Dilated Lymphatic Vessels Research Articles

Duodenal hemangiolymphangioma presenting as chronic anemia: a case report

BackgroundLymphangiomas are a heterogeneous group of congenital vascular malformations characterized by cystic dilation of lymphatic vessels. They can occur at any age, but they are more common during childhood and in cutaneous localizations. Hemangiomas and vascular malformations of the gastrointestinal tract are very uncommon. Most are asymptomatic and diagnosis is often made as an incidental finding during endoscopy. On rare occasions the initial manifestation can be chronic anemia due to low grade gastrointestinal bleeding. They constitute an unusual manifestation and there is a low incidence of this type of tumor.Case presentationWe report the case of a 43 year-old latin female, with a 2-year history of chronic anemia requiring blood transfusion. Hemoglobin and Hematocrit count were low, therefore further studies were required to rule out bleeding sources or other causes of anemia. Enteroscopy findings showed a 35 mm lesion taking up 50 % of the circumference in the distal duodenum, with raised whitish edges secondary to confluent lymphangiectasia, a center with a vascular appearance and active bleeding spots. Biopsy samples dyed with India ink confirmed the diagnosis of hemangiolymphangioma.ConclusionDiagnostic difficulties in this case, highlight the need to include hemangiolymphangioma in the differential diagnosis of chronic anemia as well as the need for multiple diagnostic methods to confirm the presence of the condition.

Acquired vulvar lymphangioma: Report of two cases

Vulvar lymphangioma is a rare case and often being misdiagnosed as genital wart. This acquired disorder manifests as dilatation of superficial lymph vessel due to obstruction. It is caused by urogenital infection and most often occurs following surgery and radiotherapy of cervical cancer. The diagnosis is established based on clinical and histopathological features. Treatment aimed to eliminate the cause of obstruction. This article reports two cases of vulvar lymphangioma found in our Hospital. First case was a 43-year-old female with a history of surgery and radiation for cervical cancer 10 years ago presented with vesicular skin lesion in genital area, oozing copious clear fluid since 4 years ago. There are multiple lenticular vesicles containing clear fluid in vulvar area accompanied with bilateral lymphedema of lower extremities. Histopathological features demonstrated dilated superficial lymph vessels. Second case was a 44-year-old female with enlargement of lower abdomen with vesicular lesion containing clear fluid in genital area since 3 years ago. Abdominal USG showed enlarged inguinal lymph node. Histopathological features demonstrated dilated superficial lymph vessels. The treatment for both cases were gradual electrosurgery. In both cases, vulvar dermis’ superficial lymph node dilatation caused the skin lesions. Obstruction of lymph vessel due to radiation and surgery for cervical cancer in the first case and of inguinal lymph node in the second case lead to increased lymphatic pressure in the dermis and later on the dilatations. The treatment in both cases using electrical excision produced good responses; however, we should be attentive on recurrent case. Keywords: acquired vulvar lymphangioma, dilatation of dermal lymph vessels, electrosurgery

High-grade squamous intraepithelial lesion arising adjacent to vulvar lymphangioma circumscriptum: a tertiary institutional experience.

Lymphangioma circumscriptum of the vulva occurs in patients who have undergone radical hysterectomy, lymph node dissection, or radiation therapy for management of advanced uterine cancer. Since vulvar lymphangioma circumscriptum typically presents as multiple, grossly verrucous vesicles of various sizes, it may be impossible to clinically distinguish vulvar lymphangioma circumscriptum from other vulvoperineal cutaneous diseases. In the present study, 16 (1.6%) out of the 1,024 vulvar biopsy or excision specimens were diagnosed as lymphangioma circumscriptum. In two (12.5%) out of the 16 cases, unusual histopathological findings were observed. Both patients had previously undergone radical hysterectomy with lymph node dissection and postoperative radiation therapy or concurrent chemoradiation therapy for advanced cervical cancer. Microscopic examination revealed high-grade squamous intraepithelial lesions, which were located immediately adjacent to the normal squamous epithelium covering the dilated subepithelial lymphatic vessels. Further, human papillomavirus genotyping confirmed that both patients were infected with high-risk human papillomavirus. High-grade squamous intraepithelial lesion cannot be grossly distinguished from vulvar lymphangioma circumscriptum because the multiple, verrucous vesicles that constitute the characteristic gross appearance of vulvar lymphangioma circumscriptum hinder its distinction. In this regard, our cases of high-grade squamous intraepithelial lesion, located adjacent to vulvar lymphangioma circumscriptum, support the notion that active surgical excision is necessary for the treatment of vulvar lymphangioma circumscriptum.

Positive Predictive Value of Mammographic Lymphography in the Evaluation of Patients with Breast Cancer: A Preliminary Study

The study aimed to investigate the positive predictive value (PPV) of mammographic lymphography (MLG) for assessing malignant breast disease and lymphatic metastasis in patients in a typical clinical setting. Patients who underwent mammography with Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5 lesions and had abnormal mammographic findings in the upper-outer quadrant of the breast were enrolled. Next, MLG was performed. A water-soluble agent was subcutaneously injected into the upper-outer periareolar region of the bilateral breast, and mammography was then performed. Morphologic characteristics, including lymphatic vessel development, the presence of lymphatic vessel defects, and dilation, were recorded for evaluation. Fifty-one patients with BI-RADS category 4 lesions and 40 patients with BI-RADS category 5 lesions were included in the study. Sixty-one patients were found to have malignant disease, whereas 30 patients were found to have benign disease. Morphologic characteristics were recorded for evaluation. The interobserver agreement was evaluated and was classified as excellent according to kappa analysis. The PPV of MLG characteristics for malignant breast disease and lymphatic metastasis was analyzed by logistic regression, and the presentation of a lymphatic vessel defect was the most predictive characteristic of a malignancy (PPV: 0.89; P value: 0.02) in patients with BI-RADS category 4 lesions. Meanwhile, in patients with malignant breast disease, the PPVs for predicting lymphatic metastasis with lymphatic vessel defect and dilation were 0.50 (P value: 0.02) and 0.67 (P value: <0.01), respectively. The assessment of morphologic characteristics by MLG has the potential to predict malignant breast disease and lymphatic metastasis.

Histopathological Features of Orofacial Granulomatosis.

Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation in the orofacial region. Although several series have been reported, biopsy has not been performed in all cases and the histopathological features have not been extensively evaluated. Our purpose was to analyze the histopathological features of our patients with OFG. Twenty-two patients diagnosed with OFG at Bellvitge Hospital (Barcelona, Spain) from 1985 to 2010 were included in the study. All of our patients (14 men and 8 women; mean age 46.77 years, SD 13.61) presented with labial swelling, involving the upper lip in 13 cases and the lower lip in 9 at presentation. Fissured tongue was observed in 9 cases. Three patients suffered facial palsy. Granulomas were observed in 16 patients. All patients showed a perivascular, lymphohistiocytic inflammatory infiltrate with prominent plasma cells in 21 cases. In 5 cases, mast cells were easily observed. In 13 patients, an interstitial infiltrate was also present. All cases showed dilated lymphatic channels, and 19 edema of the lamina propria or the dermis. Perilymphatic granulomas were observed in 12 cases, intralymphatic granulomas in 2, and intralymphatic histiocytes in 2. In conclusion, loose epithelioid cells or lymphonodular granulomas were observed in 73% of our patients. Although none of our patients developed Crohn disease, OFG is histopathologically similar to cutaneous lesions of Crohn disease. The perilymphatic disposition of granulomas and the presence in some cases of intralymphatic histiocytes or intralymphatic granulomas may explain the dilatation of lymphatic vessels and the development of edema.

Linagliptin alleviates fatty liver disease in diabetic db/db mice.

AIMTo study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease (NAFLD) in db/db mice.METHODSMale diabetic db/db mice (BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin (10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) was assessed by immunohistochemistry.RESULTSIn 18-wk-old diabetic mice, liver steatosis (predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets (92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets (20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independent to changes in the plasma glucose levels.CONCLUSIONThe DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice.

Skin-Deep: The Diagnosis of Scrotal Lymphangitis Associated With Crohnʼs Disease

Granulomatous lymphangitis is a rare cause of genital lymphedema. The presence of scrotal swelling and granulomatous lymphangitis of the external genital is an important and often missed clue to the presence of Crohn's disease. We present an 85 year old male with several days of worsening scrotal erythema and swelling. The patient has a remote history of colonic Crohn's disease diagnosed in the early 1970s resulting in a partial colectomy and end-ileostomy. He had no remaining manifestations of his Crohn's disease and was eventually lost to all follow-up. He had been having episodic flares of scrotal swelling for the past three years, often lasting 1-2 weeks. He was evaluated by multiple hospitals and specialties without a clear diagnosis. On presentation, he was afebrile. He denied symptoms of hematuria, dysuria, discharge or difficulty with urination. He had no gastrointestinal complaints. There was no known trauma or significant scrotal or penile pain. On exam his scrotum and penis were diffusely erythematous with significant edema extending onto the suprapubic region. Skin of the scrotum appeared thickened without ulcerations or nodules. There was no significant laboratory abnormalities. A CT scan of the pelvis revealed extensive scrotal edema with no discrete fluid collection or subcutaneous emphysema. A scrotal ultrasound showed diffuse scrotal wall thickening and edema. He was started on broad-spectrum antibiotics with no improvement in his symptoms. He underwent a scrotal punch biopsy which revealed lymphohistiocytic infiltrate with focal intralymphatic histiocytosis. These histological features were consistent with granulomatous lymphangitis associated with Crohn's disease. In children, the majority of genital granulomatous lymphangitis were associated with concomitant or subsequent development of Crohn's disease. In the older patient population, genital swelling often occurred after a long history of Crohn's Disease and years after a colectomy. Lymphedema is thought to be the primary process and granulomatous inflammation secondary to the microflora and waste products in the dilated lymphatic vessels. Treatment with steroids, mesalamine, or metronidazole often results in partial improvement or complete remission. The rare entity of scrotal granulomatous lymphangitis in Crohn's disease is easily missed however its accurate diagnosis has significant treatment implications.Figure 1

A Rare Presentation of Lymphangioma in a Patient With Hematochezia

Lymphangiomas are rare benign cysts caused by congenital malformation of the lymphatic system. The incidence of lymphangiomas is between 1.2:1,000 to 4:10,000 births per year. Amongst lymphangiomas 80-90% originate from the head and neck. Intra-abdominal lymphangiomas make up about 5% of lymphangiomas. There is no specific data on the incidence of colonic lesions. We present a case of a 38 year old female with no significant past medical history presenting with bright red blood per rectum. The patient had been having issues with chronic hematochezia since her teenage years, which had been attributed to hemorrhoids. The patient denied any early satiety, nausea, vomiting, unintentional weight loss, or black stools. Physical exam was unremarkable, except for a palpable mass on rectal exam. Laboratory evaluation revealed a microcytic anemia, but otherwise was within normal limits. She had never before undergone endoscopic evaluation. The patient subsequently underwent a full colonoscopy that revealed an extensive network of cyst like structures from just proximal to her dentate line to 15 cm. These lesions were examined radiographically, endoscopically, and via endoscopic ultrasound (EUS). EUS and MRI investigations demonstrated extent of disease down into the perirectal fat region, but with no invasion of adjacent structures. Biopsies of the lesion revealed multiple areas of dilated lymph vessels extending into the muscularis mucosae lined with endothelial cells, diagnostic of lymphangioma. The approach to treatment of lymphangiomas is varied, from conservative expectant course to sclerosant injections and aspiration, to surgical resection. There are reported cases of spontaneous regression, up to 15-20%. Recurrence rates of 50% are reported with surgery. Although very rare, there is a potential risk for malignant transformation. The patient ultimately elected for the expectant course. This case demonstrates a rare cause for hematochezia, which emphasizes the importance of a broad differential diagnosis, and the need to not discount patient's symptoms regardless of prior evaluations.Figure 1Figure 2

Blood and lymphatic microvessel damage in irradiated human skin: The role of TGF-β, endoglin and macrophages

Background and purposeMicrovascular damage is an important component of late radiation-induced morbidity. In our pre-clinical models, we demonstrated that repair of vessel injury is dependent on proper endoglin-mediated transforming growth factor-beta (TGF-β) signalling and that it can be affected by infiltrating macrophages. We now wanted to extend these findings in irradiated patients, using skin as a model system, and assess whether bisphosphonates could modulate the response. Materials and methodsPaired skin biopsies from irradiated and non-irradiated sites were obtained from 48 breast cancer patients. In 8 patients, biopsies were repeated after 4months of bisphosphonate treatment. Immunohistochemistry was used to assess vascular alterations and leucocyte infiltration. Western Blot and qPCR were used to assess expression of growth factors and their receptors. ResultsDecreased blood vessel numbers at early time points were followed by increased endoglin expression and restoration of vessel number. Loss of small lymphatic vessels was associated with increased TGF-β levels, whereas dilation of lymphatic vessels correlated with increased macrophage infiltration. Bisphosphonate treatment reduced leucocyte infiltration, but also prevented restoration of blood vessel numbers after irradiation. ConclusionRadiation injury of the microvasculature is mediated through TGF-β, whereas repair is modulated by the co-receptor endoglin and promoted by macrophages.

Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation

The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 μm, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (∼60 μm). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability.

Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2 mice would influence the course of disease in a model of experimental colitis. Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2 mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. We found that FoxC2 downregulation in FoxC2 mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease.

Acquired Lymphangiectasia of the Breast After Breast Conserving Surgery.

Lymphangiectasia is characterized by vesicular dilation of lymphatic vessels and is generally a complication of radiotherapy or surgery of various malignant tumors such as breast and cervical cancers. Although it is not a precancerous disease, correct diagnosis is important to rule out Stewart-Treves syndrome which is defined as lymphangiosarcoma that develops in long-standing chronic postmastectomy lymphedema. Observation alone or many therapeutic options including cryosurgery, electrocauterization, sclerotherapy, and excision have been widely used in the management. Herein, a case of breast lymphangiectasia was presented as a late and rare complication of breast cancer-related therapies.

Mesenteric Lymphangioma Presenting as Ileal Volvulus

Mesenteric Lymphangioma Presenting as Ileal Volvulus

Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSS-induced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage. The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation.

Abstract 1079: COX-2 blockade immunologically suppresses brain metastasis of lung cancer

Abstract Epidemiological studies have highlighted associations between the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) and reduced cancer risks in human. In addition, NSAIDs reduce VEGF-D production levels, which in turn inhibit lymphatic vessel dilation and eventually cancer metastasis. Most NSAIDs function as cyclooxygenase-2 (COX-2) inhibitors that prevent the production of prostaglandin E2 (PGE2). The PGE2 induces myeloid-derived suppressor cells (MDSCs) in the bone marrow of cancer-bearing hosts, which is known to be responsible for T-cell suppression in chronic inflammation. Based on these findings, we hypothesized that COX-2 blockade would suppress brain metastasis of cancers by inhibiting MDSC development and their chemokine-mediated accumulation in the tumor microenvironment (TME). In both mouse and human brain metastasis cases, the expression levels of COX-2 and CCL2, a chemokine primarily attracting MDSCs, were increased in the brain tumor tissues compared with normal brain or peripheral bloods. Concomitantly, the infiltration of MDSCs (CD11+Gr-1+ for mice and CD14-CD15+HLA-DRlow for human, respectively) was observed at high levels in the tumor tissues. In the mouse brain tumor models using LL/2 murine lung cancer cell line, treatment with NSAIDs inhibited the PGE2 production levels and the formation of brain metastases. Furthermore, the NSAID treatment reduced the CCL2 in the TME, which was associated with a reduction in Ly6ChighLy6Glow monocytic and Ly6ClowLy6Ghigh granulocytic MDSCs in both the bone marrow and the TME. Mice genetically deficient for CCR2, a receptor for CCL2, exhibited low penetration of brain metastases along with reduced infiltration of MDSCs. Collectively, our findings show that the COX-2 pathway promotes brain metastases of lung cancers by supporting systemic development of MDSC and their accumulation in the TME mediated by the CCL2-CCR2 chemokine axis. Citation Format: Mitsugu Fujita, Susumu Nakata, Takeshi Okuda, Amami Kato, Osamu Yoshie. COX-2 blockade immunologically suppresses brain metastasis of lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1079. doi:10.1158/1538-7445.AM2014-1079

Supermicrosurgical anastomosis of superficial lymphatic vessel to deep lymphatic vessel for a patient with cellulitis-induced chronic localized leg lymphedema.

Supermicrosurgical lymphaticovenular anastomosis (LVA) has been reported to be useful for the treatment of obstructive lymphedema. However, LVA has a potential risk of anastomosis site thrombosis. It is more physiological to use a lymphatic vessel as a recipient vessel of lymphatic bypass surgery, because there is no chance for blood to contact the anastomosis site. We report a chronic localized lower leg lymphedema case treated with supermicrosurgical superficial-to-deep lymphaticolymphatic anastomosis (LLA). A 66-year-old male with a 60-year history of cellulitis-induced left lower leg lymphedema suffered from very frequent episodes of cellulitis and underwent LLA under local infiltration anesthesia. LLA was performed at the dorsum of the left foot. A dilated superficial lymphatic vessel was found in the fat layer, and a nondilated intact deep lymphatic vessel was found along the dorsalis pedis artery below the deep fascia. The superficial lymphatic vessel was supermicrosurgically anastomosed to the deep lymphatic vessel in a side-to-end fashion. After the surgery, the patient had no episodes of cellulitis, and the left lower leg lymphedematous volume decreased. Superficial-to-deep LLA may be a useful option for the treatment of secondary lymphedema due to obstruction of only the superficial lymphatic system.

Cavernous lymphangioma of fetal thigh

A 35-year-old woman was referred to our institution at 19 weeks' gestation because a mass located at the right fetal thigh was noted, reporting with a 46,XX karyotype of cultured amniotic cells. Prenatal ultrasound examinations revealed a 73 mm 47 mm 35 mm irregular multiseptated cystic mass involving the whole right fetal thigh with no obvious blood flow visualized using color Doppler images (Fig. 1A and B). The remaining ultrasound images for the female fetus, placenta, and amniotic fluid were unremarkable. Given a tentative diagnosis of lymphangioma and uncertain postnatal prognosis regarding functional and aesthetic impairments after treatment, the patient made a decision to terminate the pregnancy. Postmortem photographs were compatible with the prenatal three-dimensional ultrasound images (Fig. 2A and B). The pathologic reports confirmed an isolated unencapsulated cavernous lymphangioma involving the dermis and subcutaneous layers and composed of multiple dilated thin-wall lymphatic vessels filled with proteinaceous fluid (Fig. 3). The primordial lymphatic formations, visible at 6e7 weeks of embryonic development, include two juguloaxillary lymphatic sacs, two lumboiliacal lymphatic sacs, the retroperitoneal lymphatic sac, and the chylocyst. Lymphangiomas are congenital malformations of the lymphatic systems due to either a sequestration of peripheral lymphatic tissue with no connection to the normal lymphatic system, a missing connection of primordial lymphatic sacs with the venous system, or the obstruction of lymphatic vessels [1]. Lymphangiomas may be superficial, subcutaneous, or deep enough to intertwine with muscles or organs. The nomenclature regarding lymphatic malformation is confusing. Lymphangiomas have been classified as capillary or cavernous. Capillary lymphangiomas are slightly elevated or

37. Chronic stress promotes lymph node metastasis through beta-adrenergic regulation of lymphangiogenesis

Remodelling of tumor lymphatic vasculature facilitates tumor cell metastasis to lymph nodes. However, the physiological pathways that regulate lymphatic remodelling – or lymphangiogenesis – and lymphatic metastasis are yet to be defined. To investigate the impact of beta-adrenergic signaling on lymphangiogenesis and lymphatic metastasis, we explored the effect of restraint stress in an orthotopic xenograft model of triple negative breast cancer. Longitudinal bioluminescence imaging revealed that chronic stress reduced time to lymph node metastasis and increased tumor cell load in draining lymph nodes. Pharmacological activation of beta-adrenergic pathways similarly induced lymphatic remodelling and this effect was blocked with pharmacological beta-blockade. Chronic stress increased the expression of lymphangiogenic growth factor VEGFC and its receptor Vefgr3, and shRNA knock-down of VEGFC reversed the effect of stress on lymph vessel density within primary tumors. We recently found that inflammation increased dilation of lymphatic collector vessels to promote breast cancer metastasis. Consistent with those studies, we found that stress regulated VEGFC by modulating expression of pro-inflammatory COX-2. Treatment with COX-2 inhibitor celecoxib reversed stress-induced lymph vessel dilation and blocked stress-enhanced tumor lymphangiogenesis and lymph node metastasis. These data show that stress acts through a betaAR-inflammation-VEGFC axis to promote lymph node metastasis. Importantly, these studies identify critical opportunities for therapeutic intervention that may help protect women with breast cancer from the adverse effects of stress biology.

Surto de criptosporidiose em bezerros no Sul do Rio Grande do Sul

Descrevem-se os aspectos epidemiológicos, sinais clínicos e a patologia de um surto de criptosporidiose em bezerros na região Sul do Rio Grande do Sul. De um lote de 400 bezerros de 30-45 dias de idade, 35 adoeceram e 16 morreram. Os bezerros nasciam fracos e logo após o nascimento apresentavam diarreia amarela, emagrecimento progressivo, desidratação, depressão e morte entre 10 e 15 dias após o início dos sinais clínicos. Na necropsia havia congestão dos vasos sanguíneos intestinais e mesentéricos. Havia distensão intestinal por gás e dilatação de vasos linfáticos. Microscopicamente havia achatamento das vilosidades intestinais, com necrose e atrofia. Aderidas à superfície das células epiteliais das vilosidades, havia estruturas puntiformes basofílicas de 2-5µm de diâmetro compatíveis com Cryptosporidium spp. A microscopia eletrônica revelou a presença de diferentes estágios do agente aderidos às microvilosidades de enterócitos. Alerta-se para a importância da criptosporidiose como agente primário de diarreia em bezerros. São necessárias medidas preventivas no que se refere ao manejo para diminuir as perdas econômicas e a contaminação ambiental, e, ainda, diminuir o risco para a saúde pública.

Effect of phytic acid from rice and corn on morphology, cell proliferation, apoptosis and cyclooxygenase-2 expression in swine jejunal explants

Phytic acid (IP6) is a potent antioxidant present in several natural foods. Beneficial effects on colon cancer and inflammation have been associated to IP6 in several studies, however, scarce data about the effect on small intestine are available. The aim of the present study was to evaluate the effect of different doses of IP6 from rice and corn on intestinal morphology, cellular proliferation, apoptosis and cyclooxygenase-2 (Cox-2) expression using swine jejunal explants as experimental model. This report demonstrated that explants treated with 0.5 mM, 2.5 mM and 5 mM of IP6 from rice and 2.5 mM and 5 mM from corn showed higher villi height compared to control. Explants treated with 2.5 mM and 5 mM IP6 from rice exhibited a significant reduction on intestinal histological changes (villi atrophy and fusion, edema, lymphatic vessel dilation, loss of apical enterocytes, cell vacuolation, necrotic debris, morphology of enterocytes and microvilli and number of villi). The cellular proliferation decreased in the explants treated with the dosages of 2.5 mM and 5 mM from rice and a significant decrease in cell apoptosis was observed in the treatments with 2.5 mM IP6 from rice and 5 mM IP6 from corn compared to the control. The explants treated with 2.5 mM and 5 mM IP6 from rice and corn showed a significant reduction of the Cox-2 expression. Higher dosages of IP6 from rice and corn used in this experiment increased the viability and preservation of intestinal tissue as evidenced by morphological and immunohistochemical assays.