No change in lymph node positivity rate despite increased lymph node yield and improved survival in colon cancer

AimTo analyse trends over time in the number of lymph nodes evaluated and in the proportion of node positivity and to investigate the impact on survival for patients with colon cancer.Patients and methods8616 patients resected for M0 colon cancer diagnosed in the Southern Netherlands between 2000 and 2011 were included in this study. Trends in nodal evaluation and node positivity were analysed. Multivariable logistic regressions were used to assess the influence of period of diagnosis on adequate nodal evaluation (⩾12 lymph nodes) and node positivity after adjusting for patient and tumour characteristics. Crude 5-year relative survival was used as an estimate for disease-specific survival.ResultsOverall, the proportion adequate nodal evaluation increased from 13% in 2000–2002 to 59% in 2009–2011 (p < 0.0001), whereas the proportion node positivity remained similar across study periods (approximately 35%). Patients diagnosed in later periods were more likely to have received adequate nodal yield (adjusted Odds ratio (OR) 2009–2011 versus 2000–2002 9.8, 95% Confidence interval (CI) 8.3–11.6). However, the adjusted odds of having node positive disease did not differ between periods of diagnosis. Relative excess risk of dying was independently correlated with the number of lymph nodes evaluated (1–8 LNs versus ⩾12 LNs, N0: 2.2, 95% CI 1.7–2.9; N+: 1.7, 95% CI 1.4–2.0) and period of diagnosis (2009–2011 versus 2000–2002, N+ only: 0.8, 95% CI 0.6–1.0).ConclusionThe reason for improved survival with increased nodal yield is different from simple understaging as the proportion of lymph node positivity remained constant.     

Prognostic value of lymph node metastases and lymph node ratio in esophageal squamous cell carcinoma

Aims

Although the positive lymph node (LN) metastasis in patients with thoracic esophageal squamous cell carcinoma carcinoma (SCC) has been reported to be a risk factor to reduce long-term survival, only a few studies have so far evaluated the lymph node metastasis among this group of patients. The purpose of this study was to evaluate the impact of lymph node positivity and ratio on survival of esophageal SCC.

Methods

All patients undergoing esophagectomy at the Forth Hospital of Hebei Medical University between January 1986 and December 2002 were reviewed. Survival curves were estimated using the Kaplan-Meier method.

Results

Of 1325 patients with invasive cancer, had squamous cell cancer of the esophagus. Median overall survival (OS) of the entire group was 36.7 months and 5-year OS was 39.3%. The most significant prognostic factor for overall survival was the presence of positive LN (P < 0.01). Additionally, patients with zero involved LN had a 5-year survival of 49.1%, while patients with 1–3 positive LN and >3 positive LN had 5-year survival of 19.5% and 11.0%, respectively (P < 0.01). Finally, an increasing ratio of positive to examined LN was linearly associated with a worsening 5-year survival, patients with <25%, 25%–50% and >50% positive LN had 5-year survival of 47.53%, 14.6% and 8.9%, respectively (P < 0.01).

Conclusion

Increasing number of positive LN in patients with esophageal cancer and increasing ratio of metastatic to examine LN portend a poor prognosis. These factors should play an important role in predicting prognosis of patients.     

A study of lymph node ratio as a prognostic marker in colon cancer

Aim

The aim of this study was to evaluate and describe the lymph node ratio (LNR) as a prognostic parameter for patients with colon cancer. As lymphatic involvement is the key, focus was set at stage III disease. Interest was directed at the possibility of identifying high-risk groups and the clinical implementation and consequence.

Method

The study was retrospective using a database of clinical data of all cancer patients treated at our unit. It has been continuous in registration, inclusion and update since 1999 including survival and clinical features. All patients (n = 265) diagnosed with stage III colon cancer during 1999–2003 were included for the study. LNR was calculated and quartile groups were created. LNR and associated parameters were analysed towards 3-year disease-free survival (DFS). Basic patient data as well as surgery, pathology and postoperative treatment were taken into consideration.

Results

Significant differences in disease-free survival were found for TNM N-status, tumour differentiation grade and LNR quartile group. There was a difference in 3-year DFS from 80% in LNR group 1 compared with less than 30% in group 4. These results were of prognostic interest both independently and in interaction with each other. High-risk groups could be identified and in the worst prognosis LNR group we also found a tendency towards more side effects with adjuvant chemotherapy.

Conclusion

The lymph node ratio, the quota between the number of lymph node metastasis and assessed lymph nodes, is a highly significant (p < 0.001) prognostic factor in stage III colon cancer. It can be an aid in identifying risk groups that could benefit from a more intense postoperative surveillance and possibly bring changes in adjuvant treatment strategy. More studies of clinical data, genetic and biochemical markers are needed in this patient group to understand the possible difference in tumour behaviour and tailor the treatment.     

Intracorporeal lymph node mapping in colon cancer surgery

IntroductionThe best approach to lymphadenectomy in colon cancer is still unknown. The debate has centred around different options of standardised “one size fits all” lymph node harvest techniques. A different approach is tailoring lymph node harvest to the patient's lymphatic drainage pattern.MethodsA technique for individualised lymph node mapping is proposed, which can guide the surgeon intraoperatively. It consists in the intracorporeal injection of 10 mg of indocyanine green at 4 points in the periphery of the colonic tumour. A near infrared camera is used to assess the fluorescence after specimen mobilisation but before extraction, allowing lymphadenectomy based on the patient's own lymphatic drainage.Resultsa video demonstration of the technique and preliminary results in 6 patients is presented in this short report.Conclusionintracorporeal lymph node mapping is feasible and safe. Further studies are required to determine the place of this technique in modern oncologic colon surgery.     

The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer

Aims

In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study.

Methods

Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors.

Results

One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p < 0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p = 0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p = 0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p = 0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI.

Conclusion

Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential.     

Lymphatic spread,nodal count and the extent of lymphadenectomy in cancer of the colon

In colon cancer, the biological significance of lymphatic tumour spread remains a matter of debate, which impacts on related questions such as the ideal extent of lymphadenectomy and the prognostic significance of lymph node counts. Several lines of evidence suggest that metastasis to locoregional nodes occurs early and is a stochastic, rather than a stepwise phenomenon, and in essence reflects the tumour–host–metastasis relationship. Not surprisingly, therefore, several clinical trials failed to identify a survival benefit from extensive lymphadenectomy compared to standard resection. The recently described complete mesocolic excision technique, which aims to improve survival by maximizing nodal clearance, should be subjected to a prospective randomized trial.     

Non-surgical factors influencing lymph node yield in colon cancer

There are numerous factors which can affect the lymph node (LN) yield in colon cancer specimens. The aim of this paper was to identify both modifiable and non-modifiable factors that have been demonstrated to affect colonic resection specimen LN yield and to summarise the pertinent literature on these topics. A literature review of PubMed was performed to identify the potential factors which may influence the LN yield in colon cancer resection specimens. The terms used for the search were: LN, lymphadenectomy, LN yield, LN harvest, LN number, colon cancer and colorectal cancer. Both non-modifiable and modifiable factors were identified. The review identified fifteen non-surgical factors: (13 non-modifiable, 2 modifiable) which may influence LN yield. LN yield is frequently reduced in older, obese patients and those with male sex and increased in patients with right sided, large, and poorly differentiated tumours. Patient ethnicity and lower socioeconomic class may negatively influence LN yield. Pre-operative tumour tattooing appears to increase LN yield. There are many factors that potentially influence the LN yield, although the strength of the association between the two varies greatly. Perfecting oncological resection and pathological analysis remain the cornerstones to achieving good quality and quantity LN yields in patients with colon cancer.     

Prognostic significance of preoperative inflammatory response biomarkers in patients undergoing curative thoracoscopic esophagectomy for esophageal squamous cell carcinoma

Background

Recent studies have revealed significant relationships between the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and survival in various cancers. The purpose of this study was to confirm whether the LMR, NLR, and PLR have prognostic values, independent of clinicopathological criteria, in patients undergoing curative resection for esophageal cancer.

Metastatic lymph node ratio in stage III rectal cancer; prognostic significance in addition to the 7th edition of the TNM classification

Aims

Optimal staging in rectal cancer is indispensable for the decision on further treatment and estimation of prognosis. This study assesses the prognostic capacity of the metastatic lymph node ratio (LNR) in addition to the new TNM classification.

Methods

LNR was determined, in stage III patients from the Dutch TME-trial. Six year median follow up data from the trial database were used to analyse the relation of LNR to overall survival (OS) and local recurrence (LR). The relation of LNR to lymph node yield was assessed and appropriate cut off values of LNR for clinical use were determined.

Results

605 patients were analyzed. 278 underwent pre-operative radiotherapy. 82 patients developed a local recurrence and 289 distant metastases. LNR was an independent risk factor for OS, hazard ratio (HR) 2.10 (95% CI 1.35–3.27) (in addition to age >= 65 years, involved circumferential resection margin (CRM) and new TNM stage) and LR, HR 2.25 (95% CI 1.02–4.56) (in addition to pre-operative radiotherapy and involved CRM). LNR is predictive of OS and LR from a lymph node yield of more than one and more than five respectively. A LNR value of 0.60 offers the best cut off to identify high risk patients (5-years OS was 61 vs. 32%, HR 2.45 (95% CI 1.96–3.08) and 5-years LR rate 12.6 versus 16.3%, HR 1.65 (95% CI 1.03–2.64)).

Conclusions

LNR is an independent risk factor for OS and LR in addition to the 7th edition of the TNM classification. It can aid in predicting prognosis and identifying patients that should be considered for adjuvant treatment.     

Downstaging of lymph node metastasis after neoadjuvant intraperitoneal and systemic chemotherapy in gastric carcinoma with peritoneal metastasis

PurposeThe aim of the present study was to evaluate the clinical features and prognosis of lymph node metastasis (LNM) in gastric cancer patients with peritoneal metastasis (PM) after neoadjuvant intraperitoneal and systemic chemotherapy.MethodsA total of 69 gastric cancer patients with PM and LNM who received neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) of intraperitoneal docetaxel (DXT) and cisplatin (CDDP); intravenous chemotherapy of DXT and CDDP and oral S-1in Kishiwada Tokushukai Hospital between January 2008 and February 2017. After surgical resection, the response of LNMs was studied to confirm the effect of NIPS on LNMs.ResultsAfter NIPS, 197 lymph nodes (LNs) (42.5%) were graded as G3, the progression in LNMs were significantly better than in the primary tumors. Until the last follow-up, 1-year overall survival rate was 82.6%, and the median survival period was 22.0 ± 3.7 months. In the group of patients who had achieved a more than 50% G3 grade of the response of LNMs, the median survival period is 38 months; in the less than 50% G3 grade group, it is 14 months, that is a significantly different result. Multivariate analyses showed that the factors PCI, Post-therapeutic N status and response of the LNMs were found to be as independent prognostic factors.ConclusionDownstaging of LNMs were achieved in patients of gastric cancer with PM who received NIPS. Downstaging of LNMs after NIPS is related with the prognosis of gastric cancer and should be valued in subsequent surgery for gastric cancer with peritoneal and lymph nodes metastasis.     

Prognostic value of pre-operative systemic immune-inflammation index and platelet to lymphocyte ratio in peritoneal carcinomatosis of ovarian origin

Background and objectivesThe aim of this study was to investigate the impact of systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) on the survival outcomes of patients who underwent to cytoreductive surgery (CRS) and HIPEC for ovarian peritoneal carcinomatosis.MethodsA retrospective analysis of 68 cases following surgery at our department between 2015 and 2020 was performed. Receiver Operating Characteristic (ROC) curve was used with Youden index to calculate the optimal cutoff values for SII, PLR and NLR.ResultsUnivariate analysis revealed that high preoperative values of SII, PLR and NLR were correlated with worse overall survival (OS) and disease-free survival (DFS) in these patients. In the multivariable analysis, high SII was recognized as an independent prognostic factor for OS (CI 95%: 0.002- 3.835, p = 0.097) and high PLR was recognized as an independent prognostic factor for DFS (CI 95%: 0.253–2.248, p = 0.007).ConclusionSII and PLR could be useful prognostic tools to predict outcomes of patients who underwent to CRS and HIPEC for ovarian peritoneal carcinomatosis.     

Prognostic Significance of Axillary Lymph Node Micrometastases and Microvessel Count in Breast Cancer

Objective  To investigate the influence of axillary lymph node micrometastases and the microvessel count on the prognosis of patients with breast cancer. Methods  Forty-eight patients with breast cancer, who had no tumor cells in their regional lymph nodes based on conventional histopathologic examination, were re -examined with immunohistochemical LSAB techniques. H&E, anti-EMA, CK 19 and FVIII factor staining was used to identify tumor cells in both lymph nodes and tumor tissues and to count the mtcrovessels. A total of 882 lymph nodes were examined. Results  Immunostaining-positive tumor cells were found in 9.0 %( 79/882) of the dissected lymph nodes. The positive rates were not significantly different between a surviving group and a deceased group (P>0.05). The microvessel count was significantly higher in group that had died (P<0.001). Conclusion  The lymph node micrometastases did not show any correlation with patients’ survival, but the microvessel density had a negative correlation with the survival period in breast cancer patients who had negative axillary lymph nodes.     

Prognostic significance of axillary lymph node micrometastases and microvessel count in breast cancer

Objective To investigate the influence of axillary lymph node micrometastases and the microvessel count on the prognosis of patients with breast cancer. Methods Forty-eight patients with breast cancer, who had no tumor cells in their regional lymph nodes based on conventional histopathologic examination, were re -examined with immunohistochemical LSAB techniques. H&E, anti-EMA, CK 19 and FVIII factor staining was used to identify tumor cells in both lymph nodes and tumor tissues and to count the mtcrovessels. A total of 882 lymph nodes were examined. Results Immunostaining-positive tumor cells were found in 9.0 %( 79/882) of the dissected lymph nodes. The positive rates were not significantly different between a surviving group and a deceased group (P>0.05). The microvessel count was significantly higher in group that had died (P<0.001). Conclusion The lymph node micrometastases did not show any correlation with patients’ survival, but the microvessel density had a negative correlation with the survival period in breast cancer patients who had negative axillary lymph nodes.     

Prognostic value of lymph node ratio in node-positive breast cancer in Egyptian patients

BackgroundBreast cancer in Egypt is the most common cancer among women and is the leading cause of cancer mortality. Traditionally, axillary lymph node involvement is considered among the most important prognostic factors in breast cancer. Nonetheless, accumulating evidence suggests that axillary lymph node ratio should be considered as an alternative to classical pN classification.Materials and methodsWe performed a retrospective analysis of patients with operable node-positive breast cancer, to investigate the prognostic significance of axillary lymph node ratio.ResultsFive-hundred patients were considered eligible for the analysis. Median follow-up was 35 months (95% CI 32–37 months), the median disease-free survival (DFS) was 49 months (95% CI, 46.4–52.2 months). The classification of patients based on pN staging system failed to prognosticate DFS in the multivariate analysis. Conversely, grade 3 tumors, and the intermediate (>0.20 to ⩽0.65) and high (>0.65) LNR were the only variables that were independently associated with adverse DFS. The overall survival (OS) in this series was 69 months (95% CI 60–77).ConclusionThe analysis of outcome of patients with early breast cancer in Egypt identified the adverse prognostic effects of high tumor grade, ER negativity and intermediate and high LNR on DFS. If the utility of the LNR is validated in other studies, it may replace the use of absolute number of axillary lymph nodes.     

Metastatic lymph node ratio versus number of metastatic lymph nodes as a prognostic factor in gastric cancer

Objective

Knowledge of prognostic factors in gastric cancer is essential to decide on single patient management. We aim to establish the value of lymph node ratio compared to lymph node involvement in the prediction of gastric cancer survival and treatment approach.

Methods

Charts of ninety-six consecutive patients undergoing gastrectomy for resectable gastric cancer were reviewed between January 1996 and December 2005. Receiver operating characteristic (ROC) curves were plotted to verify the accuracy of metastatic lymph node ratio (MLNR) and number of metastatic lymph node (NMLN) cut-off values for survival prediction. Patients were divided into two groups according to ROC curve cut-offs and accuracy in prognosis was reviewed.

Results

ROC curves showed that 5 metastatic nodes and a node ratio value of 20% had the best survival prognostic correlation. The median survival of patients with MLNR and NMLN were similar according to cut-off determinations (≤5/>5 metastatic nodes and ≤20/>20% lymph node ratio). Five-year survival rates were 70.9% vs 17.1% and 72.4% vs 15.6%, respectively (p < 0.001). Positive correlation coefficient was found between the number of excised nodes and the number of metastatic nodes.

Conclusion

Number of metastatic lymph nodes showed greater accuracy than lymph node ratio for survival prediction in gastric cancer.     

阳性淋巴结比率对结直肠癌患者预后的预测价值

目的 探讨阳性淋巴结比率（LNR）对有淋巴结转移的结直肠癌患者3年生存率和3年无病生存率的预测价值。方法 收集2003年7月到2007年12月接受根治性手术的102例有淋巴结转移的散发性结直肠癌患者的临床病理资料。根据四分位法将患者按LNR值分为4组,分别为LNR1（LNR≤第25百分位数）、LNR2（第25百分位数＜LNR≤第50百分位数）、LNR3（第50百分位数＜LNR＜第75百分位数）和LNR4（LNR≥第75百分位数）。用Kaplan Meier法进行生存分析,用Cox比例风险回归模型进行生存多因素分析。结果 102例Ⅲ、Ⅳ期结直肠癌患者的3年生存率为72.5％,3年无病生存率为61.8％。腺癌、低级别分化患者的3年生存率更高（P＜0.05）。LNR1、LNR2、LNR3和LNR4 4组患者的3年生存率分别为100.0％、76.9％、68.0％和42.3％（P＜0.001）,3年无病生存率分别为92.0％、61.5％、68.0％和26.9％（P＜0.001）。 Kaplan-Meier生存分析显示,LNR1+LNR2组的3年生存率和3年无病生存率显著高于LNR3+LNR4组（P＜0.05）。Cox风险回归模型显示,LNR是结直肠癌患者预后的独立预测指标（P=0.036）。结论LNR能够准确判断结直肠癌患者的预后。     

Emmunohistochemical study on angiogenesis of axillary lymph node metastasis in human invasive breast carcinoma

The axially lymph node is one of the earliest and most common metastatic positions of breast carcinoma. Hence, axillary lymph node status (metastasis or no) and the number of metastatic lymph nodes are considered to be important indicators which affect prognosis of breast cancer patients. It has been widely confirmed that malignant solid tumor growth must be dependent upon angiogenesis/neovascularization. Considerable evidence has shown that microvessel density (MVD) of breast cancer tissue c…     

中性粒细胞与淋巴细胞比值预测乳腺癌新辅助治疗后腋窝淋巴结病理学完全缓解的研究

背景与目的:中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)作为简单、客观且廉价的实验室指标,其疗效预测价值已在其他类型的癌种中得到验证.整合新辅助治疗(neoadjuvant therapy,NAT)前临床病理学特征及NLR来预测NAT后腋窝淋巴结病理学完全缓解(axi...     

Improving lymph node detection in colon cancer in community hospitals and their pathology department in southern Netherlands

Aim

The aim was to investigate whether a set of measures directed at increasing lymph node (LN) detection among colon cancer patients led to clinically relevant changes in LN detection rate.

Methods

Data of all patients with curative colon cancer (pT_any N_any M0) diagnosed in 1999–2007 whose resection specimens were evaluated by the Institute for Pathology and Medical Microbiology in Eindhoven (n = 1501) were included. Feedback to specialists, increased fixation time, and ex-vivo injection of the specimen with Patent blue V dye were used to increase LN detection rate. Trends in the proportion of patients with insufficient LNs examined were investigated; moreover, the Patent blue-stained patients (n = 86) were compared with a group of unstained patients (n = 84). Based on the decrease in the proportion of high-risk node-negative patients, a calculation of chemotherapy-related costs saved was made.

Results

The proportion of patients with <12 LNs examined decreased from 87% in 1999 to 48% in 2007 (p_trend < 0.0001). In the stained group this was 37%, versus 56% for the unstained group (p = 0.010). In 1999, 79% of stage II patients were high-risk compared to 55% in 2007, which translates to a saving of almost 1,000,000 euro based on 92 stage II patients diagnosed in 2007.

Conclusion

A diverse set of measures increased the number of examined lymph nodes among patients with colon cancer. Large savings can be made due to the reduced proportion of high-risk node-negative patients who would otherwise have received adjuvant chemotherapy.     

Prognostic impact of positive lymph node ratio in gastric carcinoma

BACKGROUND AND OBJECTIVES: To evaluate the prognostic value of metastatic lymph node ratio in gastric carcinoma. METHODS: One hundred and sixty four patients who underwent D(2) dissection for gastric carcinoma at Ankara Oncology Hospital were reviewed retrospectively. The prognostic factors including Japanese classification, AJCC/UICC TNM classification and metastatic lymph node ratio (1-10% and >10%) were evaluated in univariate and multivariate Cox regression analysis. RESULTS: The multivariate analysis showed that Borrmann classification, pN-category of AJCC/UICC classification and metastatic lymph node ratio were the most significant prognostic factors and a higher hazard ratio was obtained for metastatic lymph node ratio than pN category of AJCC/UICC classification (4.5 vs. 11.4). When the metastatic ratio groups of 1-10% and >10% were subdivided into pN(1), pN(2) and pN(3) categories of the AJCC/UICC classification, there was no statistical difference between survival curves. When pN(1), pN(2) and pN(3) categories of the AJCC/UICC classification were subdivided into the ratio groups of 1-10% and >10%, the survival rate of ratio group 1-10% was better than ratio group >10%. CONCLUSION: With its simplicity and reproducibility, metastatic lymph node ratio can be used as a reliable prognostic indicator.