Risk Of Lymphatic Metastasis Research Articles

Characteristics of small pancreatic neuroendocrine tumors and risk factors for invasion and metastasis.

The number of people with small pancreatic neuroendocrine tumors (pNETs) (tumors with a diameter less than or equal to 2cm) is gradually increasing, but the selection of treatment strategy is still controversial. Our aim was to characterize small pNETs with a poor prognosis and to define the impact of aggressive small pNETs on survival and the risk factors for the development of invasive disease. Patients with pNETs diagnosed between 2004 and 2019 and a tumor diameter of 2cm or less were selected from the SEER Registry. Kaplan-Meier survival analysis was used to identify the factors affecting patient survival, and binary logistic regression was used to identify the associated risk factors. A total of 3261 patients with pNETs were enrolled in the study. Both older and younger patients benefited from surgery. Regional invasion occurred in 10% of the patients, and distant metastases occurred in 9% of the patients, but in both categories, those who underwent surgery had better survival outcomes than those who did not. There was no difference in survival between patients with a tumor diameter of 1-2 cm and those with a tumor diameter of less than 1cm, and there was no difference in survival between patients with functional and nonfunctional small pNETs. However, the survival of patients with pNETs in the head of the pancreas was worse than that of patients with tumors in other parts of the pancreas. Survival was worse in elderly patients and in those with poorly differentiated and undifferentiated tumors. Lymphatic metastasis, regional invasion, and distant metastasis all worsened the prognosis of patients. The presence or absence of neuroendocrine function, the degree of tumor differentiation, and the location of the tumor were associated with the risk of lymphatic metastasis and regional invasion; the risk factors for distant metastasis were associated with the degree of differentiation and tumor location. The pNETs ≤ 2cm in diameter could be still aggressive, and patient prognosis worsens after invasive disease develops. Attention to the characteristics of aggressive tumors can improve patient survival.

A Visualized Dynamic Prediction Model for Lymphatic Metastasis in Ewing's Sarcoma for Smart Medical Services.

BackgroundThis study aims to predict the lymphatic metastasis in Ewing's sarcoma (ES) patients by nomogram. The risk of lymphatic metastasis in patients with ES was predicted by the built model, which provided guidance for the clinical diagnosis and treatment planning.MethodsA total of 929 patients diagnosed with ES were enrolled from the year of 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The nomogram was established to determine predictive factors of lymphatic metastasis according to univariate and multivariate logistic regression analysis. The validation of the model performed using multicenter data (n = 51). Receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the prediction accuracy of the nomogram. Decision curve analysis (DCA) was implemented to illustrate the practicability of the nomogram clinical application. Based on the nomogram, we established a web calculator to visualize the risk of lymphatic metastases. We further plotted Kaplan-Meier overall survival (OS) curves to compare the survival time of patients with and without lymphatic metastasis.ResultsIn this study, the nomogram was established based on six significant factors (survival time, race, T stage, M stage, surgery, and lung metastasis), which were identified for lymphatic metastasis in ES patients. The model showed significant diagnostic accuracy with the value of the area under the curve (AUC) was 0.743 (95%CI: 0.714–0.771) for SEER internal validation and 0.763 (95%CI: 0.623–0.871) for multicenter data external validation. The calibration plot and DCA indicated that the model had vital clinical application value.ConclusionIn this study, we constructed and developed a nomogram with risk factors to predict lymphatic metastasis in ES patients and validated accuracy of itself. We found T stage (Tx OR = 2.540, 95%CI = 1.433–4.503, P < 0.01), M stage (M1, OR = 2.061, 95%CI = 1.189–3.573, P < 0.05) and survival time (OR = 0.982, 95%CI = 0.972–0.992, P < 0.001) were important independent factors for lymphatic metastasis in ES patients. Furthermore, survival time in patients with lymphatic metastasis or unclear situation (P < 0.0001) was significantly lower. It can help clinicians make better decisions to provide more accurate prognosis and treatment for ES patients.

MAGE-C3 promotes cancer metastasis by inducing epithelial-mesenchymal transition and immunosuppression in esophageal squamous cell carcinoma.

BackgroundEvading immune surveillance is necessary for tumor metastasis. Thus, there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion. In this study, we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma (ESCC).MethodsThe expression of melanoma‐associated antigen C3 (MAGE‐C3) was detected using immunohistochemistry. Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma (ESCC) cells. Metastasis assays in mice were used to evaluate metastatic ability in vivo. Lymphocyte‐mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells. RNA sequencing was performed to identify differentially expressed genes between MAGE‐C3 overexpressing ESCC cells and control cells. Gene ontology (GO) enrichment analyses was performed to identify the most altered pathways influenced by MAGE‐C3. The activation of the interferon‐γ (IFN‐γ) pathway was analyzed using Western blotting, GAS luciferase reporter assays, immunofluorescence, and flow cytometry. The role of MAGE‐C3 in the IFN‐γ pathway was determined by Western blotting and immunoprecipitation. Furthermore, immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases.ResultsMAGE‐C3 was overexpressed in ESCC tissues. High expression of MAGE‐C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC. Functional experiments revealed that MAGE‐C3 promoted tumor metastasis by activating the epithelial‐mesenchymal transition (EMT). MAGE‐C3 repressed antitumor immunity and regulated cytokine secretion of T cells, implying an immunosuppressive function. Mechanistically, MAGE‐C3 facilitated IFN‐γ signaling and upregulated programmed cell death ligand 1 (PD­L1) by binding with IFN‐γ receptor 1 (IFNGR1) and strengthening the interaction between IFNGR1 and signal transducer and activator of transcription 1 (STAT1). Interestingly, MAGE‐C3 displayed higher tumorigenesis in immune‐competent mice than in immune‐deficient nude mice, confirming the immunosuppressive role of MAGE‐C3. Furthermore, mice bearing MAGE‐C3‐overexpressing tumors showed worse survival and more lung metastases with decreased CD8+ infiltrated T cells and increased programmed cell death 1 (PD‐1)+CD8+ infiltrated T cells.ConclusionMAGE‐C3 enhances tumor metastasis through promoting EMT and protecting tumors from immune surveillance, and could be a potential prognostic marker and therapeutic target.

Topographic distribution of lymph node metastasis in patients with stage IB1 cervical cancer: an analysis of 8314 lymph nodes

BackgroundSystematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment.MethodsA total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification.ResultsTotally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases.ConclusionsThe incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.

EIF3H knockdown inhibits malignant melanoma through regulating cell proliferation, apoptosis and cell cycle

Malignant melanoma (MM) causes 80% of skin cancer-related deaths and becomes the most lethal type of skin cancer. The molecular mechanism of MM is still not clear. This study aimed to reveal the relationship between MM and EIF3H. Clinical specimens were collected to preliminarily explore the role of EIF3H in MM. MM cell lines with EIF3H knockdown were constructed for investigating the effects of EIF3H on cell proliferation, apoptosis, cell cycle and cell motility. Mice xenograft model was constructed for verification in vivo. We found that EIF3H was obviously upregulated in MM tissues compared with normal skin tissues, which was correlated with tumor stage and risk of lymphatic metastasis. The in vitro results indicated that silencing EIF3H in MM cells could significantly suppress cell proliferation, promote cell apoptosis and induce cell cycle arrest. Moreover, EIF3H knockdown significantly restrained cell motility through regulating EMT-related proteins. The effects of EIF3H knockdown were also verified in mice xenograft model, which were represented by slower growth rate, smaller volume and lighter weight of tumors. Therefore, EIF3H was identified as a critical factor in the development and progression of MM which may be used as a novel therapeutic target in the treatment of MM.

Identification of risk factors associated with pelvic lymph node metastasis in patients with stage IB1 cervical cancer.

e18005 Background: Evaluation the distribution of nodal metastases in the stage IB1 cervical cancer and the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location. Methods: 728 patients with stage IB1 cervical cancer who underwent radical hysterectomies and systemic pelvic lymphadenectomies from January 2008 to December 2017 were retrospectively studied. All removed pelvic lymph nodes were pathologically examined, and the risk factors for LNM at the obturator, internal iliac, external iliac, and common iliac regions were evaluated by univariate and multivariate logistic regression analyses. Results: 20,134 lymph nodes were analysed with the average number of 27.80 (± SD 9.43) lymph nodes per patient. Nodal metastases were present in 266 (14.6%) patients. The obturator was the most common site for nodal metastasis (42.5%) followed by the internal iliac nodes (20.3%) and the external iliac nodes (19.9%), while the common iliac (9.8%) and parametrial (7.5%) nodes were the least likely to be involved. Tumor size more than 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion correlated independently significantly with the higher risk of the lymphatic metastasis. Obesity (BMI≥25) was independently significantly negatively correlated with the risk of lymphatic metastases. All the positive common iliac nodes were found in patients with tumors greater than 2 cm. The multivariate analysis showed that tumor size greater than 3 cm was associated with a 16.6-fold increase in the risk for common iliac LNM. Interestingly, tumor size was not an independent risk factor for pelvic LNM in the lower regions, i.e., the obturator, internal iliac and external iliac areas, where LVSI was the most significant predictor for LNM. In addition, parametrial invasion was related to external and internal iliac LNM; deep stromal invasion and age less than 50 years were associated with obturator LNM. Conclusions: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. The data offer the opportunity for tailored individual treatment in selected patients with small tumors and obesity.

Relationship Between Single Nucleotide Polymorphisms and the Toxicy and Side Effects of Paclitaxel and Platinum-Based Chemotherapy in Patients with Malignant Tumors

Objective: Investigating the relationship between single nucleotide polymorphisms (SNPs) and the toxic and adverse effects of paclitaxel and platinum-based chemotherapy in patients with malignant tumors, to provide recommendations for individualized treatment. Methods: Determinate 17 patients with malignant tumor DNA site and analysis. Results: 1. All 17 selected specimens’ fluorouracil related genes 18DPYD*2A(476002G&gt;A)GG type、153DPYD*13(1679T&gt;G)TT type 154DPYD(2846A&gt;T)TT type, and the synthesis of DPYD enzyme activity. 21GSTP1(313A&gt;G) polymorphism site mutation rate was 25.0%(4 cases), 29XRCC1(16323944T&gt;C) polymorphism site mutation rate was 90.9%(10 cases), 62ABCB1(3435C&gt;T) polymorphism site mutation rate was 52.9%(9 cases), and 68MTHFR(677C&gt;T) polymorphism site mutation rate was 50.0%(8 cases). 2. Fluorouracil related genes 18DPYD*2A(476002G&gt;A)GG type, 153DPYD*13(1679T&gt;G)TT type, 154DPYD(2846A&gt;T)TT type ,and the synthesis DPYD enzyme activity is normal. 3. Paclitaxel related genes 62ABCB1(3435T&gt;C) CC type has a lower incidence of hematotoxicity and neurotoxicity, than CT type and TT type. 13ABCB1(2677T&gt;G)GG type has a higher rate of drug resistance than TT type. 14CYP1B1*3(C&gt;G)CC type has a higher progression-free survival. Platinum-related genes 21GSTP1(313A&gt;G)AA is homozygous wild type and has a higher incidence of hematotoxicity than GA type. 29XRCC1(1196T&gt;C)CC is homozygous mutant and has a higher risk of serious neutropenia than CT type. 62ABCB1 (3435T&gt;C)CC is homozygous mutant and has a higher risk of lymphatic metastasis than TC type and TT type. 68MTHFR(677C&gt;T)TT type is homozygous mutant and has a higher mucosal toxicity and toxic and side effects than CT type and CC type. Conclusion: Single nucleotide polymorphism is related to the toxic and side effects of chemotherapy，the detection of SNP to predict the toxicity risk of drug users can be an important reference index to guide clinical individualized treatment.

Therapeutic endoscopic strategies in early esophageal cancer and dysplastic Barrett’s epithelium

Endoscopic therapy is the gold standard for curative treatment of early esophageal adenocarcinoma (EAC) including dysplastic Barrett´s epithelium (BE) and very early squamous cell carcinoma (SCC) because it is superior to surgery in regard to morbidity, mortality and cost effectiveness while yielding excellent results and low complication rates. Tumor detection at an early stage is often challenging and a multimodal approach using high resolution white light endoscopy, virtual chromoendoscopy (e.g. narrow band imaging, NBI) and endoscopic ultrasonography (EUS) is recommended. Importantly, histological diagnosis and EUS guided tumor staging should be performed before endoscopic tumor resection, although EUS validity has its limitations in terms of superficial mucosal and submucosal tumor invasion. In early esophageal adenocarcinoma, endoscopic mucosal resection (EMR) is considered the first line therapy and endoscopic submucosal dissection (ESD) is recommended only in special cases. In contrast, in very early squamous cell carcinoma, ESD is superior to EMR. This is mainly caused by a lower risk for lymphatic metastases in adenocarcinoma compared to squamous cell carinoma. If endoscopic resection is not curative or not feasible, surgery is the treatment of choice - assuming the patient´s comorbidities and performance status are no exclusion criteria.

Incidental diagnosis of the tall-cell variant of the papillary microcarcinoma of the thyroid gland requires completion lymphadenectomy: case report

Papillary thyroid carcinoma is the most common neoplasm of the thyroid gland which is usually associated with a very good prognosis. The aim of this case report is to present the disease course of a rare tumor of the thyroid gland, which is worthwhile due to its extraordinary appearance and specific management. A 46-year-old patient presented with a pronounced right-sided, but bilateral, multinodular goiter, with a volume of approximately 80 mL, as assessed on ultrasonography. Surgical removal was indicated as scintigraphy showed a 4-cm cold nodule that almost completely took up the right thyroid lobe. Because of the micronodular texture of the left thyroid lobe, complete thyroidectomy was performed according to well-established guidelines. Histopathological investigation of the specimen revealed a follicular adenoma without any malignancy in the right thyroid lobe and the tall-cell variant of the papillary thyroid microcarcinoma in the left lobe, with a capsular invasion and diameter of 0.6 cm. Because this rare tumor subtype is known for its aggressive behavior, and there was capsular invasion, low-grade differentiation, and an increased risk for lymphatic metastases, completion lymphadenectomy of the central compartments was performed after an interdisciplinary board decision. On histopathology, there were 30 tumor-free lymph nodes; final TNM classification was as follows: pT3 pN0 [0/30] L0 V0 Pn0 R0). The postoperative course was uneventful, and surgery was followed by radioiodine therapy. Six months after the surgery, clinical follow-up did revealed any sign of recurrence. The tall-cell variant is a rare and aggressive subtype of the papillary thyroid carcinoma, and it is characterized by poor 5-year survival and high recurrence rate. According to our understanding and based on current literature, this disease requires an aggressive surgical treatment and a close follow-up, as recommended by the current guidelines.

Conventional US combined with acoustic radiation force impulse (ARFI) elastography forprediction of triple-negative breast cancer and the risk of lymphatic metastasis.

To evaluate the combination of conventional ultrasound (US) and acoustic radiation force impulse (ARFI) elastography in predicting triple-negative breast cancer and the likelihood of lymphatic metastasis. A total of 178 women presenting from May 2013 to September 2015 with pathologically proven triple-negative (n = 60) or hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (n = 118) were reviewed. Conventional US and ARFI imaging including Virtual touch tissue image (VTI) and Virtual Touch tissue Quantification (VTQ), were performed for each breast nodule. Parameters collected included patient age, lymph node involvement, histological grade, tumor subtype, appearance on conventional US, shear wave velocity (SWV) value, VTI score and the boundary on VTI. The ARFI findings were compared with the pathological findings. Younger age (P < 0.001), higher histological grade (P < 0.001), lymphatic metastasis (P < 0.001), more nodes involved (P = 0.001), larger tumor size (P = 0.008), regular shape (P = 0.032), high VTI score (P = 0.006), unclear VTI boundary (P = 0.033), SWV ≥3.51 m/s (P = 0.015) were significantly associated with triple-negative breast cancer. High VTI score (P = 0.004) and a high SWV ≥4.15 m/s (P = 0.002) were significantly associated with lymphatic metastasis. Conventional US combined with ARFI may be used to predict triple-negative breast cancer. Those cancers with higher SWV and the high VTI score have a higher likelihood of lymphatic metastasis.

The role of long non-coding RNA HOTAIR in the progression and development of laryngeal squamous cell carcinoma interacting with EZH2

Conclusions: The aberrant expression of long non-coding RNA HOTAIR and transmethylase EZH2 played important roles in the progression and development of laryngeal squamous cell carcinoma (LSCC).Objectives: This research was aimed to explore the expression and correlation with clinicopathological characteristics of HOTAIR and EZH2 in LSCC, and to evaluate the function of the two in regulating the proliferation and cis-platinum resistance processes of LSCC.Methods: Quantitative real time-PCR (qPCR) was conducted to measure the expression of HOTAIR and EZH2 in tissue samples. Clinicopathological features were collected and statistically analyzed combining with the expression of HOTAIR and EZH2. The variance of EZH2 with down-regulating HOTAIR was measured by qPCR. CCK-8 proliferation test was conducted to detect the proliferation feature in LSCC cells. After cultured with a series of cis-platinum concentrations for 24 h, cell viability was detected using CCK-8 assay, and the inhibition rates were calculated.Results: HOTAIR and EZH2 were over-expressed in LSCC tissue. The higher expression was significantly related to T phase, pathological grades, and risk of lymphatic metastasis of LSCC. Suppressing HOTAIR expression stimulated EZH2 expressing, promoted the proliferation of AMC-HN8 cells, and increased the sensitivity to cis-platinum of the LSCC cells.

Endoscopic submucosal tunnel dissection for large superficial esophageal squamous cell neoplasms.

Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial esophageal squamous cell neoplasms (SESCNs) with no risk of lymphatic metastasis. However, for large SESCNs, especially when exceeding two-thirds of the esophageal circumference, conventional ESD is time-consuming and has an increased risk of adverse events. Based on the submucosal tunnel conception, endoscopic submucosal tunnel dissection (ESTD) was first introduced by us to remove large SESCNs, with excellent results. Studies from different centers also reported favorable results. Compared with conventional ESD, ESTD has a more rapid dissection speed and R0 resection rate. Currently in China, ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique, as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria. However, not all patients with SESCNs are candidates for ESTD, and postoperative esophageal strictures should also be taken into consideration, especially for lesions with a circumference greater than three-quarters. In this article, we describe our experience, review the literature of ESTD, and provide detailed information on indications, standard procedures, outcomes, and complications of ESTD.

Melanomas of the head-and-neck skin with mutation BRAF-V600K or BRAF-V600R define a melanoma subtype with particular clinical features.

9098 Background: “Malignant melanoma” is a melting pot of diverse melanocytic tumor entities, which arise in different organs under varying pathogenetic circumstances. Chronic sun exposure is a major factor for the development of cutaneous melanomas of the head-and-neck (HN) region. Methods: 131 patients with metastatic cutaneous melanomas were included in a monocentric retrospective study. The HN skin was the primary tumor site in 41 patients. The mutational hotspots of BRAF and NRAS were analysed by Sanger sequencing. In BRAF and NRAS wildtype cases, additionally exons 11, 13 and 17 of the KIT gene were investigated. HN patients with the mutations BRAF-V600K or BRAF-V600R were defined as group A (n = 11), those with other mutations or wildtype as group B (n = 30). A and B were compared with regard to the emergence of different categories of metastases, using the Kaplan-Meier method and log rank tests. The average follow-up time was 50 months. Results: BRAF-V600K occurred in 10 of the 41 HN patients and in 2 of the 90 non-HN patients (p = 0.003 by T-test), BRAF-V600R in 1 HN and in 1 non-HN patient. KIT mutations were restricted to 2 HN patients. Inversely, NRAS mutations were rare in the HN (3 of 41) versus the non-HN (26 of 90) cohort (p = 0.001). Lymphatic metastasis became apparent in each of the 11 group A patients not later than 35 months after the diagnosis of the respective primary melanoma. 5 out of the 8 group A patients, who underwent sentinel node biopsies (SNB), had nodal micrometastases. During follow-up, regional nodal macrometastases emerged earlier and at a higher rate in group A compared to B (p = 0.044 by log rank test). The same applied even more significantly for satellite/intransit metastases (p = 0.002), whereas for distant metastasis no significant difference was found. Conclusions: BRAF-V600K/R mutations in HN melanomas define a distinct melanoma subtype with an especially high risk of lymphatic metastasis. Clinical implications may be mutation analyses already for primary HN melanomas, and SNB even for thin melanomas of this subtype. Extra-guidelines should be considered for the monitoring of these patients. Special attention to this subgroup is also necessary in clinical trials.

The role of para-aortic lymphadenectomy in endometrial cancer

Endometrial cancer (EC) is the most common malignancy of the female reproductive tract and the fourth most common cancer overall. Approximately 20% of patients with EC harbor disease outside the uterus, and 10% of patients initially diagnosed with cancer confined to the uterus are found to have lymph node metastases. Para-aortic lymph node involvement occurs in approximately 7-8% of EC patients overall and in about 50% of patients with positive pelvic nodes. Metastases to the para-aortic lymph nodes are associated with poor prognosis. Factors associated with para-aortic lymph node dissemination include advanced stage, high histological grade, deep myometrial invasion, cervical involvement, lymphovascular space involvement, and the presence of pelvic lymph node metastases. Approximately 77% of patients with para-aortic nodal involvement are found to have metastases above the level of the inferior mesenteric artery. Systematic pelvic and para-aortic lymphadenectomy with dissection optimally carried out to the renal vessels is important in high-risk patients in order to identify nodes present at distant sites, particularly above the inferior mesenteric artery (IMA). While the definitive management of EC varies widely across the gynecological oncology community, there is a consensus that patients at risk for lymphatic metastases (high and intermediate risk) who are targeted with systematic lymphadenectomy may have an improved prognosis. Well-designed prospective studies evaluating the therapeutic role of systematic lymphadenectomy in EC are needed. Herein, we describe the role of para-aortic lymphadenectomy in the surgical staging of EC emphasizing its prerequisites, extent, and diagnostic and potential therapeutic advantages.

Correlation of macrophage migration inhibitory factor gene polymorphism with the risk of early-stage cervical cancer and lymphatic metastasis

Associations of functional single nucleotide polymorphisms in MIF-173G/C with early stage cervical cancer were investigated in a hospital-based case-control study on 250 patients with cervical cancer prior to surgery (including 49 cases with and 201 cases without lymphatic metastasis) and 147 healthy controls. The polymorphism was assessed using restriction fragment length polymorphism polymerase chain reaction, and the MIF serum concentration was examined using the enzyme-linked immunosorbent assay to analyze the correlation between the polymorphism and the MIF serum concentration. Carriers of the variant C allele in MIF-173 were at a significantly higher risk of cervical cancer compared to carriers of the wild-type allele (aOR=1.508; 95% CI, 1.128-2.016, p=0.05). The GC and CC genotypes may be the causative factors for cervical cancer (aOR=1.851; 95% CI, 1.132-3.027, p=0.013). Individuals with the GC+CC genotype and C allele at the MIF-173G/C site were at a significantly higher risk of cervical cancer and lymphatic metastasis. The risk of lymphatic metastasis in early stage cervical cancer was increased more than 1.6 times in patients with the CC and GC genotypes compared with those with the GG genotype. The genotype distribution and allele frequency of MIF-173G/C were statistically significant in the well-, moderately and poorly differentiated groups (P<0.05). Compared to the GG genotype and G allele, patients with GC and CC genotypes and C allele exhibited a lower degree of differentiation and a higher degree of malignancy. A significant difference was observed in MIF serum concentrations among the various subgroups (P<0.05). The early cervical cancer, lymphatic metastasis and poorly differentiated groups exhibited higher MIF levels in serum. Moreover, patients with the CC genotype exhibited higher MIF serum concentration, which could increase the risk of early stage cervical cancer and lymphatic metastasis. The results presented in this study provide the first evidence that the genetic polymorphism MIF-173 is associated with cervical cancer in humans. Detection of MIF serum concentration and genotyping may be used as biomarkers for early diagnosis and therapy for cervical cancer.

Stretching Causes Extensive Changes of Gastric Submucosa: Is It Acceptable to Define 500μm as the Safe Margin?

Endoscopic mucosal resection can cure early gastric cancer. The risk of lymphatic metastasis is related to the depth of submucosal invasion by the mucosal malignancy, with a resection depth of 500 microm generally accepted as a safe cut-off. However, excessive thinning induced by stretching of the resected tissue sometimes preventing a precise diagnosis. We studied the effects of stretching on different layers and sites of gastric tissue. Porcine stomachs were cut into 2.0x2.0 cm pieces, and pieces from body were stretched to 2.5, 3.0, and 3.5 cm. Pieces from the cardia, body, and antrum were also stretched to 3.0 cm. The thickness of each layer was measured and analyzed statistically. Whole gastric wall and submucosal layers showed gradual thinning, with stretching to 3.5 cm tearing the tissues and resulting in imperfect extension. The submucosa was thinner in body tissue than in cardia and antrum tissues. Stretching to 3.0 cm induced a consistent decrease in submucosal thickness (30-70%). The change in thickness varied widely between individual samples. A resection margin of 500 microm might be insufficient for the complete removal of malignancy. Moreover, the thickness of the submucosal layer differs with the gastric site and between individuals. Future studies are needed to confirm the findings in human tissue.

Lymphogene Metastasierung operierter Rektumkarzinome

Lymphogenic Metastatic Spread of Operated Rectal Carcinomas The aim of this study was to determine the risks of local surgery of rectal carcinoma regarding lymphogenic metastatic spread. The appearance of lymphatic metastases in 290 patients suffering from rectal carcinoma was investigated retrospectively. 112 of 290 patients revealed secondary malignancies at the time of operation. 66 patients showed single lymphatic lesions (pN1: 35, pN2: 31), 17 patients had single hematogenous lesions, and 29 patients showed both lymphatic and hematogenous metastases (pN1: 11, pN2: 18). Proximally involved lymph nodes were preferably nodes located near the superior rectal artery and at the inferior mesenteric artery; furthermore, a small number of lateral-iliacal lymph nodes were positive. In 4 cases, lymphatic metastases along the superior rectal artery were found, whereas the local lymph nodes at the tumor were free of any lesions. Low-risk tumors (with little risk of lymphatic metastasis and possible local surgery) had the following features: 1. T-stage: (p)Tis; (p)T1; in case of G1 also (p)T2; 2. Grading: highly differentiated (G1), (G2 questionable); 3. No vessel infiltration; 4. M and N negative (no enlargement of lymph nodes); 5. Tumor size: length < 2 cm, width < 1 cm, deepth < 0.5 cm, diameter < 2 cm, volume < 1 cm³; 6. Normal preoperative CEA and CA 19-9; 7. Recommended safety distance of 5–10 mm in cases of local resection. Local surgical procedures are recommended at special indications as above. However, they bear the potential risk of nonradical surgery and an incomplete staging, and there is a need for careful follow-up examinations.