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Original Article
Colorectal cancer
Lymphovascular invasion in colorectal cancers: can we predict it preoperatively?
Elbrus Zarbaliyev1orcid, Nihan Turhan2orcid, Sebahattin Çelik3orcid, Mehmet Çağlıkülekçi1orcid
Annals of Coloproctology 2024;40(3):245-252.
DOI: https://doi.org/10.3393/ac.2023.00458.0065
Published online: June 25, 2024

1Department of General Surgery, Gaziosmanpaşa Hospital, Istanbul Yeni Yüzyil University, İstanbul, Türkiye

2Department of General Surgery, Martyr Prof. Dr. İlhan Varank Sancaktepe Training and Research Hospital, İstanbul, Türkiye

3Department of General Surgery, Van Yüzüncü Yil University, Van, Türkiye

Correspondence to: Elbrus Zarbaliyev, MD Department of General Surgery, Gaziosmanpaşa Hospital, Istanbul Yeni Yüzyil University, Merkez, Çukurçeşme Cd. No:51, İstanbul 34245, Turkey Email: elben@yahoo.com.tr
• Received: July 3, 2023   • Revised: July 26, 2023   • Accepted: October 13, 2023

© 2024 The Korean Society of Coloproctology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Purpose
    This study aimed to investigate preoperative predictors of lymphovascular invasion (LVI), which is a poor prognostic factor usually detected postoperatively in patients with colorectal cancer.
  • Methods
    Results for all patients operated on for colorectal cancer between January 1, 2006, and December 31, 2021, were retrospectively analyzed. Potential preoperative factors and postoperative pathology results were recorded. The patients were categorized as those with LVI and those without LVI. Potential factors that may be associated with LVI were compared between the 2 groups.
  • Results
    The study included 335 patients. The incidence of LVI was 3.11 times higher in patients with ascending colon tumors (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.34–7.23; P=0.008) and 4.28 times higher in those with metastatic tumors (OR, 4.28; 95% CI, 2.18–8.39; P<0.001). Diabetes mellitus was inversely related to LVI in colorectal cancer patients; specifically, LVI was 56% less common in colorectal cancer patients with diabetes mellitus, irrespective of its duration (OR, 0.44; 95% CI, 0.25–0.76; P<0.001).
  • Conclusion
    The presence of preoperative LVI in colorectal cancer patients is difficult to predict. In particular, the effect of the effect of factors such as chronic disease accompanied by microvascular pathologies on LVI is still unclear. Advances in the neoadjuvant treatment of colorectal cancer patients, who are becoming more widespread every day, will encourage the investigation of different methods of preoperatively predicting LVI as a poor prognostic factor in these patients.
Colorectal cancer (CRC) is among the most common types of cancer. Approximately 1.5 million patients are newly diagnosed worldwide every year; this number will soon exceed 2 million [1]. CRC treatment generally takes a multidisciplinary approach, and surgery, chemotherapy, and radiotherapy are applied depending on the stage of the disease. In recent years, the number of studies recommending neoadjuvant chemotherapy (NCT) in CRC treatment, especially in the locally advanced stage, has been increasing [24]. Many studies investigating the effects of neoadjuvant therapy on survival and relapse have reported positive results, and CRC patients may benefit from this treatment when they have accompanying poor prognostic factors [3, 5]. Therefore, it has become crucial to determine poor prognostic factors in CRC patients [2, 4]. Preoperative radiological and laboratory methods can determine the following factors: distant metastasis, invasion of surrounding organs, and regional metastatic lymph node involvement. However, the following parameters are difficult to determine before surgery: definitive T category, definitive metastatic lymph node count, perineural invasion, and lymphovascular invasion (LVI). LVI is a prognostic factor independent of and worse than lymph node involvement, which can cause early metastasis as tumor cells cross the endothelial barrier in CRC patients [610]. In fact, LVI is a poor prognostic factor in CRC patients with negative lymph nodes [11]. Although the exact mechanism and etiological factors of LVI in tumor tissues are still unclear, studies are ongoing on this subject [9, 12]. NCT is thought to be effective for preventing the development of local micrometastases that develop early in this patient group [13]. Therefore, several studies have attempted to predict the presence of LVI preoperatively in CRC patients [1416]. However, these studies have provided limited information on the preoperative prediction of LVI due to including a small number of patients and a limited range of examinations, such as only radiological evaluation and blood test results. The effects on LVI of chronic factors such as diabetes mellitus (DM), hypertension (HT), and smoking, which cause deterioration of microvascular permeability, are not sufficiently known. For this reason, there is a need for studies involving many preoperative factors, including chronic diseases and behaviors. In this study, we aimed to examine whether various parameters are associated with LVI in CRC patients undergoing surgery to identify whether any of those parameters are useful for predicting LVI preoperatively.
Ethics statement
This study was approved by the Ethics Committee of the Istanbul Yeni Yüzyıl University (No. 2022/07-884). Written informed consents were obtained from the patients.
Study design and patients
The results of all patients of both sexes operated on for CRC between January 1, 2006, and December 31, 2021, were retrospectively examined. All patients who had been diagnosed histologically with CRC were included in this study. Patients whose treatment was not completed at our center, who received neoadjuvant chemotherapy, and whose surgery occurred under emergency conditions were excluded from the study. The study analyzed the following information: age, sex, additional chronic diseases and their duration, complete blood count results, smoking, alcohol consumption status and its duration, American Society of Anesthesiologists (ASA) physical status, tumor location, preoperative positron emission tomography–computed tomography (PET-CT) results for eradication, the tumor’s maximum standardized uptake value (SUVmax), its radiologically determined size, its estimated volume, and metastasis status. In addition, the patients’ postoperative pathology results were examined. Detection of LVI was routinely determined by 2 pathologists using hematoxylin-eosin and elastin staining. The patients were categorized as those with LVI and those without LVI.
Statistical analysis
The Kolmogorov-Smirnov test was used to assess whether the variables followed a normal distribution. Continuous variables were presented as median (range, minimum to maximum). Categorical variables were reported as numbers and percentages. According to the normality test results, the Mann-Whitney U-test was used to compare the 2 groups. The Pearson chi-square test, Fisher exact test, and Fisher-Freeman-Halton test were used for comparing categorical variables. Multiple logistic regression analysis was performed to determine the risk factors affecting the incidence of LVI. Variables were included in the multiple logistic regression model by using the forward likelihood ratio method. The significant variables in the model became independent variables. The multiple logistic regression models were statistically significant (P<0.001). IBM SPSS ver. 21.0 (IBM Corp) was used for statistical analysis, and a P-value <0.05 was set as the threshold for statistical significance.
A total of 335 patients, 146 women (43.6%) and 189 men (56.4%), were included in the study. All patients had adenocarcinoma, and 63 patients (18.8%) had mucinous components. Preoperative metastasis was present in 57 patients (17.0%); 34 patients (10.1%) had preoperative radiotherapy due to rectal cancer. Regarding tumor type, 78 patients (23.3%) had ascending tumors, 42 patients (12.5%) had transverse tumors, 44 patients (13.1%) had descending tumors, 104 patients (31.0%) had sigmoid colon tumors, and 67 patients (20.0%) had rectal tumors. LVI was present in 178 patients (53.1%) (Fig. 1). Other poor prognostic factors in CRC were significantly more common in patients with LVI (Table 1).
The univariate analysis between the groups found several factors to be more prevalent in patients with LVI, including ascending colon tumor location (P=0.007), the presence of preoperative metastasis (P<0.001), a high ASA physical status (P=0.015), low hemoglobin value (P=0.008), low lymphocyte value (P=0.043), and radiologically measured tumor thickness (P=0.020). In contrast, DM was significantly less common in patients with LVI (P=0.003) (Table 2).
The multivariate analysis, performed by including the significant factors from the univariate analysis, found that the incidence of LVI was 3.11 (Compared to the descending column's reference value of 1) times higher in patients with ascending colon tumors (P=0.008; 95% confidence interval [CI], 1.34–7.23) and 4.28 times higher in those with metastatic tumors (OR, 4.28; 95% CI, 2.18–8.39; P<0.001). DM was inversely related to LVI in colorectal cancer patients; specifically, LVI was 56% less common in colorectal cancer patients with DM, irrespective of its duration (OR, 0.44; 95% CI, 0.25–0.76; P<0.005) (Table 3).
This study aimed to identify possible preoperative factors likely to be associated with LVI in CRC. Studies have indicated that LVI is present in 5.2% to 89.5% of patients, depending on the CRC stage [1721]. In our study, this proportion was 53.13%, which is consistent with the literature.
LVI was previously considered not to be a significant factor in CRC patients [22, 23]. Later, perceptions changed, and LVI came to be viewed as a stage-independent poor prognostic factor for CRC patients. In fact, in a study examining T3N0 patients with negative lymph nodes [24], LVI was a critical negative prognostic factor after adjuvant treatment and considering it during the treatment process was suggested. Lee et al. [25] stated that LVI had a poor prognostic effect in rectal cancer (RC) patients receiving neoadjuvant chemoradiotherapy and emphasized that treatments might be more effective if LVI status were known in advance. Zhang et al. [16] reported similar results. Wang et al. [7] reported that better treatment options could be determined for CRC patients by developing a new survival nomogram containing LVI. Therefore, it is recommended to monitor treatment particularly carefully in CRC patients with LVI and follow-up frequently with them. Huh et al. [26] proposed a new histological rating to be used in the follow-up of CRC patients, which considers the presence of LVI.
Although many studies have shown that DM is associated with poor prognosis in CRC patients, as in all cancers, its effect on LVI remains a matter of debate [2729]. Little information in the literature provides an idea of how LVI is affected in CRC patients with DM. Some studies have reported that DM did not affect LVI in CRC patients [3032] or that LVI was more common in CRC patients with DM [28]. In contrast, in our study the prevalence of DM was significantly lower in patients with LVI. LVI was detected in 78 patients (38.6%) with DM and 257 patients (57.6%) without DM. The results of our study differ from those previously reported in literature, although relatively few studies have dealt with this topic. Hyperglycemia in DM patients causes endothelial and wall damage in microvascular structures by using different complex biochemical pathways, leading to dysfunction [33, 34]. Studies have shown that this process starts during the prediabetes period [35]. Increased permeability in microvascular structures damages tissues due to perivascular inflammation and fibrosis [32, 35, 36]. As a result, the microvascular and perivascular pathological condition may reduce the migration of tumor cells and lower the incidence of LVI in this patient group. Adverse effects of using metformin on tumors are known in patients with CRC with type 2 DM [37]. It is thought that metformin use may also have an effect on LVI. In our study, however, LVI was not found to be associated with the type of diabetes (P=0.301) or the duration of diabetes (P=0.061). As seen from our results, the behavior of CRC cells in the case of impaired microvascular permeability, in which complex mechanisms related to DM play a role, warrants further investigation [28, 33]. Except for DM, other chronic conditions or behavior (HT, coronary artery disease, chronic obstructive pulmonary disease, chronic renal failure, smoking, and alcohol use) were not associated with LVI.
Although LVI is a significant prognostic factor, it is usually detected postoperatively. In their respective studies, Janjan et al. [38] and Du et al. [39] reported that preoperative radiotherapy did not affect LVI. For this reason, we included RC patients who received preoperative radiotherapy in our study. Some studies investigating the presence of preoperative LVI have been reported in the literature. In their study examining RC, according to Ge et al. [15], the tumor volume obtained as a result of computed tomography may help determine LVI. Zhang et al. [16] suggested using a new multimodal radiomics model to determine the presence of LVI preoperatively in patients with RC. Kim et al. [40] tried to determine LVI in RC patients using preoperative pelvic magnetic resonance imaging. They detected LVI with 68.2% sensitivity and 93.2% specificity using perivascular infiltrative signals. Generally, such studies are related to RC, and there has been no comprehensive literature on colon cancer. In our study, no statistically significant differences were found according to tumor volume measured by preoperative radiological methods or SUVmax measured by PET-CT.
In many studies, LVI rates are high in metastatic CRC. Studies have shown that as a poor prognostic factor, LVI is associated with relapse and distant metastasis [27, 40, 41]. This resulted from the transfer of tumor cells to circulatory system due to LVI. In our study, LVI was present at a higher rate in metastatic CRC patients, which is compatible with the literature.
The prevalence of LVI varies according to the tumor location in CRC patients, and studies have generally indicated the right and left sides of the colon and the rectum region. In a retrospective cohort study involving 158,777 patients with T1 and T2 tumors, Al-Sukhni et al. [20] detected LVI in tumors originating form the appendix (25.1%), colon (28.1%), rectosigmoid (27.4%), and rectum (18.1%). Zhong et al. [8] found no significant relationship between LVI and tumor site (right colon, left colon, and rectum) in their study involving stage III CRC patients. Similarly, in other studies involving different-stage CRC patients, no relationship was observed between the tumor site and LVI [4245]. In our study, 52 patients (29.2%) with LVI had a tumor in the ascending colon, 26 patients (14.6%) had a tumor in the transverse colon, 24 patients (13.5%) had a tumor in the descending colon, 42 patients (23.6%) had a tumor in the sigmoid colon, and 34 patients (19.1%) had a tumor located in the rectum. We found that LVI was significantly more common in CRC located in the ascending colon than in the other colon segments (OR, 3.11; 95% CI, 1.34–7.23; P=0.008). Two factors may be relevant for explaining this finding: first, tumors are detected in the ascending colon more frequently in the advanced T category; and second, a high T category is associated with LVI [7, 27, 46]. In fact, 24 of 52 patients (46.2%) with T4 tumors had a mass located in the ascending colon in our study.
The major limitation of this study is that it was single-center and retrospective. In retrospective studies, errors may occur in the data because of recall bias or incorrect recording. A second significant limitation is that data on tumor markers and other factors, such as glycated hemoglobin, were not available.
In conclusion, the preoperative LVI status in CRC patients has still not been studied adequately. The effects on LVI of chronic diseases, such as DM, especially those accompanied by microvascular pathologies, remain unclear. Advances in the neoadjuvant treatment of CRC patients, who are becoming more widespread every day, will encourage the investigation of different methods of preoperatively predicting LVI as a poor prognostic factor in these patients.

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: EZ; Data curation: EZ, SÇ, Formal analysis: SÇ; Investigation: EZ, NT; Methodology: EZ, MÇ; Project administration: MÇ, SÇ; Visualization: EZ; Writing–original draft: EZ, SÇ, NT; Writing–review & editing: SÇ, MÇ. All authors read and approved the final manuscript.

Fig. 1.
The prevalence of lymphovascular invasion (LVI) by tumor location.
ac-2023-00458-0065f1.jpg
Table 1.
Other poor prognostic factors associated with lymphovascular invasion (n=335)
Factor Lymphovascular invasion
P-value
Yes (n=178) No (n=157)
T category <0.001a
 T1 0 (0) 10 (6.4)
 T2 10 (5.6) 22 (14.0)
 T3 116 (65.2) 109 (69.4)
 T4 52 (29.2) 16 (10.2)
Perineural invasion 104 (58.4) 26 (16.6) <0.001a
Nonmetastatic lymph node 17 (0–84) 17 (3–43) 0.360b
Metastatic lymph node 3 (0–55) 0 (0–66) <0.001b

Values are presented as number (%) or median (range).

aPearson chi-square test.

bMann-Whitney U-test.

Table 2.
Univariate analysis of preoperative factors for lymphovascular invasion estimation (n=335)
Factor Lymphovascular invasion
P-value
Yes (n=178) No (n=157)
Sex 0.156a
 Female 84 (47.2) 62 (39.5)
 Male 94 (52.8) 95 (60.5)
Age (yr) 67 (28–92) 64 (25–93) 0.393b
Tumor location 0.007a
 Ascending colon 52 (29.2) 26 (16.6)
 Transverse colon 26 (14.6) 16 (10.2)
 Descending colon 24 (13.5) 20 (12.7)
 Sigmoid colon 42 (23.6) 62 (39.5)
 Rectum 34 (19.1) 33 (21.0)
Tumor differentiation 0.077a
 Low 14 (7.9) 6 (3.8)
 Moderate 158 (88.7) 139 (88.6)
 Good 6 (3.4) 12 (7.6)
Preoperative metastasis 48 (27.0) 15 (9.55) <0.001a
Mucinous component 28 (15.7) 29 (18.47) 0.505a
Preoperative radiotherapy 18 (10.1) 16 (10.19) 0.981a
ASA PS classification 0.015c
 I 18 (10.1) 17 (10.8)
 II 98 (55.1) 108 (68.8)
 III 60 (33.7) 32 (20.4)
 IV 2 (1.1) 0 (0)
Hemoglobin (g/dL) 10.9 (7.8–23.3) 11.9 (6.4–16.3) 0.008b
White blood cell (×109/L) 7.38 (2.43–22.41) 7.65 (3.17–14.60) 0.377b
Platelet (×109/L) 296 (2.33–582) 268 (2.86–824) 0.248b
Neutrophil (×109/L) 4.87 (1.27–18.99) 4.92 (1.17–12.15) 0.730b
Monocyte (×109/L) 0.62 (0.06–1.84) 0.59 (0.24–1.78) 0.503b
Lymphocyte (×109/L) 1.60 (0.32–3.28) 1.70 (0.35–4.36) 0.043b
Neutrophil to lymphocyte ratio 2.84 (0.64–25.96) 2.97 (0.70–13.97) 0.337b
PET-SUV 18.8 (4.1–41.1) 19.3 (9.4–36.1) 0.536b
Body mass index (kg/m2) 26.67 (17.01–40.58) 26.67 (17.16–39.81) 0.441b
Hypertension 86 (48.3) 70 (44.6) 0.495a
 Duration (yr) 10 (1–25) 9 (1–30) 0.076b
Coronary artery disease 46 (25.84) 32 (20.38) 0.238a
 Duration (yr) 6 (2–13) 5 (1–12) 0.061b
Diabetes mellitus 30 (16.9) 48 (30.6) 0.003a
 Type 1 2 (6.7) 8 (16.7) 0.301d
 Type 2 28 (93.3) 40 (83.3)
 Duration (yr) 10 (1–20) 7 (1–31) 0.096b
Chronic obstructive pulmonary disease 8 (4.5) 8 (5.1) 0.797a
Chronic renal failure 10(5.62) 6 (3.87) 0.457a
Smoking 50 (28.1) 52 (33.1) 0.318a
 Duration (yr) 25 (5–50) 30 (5–60) 0.131b
Alcohol consumption status 6 (3.37) 12 (7.64) 0.084a

Values are presented as number (%) or median (range).

ASA, American Society of Anesthesiologists; PS, phyical status; PET, positron emission tomography; SUV, standardized uptake value.

aPearson chi-square test.

bMann-Whitney U-test.

cFisher-Freeman-Halton test.

dFisher exact test.

Table 3.
Multivariate analysis of preoperative factors for lymphovascular invasion estimation (n=335)
Factor Wald test Odds ratio 95% Confidence interval P-value
Tumor location
 Descending colon - 1 (Reference) - -
 Ascending colon 6.94 3.11 1.34–7.23 0.008
 Transverse colon 2.29 2.05 0.81–5.22 0.130
 Sigmoid colon 0.13 0.87 0.40–1.89 0.719
 Rectum 0.46 1.34 0.58–3.09 0.497
Diabetes mellitus
 No - 1 (Reference) - -
 Yes 8.49 0.44 0.25–0.76 0.004
Preoperative metastasis
 No - 1 (Reference) - -
 Yes 17.94 4.28 2.18–8.39 <0.001

Model χ2=43.93, P<0.001; Hosmer and Lemeshow test, P=0.875.

  • 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–49.ArticlePubMedPDF
  • 2. Body A, Latham S, Kong JB, Raghunath A, Segelov E. Stage III colon cancer: is neoadjuvant chemotherapy ready for prime time?: a narrative review of neoadjuvant chemotherapy for colon cancer. Dig Med Res 2021;4:16. Article
  • 3. Seymour MT, Morton D; International FOxTROT Trial Investigators. FOxTROT: an international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer. J Clin Oncol 2019;37(15_suppl): 3504. Article
  • 4. Cheong CK, Nistala KR, Ng CH, Syn N, Chang HS, Sundar R, et al. Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review. J Gastrointest Oncol 2020;11:847–57.ArticlePubMedPMC
  • 5. Kamer E, Çolak T. Role of neoadjuvant chemotherapy in locally advanced colon cancer. Turk J Colorectal Dis 2022;32:6–9.Article
  • 6. Huh JW, Kim HR, Kim YJ. Lymphovascular or perineural invasion may predict lymph node metastasis in patients with T1 and T2 colorectal cancer. J Gastrointest Surg 2010;14:1074–80.ArticlePubMedPDF
  • 7. Wang X, Cao Y, Ding M, Liu J, Zuo X, Li H, et al. Oncological and prognostic impact of lymphovascular invasion in colorectal cancer patients. Int J Med Sci 2021;18:1721–9.ArticlePubMedPMC
  • 8. Zhong JW, Yang SX, Chen RP, Zhou YH, Ye MS, Miao L, et al. Prognostic value of lymphovascular invasion in patients with stage iii colorectal cancer: a retrospective study. Med Sci Monit 2019;25:6043–50.ArticlePubMedPMC
  • 9. Jiang HH, Zhang ZY, Wang XY, Tang X, Liu HL, Wang AL, et al. Prognostic significance of lymphovascular invasion in colorectal cancer and its association with genomic alterations. World J Gastroenterol 2019;25:2489–502.ArticlePubMedPMC
  • 10. Gao M, Guo Y, Xiao Y, Shang X. Comprehensive analyses of correlation and survival reveal informative lncRNA prognostic signatures in colon cancer. World J Surg Oncol 2021;19:104. ArticlePubMedPMCPDF
  • 11. van Wyk HC, Roxburgh CS, Horgan PG, Foulis AF, McMillan DC. The detection and role of lymphatic and blood vessel invasion in predicting survival in patients with node negative operable primary colorectal cancer. Crit Rev Oncol Hematol 2014;90:77–90.ArticlePubMed
  • 12. Kariri YA, Aleskandarany MA, Joseph C, Kurozumi S, Mohammed OJ, Toss MS, et al. Molecular complexity of lymphovascular invasion: the role of cell migration in breast cancer as a prototype. Pathobiology 2020;87:218–31.ArticlePubMedPDF
  • 13. Roth MT, Eng C. Neoadjuvant chemotherapy for colon cancer. Cancers (Basel) 2020;12:2368. ArticlePubMedPMC
  • 14. Chen N, Li W, Huang K, Yang W, Huang L, Cong T, et al. Increased platelet-lymphocyte ratio closely relates to inferior clinical features and worse long-term survival in both resected and metastatic colorectal cancer: an updated systematic review and meta-analysis of 24 studies. Oncotarget 2017;8:32356–69.ArticlePubMedPMC
  • 15. Ge YX, Xu WB, Wang Z, Zhang JQ, Zhou XY, Duan SF, et al. Prognostic value of CT radiomics in evaluating lymphovascular invasion in rectal cancer: diagnostic performance based on different volumes of interest. J Xray Sci Technol 2021;29:663–74.ArticlePubMed
  • 16. Zhang Y, He K, Guo Y, Liu X, Yang Q, Zhang C, et al. A novel multimodal radiomics model for preoperative prediction of lymphovascular invasion in rectal cancer. Front Oncol 2020;10:457. ArticlePubMedPMC
  • 17. Kim S, Huh JW, Lee WY, Yun SH, Kim HC, Cho YB, et al. Lymphovascular invasion, perineural invasion, and tumor budding are prognostic factors for stage I colon cancer recurrence. Int J Colorectal Dis 2020;35:881–5.ArticlePubMedPDF
  • 18. Bozkurt O, Firat ST, Dogan E, Inane M, Deniz K, Zararsiz GE, et al. The impact of lymphovascular invasion on recurrence-free survival in patients with high-risk stage II colorectal cancer treated with adjuvant therapy. Erciyes Med J 2019;41:191–5.Article
  • 19. Sternberg A, Amar M, Alfici R, Groisman G. Conclusions from a study of venous invasion in stage IV colorectal adenocarcinoma. J Clin Pathol 2002;55:17–21.ArticlePubMedPMCPDF
  • 20. Al-Sukhni E, Attwood K, Gabriel EM, LeVea CM, Kanehira K, Nurkin SJ. Lymphovascular and perineural invasion are associated with poor prognostic features and outcomes in colorectal cancer: a retrospective cohort study. Int J Surg 2017;37:42–9.ArticlePubMed
  • 21. Yuan H, Dong Q, Zheng B, Hu X, Xu JB, Tu S. Lymphovascular invasion is a high risk factor for stage I/II colorectal cancer: a systematic review and meta-analysis. Oncotarget 2017;8:46565–79.ArticlePubMedPMC
  • 22. Khankhanian N, Mavligit GM, Russell WO, Schimek M. Prognostic significance of vascular invasion in colorectal cancer of Dukes' B class. Cancer 1977;39:1195–200.ArticlePubMed
  • 23. Minsky BD, Mies C, Recht A, Rich TA, Chaffey JT. Resectable adenocarcinoma of the rectosigmoid and rectum. II. The influence of blood vessel invasion. Cancer 1988;61:1417–24.ArticlePubMed
  • 24. Lee H, Yoo SY, Park IJ, Hong SM, Lim SB, Yu CS, et al. The prognostic reliability of lymphovascular invasion for patients with T3N0 colorectal cancer in adjuvant chemotherapy decision making. Cancers (Basel) 2022;14:2833. ArticlePubMedPMC
  • 25. Lee JH, Jang HS, Kim JG, Cho HM, Shim BY, Oh ST, et al. Lymphovascular invasion is a significant prognosticator in rectal cancer patients who receive preoperative chemoradiotherapy followed by total mesorectal excision. Ann Surg Oncol 2012;19:1213–21.ArticlePubMedPDF
  • 26. Huh JW, Lee WY, Shin JK, Park YA, Cho YB, Kim HC, et al. A novel histologic grading system based on lymphovascular invasion, perineural invasion, and tumor budding in colorectal cancer. J Cancer Res Clin Oncol 2019;145:471–7.ArticlePubMedPDF
  • 27. Akagi Y, Adachi Y, Ohchi T, Kinugasa T, Shirouzu K. Prognostic impact of lymphatic invasion of colorectal cancer: a single-center analysis of 1,616 patients over 24 years. Anticancer Res 2013;33:2965–70.PubMedPDF
  • 28. Sharma A, Ng H, Kumar A, Teli K, Randhawa J, Record J, et al. Colorectal cancer: histopathologic differences in tumor characteristics between patients with and without diabetes. Clin Colorectal Cancer 2014;13:54–61.ArticlePubMed
  • 29. Lin CY, Lin CL, Huang WT, Peng CJ, Su SB, Guo HR. Effect of diabetes mellitus comorbidity on outcomes in stages II and III colorectal cancer. Asia Pac J Clin Oncol 2022;18:e289–96.ArticlePubMedPDF
  • 30. Ota Y, Ishihara S, Yasuda K, Kawai K, Hata K, Nozawa H, et al. Prognostic impact of diabetes mellitus on colorectal cancer. Biol Med (Aligarh) 2016;8:299. ArticlePDF
  • 31. Huang CW, Sun LC, Shih YL, Tsai HL, Chen CW, Yeh YS, et al. The impact on clinical outcome of high prevalence of diabetes mellitus in Taiwanese patients with colorectal cancer. World J Surg Oncol 2012;10:76. ArticlePubMedPMCPDF
  • 32. Gao RZ, Gu J, Du CZ, Li M. Impact of diabetes mellitus on clinicopathological factors and prognosis of patients with colorectal cancer. Zhonghua Wai Ke Za Zhi 2010;48:88–92. Chinese.PubMedPDF
  • 33. Srivastava SP, Goodwin JE. Cancer biology and prevention in diabetes. Cells 2020;9:1380. ArticlePubMedPMC
  • 34. Barrett EJ, Liu Z, Khamaisi M, King GL, Klein R, Klein BE, et al. Diabetic microvascular disease: an endocrine society scientific statement. J Clin Endocrinol Metab 2017;102:4343–410.ArticlePubMedPMC
  • 35. Stehouwer CD. Microvascular dysfunction and hyperglycemia: a vicious cycle with widespread consequences. Diabetes 2018;67:1729–41.ArticlePubMedPDF
  • 36. Hung YJ, Lin KH, Chou CT, Ko CJ, Lin PY, Hsieh CE, et al. Invasion of artificial vascular graft into duodenal bulb after living donor liver transplantation. Surg Sci 2015;6:71–4.ArticlePDF
  • 37. Dulskas A, Patasius A, Linkeviciute-Ulinskiene D, Zabuliene L, Urbonas V, Smailyte G. Metformin increases cancer specific survival in colorectal cancer patients: national cohort study. Cancer Epidemiol 2019;62:101587. ArticlePubMed
  • 38. Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999;44:1027–38.ArticlePubMed
  • 39. Du CZ, Xue WC, Cai Y, Li M, Gu J. Lymphovascular invasion in rectal cancer following neoadjuvant radiotherapy: a retrospective cohort study. World J Gastroenterol 2009;15:3793–8.ArticlePubMedPMC
  • 40. Kim Y, Chung JJ, Yu JS, Cho ES, Kim JH. Preoperative evaluation of lymphovascular invasion using high-resolution pelvic magnetic resonance in patients with rectal cancer: a 2-year follow-up study. J Comput Assist Tomogr 2013;37:583–8.ArticlePubMed
  • 41. Nikberg M, Chabok A, Letocha H, Kindler C, Glimelius B, Smedh K. Lymphovascular and perineural invasion in stage II rectal cancer: a report from the Swedish colorectal cancer registry. Acta Oncol 2016;55:1418–24.ArticlePubMed
  • 42. Lim SB, Yu CS, Jang SJ, Kim TW, Kim JH, Kim JC. Prognostic significance of lymphovascular invasion in sporadic colorectal cancer. Dis Colon Rectum 2010;53:377–84.ArticlePubMed
  • 43. Shalkamy MS, Bae JH, Lee CS, Han SR, Kim JH, Kye BH, et al. Oncological impact of vascular invasion in colon cancer might differ depending on tumor sidedness. J Minim Invasive Surg 2022;25:53–62.ArticlePubMedPMC
  • 44. Matsumoto K, Nakayama Y, Inoue Y, Minagawa N, Katsuki T, Shibao K, et al. Lymphatic microvessel density is an independent prognostic factor in colorectal cancer. Dis Colon Rectum 2007;50:308–14.ArticlePubMed
  • 45. Zenger S, Gürbüz B, Can U, Bilgiç Ç, Sobutay E, Balık E, et al. Differences between right and left colon cancers in terms of clinicopathological features and long-term oncological outcomes. Turk J Colorectal Dis 2020;30:253–60.Article
  • 46. Aktekin A, Özkara S, Gürleyik G, Odabaşi M, Müftüoğlu T, Sağlam A. The factors effecting lymphovascular invasion in adenocarcinoma of the colon and rectum. Indian J Surg 2015;77:314–8.ArticlePubMedPDF

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        Lymphovascular invasion in colorectal cancers: can we predict it preoperatively?
        Ann Coloproctol. 2024;40(3):245-252.   Published online June 25, 2024
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      Lymphovascular invasion in colorectal cancers: can we predict it preoperatively?
      Image
      Fig. 1. The prevalence of lymphovascular invasion (LVI) by tumor location.
      Lymphovascular invasion in colorectal cancers: can we predict it preoperatively?
      Factor Lymphovascular invasion
      P-value
      Yes (n=178) No (n=157)
      T category <0.001a
       T1 0 (0) 10 (6.4)
       T2 10 (5.6) 22 (14.0)
       T3 116 (65.2) 109 (69.4)
       T4 52 (29.2) 16 (10.2)
      Perineural invasion 104 (58.4) 26 (16.6) <0.001a
      Nonmetastatic lymph node 17 (0–84) 17 (3–43) 0.360b
      Metastatic lymph node 3 (0–55) 0 (0–66) <0.001b
      Factor Lymphovascular invasion
      P-value
      Yes (n=178) No (n=157)
      Sex 0.156a
       Female 84 (47.2) 62 (39.5)
       Male 94 (52.8) 95 (60.5)
      Age (yr) 67 (28–92) 64 (25–93) 0.393b
      Tumor location 0.007a
       Ascending colon 52 (29.2) 26 (16.6)
       Transverse colon 26 (14.6) 16 (10.2)
       Descending colon 24 (13.5) 20 (12.7)
       Sigmoid colon 42 (23.6) 62 (39.5)
       Rectum 34 (19.1) 33 (21.0)
      Tumor differentiation 0.077a
       Low 14 (7.9) 6 (3.8)
       Moderate 158 (88.7) 139 (88.6)
       Good 6 (3.4) 12 (7.6)
      Preoperative metastasis 48 (27.0) 15 (9.55) <0.001a
      Mucinous component 28 (15.7) 29 (18.47) 0.505a
      Preoperative radiotherapy 18 (10.1) 16 (10.19) 0.981a
      ASA PS classification 0.015c
       I 18 (10.1) 17 (10.8)
       II 98 (55.1) 108 (68.8)
       III 60 (33.7) 32 (20.4)
       IV 2 (1.1) 0 (0)
      Hemoglobin (g/dL) 10.9 (7.8–23.3) 11.9 (6.4–16.3) 0.008b
      White blood cell (×109/L) 7.38 (2.43–22.41) 7.65 (3.17–14.60) 0.377b
      Platelet (×109/L) 296 (2.33–582) 268 (2.86–824) 0.248b
      Neutrophil (×109/L) 4.87 (1.27–18.99) 4.92 (1.17–12.15) 0.730b
      Monocyte (×109/L) 0.62 (0.06–1.84) 0.59 (0.24–1.78) 0.503b
      Lymphocyte (×109/L) 1.60 (0.32–3.28) 1.70 (0.35–4.36) 0.043b
      Neutrophil to lymphocyte ratio 2.84 (0.64–25.96) 2.97 (0.70–13.97) 0.337b
      PET-SUV 18.8 (4.1–41.1) 19.3 (9.4–36.1) 0.536b
      Body mass index (kg/m2) 26.67 (17.01–40.58) 26.67 (17.16–39.81) 0.441b
      Hypertension 86 (48.3) 70 (44.6) 0.495a
       Duration (yr) 10 (1–25) 9 (1–30) 0.076b
      Coronary artery disease 46 (25.84) 32 (20.38) 0.238a
       Duration (yr) 6 (2–13) 5 (1–12) 0.061b
      Diabetes mellitus 30 (16.9) 48 (30.6) 0.003a
       Type 1 2 (6.7) 8 (16.7) 0.301d
       Type 2 28 (93.3) 40 (83.3)
       Duration (yr) 10 (1–20) 7 (1–31) 0.096b
      Chronic obstructive pulmonary disease 8 (4.5) 8 (5.1) 0.797a
      Chronic renal failure 10(5.62) 6 (3.87) 0.457a
      Smoking 50 (28.1) 52 (33.1) 0.318a
       Duration (yr) 25 (5–50) 30 (5–60) 0.131b
      Alcohol consumption status 6 (3.37) 12 (7.64) 0.084a
      Factor Wald test Odds ratio 95% Confidence interval P-value
      Tumor location
       Descending colon - 1 (Reference) - -
       Ascending colon 6.94 3.11 1.34–7.23 0.008
       Transverse colon 2.29 2.05 0.81–5.22 0.130
       Sigmoid colon 0.13 0.87 0.40–1.89 0.719
       Rectum 0.46 1.34 0.58–3.09 0.497
      Diabetes mellitus
       No - 1 (Reference) - -
       Yes 8.49 0.44 0.25–0.76 0.004
      Preoperative metastasis
       No - 1 (Reference) - -
       Yes 17.94 4.28 2.18–8.39 <0.001
      Table 1. Other poor prognostic factors associated with lymphovascular invasion (n=335)

      Values are presented as number (%) or median (range).

      Pearson chi-square test.

      Mann-Whitney U-test.

      Table 2. Univariate analysis of preoperative factors for lymphovascular invasion estimation (n=335)

      Values are presented as number (%) or median (range).

      ASA, American Society of Anesthesiologists; PS, phyical status; PET, positron emission tomography; SUV, standardized uptake value.

      Pearson chi-square test.

      Mann-Whitney U-test.

      Fisher-Freeman-Halton test.

      Fisher exact test.

      Table 3. Multivariate analysis of preoperative factors for lymphovascular invasion estimation (n=335)

      Model χ2=43.93, P<0.001; Hosmer and Lemeshow test, P=0.875.


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