Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis

BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

Objective After endoscopic resection of colorectal cancer with submucosal invasion(pT1 CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pT1 CRC,especially the effect of DSI on LNM.Methods Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results Twenty-eight of the 239 patients presented with LNM(11.7%),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1%(1/95),12.5%(7/56),and 48.8%(20/41),respectively.Conclusion Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.

Deep learning-based automatic pipeline system for predicting lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma using computed tomography:A multi-center study

Objective:The assessment of lateral lymph node metastasis(LLNM)in patients with papillary thyroid carcinoma(PTC)holds great significance.This study aims to develop and evaluate a deep learning-based automatic pipeline system(DLAPS)for diagnosing LLNM in PTC using computed tomography(CT).Methods:A total of 1,266 lateral lymph nodes(LLNs)from 519 PTC patients who underwent CT examinations from January 2019 to November 2022 were included and divided into training and validation set,internal test set,pooled external test set,and prospective test set.The DLAPS consists of an auto-segmentation network based on RefineNet model and a classification network based on ensemble model(ResNet,Xception,and DenseNet).The performance of the DLAPS was compared with that of manually segmented DL models,the clinical model,and Node Reporting and Data System(Node-RADS).The improvement of radiologists’diagnostic performance under the DLAPS-assisted strategy was explored.In addition,bulk RNA-sequencing was conducted based on 12 LLNs to reveal the underlying biological basis of the DLAPS.Results:The DLAPS yielded good performance with area under the receiver operating characteristic curve(AUC)of 0.872,0.910,and 0.822 in the internal,pooled external,and prospective test sets,respectively.The DLAPS significantly outperformed clinical models(AUC 0.731,P<0.001)and Node-RADS(AUC 0.602,P<0.001)in the internal test set.Moreover,the performance of the DLAPS was comparable to that of the manually segmented deep learning(DL)model with AUCs ranging 0.814−0.901 in three test sets.Furthermore,the DLAPSassisted strategy improved the performance of radiologists and enhanced inter-observer consistency.In clinical situations,the rate of unnecessary LLN dissection decreased from 33.33%to 7.32%.Furthermore,the DLAPS was associated with the cell-cell conjunction in the microenvironment.Conclusions:Using CT images from PTC patients,the DLAPS could effectively segment and classify LLNs non-invasively,and this system had a good generalization ability and clinical applicability.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Gastrointestinal stromal tumor of stomach with inguinal lymph nodes metastasis: A case report

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the alimentary tract. To the best of our knowledge, few cases have been reported in the literature about the peripheral lymph node metastasis of GIST. Here we report an unusual case of gastric GIST with inguinal lymph nodes metastasis. After the metastatic lymph nodes were resected, the. patient started to take imatinib 400 mg/d for 12 mo. There were no signs of tumor recurrence at follow-up after 29 mo. This case suggests that the inguinal lymph nodes can be a potential metastatic site of GIST.

Gastrointestinal stromal tumor of the stomach with axillary lymph node metastasis: A case report

Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum. We did not detect evidence of metastases to the liver, or other sites including the perigastric lymph nodes, although findings from the surgically resected axillary lymph nodes were compatible with GIST metastasis. Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery. Despite continuing medical treatment(sunitinib and regorafenib), the patient died of liver metastases 23 mo after the surgery. Based on our findings, it appears that the axillary lymph nodes can be a potential metastatic site for GIST metastasis.

Radiomics for differentiating tumor deposits from lymph node metastasis in rectal cancer

BACKGROUND Tumor deposits(TDs)are not equivalent to lymph node(LN)metastasis(LNM)but have become independent adverse prognostic factors in patients with rectal cancer(RC).Although preoperatively differentiating TDs and LNMs is helpful in designing individualized treatment strategies and achieving improved prognoses,it is a challenging task.AIM To establish a computed tomography(CT)-based radiomics model for preoperatively differentiating TDs from LNM in patients with RC.METHODS This study retrospectively enrolled 219 patients with RC[TDs+LNM-(n=89);LNM+TDs-(n=115);TDs+LNM+(n=15)]from a single center between September 2016 and September 2021.Single-positive patients(i.e.,TDs+LNM-and LNM+TDs-)were classified into the training(n=163)and validation(n=41)sets.We extracted numerous features from the enhanced CT(region 1:The main tumor;region 2:The largest peritumoral nodule).After deleting redundant features,three feature selection methods and three machine learning methods were used to select the best-performing classifier as the radiomics model(Rad-score).After validating Rad-score,its performance was further evaluated in the field of diagnosing double-positive patients(i.e.,TDs+LNM+)by outlining all peritumoral nodules with diameter(short-axis)>3 mm.RESULTS Rad-score 1(radiomics signature of the main tumor)had an area under the curve(AUC)of 0.768 on the training dataset and 0.700 on the validation dataset.Rad-score 2(radiomics signature of the largest peritumoral nodule)had a higher AUC(training set:0.940;validation set:0.918)than Radscore 1.Clinical factors,including age,gender,location of RC,tumor markers,and radiological features of the largest peritumoral nodule,were excluded by logistic regression.Thus,the combined model was comprised of Rad-scores of 1 and 2.Considering that the combined model had similar AUCs with Rad-score 2(P=0.134 in the training set and 0.594 in the validation set),Rad-score 2 was used as the final model.For the diagnosis of double-positive patients in the mixed group[TDs+LNM+(n=15);single-positive(n=15)],Rad-score 2 demonstrated moderate performance(sensitivity,73.3%;specificity,66.6%;and accuracy,70.0%).CONCLUSION Radiomics analysis based on the largest peritumoral nodule can be helpful in preoperatively differentiating between TDs and LNM.

Comparison of efficacy and safety between late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy for cervical cancer complicated with pelvic lymph node metastasis

Objective This study aimed to compare and analyze the clinical efficacy and safety of late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy(IMRT) for cervical cancer complicated with pelvic lymph node metastasis. Methods Sixty patients with cervical cancer complicated with pelvic lymph node metastasis who were admitted to our hospital from January 2013 to January 2015 were enrolled. The patients were randomly divided into the late-course dose-increasing IMRT group and the simultaneous integrated dose-increasing IMRT group, with 30 cases included in each group, respectively. All patients were concurrently treated with cisplatin. After treatment, the clinical outcomes of the two groups were compared. Results The remission rate of symptoms in the simultaneous integrated dose-increasing IMRT group was significantly higher than that in the late-course dose-increasing IMRT group(P < 0.05). The follow-up results showed that the overall survival time, progression-free survival time, and distant metastasis time of patients in the simultaneous integrated dose-increasing IMRT group were significantly longer than those in the late-course dose-increasing IMRT group(P < 0.05). The recurrent rate of lymph nodes in the radiation field in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in the incidence of cervical and vaginal recurrence and distant metastasis between the two groups(P > 0.05). The radiation doses of Dmax in the small intestine, D1 cc(the minimum dose to the 1 cc receiving the highest dose) in the bladder, and Dmax in the rectum in the simultaneous integrated dose-increasing IMRT group were significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in intestinal D2 cc(the minimum dose to the 2 cc receiving the highest dose) between the two groups(P > 0.05). The incidence of bone marrow suppression in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group.Conclusion The application of simultaneous integrated dose-increasing IMRT in the treatment of cervical cancer patients complicated with pelvic lymph node metastasis can significantly control tumor progression, improve the long-term survival time, and postpone distant metastasis time with high safety.

Residual tumor and central lymph node metastasis after thermal ablation of papillary thyroid carcinoma: A case report and review of literature

BACKGROUND Debate exists regarding the use of thermal ablation(TA)to treat papillary thyroid carcinoma(PTC).Some studies have recommended TA as a new,ef
cient and safe technology for PTC.In this article,we report one case of a residual tumor and central lymph node metastasis(CLNM)after TA for PTC.CASE SUMMARY A 63-year-old female underwent bilateral ultrasound(US)-guided radiofrequency ablation for PTC.Three months later,she was diagnosed as thyroid cancer with suspected CLNM by US and contrast-enhanced computed tomography.The subsequent fine-needle aspiration(FNA)biopsies were negative.Due to her strong personal preference,she underwent total thyroidectomy and central lymph node dissection.Local tissue adhesion and a difficult dissection were noted during the operation.The pathology of the frozen sections during the operation was still negative.The final pathology results of paraffin-embedded sections revealed residual tumor cells at the edge of the PTC and CLNM.CONCLUSION TA may lead to a residual tumor in patients with PTC.Follow-up using US and FNA biopsy may not be adequate to evaluate the residual tumor.TA should be carefully considered in PTC treatment.

Risk factors of lymph node metastasis in rectal neuroendocrine tumors

Objective The aim of this study was to investigate the risk factors of lymph node metastasis in rectal neuroendocrine neoplasms(RNENs).Methods We enrolled 168 patients with RNENs as the research object,and their clinicopathological and survival data were collected.The risk factors affecting lymph node metastasis were analyzed retrospectively,and independent risk factors affecting prognosis were evaluated.Results Analysis showed that age,tumor diameter,tumor function,grade,and T stage were correlated with lymph node metastasis(P<0.05).Multiple logistic regression analysis showed that tumor size,grade,and T stage were independent risk factors for lymph node metastasis in patients with RNENs.Kaplan-Meier analysis showed that the 5-year overall survival(OS)of patients with lymph node metastasis was 40.0%(10/25),and that of patients without lymph node metastasis was 93.0%(133/143).The prognosis of RNENs patients with lymph node metastasis along with patients with large tumor diameter and high grade was poor.Cox multivariate analysis showed that tumor diameter(HR=1.985,P=0.008),grade(HR=3.416,P=0.004),T stage(HR=2.413,P=0.014),and lymph node metastasis(HR=3.119,P=0.000)were independent risk factors affecting the prognosis of patients with RNENs.Conclusion Tumor size,grade,and T stage are the main risk factors for lymph node metastasis and prognosis in patients with RNENs.These risk factors should be fully evaluated before surgery.

Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer

AIM： To evaluate the effect of mitochondrial tumor ne- crosis factor receptor-associated protein-1 （TRAP-l） on the lymph node metastasis （LNM） in Chinese colorectal cancer （CRC） patients, and develop potential LNM- associated biomarkers for CRC using quantitative real- time polymerase chain reaction （RT-PCR） analysis. METHODS： Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM （LNM CRC） and without LNM （non-LNM CRC） were assessed in 96 Chinese colorectal carcinoma samples using quantita- tive RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diaclnostic biomarkers was also examined.RESULTS： TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immuno- histochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramati- cally higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM （90.2% in LNM group vs 22% in non-LNM group, P 〈 0.001）, the advanced tumor node metastasis stage （89.1% in LNM group vs 26.9% in non-LNM group, P 〈 0.001）, the increased 5-year recurrence rate （82.7% in LNM group vs 22.6% in non-LNM group, P 〈 0.001） and the decreased 5-year overall survival rate （48.4% in LNM vs 83.2% in non-LNM group, P 〈 0.001）. Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients （Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028）. CONCLUSION： Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential bio- marker for LNM and a prognostic factor in CRC. Over- expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients. 2012 Baishideng. All rights reserved

Supraclavicular lymph node metastases from malignant gastrointestinal stromal tumor of the jejunum: A case report with review of the literature

Gastrointestinal stromal tumors(GISTs) represent the most common mesenchymal tumors of the alimentary tract. These tumors may have different clinical and biological behaviors. Malignant forms usually spread via a hematogenous route, and lymph node metastases rarely occur. Herein, we report a patient with a jejunal GIST who developed supraclavicular lymph node metastasis. We conclude that lymphatic diffusion via the mediastinal lymphatic station to the supraclavicular lymph nodes can be a potential metastatic route for GISTs.

Lateral pelvic lymph nodes for rectal cancer:A review of diagnosis and management

The current status and future prospects for diagnosis and treatment of lateral pelvic lymph node(LPLN)metastasis of rectal cancer are described in this review.Magnetic resonance imaging(MRI)is recommended for the diagnosis of LPLN metastasis.A LPLN-positive status on MRI is a strong risk factor for metastasis,and evaluation by MRI is important for deciding treatment strategy.LPLN dissection(LPLD)has an advantage of reducing recurrence in the lateral pelvis but also has a disadvantage of complications;therefore,LPLD may not be appropriate for cases that are less likely to have LPLN metastasis.Radiation therapy(RT)and chemoradiation therapy(CRT)have limited effects in cases with suspected LPLN metastasis,but a combination of preoperative CRT and LPLD may improve the treatment outcome.Thus,RT and CRT plus selective LPLD may be a rational strategy to omit unnecessary LPLD and produce a favorable treatment outcome.

Colorectal cancer lymph node dissection and disease survival

The debate regarding the two possible roles of lymphadenectomy in surgical oncology,prognostic or therapeutic,is still ongoing.Furthermore,the use of lymphadenectomy as a proxy for the quality of the surgical procedure is another feature of discussion.Nevertheless,this reckoning depends on patient conditions,aggressiveness of the tumor,the surgeon,and the pathologist,and then it is not an absolute surrogate for the surgical quality.The international guidelines recom-mend a minimum of 12 lymph nodes harvested for pathological examination in colorectal cancer(CRC)surgery.There is a growing literature on reporting better survival when the lymph node yield is high,even when these nodes are negative for malignancy.On the other hand,there are studies reporting no survival benefit with high lymph node yield in stage I-II of CRC.Herein we review the roles of the lymphadenectomy in CRC,and discuss the results of studies on lymph node harvesting.

Does lymph node dissection improve the prognosis of patients with colorectal cancer?

The number of lymph nodes(LNs)dissected during surgery has become an interesting topic.Simple intuition always leads us to believe that dissecting more LNs will result in more accurate pathological staging and assurance of surgical quality.However,when the number of LNs dissected reaches a certain threshold,the patient’s prognosis does not continue to improve as the number of dissected nodes increases.Instead,an increase in the number of dissected LNs may be accompanied by a higher incidence of complications.Currently,there are only less than 40%of colorectal cancer patients undergoing adequate LN evaluation.Therefore,obtaining a sufficient number of LNs in clinical practice is extremely challenging.How to further address the insufficiency of LN dissection due to various reasons,which results in concerns of surgeons about patient prognosis,is currently a critical focus.

Risk factors for lymph node metastasis in patients with pancreatic neuroendocrine neoplasms

BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers,some PNENs display malignant behavior including lymph node(LN)metastasis.Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs.However,the indications for LN dissection are still controversial.Over the last decade,minimally invasive surgery such as laparoscopic pancreatic surgery(LPS)has been increasingly performed for pancreatic tumors including PNENs.AIM To investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.METHODS From April 2001 to December 2019,92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital.Finally,82 patients were enrolled in this study.Using perioperative factors,we examined the predictive factors for LN metastasis in PNENs.RESULTS Among the 82 patients,the percentage of LN metastasis according to the pathological findings was 12%(10/82 cases).The median tumor size was 12 mm(range:5-90 mm).The median tumor size in the LN-positive group(37 mm)was significantly larger than that in the LN-negative group(12 mm)(P=0.0001).Multivariate analyses revealed that larger tumor size(≥20 mm)was an independent risk factor for LN metastasis(odds ratio 16.8,P=0.0062).In patients with small tumors(≤10 mm),LN metastasis was not found.CONCLUSION Larger tumor size(≥20 mm)is an independent risk factor for LN metastasis in PNENs.In smaller PNENs(≤10 mm),we may be able to choose limited surgery without LN dissection.

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.

Assessment of lymph node involvement in colorectal cancer

Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with nodenegative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.

Impact of metastatic lymph node ratio in node-positive colorectal cancer

Colorectal cancer(CRC) is one of the most common malignant diseases in the world.Presently,the most widely used staging system for CRC is the tumor nodes metastasis classification system,which classifies patients into prognostic groups according to the depth of the primary tumor,presence of regional lymph node(LN) metastases,and evidence of distant metastatic spread.The number of LNs with confirmed metastasis is related to the severity of the disease,but this number depends on the number of LNs retrieved,which varies depending on patient age,tumor grade,surgical extent,and tumor site.Numerous studies and a recent structured review have demonstrated associated improvements in the survival of CRC patients with increasing numbers of LNs retrieved for examination.Hence,the impact of lymph node ratio(LNR),defined as the number of metastatic LNs divided by the number of LNs retrieved,has been investigated in various malignancies,including CRC.In this editorial,we review the literature demonstrating the clinicopathological significance of LNR in CRC pati-ents.Some reports have indicated the advantage of considering the LNR compared to the number of LNs retrieved and/or LN status.When the LNR is taken into consideration for survival analysis,the number of LNs retrieved and/or the LN status is not always found to be a prognostic factor.The cut-off points for LNRs were proposed in numerous studies.However,optimal thresholds for LNRs have not yet received consensus.It is still unclear whether the LNR has more prognostic validity than N stage.For all these reasons,the potential advantages of LNRs in the staging system should be investigated in large prospective data sets.

Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice

AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macro-phages in lymph nodes were observed with in situ DNA fragmentation. RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of HcaF was 80%(16/20), whereas that of Hca-P was 25%(5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P【0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P 【0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells. CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.