Lymphatic Lesions Research Articles

Preclinical Activity Profile and Therapeutic Efficacy of the HSP90 Inhibitor Ganetespib in Triple-Negative Breast Cancer

Treatment options for patients with triple-negative breast cancer (TNBC) are largely limited to systemic chemotherapies, which have shown disappointing efficacy in the metastatic setting. Here, we undertook a comprehensive evaluation of the activity of ganetespib, a potent inhibitor of HSP90, in this malignancy. The antitumor and antimetastatic activity of ganetespib was investigated using TNBC cell lines and xenograft models. Combinatorial drug analyses were performed with chemotherapeutic agents and concomitant effects on DNA damage and cell-cycle disruption were assessed in vitro; antitumor efficacy was assessed in vivo. Metabolic and objective tumor responses were evaluated in patients with metastatic TNBC undergoing ganetespib treatment. Ganetespib simultaneously deactivated multiple oncogenic pathways to potently reduce cell viability in TNBC cell lines, and suppressed lung metastases in experimental models. Ganetespib potentiated the cytotoxic activity of doxorubicin via enhanced DNA damage and mitotic arrest, conferring superior efficacy to the doxorubicin-cyclophosphamide regimen in TNBC xenografts. Ganetespib also promoted mitotic catastrophe and apoptosis in combination with taxanes in vitro, and these effects translated to significantly improved combinatorial activity in vivo. Marked tumor shrinkage of metastatic lung and lymphatic lesions were seen in patients on ganetespib monotherapy. The preclinical activity profile and clinical evidence of tumor regression suggest that ganetespib offers considerable promise as a new therapeutic candidate to target TNBC.

Cardiorespiratory Impact of Transesophageal Endoscopic Mediastinoscopy Compared With Cervical Mediastinoscopy

Transesophageal natural-orifice transluminal endoscopic surgery (NOTES) mediastinoscopy has been described as a feasible, less-invasive alternative to video-assisted mediastinoscopy (VAM). We aimed to investigate hemodynamic and respiratory effects during transesophageal NOTES mediastinoscopy compared with VAM. This was a short-survival experiment in 20 female pigs randomized to NOTES (n = 10) or VAM (n = 10) mediastinoscopy. In the NOTES group, an endoscopist accessed the mediastinum through a 5-cm submucosal tunnel in the esophageal wall, and CO2 was used to create the pneumomediastinum. Conventional VAM was carried out by thoracic surgeons. A 30-minute systematic exploration of the mediastinum was then performed, including invasive monitoring for hemodynamic and respiratory data. Blood samples were drawn for gas analyses. All experiments except 2 in the NOTES group (one because of technical difficulties, the other because of thoracic lymphatic duct lesion) were completed as planned, and animals survived 24 hours. Also, 3 animals in the NOTES group presented a tension pneumothorax that was immediately recognized and percutaneously drained. VAM and NOTES animals showed similar pulmonary and systemic hemodynamic behavior during mediastinoscopy. Pulmonary gas exchange pattern was mildly impaired during the NOTES procedure, showing lower partial arterial oxygen pressure associated with higher airway pressures (more important in animals that presented with pneumothorax). NOTES mediastinoscopy induces minimal deleterious respiratory effects and hemodynamic changes similar to conventional cervical VAM and could be feasible when performed under strict hemodynamic and respiratory surveillance. Notably, serious complications caused by the injury of pleura are more frequent in NOTES, which mandates an improvement in technique and suitable equipment.

Traitement des varices et lymphœdèmes des membres

Two questions arise when considering the treatment of varicose veins and the development of lymphedema: can the treatment cause lymphedema? Can it worsen it? Primary lymphedema is rarely associated with varicose veins except in the lymphedema-distichiasis syndrome. Data available in the literature is essentially based on surgical treatment. Stripping on a normal limb may induce chronic lymphedema in almost 0.1% of cases. The risk of lymphedema after stripping in patients with previous pelvic surgery including lymph node excision and/or radiotherapy remains unknown. In patients with lower limb lymphedema wearing strong elastic compression stockings, stripping provides little clinical improvement and can worsen volume. The main objective is also to avoid venous complications. Lymphatic lesions related to stripping can be evaluated by lymphography or lymphoscintigraphy. New techniques for treating varicose veins (sclerotherapy, endovenous laser treatment, radiofrequency ablation) seem to induce fewer lymphatic complications. Further studies are required to confirm these results. Indications for treatment should be unquestionable and patients must be alerted to the potential risk of lymphedema or its worsening.

Microsurgery in the prevention and early treatment of lymphatic complications after surgical oncology

This study presents our case series of microsurgical procedures in the prevention and treatment of lymphatic lesions in surgical oncology. Complications from lymphadenectomies for breast cancer and malignant melanoma, and, in particular, in the axillary region for breast cancer or/and malignant melanoma, and in the inguinal-crural-obturator region, for malignant melanoma, were specially focused upon. According to recent international literature, the incidence of lymphatic lesions is quite high, as highlighted by unequivocal data on the onset of post-operative lymphoedema.

Brugia pahangi: Immunization with early L3 ES alters parasite migration, and reduces microfilaremia and lymphatic lesion formation in gerbils (Meriones unguiculatus)

Previous studies have shown that intradermally (ID) injected Brugia pahangi L3s migrate through various tissues and into the lymphatics of gerbils in a distinct pattern. Excretory/secretory products (ES) produced at the time of invasion of B. pahangi are likely to be important in this early migration phase of the parasite life cycle in their rodent host. Hence, early L3 ES was collected from 24h in vitro cultures of B. pahangi L3 larvae and used in immunization experiments to investigate the effect of immunity to early L3 ES on worm migration, survival and development of B. pahangi. Immunization of gerbils with ES in RIBI adjuvant produced antibodies to numerous ES proteins eliciting a strong humoral response to ES and indirect fluorescent antibody (IFA) assay using anti-ES serum recognized the ES proteins on the surface of B. pahangi L3 larvae. Following ES immunization, gerbils were challenged either ID or intraperitoneally (IP) with 100 L3s of B. pahangi and euthanized at 3 or 106days post inoculation (DPI). Immunization with early ES slowed the migration of ID inoculated L3 at 3DPI and significantly altered the locations of adult worms at 106DPI. Immunization did not induce protection in any treatment group. However, immunized animals had significantly fewer microfilariae per female worm suggesting the antigens in ES are important in microfilariae development or survival in the host. The number of lymphatic granulomas was also significantly reduced in ES immunized animals. It is important to note that microfilariae serve as a nidus in these granulomas. Our results shows immunization with early Brugia malayi L3 ES alters the worm migration, affects circulating microfilarial numbers and reduces lymphatic granulomas associated with B. pahangi infection in gerbils.

Establishment of Fischer 344 rat model of ovarian cancer with lymphatic metastasis

To establish a model of ovarian cancer with highly lymphatic metastasis in immunocompetent rats. Thirty-two female Fischer 344 rats were divided randomly and equally into two groups: footpad group and intraperitoneal (i.p.) group. At 8 weeks after injection with NuTu-19 ovarian cancer cells, lymphatic metastasis were analyzed by pathohistology; body weight was monitored per week, Survival curves were determined by Kaplan-Meier analysis. Footpad injection could efficiently generate the lymphatic metastasis; specifically, the incidences of metastasis in the ipsilateral popliteal, inguinal and para-iliac lymph nodes were 100% (8/8), 75% (6/8), and 37.5% (3/8), respectively. The mean volume and weight of the ipsilateral popliteal lymph nodes were 0.405 ± 0.096 cm(3) and 0.418 ± 0.118 g in footpad group. However, no lymphatic metastasis lesions were found in i.p. group. Moreover, Kaplan-Meier analysis showed that the average survival time of the footpad group was significantly longer than that of the i.p. group (18.429 ± 1.112 vs. 10.286 ± 0.505 weeks). Our experiments suggest that footpad injection is a very efficient method to generate ovarian cancer with lymphatic metastasis in an immune-competent animal, and we believe that this model will be very helpful for shedding light on the mechanism of lymphogenous metastasis and developing novel therapeutic targets for ovarian cancer patients.

Evolution of chylous fistula management after neck dissection

The present review is focused on the management of lymphatic, chylous, and thoracic duct lesions following head and neck surgery, with particular attention to these complications after neck dissection. Postoperative scenarios may include chylous fistula, chylothorax, chylomediastinum, chylopericardium, lymphocele, persistent lymphorrhea, and secondary lymphedema. There is a paucity of literature on the treatment of lymphatic, chylous, and thoracic duct injuries following head and neck surgery; however, this review suggests that the most appropriate treatment should include both conservative and surgical approaches. Nonsurgical options consist of low-fat diet with medium-chain triglycerides, total parenteral nutrition, careful monitoring of fluid and electrolytes, drainage of the leakage, somatostatin analogs such as octreotide, and negative-pressure wound therapy. On the other hand, surgical management includes therapeutic percutaneous lymphography-guided thoracic duct cannulation and embolization, thoracic duct ligation, excision and imbrication of leaking lymphatics, chylous fistula surgical/microsurgical repair, fistula closure by locoregional flaps, video-assisted thoracoscopic surgery, thoracotomy, pleurodesis and decortication, pericardial 'window', and pleura-venous/pleura-peritoneal shunts. In addition, single or, preferably, multiple lymphovenous anastomoses may be taken into account. The various possible clinical presentations of such challenging lymphatic, chylous, and thoracic duct injuries require an appropriate multidisciplinary approach by experienced teams. Primary prevention of these complications can be achieved through adequate surgical planning to minimize lesions, including structured and thorough patient assessment, and centralization of resources and teams.

Vulvar Vascular Tumors

The subepidermal hormonally sensitive tissue of the vulva is anatomically unique and may give rise to a wide variety of vascular tumors. As a consequence, classifying vulvar vascular lesions has been challenging due both to the wide variety of lesions that may be encountered and the heterogeneity in reporting across several disciplines. The purpose of this study is to present an institutional experience of vulvar vascular lesions. Overall, 85 patients were identified over a 26-year period. Vascular lesions belonging to the following classes included (n, %total) benign vascular tumors (32, 38%), dilatations of preexisting vessels (31, 36%), hyperplasia/reactive (7, 8%), tumors with significant vascular component (11, 13%), malformations (3, 4%), and malignant vascular tumors (1, 1%). Two reaction patterns based on vulvar lymphatic pathology were identified: one is a stromal dominant pattern and the other is a vascular dominant pattern. Vulvar vascular malformations and true vascular malignancies, although rare, may have associated high morbidity. To accurately classify vulvar lymphatic lesions, the pathologist must carefully consider the patient's clinical history taking into account features such as preexisting lymphedema.

Vulvar Manifestations of Crohn's Disease

Crohn's disease is an inflammatory bowel disorder with several well-known extraintestinal manifestations, such as erythema nodosum, uveitis, and arthritis. Less commonly observed are vulvar manifestations, which have primarily been discussed in case reports or small case series. These cases generally highlight patients with histopathology limited to noncaseating granulomas. As these histological findings are identified in bowel biopsies from only approximately 50% of patients with gastrointestinal Crohn's disease, there is likely an under-recognition and underdiagnosis of vulvar lesions as Crohn's disease manifestations. We describe the largest case series to date involving patients with vulvar Crohn's disease, discuss the varied clinical presentations, and describe the histopathological findings, which include noncaseating granulomas, ulcerations, lymphatic lesions, and even dysplasia and carcinoma. Our findings underscore the importance of keeping vulvar Crohn's disease on the differential diagnosis when faced with a range of vulvar symptoms and suggest that regular gynecological surveillance in patients with Crohn's disease may be of benefit.

Propranolol Therapy for Hemorrhagic Lymphangioma of the Tongue

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Benign “Waxing–Waning” Vascular Proliferations in Previously Irradiated Skin

Benign “Waxing–Waning” Vascular Proliferations in Previously Irradiated Skin

Interventional Management of Vascular Malformations

Vascular malformations are either of slow-flow type, including capillary, venous, and lymphatic lesions, or fast-flow, such as arteriovenous malformations. These anomalies are fundamentally congenital-though some may present later in life-, grow with the patient, and, with rare exceptions, do not disappear spontaneously. This article briefly discusses the diagnosis and interventional management of vascular malformations.

Low flow vascular malformations of the head and neck: a study on brightness mode, color coded duplex and spectral Doppler sonography

The clinical presentation of low flow vascular malformations of the head and neck (LFVM) can range from a birthmark to severe disfigurement, functional impairment or relevant hemorrhage. The values of Brightness mode (B-mode) ultrasound and Doppler sonography in the investigation, identifying and differentiating of these lesions has been sparingly documented in the literature. This study evaluates the sonografic features of different morphological subtypes of LFVM. This is a 2-year retrospective study of 51 patients who presented with LFVM based on routine ultrasound exam in the context of their clinical consultation. Diagnosis was based on the clinical and histological findings. B-mode, color coded duplex and spectral Doppler measurements were performed for venous, lymphatic, capillary, and mixed venous-lymphatic lesions of the head and neck. The echogenicity of the majority of venous malformations was heterogenic, of most lymphatic malformations hypoechoic, and of all capillary malformations isoechoic. Blood flow was detected in only 11 cases (36.7%) of venous malformations with a monophasic pattern. There was a statistical significant difference in the mean minimum and maximum Doppler shifts between venous and lymphatic malformation for cases when the blood flow was evident. No statistical significant difference in Doppler parameters existed between capillary and lymphatic, neither between venous and capillary nor mixed malformations. Phleboliths were present in eight cases (26.7%) of venous malformations and were not detectable in any other subtype of LFVM. The detection of flow in ultrasound was only possible in a small portion of LFVM. When considering differentiating among LFVM, features such as the echogenecity, spectral Doppler wave forms, and the evidence of phleboliths contribute to establish the correct diagnosis.

Alterações linfocintilográficas após retirada da veia safena para ponte da artéria coronária

Bridged incisions do not eliminate lesions to the lymphatic vessels and so the identification of risk factors associated to lymphatic lesions is important.

Pancreatic involvement detected with 18F-FDG PET/CT in disseminated sarcoidosis

Sarcoidosis is a granulomatous disease of unknown etiology. It may mimic malignancy and may affect multiple organs, with a variable clinical course. Pancreatic involvement is very rare. We present the case of a 78-year-old woman with systemic sarcoidosis whose 18F-FDG PET/CT scan showed a pancreatic lesion and multiple lymphatic (thoracic and non-thoracic) and visceral lesions. The abnormal 18F-FDG uptake in the pancreas was limited to the tail. A second 18F-FDG PET/CT study performed 4 months and 3 weeks after the first PET/CT, following corticosteroid therapy during three and a half months, evidenced partial regression of the disease, with persistent 18F-FDG pathological uptake in the pancreatic lesion.

Current concepts in the classification, diagnosis and treatment of vascular anomalies

Patients with extended vascular anomalies may suffer from significant aesthetic and functional impairment and represent a challenge to therapeutic planning, which is best met by an interdisciplinary concept. In agreement with the International Society for the Study of Vascular Anomalies (ISSVA), vascular lesions are classified into haemangiomas as proliferating endothelial tumours on the one hand and congenital vascular malformations on the other. According to the preponderant vascular channels and hemodynamic characteristics, malformations are subdivided into low flow (venous, lymphatic and capillary) lesions and high-flow malformations. Diagnostic imaging should be targeted at the specific structural and functional informations required for treatment planning. The imaging modality of choice to provide these informations is magnetic resonance imaging (MRI) supplemented by magnetic resonance angiography (MRA) with high spatial and temporal resolution. Treatment indications for haemangiomas depend on the proliferative behaviour of the lesion and comprise β-blockers in order to induce involution as well as cryotherapy, laser and open surgery. Interventional radiological procedures have evolved as an essential element in an interdisciplinary treatment plan for vascular malformations and include percutaneous sclerotherapy with ethanol and OK-432 for venous and lymphatic malformations and transarterial embolization for high-flow lesions.

Preservação da veia safena magna na cirurgia de varizes dos membros inferiores

A veia safena magna autóloga é o melhor substituto arterial nas revascularizações dos membros inferiores, importante na revascularização do miocárdio e pode ser utilizada nas cirurgias do sistema venoso e nos traumas das extremidades. A fleboextração aumenta os riscos de lesões linfáticas e neurológicas. Assim, no tratamento das varizes primárias dos membros inferiores por meio da cirurgia ou de outras técnicas, a preservação da safena é recomendável se ela for normal ou apresentar alterações que ainda permitam sua preservação pela correção da causa desencadeante. Tal correção pode ser feita por técnicas cirúrgicas. Entre elas, a cura hemodinâmica da insuficiência venosa em ambulatório (CHIVA) tem mostrado bons resultados. Recentemente, um ensaio clínico randomizado e controlado foi publicado comprovando sua eficácia. Outra técnica bastante utilizada é a da ligadura rasante da junção safenofemoral + crossectomia + ligadura das tributárias de crossa, com a qual se tem obtido resultados contraditórios. Finalmente, as técnicas que corrigem a insuficiência da safena reparando as valvas ostial e pré-ostial (valvoplastia externa) são mais fisiológicas. Um ensaio clínico internacional multicêntrico, randomizado e controlado, testando um novo dispositivo, está sendo realizado, com resultados iniciais favoráveis. Este estudo pretende fazer uma revisão sobre as técnicas utilizadas na preservação da safena magna.

The Role of Thrombosis as a Mechanism of Exacerbation in Venous and Combined Venous Lymphatic Vascular Malformations of the Orbit

To describe venous thrombosis as a mechanism of clinical change in venous and combined venous lymphatic malformations of the orbit and to attempt histopathologically to distinguish the various vascular components of these lesions using immunohistochemistry with CD31 and D2-40 antibodies. Retrospective, comparative, interventional case series. Twelve patients with clinically and radiologically well-documented episodes of thrombosis in venous malformations (n = 7; group A) and combined venous lymphatic malformations (n = 5; group B). Surgical excision of lesion in selected patients, 2 from group A and 5 from group B. Age at presentation, gender, onset, symptoms and signs, investigative findings (imaging and histopathologic review), management, and outcome. In group A, 4 patients were male and 3 were female, and in group B, 4 patients were female and 1 was male. The mean age+/-standard deviation at presentation was 57.6+/-10.9 years (range, 45-71 years) and 11+/-11.6 years (range, 1.5-26 years), respectively. The pattern of onset was acute in all cases. The most common signs and symptoms in group A were pain (n = 7), proptosis (n = 6), and nausea (n = 5), whereas in group B they were periorbital swelling (n = 5), proptosis (n = 5), and ecchymosis (n = 4). The immunohistochemistry results were positive for vascular (CD31) and lymphatic (D2-40) endothelium in all of the specimens. The combined venous lymphatic lesions divided themselves into 2 main categories based on the D2-40 findings in relationship to percentage of lymphatic vessels. These were lesions that were either lymphatic dominant (n = 3) or venous dominant (n = 2). Clinically, the 2 groups behave differently. Group A lesions present in adults with acute pain, proptosis, and nausea and may resolve spontaneously on follow-up. Intervention may be required in cases of severe pain, proptosis, or dysfunction. Group B lesions present early in life with frequent bouts of periorbital swelling, progressive proptosis, and ecchymosis. Therefore, early intervention is advised. Finally, when requesting imaging for such lesions, early- and late-phase contrast imaging should be used because thrombosis typically is better demonstrated in the late phase. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Macrocystic Lymphatic Malformation in the Pulmonary Parenchyma

We present a young girl with a diffuse, macrocystic lymphatic malformation with associated venous dilation involving the left lower pulmonary lobe and mediastinum. Recurrent hemoptysis necessitated left lower lobectomy. This is the first reported case of a macrocystic lymphatic lesion with venous anomalies located within the parenchyma of the lung.

How size evaluation of lymph node is protocol dependent in MRI when using ultrasmall superparamagnetic iron oxide nanoparticles

In this study, the volume of susceptibility artifact was evaluated in T1 and T2-weighted spin echo (SE) and gradient echo (GRE) images at various parameters using registration and subtraction methods. In order to state an important misinterpretation problem in lymphography, it was demonstrated that a lymph node size may be enlarged approximately 10 times when a T2*-weighted GRE protocol is used. To overcome this problem a technical consideration using multisequence (GRE and SE) paradigm was suggested to ensure both lymph node detection and metastasis identification in lymphatic system. The paradigm was also extended by post-processing manipulation of the SE images using a registration and subtraction approach for detection of lymphatic lesions.