Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.
Angiopoietins ; Endothelial Cells/metabolism* ; Humans ; Lymphatic Diseases ; Lymphatic System/metabolism* ; Receptor, TIE-2/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A

OBJECTIVE: To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT).METHODS: Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors.RESULTS: A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282–0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189–0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067).CONCLUSION: Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.
Adenocarcinoma ; Cervix Uteri ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Humans ; Hysterectomy ; Lymphatic Diseases ; Neoplasm, Residual ; Recurrence ; Standard of Care ; Uterine Cervical Neoplasms

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis, which is characterized by fever, lymphadenopathy, and sore throat. On the other hand, gastrointestinal symptoms of EBV infection like dyspepsia, abdominal pain are non-specific and rarely encountered, which means it is difficult to diagnose gastric involvement of EBV infection without suspicion. The relation between gastric carcinoma and gastric lymphoma associated with EBV infection is well defined, but relations with other EBV-associated gastrointestinal diseases such as gastritis and peptic ulcer disease have rarely been reported. We report a case of benign gastric ulcer with EBV infection confirmed by endoscopic and histological findings.
Abdominal Pain ; Dyspepsia ; Epstein-Barr Virus Infections ; Fever ; Gastritis ; Gastrointestinal Diseases ; Hand ; Helicobacter pylori ; Herpesvirus 4, Human ; In Situ Hybridization ; Infectious Mononucleosis ; Lymphatic Diseases ; Lymphoma ; Peptic Ulcer ; Pharyngitis ; Stomach Ulcer

Castleman disease is a relatively rare disease, characterized by well-circumscribed benign lymph-node hyperplasia. The disease may develop anywhere in the lymphatic system, but is most commonly reported as unicentric Castleman disease in the mediastinum along the tracheobronchial tree. It is usually asymptomatic and detected on plain chest radiography as an incidental finding. We report an incidentally detected case of Castleman disease in the paravertebral space that was preoperatively diagnosed as a neurogenic tumor and treated by complete surgical resection.
Giant Lymph Node Hyperplasia ; Hyperplasia ; Incidental Findings ; Lymphatic System ; Mediastinal Neoplasms ; Mediastinum ; Radiography ; Rare Diseases ; Thorax ; Trees

We report the first case demonstrating an association between Kawasaki disease (KD) and erythema nodosum (EN). A 3-year-old girl presented with EN as an initial manifestation of KD. At the initial visit, she showed high fever of 40℃, injection of the oropharynx, cervical lymphadenopathy, and red-purple cutaneous nodules, particularly on the lower limbs. She complained of severe pain in the neck and cutaneous lesions. Initially, the development of EN was attributed to Salmonella spp infection, which was detected in stool culture. However, the patient did not respond to high-dose ampicillin/sulbactam to which the Salmonella spp is sensitive. Echocardiography performed as screening for fever of unknown origin revealed medium-sized aneurysms of the left anterior descending artery. EN masked the diagnosis of KD, and the patient developed a coronary artery lesion. KD should be considered in the differential diagnosis of refractory EN in pediatric patients.
Aneurysm ; Arteries ; Bacterial Infections ; Child, Preschool ; Coronary Vessels ; Diagnosis ; Diagnosis, Differential ; Echocardiography ; Erythema Nodosum ; Erythema ; Exanthema ; Female ; Fever ; Fever of Unknown Origin ; Humans ; Lower Extremity ; Lymphatic Diseases ; Masks ; Mass Screening ; Mucocutaneous Lymph Node Syndrome ; Neck ; Oropharynx ; Salmonella ; Skin ; Subcutaneous Tissue

Malignant melanoma can be classified as both cutaneous and mucosal types. The former comprises more than 98% of all melanomas and is related to ultraviolet exposure, whereas the latter occupies only 1.3%. More than half of mucosal melanoma arises in the head and neck region, and the sinonasal tract is also one of its predilection sites. On the other hand, the metastatic melanoma of head and neck is lower incidence than primary lesion and the unknown primary site is about two to five percent. Moreover, a lymphatic metastasis to the posterior neck is a more unusual clinical pattern. A 71-year-old man with a solitary subcutaneous posterior neck mass visited our clinic. He was confirmed with metastatic melanoma in the lymph node through excisional biopsy. However, the primary site was not found with whole radiologic examinations. We report a very rare disease entity with a brief literature review.
Aged ; Biopsy ; Hand ; Head ; Humans ; Incidence ; Lymph Nodes ; Lymphatic Metastasis ; Melanoma ; Neck ; Rare Diseases

Splenic B-cell lymphomas (SBCLs) show characteristically pronounced splenomegaly without significant lymphadenopathy. Distinguishing hairy cell leukemia (HCL) from other SBCLs (splenic marginal zone lymphoma [SMZL], variant HCL [v-HCL], and splenic diffuse red pulp small B-cell lymphoma [SDRPL]) is essential to determine suitable treatments and prognoses. With advances in diagnostic modalities and therapies, splenectomy is not commonly performed, and thus diagnosis of HCL must be based on the results obtained using blood and bone marrow samples. Annexin A1 is known as the most specific marker for HCL. There has yet been no report of the assessment of annexin A1 immunostaining from Korea. In this study we analyzed samples from 13 Korean patients with SBCLs (three HCL, three v-HCL, six SMZL, and one SDRPL) from May 2001 to December 2016. Immunohistochemical analyses for annexin A1 and CD20 were performed using bone marrow sections; molecular analyses for detection of the BRAF V600E mutation were also performed. All HCL patients showed positive results for annexin A1 immunostaining and the presence of the BRAF V600E mutation, and negative results for other SBCLs. Our results confirmed the high specificity of annexin A1 and the BRAF V600E mutation as HCL markers. Molecular analysis requires expensive equipment and substantial manpower. Annexin A1 is a better alternative as an HCL marker than the BRAF V600E mutation in terms of cost-effectiveness.
Annexin A1 ; Bone Marrow ; Diagnosis ; Humans ; Korea ; Leukemia, Hairy Cell ; Lymphatic Diseases ; Lymphoma ; Lymphoma, B-Cell ; Prognosis ; Sensitivity and Specificity ; Splenectomy ; Splenomegaly

BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.
Acute Generalized Exanthematous Pustulosis ; Adrenal Cortex Hormones ; Allopurinol ; Anti-Bacterial Agents ; Carbamazepine ; China ; Cicatrix ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Humans ; Lymphatic Diseases ; Mortality ; Prognosis ; Public Health ; Retrospective Studies ; Skin ; Stevens-Johnson Syndrome ; Tertiary Healthcare

Orbital tuberculosis is a rare form of extrapulmonary tuberculosis, even in endemic areas. It may involve the soft tissue, lacrimal gland, periosteum, or bones of the orbital wall. We present a case of orbital tuberculosis on the lower eyelid. An 18-year-old woman with no underlying disease visited our clinic for evaluation of an oval nodule (1.5× 1.2 cm) on the right lower eyelid. Incision and drainage without biopsy was performed 2 months ago in ophthalmology department, but the periorbital mass had deteriorated, as the patient had erythematous swelling, tenderness, and cervical lymphadenopathy. Visual acuity was normal; there were no signs of proptosis, diplopia, or ophthalmoplegia. Computed tomography revealed a small abscess cavity without bony involvement. We performed an excision and biopsy through a percutaneous incision under local anesthesia. Histological examination revealed a granuloma and was diagnosed as orbital tuberculosis. The patient was additionally treated with anti-tuberculosis therapy for 6 months and recovered without complication or recurrence by 7 months. Orbital tuberculosis occurs in patients with or without associated pulmonary tuberculosis, and should be considered as a differential diagnosis in patients with inflammatory orbital disease and an orbital mass. If recurrence occurs despite adequate initial treatment, we recommend an additional examination and excisional biopsy.
Abscess ; Adolescent ; Anesthesia, Local ; Biopsy ; Diagnosis, Differential ; Diplopia ; Drainage ; Exophthalmos ; Eyelids ; Female ; Granuloma ; Humans ; Lacrimal Apparatus ; Lymphatic Diseases ; Ophthalmology ; Ophthalmoplegia ; Orbit ; Orbital Diseases ; Periosteum ; Recurrence ; Tuberculosis ; Tuberculosis, Pulmonary ; Visual Acuity

BACKGROUND: Lymphaticovenous anastomosis is an important surgical treatment for lymphedema, with lymphaticovenous side-to-end anastomosis (LVSEA) and lymphaticovenous end-to-end anastomosis being the most frequently performed procedures. However, LVSEA can cause lymphatic flow obstruction because of regurgitation and tension in the anastomosis. In this study, we introduce a novel and simple procedure to overcome this problem. METHODS: Thirty-five female patients with lower extremity lymphedema who underwent lymphaticovenous anastomosis at our hospital were included in this study. Eighty-five LVSEA procedures were performed, of which 12 resulted in insufficient venous blood flow. For these 12 anastomoses, the proximal lymphatic vessel underwent clipping after the anastomotic procedure and the venous inflow was monitored. Subsequently, the proximal ligation after side-to-end anastomosis recovery (PLASTER) technique, which involves ligating the proximal side of the lymphatic vessel, was applied. A postoperative evaluation was performed using indocyanine green 6 months after surgery. RESULTS: Despite the clipping procedure, three of the 12 anastomoses still showed poor venous inflow. Therefore, it was not possible to apply the PLASTER technique in those cases. Among the nine remaining anastomoses in which the PLASTER technique was applied, three (33%) were patent. CONCLUSIONS: Our findings show that achieving patent anastomosis is challenging when postoperative venous inflow is poor. We achieved good results by performing proximal ligation after LVSEA. Thus, the PLASTER technique is a particularly useful recovery technique when LVSEA does not result in good run-off.
Edema ; Female ; Humans ; Indocyanine Green ; Ligation ; Lower Extremity ; Lymphatic Diseases ; Lymphatic Vessels ; Lymphedema ; Microsurgery