High Risk Of Lymph Node Metastasis Research Articles

Systematic review and meta‐analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer

Lymph node (LN) metastases are present in up to 17% of early colorectal cancers (pT1). Identification of associated histopathological factors would enable counselling of patients regarding this risk. Pubmed and Embase were employed utilizing the terms 'early colorectal cancer', 'lymph node metastasis', 'submucosal invasion', 'lymphovascular invasion', 'tumour budding' and 'histological differentiation'. Analysis was performed using REVIEW MANAGER 5.1. Twenty-three cohort studies including 4510 patients were analysed. There was a significantly higher risk of LN metastasis with a depth of submucosal invasion >1mm than with lesser degrees of penetration (OR 3.87, 95% CI 1.50-10.00, P=0.005). Lymphovascular invasion was significantly associated with LN metastasis (OR 4.81, 95% CI 3.14-7.37, P<0.00001). Poorly differentiated tumours had a higher risk of LN metastasis compared with well or moderately differentiated tumours (OR 5.60, 95% CI 2.90-10.82, P<0.00001). Tumour budding was found to be significantly associated with LN metastasis (OR 7.74, 95% CI 4.47-13.39, P<0.001). Meta-analysis of the current literature demonstrates that in early colorectal cancer a depth of submucosal invasion by the primary tumour of >1mm, lymphovascular invasion, poor differentiation and tumour budding are significantly associated with LN metastasis.

Clinicopathological characteristics and prognosis of early gastric cancer after gastrectomy

Assessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions. However, the relationship between clinicopathological characteristics and LNM in EGC remains unclear. This study therefore explored favorable predictors of LNM in EGC. A total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed. Forty-five cases were EGC, and clinicopathological characteristics such as gender, age, tumor size, location, gross type, differentiation, invasion depth, and vessel involvement were assessed to identify predictive factors for LNM and survival time. The overall cumulative 5-year survival rate of EGC patients was 88.92%. Among these, 22.4% developed LNM, which was associated with a poor 5-year survival rate of only 72.7%. Patients with tumors larger than 2 cm in diameters, with depth of tumor invasion to the submucosa, and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances. EGC limited to the mucosa but poorly differentiated also had a high risk for LNM. Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients. Careful planning is required in EGC patients at high risk of lymph node metastases. Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC, and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.

Current Issues Involving the Treatment of Small Rectal Carcinoid Tumors

See Article on Page 201-204 Recently, the number of cases of neuroendocrine tumors, mainly small rectal carcinoid tumors detected during colonoscopy screening, has increased rapidly [1, 2]. However, a standardized management for small rectal carcinoid tumors still remains to be established. Thus, several issues remain to be addressed. First, which tumors have high risk for lymph-node metastasis? Small rectal carcinoid tumors without metastasis can be treated by using local excision methods, including endoscopic resection or local surgical excision. Tumor size, the depth of invasion, the presence of angiolymphatic invasion, and the mitotic rate have been shown to be risk factors for lymph-node metastasis [3-5]. However, identifying the high-risk group preoperatively is difficult. Preoperative endoscopic ultrasonography or computed tomography (CT) may be helpful, but the clinical role of those modalities is limited. In fact, Kim et al. [6] reported that fewer than half of the 38 patients enrolled in the study had received preoperative radiologic evaluations. Second, which is the best method to use for the local resection of tumors? The tumors are usually located in the submucosal layer; thus, achieving a tumor-free margin by using a conventional endoscopic resection, such as a snare polypectomy or a strip biopsy, is difficult. Recently, Son et al. [7] reported pathologically-determined complete-resection (P-CR) rates for small rectal carcinoid tumors excised by using several methods. The P-CR rates were 30.9%, 72.0%, and 81.8% for a conventional endoscopic polypectomy, an advanced endoscopic technique, including endoscopic mucosal resection with cap or endoscopic submucosal dissection, and local surgical excision, including transanal excision and transanal endoscopic microsurgery (TEM). In a study by Kim et al. [6], the complete resection rate for TEM was over 97%. Although TEM is superior to other endoscopic procedures, TEM must be considered to be more invasive because of the risk associated with the use of anesthesia. Third, guidelines for follow-up examination after initial treatment for a small rectal carcinoid tumor have not yet been established. Some authors recommend annual follow-up examination including a CT scan while others suggest that follow-up is not necessary [8-11]. Actually, Kim et al. [6] reported that only 38 patients of 109 patients with a rectal carcinoid tumor who had undergone TEM had more than three years of follow-up. Regretfully, the study of Kim et al. [6] is one of small case series on the treatment of rectal carcinoid tumors. Hopefully, large-scale multicenter studies on the management of rectal carcinoid tumors will be reported sooner or later.

SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer

BackgroundThe transcription factor SOX2, which is involved in the induction of pluripotent stem cells and contributes to colorectal carcinogenesis, is associated with a poor prognosis in colon cancer (CC). Furthermore, SOX2 is a repressor of the transcriptional activity of β-catenin in vitro. Since the majority of CC develop via an activation of the Wnt/β-catenin signalling pathway, indicated by nuclear expression of β-catenin, we wanted to investigate the expression patterns of SOX2 and β-catenin and correlate them with the occurrence of lymph node and distant metastases as indicators of malignant progression.MethodsThe expression of SOX2 and β-catenin was investigated in a case control study utilizing a matched pair collection (N = 114) of right-sided CCs with either corresponding distant metastases (N = 57) or without distant spread (N = 57) by applying immunohistochemistry.ResultsElevated protein expression of SOX2 significantly correlated with the presence of lymph node- (p = 0.006) and distant metastases (p = 0.022). Nuclear β-catenin expression correlated significantly only with distant metastases (p = 0.001). Less than 10% of cases showed a coexpression of high levels of β-catenin and SOX2. The positivity for both markers was also associated with a very high risk for lymph-node metastases (p = 0.007) and distant spread (p = 0.028).ConclusionWe demonstrated that increased expression of either SOX2 or nuclear β-catenin are associated with distant metastases in right-sided CC. Additionally, SOX2 is also associated with lymph-node metastases. These data underline the importance of stemness-associated markers for the identification of CC with high risk for distant spread.

Lymph Node Metastasis of Gastric Cancer Is Associated with the Interaction Between Poly (ADP-Ribose) Polymerase 1 and Matrix Metallopeptidase 2

Poly (ADP-ribose) polymerase 1 (PARP1), which plays a critical role in the base excision DNA repair mechanism, and matrix metallopeptidase 2 (MMP2), a member of the matrix metalloprotease family, are involved in tumor formation and metastasis, respectively. In the present study, the possible association of single nucleotide polymorphisms (SNPs) and gene-gene interaction between PARP1 and MMP2 with the increased incidence of gastric cancer (GC) development and lymph node metastasis (LNM) was investigated in a Korean population. Samples were obtained from 326 patients with chronic gastritis and 153 patients with GC and genotyped using the GoldenGate® method. The PARP1 rs1136410 genotype showed a significant association with the frequency of LNM of GC (odds ratio [OR] = 2.19, p = 0.02), LNM stage (p = 0.035), and tumor invasion (p = 0.035). The allele frequency of MMP2 rs243865 was not associated with the development of GC or with the development of LNM of GC. Epistasis between the PARP1 SNP and the MMP2 SNP was associated with the development of LNM of GC. The combination of the MMP2 rs243865 CC genotype and the PARP1 rs1136410 CC or CC+CT genotypes showed a high risk of LNM of GC (OR = 2.47, p = 0.01; OR = 2.28, p = 0.01, respectively). In summary, PARP1 is associated with the risk of LNM of GC and the stage of LNM and tumor invasion. Epistasis between PARP1 rs1136410 and MMP2 rs243865 increased the risk of LNM of GC.

Is pT2 Subclassification Feasible to Predict Patient Outcome in Colorectal Cancer?

This study aimed to evaluate the prognostic impact of pT2 subclassification according to the depth of muscularis propria (MP) invasion and to explore the clinicopathologic factors correlated with lymph node metastasis (LNM) and postoperative hematogenous metastasis in pT2 colorectal cancer. A total of 317 patients with pT2 colorectal cancer were reviewed. pT2a represents the infiltration of the inner circumferential layer of the MP, and pT2b represents the infiltration of the outer longitudinal layer of the MP. Clinicopathologic factors and overall survival rates were compared in patients with pT2a and pT2b stage cancers. Multivariate analysis was performed to identify the significantly important prognostic factors. Univariate and multivariate analyses were performed, respectively, to identify the significantly important clinicopathologic factors correlated with LNM and postoperative hematogenous metastasis in pT2 colorectal cancer. According to the depth of MP invasion, 107 patients were classified as pT2a and 210 patients were classified as pT2b. Among them, there were 55 patients with LNM, 34 patients with postoperative hematogenous metastasis. There was significant difference in most of clinicopathologic features between patients in the pT2a and pT2b stages. Multivariate analysis identified pN stage (P < .001) and tumor location (P = .036) were independent factors affecting the prognosis. However, no apparent difference was observed between pT2a versus pT2b cancer. Univariate and multivariate analyses uniformly identified lymphovascular invasion (P = .035) and the depth of MP invasion (P = .005) as significantly correlated with LNM. Multivariate analysis found tumor location (P = .021) and the presence or absence of LNM (P < .001) were important factors affecting postoperative hematogenous metastasis. In pT2 colorectal cancer treated with R0 surgery, there is a high risk of LNM in deep MP invasion versus superficial MP invasion. The pT2 subclassification system had no significant advantage in identifying a different prognosis, except for predicting the LNM before surgery. Rectal cancer and the presence of LNM were high-risk factors resulting in hematogenous metastasis postoperatively.

Clinical and Imaging Assessment of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinomas

The goals of this study were to analyze clinical factors that affect cervical lymph node metastasis (LNM) in papillary thyroid cancer (PTC), and to evaluate the diagnostic accuracy of preoperative ultrasound (US) and computed tomography (CT) of the neck. The study sample included 589 consecutive patients who underwent surgery for PTC. Patient age and sex, number, size, and location of tumors, lymphovascular invasion, and extrathyroidal extension were evaluated as risk factors for central and lateral LNM. Increased risk of lymph node metastasis was found for male patients, <45 years old, with tumor size >1 cm, lymphovascular invasion, and extrathyroidal invasion. Cancers located in the upper neck had a higher relative risk of lateral metastasis than cancers located in the lower neck. Sensitivity of both US and CT imaging was higher for lateral (70-80%) than for central (42-47%) LNM. Specificity of US and CT was high (92-97%) for both central and lateral LNM. Using central lymph node size of greater than 5 mm as an indicator of metastasis, preoperative US had 58.3% sensitivity and 71.4% specificity. Preoperative US and CT imaging are useful for identifying features that indicate a high risk of LNM and for determining appropriate management of PTC.

Expansion of the indications for endoscopic mucosal resection in patients with superficial esophageal carcinoma

Endoscopic mucosal resection (EMR) is a minimally invasive local treatment for superficial esophageal carcinoma (SEC). The use of EMR in patients with m3 or sm1 SEC remains controversial, however. The aim of this retrospective study was to evaluate the histopathological risk factors for lymph-node metastasis and recurrence in patients with m3 or sm1 SEC. The study subjects were 43 patients with m3 or sm1 esophageal squamous-cell carcinomas: 23 patients were treated surgically (the surgery group), and 20 were treated by EMR (the EMR group). We assessed the following variables of the specimens resected by surgery or EMR: tumor depth, maximal surface diameter of the tumor (superficial size), maximum diameter of tumor invasion at the lamina muscularis mucosae (LMM invasion width), and lymphatic invasion. The relationships of these variables to lymph-node metastasis and recurrence were examined. In the surgery group, lymph-node metastasis was found in four patients, all of whom had tumors with lymphatic invasion, a superficial size of at least 25 mm, and an LMM invasion width of at least 2500 microm. In the EMR group, no patient met all three of these criteria, and there was no evidence of lymph-node metastasis or distant metastasis on follow-up after EMR (median follow-up 39 months). In patients with m3 or sm1 SEC, tumors that have lymphatic invasion, larger superficial size, and wider LMM invasion are associated with a high risk for lymph-node metastasis. EMR might be indicated for the treatment of patients with m3 or sm1 SECs without these characteristics.

Clinicopathological Significance of p53 and HSP27 in Gastric-cancer Patients

Purpose: The tumor suppressor gene p53 has been shown to be a factor in the carcinogenesis or progression of gastric cancer. The mutant p53 has been reported to cause a higher risk of lymph-node metastasis. Futhermore, mutation of the p53 has been linked to a poor prognosis for gastric cancer. The heat shock protein-27 (HSP27), a stress protein, has also been reported to be a poor prognostic factor in ovarian and breast cancers. However, in gastric-cancer patients, controversies exist as to its influence on the prognosis. In the present study, we used an immunohistochemical stain to observe the effects of p53 and HSP27 on the clinicopathological factors and on the prognosis for gastric-cancer patients. Materials and Methods: To evaluate the significance of p53 and HSP27 in gastric cancer patients, we analyzed 212 cases of gastric cancer (stage I.IV). Tissue samples of 212 patients were stained immunohistochemically for the mutant p53 protein and for HSP27. The correlations between protein expression and the clinicopathological factors were investigated. Results: The overall expression rates for p53 and HSP27 were , respectively. p53 and HSP27 were correlated to each other because the HSP27 expression rate was higher in the p53-positive group (P=0.046). Statistically, the p53 and the HSP27 expression rates were significantly increased in the case of tumor invasiveness, lymphatic metastasis and vessel involvement. Therefore, they play a role in cancer progression. The 5-year survival rates of the p53-positive and the p53-negative groups were , respectively (P=0.793) while the 5-year survival rates for the HSP27-positive and HSP27-negative groups were , respectively (P=0.090). Conclusion: p53 and HSP27 were correlated to each other in our immunohistochemical study of gastric carcinomas and they were not independent prognostic factors in gastric- cancer patients. However, further studies are needed to determine their prognostic values for gastric-cancer patients.

Validation of a biopsy-based pathologic algorithm for predicting lymph node metastases in patients with clinically localized prostate carcinoma.

The authors validated an algorithm for the preoperative prediction of lymph node (LN) metastases in patients with clinically localized prostate carcinoma. The algorithm was applied to sextant biopsy material and radical retropubic prostatectomy (RRP) stage obtained from a cohort of men who were treated at the authors' institution. Four hundred forty-three patients underwent systematic sextant biopsy and RRP with staging lymphadenectomy. The original algorithm was based on systematic sextant biopsy data and classified patients into three risk groups for LN metastases based on the biopsy result. If > or = 4 of 6 biopsies contained any Gleason Pattern 4 disease, then the patient was at high risk for LN metastases (45%). Patients with > or = 1 of 6 biopsies with dominant Gleason Pattern 4 disease (excluding high-risk patients) had an intermediate predicted risk (19%) of LN metastases. All other patients had a low predicted risk of LN metastases (2.2%). The authors assed the percentage of patients who were positive and negative for LN metastases and calculated the specificity and negative predictive value in the series when patients were classified according to the original algorithm. Twenty of 443 patients had intraoperative LN metastases. When applied to the current data, the Hamburg algorithm classified 404 patients in the low-risk group, 30 patients in the intermediate-risk group, and 9 patients in the high risk group. The incidence of LN metastases was 2.47% in the low-risk group, 20% in the intermediate-risk group, and 44.4% in the high-risk group. The negative predictive value for the low-risk group was 97.52%, and the specificity was 94.14%. The Hamburg algorithm proved a valid tool for the prediction of lymphatic spread in this validation study on data from the authors' institution. The algorithm may serve as a tool to select patients who do not need to undergo pelvic lymphadenectomy at the time they undergo RRP, hence reducing morbidity and expense. More importantly, with the increasing numbers of men undergoing treatment options in whom LN dissection is not performed, this validated algorithm provides an important selection basis regarding the appropriateness of a therapy that does not routinely include LN staging.