Risk Factors For Lymph Node Metastasis Research Articles

Diagnosis, Pathological Findings, and Clinical Management of Gangliocytic Paraganglioma: A Systematic Review.

Background: Although gangliocytic paraganglioma (GP) is considered a rare benign neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is misdiagnosed as neuroendocrine tumor G1, which is associated with a poorer prognosis than GP. To avoid such misdiagnoses, it is important to understand the clinicopathological characteristics of GP. Thus, herein, we discuss the current literature on the clinicopathological characteristics of GP.Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed and Japana Centra Revuo Medicina searches were used to identify papers describing GP. Inclusion criteria included confirmation of epithelioid, spindle-shaped, and ganglion-like cells in the main article and/or figures and whether the paper was cited in other studies of GP. Data were collected on age, sex, site of the primary lesion, tumor size, treatment, prognosis, lymph node metastasis (LNM), depth of tumor invasion, rate of preoperative diagnosis, and clinical symptoms.Results: In total, 162 papers containing 263 cases of GP met the criteria. The mean age at diagnosis was 53.5 years. The male-to-female ratio was 157:104. The mean tumor size was 25.7 mm. The predominant site of the primary tumor was the duodenum (89.7%). The most common clinical sign of GP was gastrointestinal bleeding (47.9%). Other signs and symptoms of GP included abdominal pain (44.7%), anemia (20.3%), incidental findings (12.9%), nausea (6.9%), weight loss (5.5%), general fatigue (5.1%), jaundice (4.6%), and incidental autopsy findings (5.1%). LNM was observed in 11.4% of patients. Liver metastasis was observed in 1.1% of patients. Depth of tumor invasion (penetrating beyond the submucosal layer or sphincter of Oddi) was by far the most significant risk factor for LNM in patients with GP. This suggests, along with histological heterogeneity, that GP may have hamartomatous characteristics. Furthermore, immunohistochemical expression of progesterone receptor and pancreatic polypeptide were useful in distinguishing between GP and neuroendocrine tumor G1, even in small biopsy specimens.Conclusions: We reveal the clinicopathological characteristics of GP, including risk factors for LNM, differential diagnostic approaches, and improvements in the clinical management of this tumor.In addition, GP may have hamartomatous characteristics.

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis.

Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry. The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs. Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC. This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC.

A nomogram for predicting lymph node metastasis in surgically resected T1 esophageal squamous cell carcinoma.

Endoscopic therapies for T1 esophageal carcinoma have been increasingly used around the world. However, the procedures are limited by without lymph nodes harvested. The risk of lymph node metastasis (LNM) should been established. Our objective was to construct a nomogram model for predict risks of LNM in patients with pT1 esophageal squamous cell carcinoma (ESCC). We reviewed the records of 221 patients with pT1 ESCC who underwent surgical resection and radical lymphadenectomy. Clinicopathological variables were analyzed univariate and multivariate logistic regression analysis. A nomogram for predicting risk of LNM was constructed and validated using bootstrap resampling. Of the 221 patients, 53 patients had been examined as LNM. Following multivariate analysis, poor differentiation (P=0.0006), lymphovascular invasion (P<0.0001) and SM3 (tumor invades the lower third of the submucosal layer) (P=0.0192) cancer were significantly independent risk factors for LNM and were entered into the nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.8667. The calibration curves for the probability of LNM showed optimal agreement between the probability as predicted by the nomogram and the actual probability. We established a nomogram that can provide individual predicting for LNM in T1 ESCC, and this model has the potential clinical utility in making therapeutic procedures.

Predictive value of quantitative image analysis for lymph node metastasis in patients with rectal cancer

Objective To evaluate the values of the quantitative parameters obtained from 18F-fluorodeoxyglucose (FDG) PET/CT imaging and MRI in prediction of lymph node metastasis (LNM) in patients with rectal cancer. Methods From May 2013 to October 2015, 80 patients with rectal cancer (63 males, 17 females, age range: 37-85 years) that underwent preoperative MRI-diffusion weighted imaging (DWI) and 18F-FDG PET/CT were enrolled. All patients had pathological results. Auto-segmentation methods of various thresholds were selected to determine the FDG metabolic parameters and whole volume region of interest (ROI) method was performed to measure apparent diffusion coefficient (ADC) in lymph node. Maximum standardized uptake value (SUVmax)=2.5, 20%SUVmax, 30%SUVmax, 40%SUVmax and 50%SUVmax were selected as the cut-off values (COV), and named as COV1, COV2, COV3, COV4 and COV5, respectively. ROI was drawn automatically and the corresponding mean standardized uptake value (SUVmean)1-SUVmean5, metabolic tumor volume (MTV)1-MTV5 and total lesion glycolysis (TLG)1-TLG5 were calculated. χ2 test and logistic regression analysis were used to analyze the associations between the LNM and pathological factors, as well as 18F-FDG metabolic parameters and ADC. Results LNM was found in 55% (44/80) of the patients. The metabolic parameters of primary tumor in patients with LNM were significantly higher than those in patients without LNM (u values: 152.0-555.0, all P<0.05); the ADC was significantly lower in LNM positive cases than that in LNM negative cases: 0.96(0.93, 1.02)×10-3 mm2/s vs 1.07(1.01, 1.11)×10-3 mm2/s, u=249.0, P<0.05. Univariate analysis showed that T stage, SUVmax, SUVmean1-SUVmean5, MTV1-MTV5, TLG1-TLG5, ADC value were associated with pathologic lymph node involvement (χ2 values: 7.730-48.198, all P<0.05). Multivariate analysis indicated that MTV1 (odds ratio (OR)=0.110, 95% CI: 0.014-0.840), MTV2 (OR=0.075, 95% CI: 0.007-0.852) and ADC (OR=0.034, 95% CI: 0.003-0.381) of tumor were significant risk factors associated with LNM (all P<0.05). The optimal COV of MTV1, MTV2 and ADC were 20.26 cm3, 18.47 cm3 and 1.00×10-3 mm2/s. Conclusion MTV1, MTV2 measured by 18F-FDG PET/CT and ADC measured by MRI-DWI of the primary tumor are risk factors of LNM from rectal cancer, and they may be useful to predict LNM in patients with rectal cancer. Key words: Rectal neoplasms; Neoplasm metastasis; Lymph nodes; Positron-emission tomography; Tomography, X-ray computed; Magnetic resonance imaging; Deoxyglucose

Management of Early-Stage Adenocarcinoma of the Esophagus: Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection.

Barrett's esophagus with high-grade dysplasia and early-stage adenocarcinoma is amenable to curative treatment by endoscopic resection. Histopathological correlation has established that mucosal cancer has minimal risk of nodal metastases and that long-term complete remission can be achieved. Although surgery is the gold-standard treatment once there is submucosal involvement, even T1sm1 (submucosal invasion ≤ 500μm) cases without additional risk factors for nodal metastases might also be cured with endoscopic resection. Endoscopic resection is foremost an initial diagnostic procedure, and once histopathological assessment confirms that curative criteria are met, it will be considered curative. Endoscopic resection may be achieved by endoscopic mucosal resection, which, although easy to perform with relatively low risk, is limited by an inability to achieve en bloc resection for lesions of size more than 1.5cm. Conversely, the technique of endoscopic submucosal dissection is more technically demanding with higher risk of complications but is able to achieve en bloc resection for lesions larger than 1.5cm. Endoscopic submucosal dissection would be particularly important in specific situations such as suspected submucosal invasion and lesion size more than 1.5cm. In other situations, since endoscopic resection would always be combined with radiofrequency ablation to ablate the remaining Barrett's epithelium, piecemeal endoscopic mucosal resection would suffice since any remnant superficial invisible dysplasia would be ablated.

Clinical analysis of cervical lymph node metastasis risk factors in patients with papillary thyroid microcarcinoma

PurposeLymph node metastasis (LNM) is a vital prognosis factor in patients with papillary thyroid microcarcinoma (PTMC). The study tried to identify clinicopathological factors for LNM of PTMC.MethodsThe clinicopathological data of 1031 patients with PTMC were extracted and analyzed. Univariate and multivariate analyses were used to identify risk factors associated with cervical lymph node metastasis. ROC analysis was used to determine the ideal critical points of the sum of the maximum diameter of multifocal in a unilateral lobe.ResultsThe probability of LNM, central lymph node metastasis (CLNM) and lateral lymph node metastasis(LLNM)of PTMC patients were 35.6, 33.7 and 5.6%, respectively. In addition, 1.9% PTMC had LLNM only. Male, age ≤ 40 years, tumor largest diameter ≥ 5 mm, multifocal, non-uniform echoic distribution, the sum of the maximum diameter of multifocal in a unilateral lobe ≥ 8.5 mm, tumors in the lower pole location were prone to CLNM. Ultrasound mix-echo, the sum of the maximum diameter of the multifocal ≥ 10.75 mm, tumors in the upper pole location were extremely prone to LLNM. T3 were prone to LLNM or skip LLNM.ConclusionsAccording to the clinicopathological characteristics of PTMC, the cervical lymph nodes should be correctly evaluated to guide the surgical treatment.

Diagnostic accuracy of dual-energy CT-based nomograms to predict lymph node metastasis in gastric cancer.

To develop and validate a dual-energy CT based nomogram for the preoperative prediction of lymph node metastasis (LNM) in patients with gastric cancer (GC). A total of 210 surgically confirmed GC patients (159 males, 51 females; mean age: 59.8 ± 7.7 years, range: 28-79 years) who underwent spectral CT scans were retrospectively enrolled and split into a primary cohort (n = 140) and validation cohort (n = 70). Clinical information and follow-up data including overall survival (OS) and progression-free survival (PFS) were collected. The iodine concentration (IC) of the primary tumors at the arterial phase (AP) and venous phase (VP) were measured and then normalized to the aorta (nICs). Univariate, multivariable logistic regression and Cox regression analyses were performed to screen predictive indicators for LNM and outcome. A nomogram for risk factors of LNM was developed, and its performance was measured using the ROC, accuracy and Harrell's concordance index (C-index). Tumor thickness, Borrmann classification and ICVP were independent predictors of LNM. The nomogram was significantly associated with LN status (p < 0.001). It yielded an AUC of 0.793 [95% confidence interval (95% CI), 0.678-0.908] and an accuracy of 0.757 (95% CI, 0.640-0.852) in the internal-validation cohort. The nomogram also exhibited a prognostic ability with C-indices of 0.675 (95% CI, 0.571-0.779; p < 0.001) for PFS and 0.643 (95% CI, 0.518-0.768; p = 0.025) for OS. This study presented a dual-energy quantification-based nomogram, which can be used to facilitate the preoperative individualized prediction of LNM in patients with GC. • This study first developed and internally validated a dual-energy CT-based nomogram to predict lymph node metastasis in patients with gastric cancer. • The nomogram incorporated the clinical risk factors and iodine concentration, which would enable superior preoperative individual prediction of lymph node metastasis and add more information for the optimal therapeutic strategy. • The nomogram also exhibited a significant prognostic ability for progression-free and overall survival.

A Risk-Scoring Model for Predicting Lymph Node Metastasis in Early Gastric Cancer Patients: a Retrospective Study and External Validation

BackgroundThe possibility of lymph node metastasis (LNM) is critical to the assessment of the indication for endoscopic submucosal dissection. Thus, the aim of this study is to identify the risk factors for LNM and construct a risk-scoring model for patients with early gastric cancer to guide treatment. MethodsA retrospective examination of reports and studies carried out January 2000 and December 2014 was conducted. A risk-scoring model for predicting LNM was developed based on the data thus collected. In addition, the model is subject to verification and validation by three institutions. ResultsOf the 1029 patients, 228 patients (22%) had LNM. Multivariate analysis showed that female, depressed type, undifferentiated type, submucosa, tumor size, and lymphovascular invasion were significantly associated with LNM. An 11-point risk-scoring model was used to predict LNM risk. An area under the receiver operating characteristic (AUROC) of the risk-scoring model was plotted using the development set and the AUROC of the model [0.76 (95% CI 0.73–0.80)] to predict LNM risk. After internal and external validation, the AUROC curve for predicting LNM was 0.77 (95% CI 0.68–0.86), 0.82 (95% CI 0.72–0.91), and 0.82 (95% CI 0.70–0.94), respectively. ConclusionsA risk-scoring model for predicting LNM was developed and validated. It could help with personalized care for patients with EGC.

Risk factor analysis and prediction model establishment of lymph node metastasis in remnant gastric cancer

To explore the risk factors and establish an effective model to predict lymph node metastasis (LNM) for remnant gastric cancer (RGC). Clinicopathological characteristics of 91 RGC patients undergoing radical gastrectomy at Sun Yat-sen University Cancer Center from January 2000 to December 2017 were retrospectively analyzed. RGC was defined as cancer detected in the remnant stomach >5 years for primary benign diseases or >10 years for malignant diseases following distal gastrectomy. Risk factors of LNM in RGC were identified using logistic regression (P<0.1). Covariates were then scored according to the β regression coefficient in the multivariate analysis, and a score model was established, in which higher score indicated higher risk of LNM. Finally, receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of risk factors and the score model. Among the 91 RGC patients, 84 were male and 7 were female with the age ranging from 47 to 82 years (63.7±8.5) years. Mean harvested lymph node (LN) was 16.0±11.8, including ≥15 LNs in 42(46.2%) patients and <15 LNs in 49(53.8%) patients. Forty-six (50.5%) patients were identified as LNM. Univariate analysis showed that tumor size ≥4 cm (χ2=8.106, P=0.004), Borrmann III(-IIII( gross type (χ2=6.129, P=0.013), increased CEA level (χ2=4.041, P=0.044) and T3-4 stage (χ2=17.321, P=0.000) were associated with LNM in RGC. In Logistic multivariate analysis, tumor size ≥4 cm (OR: 2.362, 95%CI: 0.829-6.730, P=0.100, β regression coefficient: 0.859) and T3-4 stage (OR: 7.914, 95%CI: 1.956-32.017, P=0.004, β regression coefficient: 2.069) remained as the independent risk factors for LNM, and were scored as 1 and 2 point in the final prediction model. In the final score model, LNM of patients with 0, 1, 2, 3 point were 11.1%(2/18), 1/5, 51.6%(16/31) and 73.0%(27/37), respectively. The AUC of the prediction model was 0.756 (P=0.000). Increased CEA level, tumor size ≥4 cm, Borrmann III(-IIII( gross type, and deeper T stage are associated with LNM in RGC. Moreover, the score model combining with tumor size and T stage can effectively predict the LNM in RGC.

The anatomical configuration of the splenic artery influences suprapancreatic lymph node dissection in laparoscopic gastrectomy: analysis using a 3D volume rendering program.

The aim of this study is to categorize splenic artery and vein configurations, and examine their influence on suprapancreatic lymph node (LN) dissection in laparoscopic gastrectomy. Digital Imaging and Communications in Medicine images from 169 advanced cancer patients who underwent laparoscopic gastrectomy with D2 dissection were used to reconstruct perigastric vessels in 3D using a volume rendering program (VP Planning®). Splenic artery and vein configuration were classified depending on the relative position of their lowest part in regard to the pancreas. Number of resected LNs and surgical outcomes were analyzed. The splenic artery was categorized as superficial (36.7%), middle (49.1%), and concealed (14.2%), and the splenic vein was categorized as superior (6.5%), middle (42.0%), and inferior to the pancreas (51.5%). The number of resected LNs around the proximal half of the splenic artery (#11p) and the proportion of the splenic vein located inferiorly to the pancreas were significantly higher in splenic arteries of concealed types. LN metastasis of station #7 was an independent risk factor of LN metastasis in station #11p (p = 0.010). Concealed types showed a tendency towards longer operating times, more blood loss, longer hospital stays, and a higher postoperative morbidity. Concealed types of splenic artery are associated with an increased difficulty in the dissection of LN station #11p around the splenic artery. A 3D volume rendering program is a useful tool to rapidly and intuitively identify individual anatomical variations, to plan a tailored surgical strategy, and to predict potential challenges.

Predictors of Nodal Metastases for Clinical T2N0 Esophageal Adenocarcinoma

Induction therapy has not been proven to be beneficial for patients with clinical T2N0 esophageal adenocarcinoma. Surgery alone is associated with disappointing survival for patients found to have nodal disease on final pathologic examination. The aim of this study was to identify factors that predict pathologic nodal involvement in patients with endoscopic ultrasound (EUS)-proven T2N0 esophageal adenocarcinoma. We retrospectively reviewed patients with EUS-staged T2N0 (uT2N0) esophageal adenocarcinoma treated with surgery alone. Final pathologic staging was compared with clinical staging. Demographic and clinicopathologic variables were evaluated as putative risk factors for nodal metastases. Logistic regression models were used to identify factors associated with nodal involvement. Kaplan-Meier analysis was performed to compare overall and recurrence-free survival between patients with (N+) and without (N-) nodal disease. We identified 80 patients with uT2N0 esophageal adenocarcinoma treated with surgery alone. Clinical staging with EUS was inaccurate for 73 patients (91%). Twenty-eight patients (35%) had pathologic N+ disease at resection. Five-year overall survival was 67% for N- patients and 41% for N+ patients (p= 0.006). Recurrence-free survival was 65% for N- patients and 32% for N+ patients (p= 0.0043). Univariable analysis identified vascular invasion and neural invasion as risk factors for nodal metastasis. Multivariable analysis identified vascular invasion asan independent predictor of pathologic nodal involvement. EUS is inaccurate for staging of T2N0 esophageal adenocarcinoma and often fails to identifynodal involvement. Identification of vascular invasion on preoperative biopsy should be explored as a prognostic marker to select patients for induction therapy.

Curative Criteria After Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinomas.

According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200μm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. The mean observation period was 75months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.

Prognostication of superficial Barrett’s carcinoma: a Japanese multicenter study

Endoscopic resection (ER) has become the standard therapy for superficial Barrett's carcinoma (BC) in Japan and other countries. Patients undergoing ER sometimes require additional treatment because of recurrence of lymph node metastasis (LNM). We attempted to clarify the histopathologic risk factors for LNM, and the difference between these risk factors for Japanese patients and the conventional risk factors documented for Western patients. This multi-center study included 12 leading institutions belonging to the Japan Research Society for Early Esophageal Cancer and Chromoendoscopy, and was based on a questionnaire designed to gather data on the features of superficial BC cases, except for high-grade intraepithelial neoplasia, treated at those institutions. These features were assessed using the standardized pathologic approach employed in Japan, whereby surgically and endoscopically resected specimens are cut into parallel slices 4-5 mm and 2 mm thick, respectively. Seventy-four surgically resected (SR) and 201 ER specimens were analyzed separately. Significant risk factors for LNM were almost the same as conventional risk factors, such as tumor size (cut-off value; 17.5 mm) and depth, vessel infiltration, presence of poorly differentiated components, and the depth (cut-off value; 990 μm) and width (cut-off value; 4300 μm) of the submucosal component, in addition to growth pattern (a protruding or flat elevated pattern) and the presence of infiltrative growth. Histopathologic examination revealed that BC cases without invasion to the deep muscularis mucosae (DMM) had almost no risk of LNM. Detailed histopathologic evaluation of thin-slice preparations of ER specimens is considered highly important for prognostication.

The significance of tumor budding in T1 colorectal carcinoma: the most reliable predictor of lymph node metastasis especially in endoscopically resected T1 colorectal carcinoma

Endoscopic resection is widely recognized as a first-line treatment for T1 colorectal cancers (CRC), although additional surgical intervention may be indicated based on the risk of lymph node (LN) metastasis. However, risk factors for LN metastasis in T1 CRC not fully established. We investigated the clinicopathological features of T1 CRC and evaluated their association with lymph node metastasis in 133 cases of T1 CRC, consisting of 87 cases with first-line endoscopic resection (EMR) followed by additional surgery and 46 cases with primary surgical resection. Among the total 133 cases, 16 cases (12.0%) showed LN metastasis; 13 cases (13/16, 81.25%) were included in endoscopic resection cohort. These were all of the non-pedunculated gross type and most of LN+ tumors invaded submucosa over 1000 μm (surgical cohort versus endoscopic resection cohort; 3 versus 11). However, there was no statistical difference in the depth of submucosal invasion between the LN+ and LN- in both surgical cohort (2799.42 μm ± 401.56 versus 3000.00 μm ± 721.69, P = .897) and endoscopic resection cohort (2066.55 μm ± 142.96 versus 2305.77 μm ± 345.62, P = .520). Conversely, presence of and a higher number of tumor budding foci were associated with an increase in the incidence of LN metastasis in both cohort (P < .0001). Positive resection margins as well as absence of adenoma component were also an independent predictive factor for lymph node metastasis in 87 cases with first-line endoscopic resection followed by additional surgery. We found that tumor budding was the most reliable LN metastasis predictor in T1 CRC in both surgically resected and endoscopic resection specimens.

Novel Nomograms to Predict Lymph Node Metastasis and Liver Metastasis in Patients with Early Colon Carcinoma

Lymph node status and liver metastasis (LIM) are important in determining the prognosis of early colon carcinoma. We attempted to develop and validate nomograms to predict lymph node metastasis (LNM) and LIM in patients with early colon carcinoma. A total of 32,819 patients who underwent surgery for pT1 or pT2 colon carcinoma were enrolled in the study based on their records in the SEER database. Risk factors for LNM and LIM were assessed based on univariate and multivariate binary logistic regression. The C-index and calibration plots were used to evaluate LNM and LIM model discrimination. The predictive accuracy and clinical values of the nomograms were measured by decision curve analysis. The predictive nomograms were further validated in the internal testing set. The LNM nomogram, consisting of seven features, achieved the same favorable prediction efficacy as the five-feature LIM nomogram. The calibration curves showed perfect agreement between nomogram predictions and actual observations. The decision curves indicated the clinical usefulness of the prediction nomograms. Receiver operating characteristic curves indicated good discrimination in the training set (area under the curve [AUC] = 0.667, 95% CI=0.661-0.673) and the testing set (AUC=0.658, 95% CI=0.649-0.667) for the LNM nomogram and encouraging performance in the training set (AUC=0.766, 95% CI=0.760-0.771) and the testing set (AUC=0.825, 95% CI=0.818-0.832) for the LIM nomogram. Novel validated nomograms for patients with early colon carcinoma can effectively predict the individualized risk of LNM and LIM, and this predictive power may help doctors formulate suitable individual treatments. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81572407, 81602112, 81672405, 81702404 ); Key project of Natural Science Foundation of Guangdong Province, China (No. 4210016041); Science and Technology Program of Guangdong Province, China (No.2015A030313096, 2016A030313184, 2017A030313536); Natural Science Foundation of Guangzhou, China (No. 4250016043). Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: The ethics committee board of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, approved the use of patients with early colon carcinoma for this study.

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa.

AIMTo investigate the relationship between histological mixed-type of early gastric cancer (EGC) in the mucosa and submucosa and lymph node metastasis (LNM).METHODSThis study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated (pure D), pure undifferentiated (pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. Furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTSOf the 298 patients, 165 (55.4%) had mucosa-confined EGC and 133 (44.6%) had submucosa-invasive EGC. Only 13 (7.9%) cases of mucosa-confined EGC and 30 (22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion (OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type (OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixed-type (OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixed-type group (P = 0.012) and pure U group (P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group (P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixed-type (P = 0.012) and pure U group (P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group (P = 0.375). Multivariate logistic analysis showed that only female sex (OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion (OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC (P = 0.106).CONCLUSIONFor mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

The Characteristics, Prognosis, and Risk Factors of Lymph Node Metastasis in Early Gastric Cancer.

Background Lymph node metastasis (LNM) is the most important risk factor for endoscopic treatment in early gastric cancer (EGC) patients. We aimed to investigate the rate of LNM, the risk factors, and the prognosis of EGC patients with LMN. Methods A total of 10,039 patients who underwent gastrectomy with lymphadenectomy were reviewed between January 2010 and December 2015 at Jiangsu Province Hospital in China. Among them, we identified 1004 (10%) EGCs. First, endoscopic and clinicopathological features related to LNM were analyzed, and then risk factors for LNM were identified using univariate and multivariate analysis. Finally, the short- and long-term outcomes were compared between the groups. Results LNM occurred in 123 (12.3%) EGCs. Most of EGCs were male (n = 720, 71.7%) and mean age was 59.65 ± 11.09 years. The rate of H. pylori infection was 78.0% (783/1004). LNM was significantly associated with age, sex, location, lesion size, macroscopic type, depth of invasion, differentiation type, histological morphology, lymphovascular invasion (LVI), and TMN stage. By multivariate analysis, significant independent risk factors for LNM in EGC were identified as following: male sex (OR 2.365, P = 0.035), age ≦ 40 (OR 0.055, P = 0.012), depressed type (OR 2.721, P = 0.013), submucosa invasion (OR 2.987, P = 0.032), LVI (OR 5.186, P = 0.003), tumor located in corpora (OR 8.904, P = 0.047), and in angle (OR 12.998, P = 0.024). 86.5% were successfully followed up for 3 years. The overall 1- and 3-year survival rates in LNM group were 100% and 91.1%, respectively, and those with no LNM were 100% and 100%, respectively. Conclusion EGCs were investigated in 10.0% of gastric cancer, which LNM occurred in 12.3% of EGC. Independent risk factors of LNM included male sex, age (>40), the depth of invasion, LVI, and tumor located in corpora or angle. The 3-year overall survival rate was greater in EGC patients without LNM.

Construction and external validation of a nomogram that predicts lymph node metastasis in early gastric cancer patients using preoperative parameters.

ObjectiveTo create a nomogram to predict the incidence of lymph node metastasis (LNM) in early gastric cancer (EGC) patients and to externally validate the nomogram.MethodsTo construct the nomogram, we retrospectively analyzed a primary cohort of 272 EGC patients. Univariate analysis and a binary logistic regression were performed. A nomogram predicting the incidence of LNM in EGC patients was created. The discrimination ability of the nomogram was measured using the concordance index (c-index), and the nomogram was also calibrated. Then, another prospective cohort of 81 patients was analyzed to validate the nomogram.ResultsIn the primary cohort, LNM was pathologically confirmed in 37 (13.6%) patients. In multivariate analysis, the presence of an ulcer, the maximum lesion diameter observed via gastroscopy, the thickness of the lesion observed via endoscopic ultrasonography, and the presence of enlarged lymph nodes on computed tomography (CT) were independent risk factors for LNM. A nomogram was then created based on the regression model with the c-index of 0.905, and the calibration curve of the nomogram fell approximately on the ideal 45-degree line. The cut-off score of the nomogram was 110, and the sensitivity, specificity, positive predictive and negative predictive values of the nomogram in the primary cohort were 81.1%, 86.0%, 47.6% and 96.7%, respectively, and in the prospective validation cohort were 75.0%, 91.0%, 60.0% and 95.5%, respectively. The calibration curve of the external validation cohort was almost on the 45-degree line.ConclusionsWe developed an effective nomogram predicting the incidence of LNM for EGC patients.

Lymph-node metastasis following total laryngectomy and total pharyngolaryngectomy for laryngeal and hypopharyngeal squamous cell carcinoma: Frequency, distribution and risk factors

ObjectivesTo evaluate the prevalence and distribution of lymph-node metastasis after total laryngectomy or total pharyngolaryngectomy. Material and methodsRetrospective single-center series of 136 successive patients undergoing total laryngectomy or total pharyngolaryngectomy with neck dissection for squamous cell carcinoma of the larynx or hypopharynx. ResultsThe primary site was laryngeal in 110 cases and hypopharyngeal in 26. In 63 patients, surgery was first-line treatment; 73 were operated on for recurrence. The lymph-node metastasis rate, confirmed on histology, was 44.8% regardless of primary site. Hypopharyngeal location was a risk factor for lymph-node metastasis (73.1%, P=0.002) as was the supraglottic subsite (64.3%, P=0.039). Levels IIa and III were invaded in 28.7% and 25.7% of cases, respectively. Level VIb lymph-node involvement was 23.8% in patients who underwent level VIb neck dissection. Lymph-node recurrence rate was 10.3% in levels II to IV and 13.2% in VIb. ConclusionsWhatever the tumor site, levels IIa and III were most frequently invaded. The high rate of histological involvement of level VIb and of recurrence argues for systematic elective bilateral neck dissection of these territories in some primary sites.

Establishment of pathological quantitative method for determining undifferentiated component ratio in patients with differentiated/undifferentiated mixed-type early gastric cancer and clinical significance of this ratio.

The purpose of this study was to establish a pathological quantitative method for determining the undifferentiated components ratio (UCR) in patients with differentiated/undifferentiated mixed-type (Mixed-type) early gastric cancer (EGC) and to examine the clinical significance. The subjects were 410 patients who underwent surgical resection for EGC with the invasion limited to m or sm1. Analysis 1: In 12 randomly selected patients with Mixed-type cancer, we calculated the area ratio and the ratio of the length ratio using ImageJ and analyzed the correlation between them. Analysis 2: We generated ROC curves, and determined the cutoff UCR on the basis of the predictive risk factors for lymph node metastasis (LNM). Analysis 3: We analyzed the relationship between clinicopathological factors including UCR/length of undifferentiated component (LUC=maximum dimensions of tumor×UCR) and LNM. Analysis 1: The length ratio can be used as a substitute parameter for the UCR (r=0.996). Analysis 2: The cutoff UCR as a risk factor for LNM was 58% (sensitivity=1, 1-specificity=0.404). Analysis 3: Lymphovascular invasion (p<0.0001), UCR≥58% (p=0.023), and LUC≥25mm (p=0.005) were identified as significant risk factors for LNM. No LNM was observed in patients with invasion limited to m or sm1 and negativity for lymphovascular invasion and UCR<58% (0/215). In the patients with Mixed-type EGC, the length ratio of undifferentiated components can be a substitute parameter for the UCR. LNM rarely occurs in patients without lymphovascular invasion and with an UCR<58%. The analysis of the UCR has great significance in determining whether additional surgical resection is required after endoscopic resection.