The prognostic significance of apical lymph node metastasis in patients with high-risk stage III colon cancer

Ishii, Kenichi; Watanabe, Jun; Goto, Kazumi; Suwa, Yusuke; Nakagawa, Kazuhiko; Suwa, Hirokazu; Ozawa, Mahito; Ishibe, Atsushi; Kunisaki, Chikara; Endo, Itaru

doi:10.1038/s41598-022-06054-5

Cited by 5 publications

(12 citation statements)

References 24 publications

(44 reference statements)

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“…30 It is possible that having a clear definition of the central lymph nodes (D3 volume) allows for the complete removal of these nodes in most patients, thus reducing the incidence of recurrence in them. 17,18,24 When analyzing the articles on both parallel progression theory 37,38 (both the primary tumor and lymph node metastases are polyclonal and seeding occurs in multiple waves) or linear progression theory 39,40 (cancer cells of primary tumors reach the apical lymph node along the adjacent lymph node pathway, leading to distant metastases), a common denominator can be found: radical resection may have a therapeutic effect by removing occult metastatic lymph nodes, implying that tumor biology plays a crucial role in the evolution of the disease. Lal et al 41 have recently shown a relationship between the primary tumor immune response and lymph node yield, resulting in improved survival.…”

Section: Discussionmentioning

confidence: 99%

“…This may imply that a more extensive mesenterectomy could lead to improved survival rates. 17 The aim of the current study was to re-stratify patients with stage I-III right-sided colon cancer based on the presence or absence of OTC and/or metastatic lymph nodes in the different levels of surgical dissection and to investigate the impact on oncologic outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I–III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection

Banipal

Štimec²,

Andersen³

et al. 2022

Journal of Gastrointestinal Surgery

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Background To establish the impact of re-stratification on the outcomes of patients (stage I–III right-sided colon cancer) based on the presence/absence of occult tumor cells (OTC) and/or metastatic lymph nodes in the different levels of surgical dissection. Methods Consecutive patients were drawn from a multicenter prospective trial. After surgery, the surgical specimen was divided into the D1/D2 and D3 volumes before being further analyzed separately. All lymph nodes were examined with cytokeratin CAM 5.2 immunohistochemically. Lymph nodes containing metastases and OTC (micrometastases; isolated tumor cells) were identified. Re-stratification was as follows: RS1, stages I/II, no OTC in D1/D2 and D3 volumes; RS2, stages I/II, OTC in D1/D2 and/or D3; RS3, stage III, lymph node metastases in D1/D2, with/without OTC in D3; RS4, stage III, lymph node metastases in D3, with/without OTC in D3. Results Eighty-seven patients (39 men, 68.4 + 9.9 years) were included. The standard stratified (SS) group contained the following: stages I/II (SS1) 57 patients; stage III (SS2) 30 patients. Re-stratified (RS) contained RS1 (38), RS2 (19), RS3 (24), and RS4 (6) patients. Lymph node ratio (OTC) RS2: 0.157 D1/D2; 0.035 D3 and 0.092 complete specimens. Lymph node ratio RS3: 0.113 D1/D2; complete specimen 0.056. Overall survival and disease-free survival were p = 0.875 and p = 0.049 for SS and p = 0.144 and p = 0.001 for RS groups, respectively. Conclusion This re-stratification identifies a patient group with poor prognosis (RS4). Removing this group from SS2 eliminates all the differences in survival between RS2 and RS3 groups. The level of dissection of the affected nodes may have an impact on survival. Clinical Trial “Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography” registered at http://clinicaltrials.gov/ct2/show/NCT01351714

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I–III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection

Banipal

Štimec²,

Andersen³

et al. 2022

Journal of Gastrointestinal Surgery

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“…Colon cancer (CC) is a common malignancy of the gastrointestinal tract and the third leading cause of cancer-related mortality worldwide ( 1 ). A large number of studies have shown that lymph node metastasis (LNM) is an independent risk factor for the prognosis of patients with CC ( 2 , 3 ). In addition, the scope of surgery for patients with CC should take full account of the preoperative lymph node status to avoid overtreatment ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

A novel potential inflammation-nutrition biomarker for predicting lymph node metastasis in clinically node-negative colon cancer

Duan

Wang

2023

Front. Oncol.

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BackgroundThe purpose of this study is to investigate the predictive significance of (platelet × albumin)/lymphocyte ratio (PALR) for lymph node metastasis (LNM) in patients with clinically node-negative colon cancer (cN0 CC).MethodsData from 800 patients with primary CC who underwent radical surgery between March 2016 and June 2021 were reviewed. The non-linear relationship between PALR and the risk of LNM was explored using a restricted cubic spline (RCS) function while a receiver operating characteristic (ROC) curve was developed to determine the predictive value of PALR. Patients were categorized into high- and low-PALR cohorts according to the optimum cut-off values derived from Youden’s index. Univariate and multivariate logistic regression analyses were used to identify the independent indicators of LNM. Sensitivity analysis was performed to repeat the main analyses with the quartile of PALR.ResultsA total of eligible 269 patients with primary cN0 CC were retrospectively selected. The value of the area under the ROC curve for PALR for predicting LNM was 0.607. RCS visualized the uptrend linear relationship between PALR and the risk of LNM (p-value for non-linearity > 0.05). PALR (odds ratio = 2.118, 95% confidence interval, 1.182-3.786, p = 0.011) was identified as an independent predictor of LNM in patients with cN0 CC. A nomogram incorporating PALR and other independent predictors was constructed with an internally validated concordance index of 0.637. The results of calibration plots and decision curve analysis supported a good performance ability and the sensitivity analysis further confirmed the robustness of our findings.ConclusionPALR has promising clinical applications for predicting LNM in patients with cN0 CC.

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“…Activated cancer cells developing high invasive potential contribute to tumor spread through metastasis process via blood vessels and lymphatic system ( Pretzsch et al, 2019 ). Metastatic CRC (mCRC) patients, clinically described for the presentation of distant lymph node metastasis, have a high mortality rate ( Ishii et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The Anticancer Effects of the Pro-Apoptotic Benzofuran-Isatin Conjugate (5a) Are Associated With p53 Upregulation and Enhancement of Conventional Chemotherapeutic Drug Efficiency in Colorectal Cancer Cell Lines

et al. 2022

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The present study aimed to investigate in-depth a cytotoxic novel benzofuran-isatin conjugate (5a, 3-methyl-N'-(2-oxoindolin-3-ylidene)benzofuran-2-carbohydrazide) with promising potential anticancer activities in colorectal adenocarcinoma HT29 and metastatic colorectal cancer (CRC) SW620 cell lines. Thus, the primary cell events involved in tumorigenicity, tumor development, metastasis, and chemotherapy response were explored. Both CRC cell lines were exposed to different concentrations of Compound 5a and then subjected to real-time cell viability, migration, and invasion assays, colony formation and cytotoxicity assays, and flow cytometry for cell cycle analysis and apoptosis determination. Western blot and RT-qPCR were performed to assess the protein and transcript expression levels of epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis markers. We showed that the Compound 5a treatment exhibited anticancer effects through inhibition of HT29 and SW620 cell viability, migration, and invasion, in a dose-dependent manner, which were associated with the upregulation of the tumor suppressor p53. Compound 5a also inhibited the colony formation ability of HT29 and SW620 cells and reversed EMT markers E-cadherin and N-cadherin expression. CRC cell exposure to Compound 5a resulted in a cell cycle arrest at the G1/G0 phase in HT29 cells and at the G2/M phase in SW620 cells, along with the downregulation of cyclin A1 expression, described to be involved in the S phase entry. Furthermore, Compound 5a-induced apoptosis was associated with the downregulation of the anti-apoptotic Bcl-xl marker, upregulation of pro-apoptotic Bax and cytochrome c markers, and increased mitochondrial outer membrane permeability, suggesting the involvement of mitochondria-dependent apoptosis pathway. In addition, the combination studies of Compound 5a with the main conventional chemotherapeutic drugs 5-fluorouracil, irinotecan, and oxaliplatin showed a more potent cytotoxic effect in both CRC cells than a single treatment. In conclusion, our findings described the interesting in vitro anticancer properties of Compound 5a, shown to have possible antitumor, antimetastatic, and pro-apoptotic activities, with the enhancement of the cytotoxic efficiency of conventional chemotherapeutic drugs. In vivo studies are requested to confirm the promising anticancer potential of Compound 5a for CRC therapy.

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The prognostic significance of apical lymph node metastasis in patients with high-risk stage III colon cancer

Cited by 5 publications

References 24 publications

Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I–III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection

Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I–III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection

A novel potential inflammation-nutrition biomarker for predicting lymph node metastasis in clinically node-negative colon cancer

The Anticancer Effects of the Pro-Apoptotic Benzofuran-Isatin Conjugate (5a) Are Associated With p53 Upregulation and Enhancement of Conventional Chemotherapeutic Drug Efficiency in Colorectal Cancer Cell Lines

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