, the incidence of lymph node metastasis increased with the depth of tumor invasion going deeper. No lymph node involvement was found in tumors invading proper mucosa (M2), while the distribution of positive lymph nodes in tumors invading the deepest 1/3 submucosa was similar to that in advanced ESCC. Lymphatic invasion, tumor location and upper mediastinal lymph node involvement were independent predictors for cervical lymph node metastasis. For patients without lymphatic invasion, the positive predictive value of upper mediastinal lymph node metastasis for positive cervical lymph node was low (0∼25%), while the negative predictive value was very high, wherever the tumor located (93.8∼100%). Conclusion Tumors invading till proper mucosa was the best indication for endoscopic mucosa resection; Tumors invading the deepest 1/3 submucosa might benefit from neoadjuvant therapy; Mediastinal-abdominal lymphadenectomy was essential for sESCC. For those without lymphatic invasion, cervical lymphadenectomy might be avoided in case of negative upper mediastinal lymph node. Disclosure All authors have declared no conflicts of interest.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 171-171
Author(s):  
Il Kim ◽  
DaeYoung Cheung ◽  
Jin Il Kim ◽  
Jae J. Kim

171 Background: The aims of this retrospective study were to analyze risk factors of lymph node metastasis undifferentiated-type early gastric cancer (UD-type EGC) and to select the suitable patient for endoscopic resection. Methods: We analyzed 368 patients who had undergone gastrectomy with lymphadenectomy for UD-type EGC between November 2001 and July 2016 at the Yeouido St. Mary’s Hospital. Using clinicopathological factors of patient age, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by univariate analysis and multivariate analysis. Results: Of the 368 patients, the lymph node metastases rate in patients with EGC was 48 patients (13%). 204 (55 %) had mucosal cancers and 164 (45 %) had submucosal cancers. Univariate analysis revealed > 60 age, > 2 cm, submucosal(sm), poorly cohesive carcinoma as significant prognostic factors. On multivariate analysis, > 60 age (odd ratio , 2.20; 95% confidence interval, 1.19~4.06), submucosal(odd ratio , 9.38; 95% confidence interval, 4.08~21.56), poorly cohesive carcinoma (odd ratio, 0.33; 95% confidence interval, 0.12~0.86) were independent risk factors for lymph node involvement. Conclusions: LNM-related factors in undiff-EGC were age, depth and pathology. We proposed that risk factors for metastases should be considered when choosing surgery for EGC.


2017 ◽  
Vol 106 (3) ◽  
pp. 264-273 ◽  
Author(s):  
Francesca Marciello ◽  
Olaf Mercier ◽  
Piero Ferolla ◽  
Jean-Yves Scoazec ◽  
Pier Luigi Filosso ◽  
...  

Background: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. Methods: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. Results: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. Conclusions: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16114-e16114
Author(s):  
Utku Oflazoglu ◽  
Temmuz Gurdal Insan ◽  
Yuksel Kucukzeybek ◽  
Umut Varol ◽  
Tarik Salman ◽  
...  

e16114 Background: We aimed to assess the prognostic effect of preoperative De Ritis (aspartate aminotransaminase/Alanine aminotransaminase) ratio and pathological variables to find out whether it is an independent prognostic factor in patients with non-metastatic CRC. Methods: We retrospectively evaluated the patients who underwent curative surgery for non-metastatic CRC between 2006 and 2017. The potential prognostic value of De Ritis ratio was assessed by using a ROC curve analysis. The effect of the De Ritis ratio was analyzed by the Kaplan–Meier method and Cox regression hazard models for patients’ disease-free survival (DFS) and overall survival (OS). Results: We had 921 CRC patients in total. The univariate analysis demonstrated that low De-Ritis ratio and several well-established prognostic factors, including well-differentiated tumor,negative lymph node involvement, lymphatic invasion, perineural invasion and surgical margin, left tumor localization and early-stage tumor were good prognostic factors in terms of DFS and OS. On the multivariate analysis, De-Ritis ratio, lymph node involvement, perineural invasion status, surgical margin statusand tumor localization were independent prognostic factors for DFS [ De-Ritis ratio HR 0.468, 95% CI 0.358-0.613,p < 0.001]. We also found that De-Ritis ratio, degree of differentiation, lymphatic invasion status, perineural invasion statusand stage were independent prognostic factors for OS on multivariate analysis [ De-Ritis ratio HR 0.354, 95% CI 0.407-0.702, p < 0.001]. Conclusions: Our study first established a connection between the preoperative De-Ritis ratio and patients undergoing curative resection for non-metastatic colorectal cancer, suggesting that De-Ritis ratio was a simple, inexpensive, and easily measurable marker as a prognostic factor and may help to identify high-risk patients for treatment decisions.


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