Objective: To evaluate the feasibility of identification and preservation of arm lymphatics (DEPART) in axillary lymph node dissection (ALND) for breast cancer to prevent arm lymphedema. Methods: A randomized controlled study method was used. Two hundred and sixty-five patients who underwent breast cancer surgery at the Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University from November 2017 to June 2018 were included, and the patients were randomly divided into ALND+ DEPART group (132 patients) and standard ALND group (133 patients) by random number table method. In the ALND+ DEPART group, indocyanine green and methylene blue were injected as tracers before surgery, and the arm sentinel nodes was visualized by staged tracing during intraoperative dissection of axillary lymph nodes. Partial frozen sections were made of arm lymph nodes >1 cm in length and hard and suspicious of metastasis, and arm lymph nodes and lymphatic vessels were selectively preserved. Patients in the standard ALND group underwent standard ALND. Objective and subjective indexes of arm lymphedema were evaluated by 5-point circumference measurement and Norman questionnaire. Results: Among 132 breast cancer patients in the ALND+ DEPART group, 121 (91.7%) completed DEPART. There were no statistically significant differences in age, body mass index, pathological type, dissection number of axillary lymph node, N stage, TNM stage, molecular typing, and regional radiotherapy between the ALND+ DEPART and standard ALND groups (P>0.05). At a median follow-up of 24 months, assessment by the 5-point circumference measurement showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.0% (6/121) and 15.8% (21/133), respectively, with statistically significant differences (P=0.005). Assessment by the Norman questionnaire showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.8% (7/121) and 21.8% (29/133), respectively, with a statistically significant difference (P<0.001). No local regional recurrence was observed in either group during the follow-up period. Conclusion: For breast cancer patients with positive axillary lymph nodes, the administration of DEPART during ALND can reduce or avoid the occurrence of arm lymphedema without compromising oncology safety.
Arm/pathology* ; Axilla/pathology* ; Breast Neoplasms/pathology* ; Female ; Humans ; Lymph Node Excision/methods* ; Lymph Nodes/surgery* ; Lymphatic Vessels/pathology* ; Lymphedema/surgery* ; Sentinel Lymph Node Biopsy/adverse effects*

OBJECTIVE: To examine the correlation of CCBE1 expression in adjacent tissues of tongue squamous cell carcinoma (TSCC) with pericancerous lymphatic vessel proliferation, cervical lymph node metastasis and survival outcomes of the patients. METHODS: Lymphatic vessel density was quantified in pericancerous tissue sections of 44 cases of cT_1-2N₀ TSCC using D2-40 as the lymphatic vessel endothelial marker for calibration and counting of the lymphatic vessels. Of these 44 cases, 22 showed a relatively low lymphatic vessel density (group A) and the other 22 had a high lymphatic vessel density (group B), and the expression levels of CCBE1 in the adjacent tissues determined using immunohistochemistry, immunofluorescence assay and Western blotting were compared between the two groups. The expression level of CCBE1 was also measured in another 90 patients with TSCC using immunohistochemistry, and all the patients were followed up for their survival outcomes. RESULTS: Immunohistochemistry and Western blotting showed a significantly lower rate of high CCBE1 expression in group A than in group B (P < 0.05). Immunofluorescence assay showed co-localization of CCBE1 and D2-40 in the adjacent tissues of TSCC. In the 90 TSCC patients with complete follow-up data, a high expression of CCBE1 was found to correlate with lymph node metastasis and a poor 5-year survival outcomes of the patients (P < 0.05). CONCLUSION A high expression of CCBE1 in the adjacent tissues of TSCC is closely related with pericancerous lymphatic vessel proliferation, cervical lymph node metastasis and a poor 5-year survival of the patients, suggesting the value of CCBE1 as a potential prognostic predictor for TSCC.
Humans ; Tongue Neoplasms/pathology* ; Carcinoma, Squamous Cell/metabolism* ; Lymphatic Metastasis ; Prognosis ; Lymphatic Vessels/pathology* ; Cell Proliferation ; Tongue/pathology* ; Calcium-Binding Proteins/metabolism* ; Tumor Suppressor Proteins/metabolism*

OBJECTIVE: To analyze the changes in tumor lymphatic vessel density (LVD) in patients with lung adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) and explore the regulatory factors of LVD. METHODS: Complete clinicopathological data were collected form a total of 301 patients with lung adenocarcinoma, including 28 (9.3%) with AIS, 86 (28.6%) with MIA, and 187 (62.1%) with IA. The LVD of all the adenocarcinomas were calculated after D2-40 immunohistochemical staining, and MT1-MMP and VEGF-C expression levels were also evaluated. The differences in LVD among the groups and the correlations of tumor LVD with the expressions of MT1-MMP and VEGF-C and the clinicopathological factors were analyzed. RESULTS: The LVD differed significantly among AIS, MIA, and IA groups (= 0.000). The LVDs was significantly correlated with the level of VEGF-C protein expression (=0.917, =0.009), tumor size (= 0.686, =0.017), lymph node metastasis (=0.739, =0.000), and clinical stage (=0.874, =0.012) of the patients. CONCLUSIONS Tumor lymphangiogenesis plays an important role in lung adenocarcinoma progression, and VEGF-C may promote this process.
Adenocarcinoma ; chemistry ; pathology ; Adenocarcinoma of Lung ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Lymphangiogenesis ; Lymphatic Vessels ; chemistry ; pathology ; Neoplasm Staging ; Prognosis ; Tumor Burden ; Vascular Endothelial Growth Factor C ; analysis

OBJECTIVETo investigate the prognostic factors of patients with lymph node-negative metastasis gastric cancer (pN0).

METHODSClinicopathological data of patients with pN0 gastric cancer who underwent radical operation at the Department of Surgical Oncology, The First Hospital of China Medical University from May 1980 to August 2012 were collected and analyzed retrospectively.

INCLUSION CRITERIA(1) Patients were diagnosed as gastric adenocarcinoma; (2) Postoperative pathology confirmed T1a to 4bN0M0 gastric cancer; (3) Total number of harvested lymph node was more than 15. The patients, who died within 1 month after the operation, died of other diseases, had remnant gastric cancer, or had incomplete follow-up data, were excluded. Univariate analysis was used to analyze the clinical factors that may influence the prognosis of patients with stage pN0 gastric cancer, then, those significant variables were entered into the Cox's proportional hazards regression model for multivariate analysis to obtain the independent prognostic factors for patients with pN0 gastric cancer finally. Furthermore, the prognosis of patients with pN0 advanced gastric cancer (invasive depth ≥ T2) were analyzed using the same method.

RESULTSA total of 610 patients with pN0 gastric cancer were enrolled in the study, including 441 males and 169 females with age ranging from 19 to 83 (mean 56.4±11.0) years, D1 lymph node dissection in 45 cases, D2 lymph node dissection in 543 cases, D3 lymph node dissection in 22 cases, and 384 cases of advanced gastric cancer. The overall followed-up was 1 to 372 (median 32) months. Ninety cases (14.8%) were dead during the follow-up. The median survival was 277.7(95%CI: 257.6 to 297.8) months, and the 1-, 3-, 5-year survival rates were 96.5%, 87%, 83.2%. Univariate analysis showed that tumor diameter, depth of invasion, gross type, lymph node dissection and lymph vessel cancer embolus were related to the prognosis (all P<0.05). The 5-year survival rate of patients with tumor diameter >4 cm was significantly lower than those with tumor diameter ≤4 cm (75.6% vs. 87.8%, P=0.000). The 5-year survival rates of T1a, T1b, T2, T3 and T4 were 98.4%, 92.8%, 84.2%, 61.0% and 31.4% respectively, and the difference was statistically significant (P=0.000). In gross type, 5-year survival rate of early gastric cancer was 96.0%, and of Borrmann I( to IIII( type gastric cancer was 100%, 83.4%, 73.7% and 68.9% respectively, whose difference was statistically significant(P=0.000). The 5-year survival rates in patients undergoing lymph node dissection D1, D2 and D3 were 100%, 83.3% and 58.7%, and the difference was significant (P=0.005). The 5-year survival rate of patients with positive lymphatic cancer embolus was lower than those with negative ones (69.4% vs. 86.9%, P=0.000). Multivariate analysis showed that the gross type [Borrmann II(/early gastric cancer: HR(95% CI)=15.129(3.284 to 69.699), Borrmann III(/early gastric cancer: HR(95% CI)=14.613 (3.292 to 64.875), Borrmann IIII(/early gastric cancer: HR (95% CI)=15.430 (2.778 to 85.718),Borrmann IIIII(/early gastric cancer: HR(95%CI)=12.604 (1.055 to 150.642), P=0.025] and the positive lymphatic cancer embolus [HR(95% CI)=3.241 (2.056 to 5.108), P=0.000] were the independent prognostic factors of patients with pN0 gastric cancer. For pN0 patients with advanced gastric cancer, multivariate analysis showed that the depth of invasion [stage T3/stage T2: HR(95%CI)=1.520 (0.888 to 2.601), stage T4/stage T2: HR(95%CI)=2.235(1.227 to 4.070); P=0.031] and the positive lymphatic cancer embolus [HR(95%CI)=3.065 (1.930 to 4.868); P=0.000] were the independent risk factors influencing the prognosis.

CONCLUSIONSPositive lymphatic cancer embolus and worse gross pattern indicate poorer prognosis of patients with pN0 gastric cancer, which may be used as effective markers in evaluating the prognosis. As for pN0 advanced gastric cancer, invasion depth and positive lymphatic cancer embolus can play a more important role in the prediction.

Adenocarcinoma ; classification ; diagnosis ; mortality ; Adult ; Aged ; Aged, 80 and over ; China ; Female ; Humans ; Lymph Node Excision ; statistics & numerical data ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; physiopathology ; Lymphatic Vessels ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; pathology ; physiopathology ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; classification ; diagnosis ; mortality ; Survival Rate

OBJECTIVEWe analyzed the lymph node (MLNs) metastasis of thoracic esophageal squamous cell carcinoma (ESCC) to explore the patterns of lymphatic spread and the rational surgical procedure and extent of lymph node dissection for ESCC.

METHODSWe retrospectively evaluated 313 consecutive patients treated in our hospital between January 2010 and May 2014 who underwent minimally invasive esophagectomy (MIE) for ESCC. The information of lymph node status was obtained and the features of lymph node metastasis were analyzed.

RESULTSOf the 313 cases, 122 (39.0%) were found to have lymph node metastasis. In the 4461 dissected lymph nodes, metastasis was identified in 294 (6.6%) lymph nodes. The recurrent laryngeal nerve lymph nodes were the most frequent metastatic nodes with a metastasis rate of 25.2%, followed by the paracardiac and left gastric artery lymph nodes (18.2%). Chi-square test showed that the lymph node metastasis is associated with tumor invasion and tumor differentiation (P<0.001 for both). Metastases were more frequently found in the recurrent laryngeal nerve lymph nodes in patients with tumors in the upper third esophagus and with histologically poor differentiation (P<0.05 for both). The metastasis rate of para-cardiac and left gastric artery lymph nodes was associated with tumor in the lower third of esophagus, T stage and differentiation (all P<0.05). Logistic regression analysis showed that tumor differentiation and location are independent factors affecting the metastasis of recurrent laryngeal nerve lymph nodes (P<0.05 for all). T stage, tumor differentiation and location were independent factors associated with metastasis of para-cardiac and left gastric artery lymph nodes (P<0.05 for all).

CONCLUSIONS(1) Metastases of thoracic esophageal carcinoma are often found in the recurrent laryngeal nerve lymph nodes, para-cardiac and left gastric artery lymph nodes. (2) Extensive lymph node dissection should be performed for ESCC with poor differentiation and deep tumor invasion.

Carcinoma, Squamous Cell ; secondary ; surgery ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Lymphatic Vessels ; Recurrent Laryngeal Nerve ; Retrospective Studies

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the "clearance" process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and "Bi" theory of Chinese medicine (CM), and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking "Bi" theory of CM to lymphatic dysfunction in arthritis.
Animals ; Arthritis ; etiology ; therapy ; Disease Models, Animal ; Humans ; Joints ; pathology ; Lymphangiogenesis ; Lymphatic Vessels ; pathology ; Medicine, Chinese Traditional

OBJECTIVE: To analyze the correlated factors of cervical lymphatic metastasis of T3 and T4 glottic carcinoma. METHOD: We did a retrospective analysis of 91 glottic carcinoma patients' clinical data to analyze cervical lymph node metastasis on different T stage, pathologic degree and the tumor sites. RESULT: The cervical lymph node metastasis rate of 91 cases of T3 and T4 glottic carcinoma was 21.98%. T3 group's metastasis rate was 18.06% (13/72), T4 group's metastasis rate was 36.84% (7/19), P > 0.05. Grouped according to the degree of pathological differentiation, well-differentiated squamous cell carcinoma metastasis rate is 13.89% (5/36), middle-differentiated squamous cell carcinoma metastasis rate is 26.00% (13/50), and poorly-differentiated squamous cell carcinoma metastasis rate is 40.00% (2/5), P > 0.05. Cervical lymph node metastasis rate was 16.22%, when the tumor invading supraglottic region. Cervical lymph node metastasis rate was 15.38%, when the tumor invading subraglottic region. Cervical lymph node metastasis rate was 46.15%, when the tumor invading supraglottic and subraglottic region (P < 0.01). CONCLUSION Cervical lymph node metastasis in cN0 patient with supraglottic carcinoma is effected by T classification, cervical lymphatic metastasis of T3 and T4 glottic carcinoma is not entirely effected by T stage and pathologic degree. When the tumor invades supraglottic and subraglottic region, cervical lymph node metastasis is significantly higher. Therefore, the area of tumor invasion is an important factor for lymph node metastasis.
Humans ; Laryngeal Neoplasms ; pathology ; Lymph Nodes ; Lymphatic Metastasis ; Lymphatic Vessels ; Neck ; Neck Dissection ; Neoplasm Staging ; Retrospective Studies

OBJECTIVETo investigate the evaluation of lymphatic emboli by D2-40/CKpan dual immunostain and its prognostic significance in advanced primary gastric adenocarcinoma.

METHODSTissue samples of 108 cases of advanced gastric adenocarcinoma with radical gastrectomy were collected from Chinese PLA General Hospital in 2001. Lymphatic emboli were evaluated by D2-40/CKpan dual immunostain on consecutive sections, and compared with routine HE staining. The correlation of lymphatic emboli with lymph node metastasis and overall survival was analyzed by Pearson Chi-squared test and univariate survival analysis, respectively.

RESULTSLymphatic emboli were detected in 73/108 (67.6%) cases by D2-40/CKpan staining, compared to 57/108 (52.8%) by HE staining. There was significant difference (P=0.007). Lymphatic emboli on HE staining revealed false negative in 24/108 cases and false positive in 8/108 cases. A significant correlation was found between lymphatic emboli and lymph node metastasis on HE staining (P=0.024), while it was not found on D2-40/CKpan staining (P=0.422). The overall survival rate was significantly different between lymphatic emboli positive and negative cases on HE staining (P=0.043). The overall survival rate was lower in lymphatic emboli positive cases on HE staining. Lymphatic emboli evaluated on D2-40/CKpan staining had no prognostic value (P=0.402).

CONCLUSIOND2-40/Ckpan dual immunostaining is more sensitive for lymphatic emboli in gastric adenocarcinoma but may not predict lymph node metastasis and survival, while HE staining may.

Gastrectomy ; Humans ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Prognosis ; Stomach Neoplasms ; pathology

Congenital pulmonary lymphangiectasia (CPL) is a rare lymphatic pulmonary abnormality. CPL with respiratory distress has a poor prognosis, and is frequently fatal in neonates. We report a case of pneumonectomy for CPL in a newborn. An infant girl, born at 39 weeks' after an uncomplicated pregnancy, exhibited respiratory distress 1 hr after birth, which necessitated intubation and aggressive ventilator care. Right pneumonectomy was performed after her symptoms worsened. Histologic examination indicated CPL. She is currently 12 months old and developing normally. Pneumonectomy can be considered for treating respiratory symptoms for improving chances of survival in cases with unilateral CPL.
Female ; Gestational Age ; Humans ; Infant, Newborn ; Lung/pathology ; Lung Diseases/*congenital/diagnosis/pathology/radiography ; Lymphangiectasis/*congenital/diagnosis/pathology/radiography ; Lymphatic Vessels/pathology ; Tomography, X-Ray Computed

The purpose of this review is to provide an overview of the effect of (lymph)angiogenic cytokines on hematopoietic cells involved in acute myeloid leukemia (AML). Like angiogenesis, lymphangiogenesis occurs in pathophysiological conditions but not in healthy adults. AML is closely associated with the vasculature system, and the interplay between lymphangiogenic cytokines maintains leukemic blast survival in the bone marrow (BM). Once AML is induced, proangiogenic cytokines function as angiogenic or lymphangiogenic factors and affect hematopoietic cells, including BM-derived immune cells. Simultaneously, the representative cytokines, VEGFs and their receptors are expressed on AML blasts in vascular and osteoblast niches in both the BM and the peripheral circulation. After exposure to (lymph)angiogenic cytokines in leukemogenesis and infiltration, immune cell phenotypes and functions are affected. These dynamic behaviors in the BM reflect the clinical features of AML. In this review, we note the importance of lymphangiogenic factors and their receptors in hematopoietic cells in AML. Understanding the functional characterization of (lymph)angiogenic factors in the BM niche in AML will also be helpful in interrupting the engraftment of leukemic stem cells and for enhancing immune cell function by modulating the tumor microenvironment.
Animals ; Cytokines/*immunology ; Hematopoietic Stem Cells/immunology/*pathology ; Humans ; Immunity, Cellular ; Leukemia, Myeloid, Acute/immunology/*physiopathology ; *Lymphangiogenesis ; Lymphatic Vessels/immunology/*physiopathology ; Vascular Endothelial Growth Factor A/immunology