Effect of HIF-1αon VEGF-C Induced Lymphangiogenesis and Lymph Nodes Metastases of Pancreatic Cancer

The effect of hypoxia inducible factor-1 α （HIF-1 α） on vascular endothelial growth factor C （VEGF-C） and the correlation between HIF- 1 α and lymphangiogenesis and lymph nodes metastases （LNM） in pancreatic cancer were investigated. Immunohistochemical SP method was used to detect the protein expression of HIF-1 α and VEGF-C, and Lymphatic vessel density （LVD） was determined by stain of VEGFR-3, collagen type IV in 75 pancreatic head cancers from regional pancreatectomy （RP） during Dec. 2001 to Dec. 2003. The relationship between HIF-1α and VEGF-C, lymphangiogenesis, LNM was analyzed statistically. The results showed that the positive expression rate of HIF-1α and VEGF-C in pancreatic cancer tissues was 48.00 % （36/75） and 65.33 % （49/75） respectively. In positive group of HIF-1α, the positive rate of VEGF-C and LVD, and LVD rate was 80.56 % （29/36）, 13.22±3.76 and 88.89 % （32/36） respectively, and in negative group of HIF-10t, positive rate of VEGF-C and LVD was 51.28 % （20/39）, 5.98±2.17 and 66.67 % （26/39） respectively （P〈0.01 or P〈0.05）. It was suggested that HIF-1α could promote the expression of VEGF-C, lymphangiogenesis and LNM in pancreatic cancer.

Feasibility and limitations of combined treatment for lateral pelvic lymph node metastases in rectal cancer

Colorectal cancer ranks among the most commonly diagnosed cancers globally,and is associated with a high rate of pelvic recurrence after surgery.In efforts to mitigate recurrence,pelvic lymph node dissection(PLND)is commonly advocated as an adjunct to radical surgery.Neoadjuvant chemoradiotherapy(NACRT)is a therapeutic approach employed in managing locally advanced rectal cancer,and has been found to increase the survival rates.Chua et al have proposed a combination of NACRT with selective PLND for addressing lateral pelvic lymph node metastases in rectal cancer patients,with the aim of reducing recurrence and improving survival outcomes.Nevertheless,certain studies have indicated that the addition of PLND to NACRT and total mesorectal excision did not yield a significant reduction in local recurrence rates or improvement in survival.Consequently,meticulous patient selection and perioperative chemotherapy may prove indispensable in ensuring the efficacy of PLND.

Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes

Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,

Immunoexpression of cyclooxygenase-2 in primary gastric carcinomas and lymph node metastases

AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases. METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue microarray slices obtained from 36 specimens of gastrectomy and satellite lymph nodes from patients with gastric carcinoma. RESULTS: Immunostaining was seen in most cases, and COX-2 expression was higher in lymph node me-tastases than in corresponding primary gastric tumors of intestinal, diffuse and mixed carcinomas, with a statistically signif icant difference in the diffuse histotype (P = 0.0108). CONCLUSION: COX-2 immunoexpression occurs frequently in primary gastric carcinomas, but higher expression of this enzyme is observed in lymph node metastases of the diffuse histotype.

EFFECT OF PREOPERATIVE CHEMOTHERAPY ON METASTASIZED LYMPH NODES IN PATIENTS WITH ADVANCED ESOPHAGEAL CARCINOMA

Objective To investigate the effect and clinical value of preoperative chemotherapy on the treatment of metastasized lymph nodes in patients with advanced esophageal carcinoma. Methods We studied the pathological results of primary lesions and lymph nodes of 97 patients with advanced esophageal cancer between 1996 and 1999,62 patients were treated by preoperative chemotherapy and 35 patients were treated by surgery only. Results The metas- tasized rate and degree of mediastinum in preoperative group were 16.1% and 4.7% ,whereas 65.7% and 34.2% in the surgery only group (P<0.05) ;That of abdomen in preoperative group were 25.8% and 6.6% ,whereas 48.6% and 12.0% in the surgery only group (P<0.05). Conclusion Preparative chemotherapy is effective not only against the primary lesions but also the metastasized lymph nodes. The lower complete response rate of the metastasized lymph may account for the unsatisfied long-term results. Whole resection of primary lesions and lymph nodes are still very important for a better prognosis even for patients who have a good response for the preoperative chemotherapy.

EDGE non-invasive radiosurgery for gastric neuroendocrine hepatic portal lymph node metastases:a case report

Treating metastatic gastric neuroendocrine neoplasms （gNENs） is challenging, especially for those with progressive disease during somatostatin analog processing. In this report, we present a case of a welldifferentiated grade 2, type 3 gNEN with metastatic hepatic portal lymph nodes. EDGE non-invasive radiosurgery （800 cGy x 5 F） was performed to radiate the metastatic hepatic portal lymph nodes. Three months after the hyperfractionated radiotherapy, no signs of metastatic hepatic portal lymph nodes were observed using 8Ga-dotatate positron emission tomography-computed tomography or magnetic resonance imaging. Therefore, EDGE non-invasive radiosurgery could be a potential option for treating local metastatic nodes.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Magnetic Resonance Evaluation of Transplanted Endometrial Carcinoma and Its Lymph Node Metastasis in Rabbits

Objective： To establish a rabbit model of transplanted endometrial carcinoma with lymph node metastasis and observe its magnetic resonance imaging （MRI） features. Methods： VX2 tumor grafts were orthotopically embedded in the endometrium of rabbits, and 3 weeks after the transplantation, thetumor and its metastasis to the retroperitoneal lymph nodes were examined by MRI, and the signal intensities and size of the lymph nodes were compared with those of normal rabbits. Results： The orthotopic transplantation of the tumor grafts resulted in tumor growth in all the 12 recipient rabbits. The tumors infiltrated the serosa of the uterus and metastasized to the retroperitoneal lymph nodes 3 w after transplantation. MRI demonstrated that the lymph nodes of the tumor-bearing rabbits were larger in size than those of normal control rabbits, but the signal intensity of the lymph nodes was not significantly different between them. Conclusion： This transplanted endometrial carcinoma model is characterized by high success rate and similar tumor metastasis behaviors with human endometrial carcinoma, therefore may serve as a good model for testing the efficacy of contrast agents for MR lymphography.

Predictive Factors of Lymph Node Metastasis in Early Mucinous Adenocarcinoma

OBJECTIVE To identify clinicopathologic factors which predictlymph node metastases (LNM) in early mucinous adenocarcinomapatients, and to further explore the possibility of using minimallyinvasive treatment for patients with the disease.METHODS Data was collected from 38 patients with earlymucinous adenocarcinoma who were surgically treated, and theassociation between clinicopathologic factors and the presenceof LNM was retrospectively analyzed using univariate andmultivariate logistic regression analysis.RESULTS Tumor size greater than 2.0 cm, the developmentof submucosal invasion, and the presence of lymphatic vesselinvolvement (LVI) were confirmed through univariate analysis ashaving a significant association with LNM and were consideredto be significant and independent risk factors for LNM throughmultivariate analysis.CONCLUSION Tumor size > 2.0 cm, the development ofsubmucosal invasion, and the presence of LVI are independentpredictive factors for LNM in early mucinous adenocarcinoma.Minimally invasive treatment may be an effective treatment forintramucosal early mucinous adenocarcinoma when the tumorsize is 2.0 cm or less, and if LVI has not occurred, as confirmed bypostoperative histologic examination.

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients betweenNovember 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classifiedinto 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymphnode (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and livermetastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane(below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostatecancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showedthat patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, andpatients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those inG5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015;medianOS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC,and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicatethat the farther the NRLNs are located, the more aggressive the disease is.

Early gastric cancer:A challenge in Western countries

Early gastric cancer(EGC)is an invasive carcinoma involving only the stomach mucosa or submucosa,independently of lymph node status.EGC represents over 50%of cases in Japan and in South Korea,whereas it accounts only for approximately 20%of all newly diagnosed gastric cancers in Western countries.The main classification systems of EGC are the Vienna histopathologic classification and the Paris endoscopic classification of polypoid and non-polypoid lesions.A careful endoscopic assessment is fundamental to establish the best treatment of EGC.Generally,EGCs are curable if the lesion is completely removed by endoscopic resection or surgery.Some types of EGC can be resected endoscopically;for others the most appropriate treatment is surgical resection and D2 lymphadenectomy,especially in Western countries.The favorable oncological prognosis,the extended lymphadenectomy and the reconstruction of the intestinal continuity that excludes the duodenum make the prophylactic cholecystectomy mandatory to avoid the onset of biliary complications.

Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer

AIM To compare the expression levels of interleukin(IL)-6 in colorectal cancer(CRC) tissues and adjacent noncancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC. METHODS Fifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis.RESULTS IL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues(P < 0.001). IL-6 expression was positively correlated with tumour TNM stage(P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC(P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC. CONCLUSION IL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.

Invasive micropapillary carcinoma:A distinct type of adenocarcinomas in the gastrointestinal tract

Invasive micropapillary carcinoma (IMPC) is a rare histological type of tumor, first described in invasive ductal breast cancer, than in malignancies in other organs such as lungs, urinary bladder, ovaries or salivary glands. Recent literature data shows that this histological lesion has also been found in cancers of the gastrointestinal system. The micropapillary components are clusters of neoplastic cells that closely adhere to each other and are located in distinct empty spaces. Moreover, clusters of neoplastic cells do not have a fibrous-vascular core. The IMPC cells show reverse polarity resulting in typical &#x02018;&#x02019;inside-out&#x02019;&#x02019; structures that determines secretary properties, disturbs adhesion and conditions grade of malignancy in gastrointestinal (GI) tract. Invasive micropapillary carcinoma in this location is associated with metastases to local lymph nodes and lymphovascular invasion. IMPC can be a prognostic factor for patients with cancers of the stomach, pancreas and with colorectal cancer since it is related with disease-free and overall survival. The purpose of this review is to present the characterization of invasive micropapillary carcinoma in colon, rectum, stomach and others site of GI tract, and to determine the immunohistological indentification of IMPC in those localization.

Occult cervical lymph node metastases in 100 consecutive patients with cNO tongue cancer

Background Squamous cell carcinoma （SCC） of the tongue maxillofacial region. To provide clinical evidence for selective analyzing the characteristics and correlation of factors of occult with SCC of the tongue. is one of the most common cancers in the oral and neck dissection in management of cN0 patients by cervical lymph node metastases （OCLNM） in patients Methods From 2002 to 2006, 100 consecutive patients with SCC of the tongue were reviewed by analyzing the characteristics of OCLNM, diameter of the tumor, T classifications, depth of invasion, forms of growth, pathological grade and degree of differentiation. Results The rate of OCLNM in 100 patients with SCC of the tongue was 22%. The most common region with OCLNM was level Ⅱ in the ipsilateral neck, followed by levels Ⅰ and Ⅲ. There were 51.61% （16/31） of OCLNM in level Ⅱ and 87.10% （27/31） of OCLNM in levels Ⅰ-Ⅲ. There was no significant correlation between the diameter of tumor and OCLNM （P 〉0.05）. OCLNM was statistically significantly correlated with the depth of invasion, forms of growth, pathological grade and degree of differentiation （P 〈0.05）. The rate of occult metastases increased with the increased pathological grade, the decreased degree of differentiation and the increased depth of invasion. Conclusions The most common regions with OCLNM in cN0 patients with SCC of the tongue were levels Ⅰ-Ⅲ in the ipsilateral neck. Supraomohyoid neck dissection should be the elective treatment to the neck in patients with cN0 SCC of the tongue by consideration of the clinical and pathological factors for the depth of invasion, forms of growth, pathological grade, and degree of differentiation.

Management of sub-5mm rectal carcinoids with lymph node metastases

Minute(<5mm)and small(5-10mm)rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive,and the management and surveillance of patients with this entity are usually limited.We present the case of a 61-year-old Chinese female with multiple sub-5mmcarcinoid tumours in the rectum without any computed tomography(CT)evidence of lymph node or distant metastases.She underwent an ultra-low anterior resection for a sessile rectal polyp with the histological appearance of a moderately differentiated adenocarcinoma.Seven foci of minute carcinoids in the rectum and perirectal lymph node metastastic spread from the carcinoid tumours were also discovered on histopathology.There were no lymph node metastases originating from adenocarcinoma.This case report and review of the literature suggests that minute rectal carcinoids are at risk of metastasizing and that these patients should be investigated for lymph node and distant metastatic spread with CT and somatostatin receptor scintigraphy or its equivalent,as this would influence prognosis and surgical management of these patients.Findings relating to lymphovascular invasion,perineural invasion,high Ki-67,mitotic rate,depth of tumour invasion,central ulceration,multifocal tumours and size are useful in predicting metastases and may be used in scoring tools.Size alone is not a good predictor of metastastic spread.

MTDH Expression in Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To clarify the expression of MTDH in invasive micropapillary carcinoma of the breast （IMPC） and analyze the relationship between MTDH expression and clinicalpathologic parameters of the IMPC patietns.

Resection of hepatocellular carcinoma after combined treatment with transarterial chemoembolization and sorafenib:a case report and literature review

Hepatocellular carcinoma(HCC)with inferior vena cava(IVC)invasion and metastatic lymph node metastases has a poor prognosis,and surgical resection is seldom indicated.We report how an initially unresectable HCC in a 36-year-old Chinese male with distant lymph node metastases and tumor thrombosis in the IVC was successfully downstaged and ultimately resected together with the IVC.After the disease had been downstaged,curative resection of the tumor and IVC was conducted with immediate reconstruction of the IVC.The patient has survived for more than 2 years after the surgery.In conclusion,tumor and IVC resection can cure metastatic HCC after downstaging treatment combining sorafenib and transarterial chemoembolization.