- Email: [email protected]
Management of visceral vascular anomalies
Seminars in Pediatric Surgery 23 (2014) 216–220
Contents lists available at ScienceDirect
Seminars in Pediatric Surgery journal homepage: www.elsevier.com/locate/sempedsurg
Management of visceral vascular anomalies Roshni Dasgupta, MD, MPHa,n, Steven J. Fishman, MDb a b
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Medical Center, University of Cincinnati, 3333 Burnett Ave, Cincinnati, Ohio 45229 Department of Pediatric Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
a r t i c l e in f o
abstract
Keywords: Visceral vascular anomalies Blue rubber bleb nevus syndrome Klippel–Trenaunay syndrome CLOVES syndrome
Vascular malformations affect the viscera less commonly than the head and neck, extremities, and extracavitary soft tissues. They present with a wide spectrum of symptoms and findings including pain, respiratory compromise, hemoptysis, chylothorax, ascites, gastrointestinal bleeding, and obstruction. Management options depend upon the subtype of malformation and anatomic extent and may include sclerotherapy, embolization, surgical extirpation, coloanal pull-through, and occasionally more innovative individualized surgical approaches. & 2014 Elsevier Inc. All rights reserved.
Management of visceral vascular malformations Vascular malformations can affect all regions of the body. Visceral involvement can be extensive and problematic. Presentation, complications, and management options are determined by the type of lesion, the organ systems affected, and extent of involvement. Vascular malformations are anomalies that occur during the morphological development of the vascular system. These lesions are present at birth, generally growing with the child, but often undetected until symptoms occur. Some are associated with or are direct extensions of more visible cutaneous and soft tissue lesions. These malformations can be exacerbated by trauma, infection, or hormonal changes. Herein we present an overview of some of the types of visceral vascular malformations and management options. For more comprehensive descriptions and discussion of more rare entities, the reader is referred to Chapter 25 of Mulliken and Young's Vascular Anomalies, 2nd Edition.1
Thoracic vascular malformations Lymphatic malformations Most vascular malformations in the thoracic cavities and mediastinum are lymphatic malformations (LMs). Mass lesions can be macrocystic, microcystic, or combined. Microcystic malformations are sponge-like masses with individual cysts that are too small to drain. Macrocystic lesions are almost always multicystic n
Corresponding author. E-mail address: [email protected] (R. Dasgupta).
http://dx.doi.org/10.1053/j.sempedsurg.2014.07.003 1055-8586/& 2014 Elsevier Inc. All rights reserved.
masses similar in appearance to compressed bunches of variably sized grapes. Thoracic LMs are most commonly in the mediastinum or retropleural space. They can be in contiguity with lesions in the thoracic inlet, neck, retroperitoneum, or torso soft tissues. Small asymptomatic lesions can be followed without intervention. Lesions causing or threatening airway compression or that are so large as to impact pulmonary development should be treated. Macrocystic lesions are generally best ameliorated with imageguided intralesional sclerotherapy, as described in detail by Elluru and Padua elsewhere in this monograph. Large predominantly microcystic lesions require resection. These lesions are not malignant, so vital structures should not be sacrificed; however, leaving large amounts of residual LMs will generally lead to re-expansion of the lesion. Reoperation to remove residual scarred mass is very challenging and creates significant increased risk for neurovascular injury. Thus, the surgeon undertaking such a resection should be prepared to meticulously remove nearly the entirety of the lesion in a defined anatomic region regardless of operative duration. LM masses in the lung parenchyma are extremely rare. Lobectomy cured life-threatening hemoptysis in one case.2 The most common intrapulmonary lymphatic anomaly is congenital pulmonary lymphangiectasia (CPL). CPL is a rare disorder that is thought to result from a diffuse dysplasia of the lymphatic network. It is characterized by dilation of the pulmonary lymphatics that drain the subpleural and interstitial spaces of the lung. Autopsy results suggest that CPL has an incidence of 0.5–1% in infants who die in the neonatal period.3 Cases are thought to be sporadic although associations with Noonan's, Downs, and Ullrich–Turner syndromes are known. There are preliminary reports that VEGF-C overexpression can induce pulmonary lymphangiectasia during development.4 Patients can present in utero as a hydrops fetalis with pleural effusions.5 It appears at birth with intractable respiratory
R. Dasgupta, S.J. Fishman / Seminars in Pediatric Surgery 23 (2014) 216–220
distress in the newborn, often associated with chylous pleural effusions.6 It may also present as part of generalized lymphangiectasias, as secondary to pulmonary venous hypertension or venous obstruction, or as isolated lesions. Diagnosis is made with a combination of radiologic, pathologic studies in conjunction with the clinical presentation. A chest radiograph has increased interstitial markings, hyperexpansion, and may have pleural effusions. Chest computerized tomography (CT) scans show ground glass infiltrates, interstitial densities, and pleural effusions. Lung biopsy is the most definitive means of diagnosing these patients. Biopsy reveals dilated lymphatics within the interstitium of the lung. Treatment of this disease is supportive with gentle ventilation strategies, extra-corporeal membrane oxygenation (ECMO), and nutritional support, all playing important roles. Localized lesions are sometimes amenable to surgery. The overall prognosis, however, remains poor when patients present in the neonatal period despite advances in neonatal intensive care.3 Particularly problematic lymphatic conditions in the chest include those resulting in pleural effusion and/or chylothorax. These include generalized lymphatic anomaly, Gorham–Stout disease,5 and poorly characterized central conducting lymphatic anomalies. Medical management for chylothorax has included octreotide, interferon,7,8 and, more recently, sirolimus therapy has been utilized.9 There is also some preliminary data that radiation therapy may effectively prevent bony disease progression and may also aid in management of resistant chylothoraces, using total doses ranging from 30 to 45 Gy.10 The long-term outcome of radiation treatment is still unclear in these patients. Surgical management of chylothorax secondary to lymphatic disease can be quite challenging and is often unsuccessful. Pleurodesis, ligation of the thoracic duct, and pleurectomy have all been reported with some success in the management of effusions. Recently, there have been reports of the use of embolization of the thoracic duct to treat chylothorax.11 Reconstruction of the thoracic duct by lymphovenous anastomosis has been performed successfully, but its general applicability remains to be established.12 Often, a combination of both medical and surgical treatment is the best means of management of these difficult problems.13
217
Abdominal vascular malformations Lymphatic malformations Abdominal lymphatic malformations often arise from the mesentery, omentum, or retroperitoneum. These may remain asymptomatic for long durations and thus sometimes do not become apparent until adulthood. Intra-abdominal LM is more commonly macrocystic than microcystic. Children tend to present acutely with abdominal pain, distention, nausea, diarrhea, or constipation.15 The cysts are generally anechoic or contain echogenic debris. Imaging studies reveal a uni- or multi-septated mass with thin walls (Figure 1). Initial study should be ultrasonography, and for those in whom sonography does not provide enough anatomic information, MR imaging should be undertaken. Treatment of symptomatic or large intra-abdominal LMs is indicated. Traditionally, surgical resection was the primary treatment of choice; however, this may involve significant risk of bowel injury, persistent chylous ascites, and re-enlargement of residual lesion. Segmental bowel resection is only justified for a limited regional lesion that can be completely excised. Macrocystic lesions can usually be easily substantially reduced with percutaneous imageguided intralesional sclerotherapy. Doxycycline is the most commonly used agent.16,17 Lymphatic cysts are aspirated under US guidance and the sclerosant is injected into the cyst, under fluoroscopic guidance to ensure proper distribution of the agent. In larger malformations, a closed suction drain may be placed to aspirate ongoing fluid drainage and perform repeated doxycycline instillations. Microcystic lesions are more commonly asymptomatic. Surgical resection is occasionally required for large lesions causing mass effect, such as urinary tract obstruction. Occasionally a LM, either macrocystic or microcystic, can mimic an inguinal hernia, sometimes extending fully into the scrotum (Figure 2). Macrocystic lesions can be sclerosed. Microcystic lesions require meticulous dissection since they are usually intimately associated with the vital structures of the spermatic cord. Partial resection will result in re-expansion of the residual malformation in the
Venous malformations Endothoracic venous malformations (VMs) of significance are uncommon and are usually extensions of chest wall or neck lesions. Treatment is rarely necessary, and image-guided endovascular techniques are almost always preferred. Although subtotal surgical resection of large chest wall VMs can be performed without exsanguination by closing skin over residual lesion, this is not possible inside the chest. Thus, endothoracic surgical resection of a poorly circumscribed VM is almost never indicated. Arteriovenous malformations Arteriovenous malformations (AVMs) in the thorax are also uncommon. Most are best managed, if not cured, with endovascular obliterative techniques, discussed by Richter and Alomari elsewhere in this issue. Intrapulmonary arteriovenous malformations can cause hemoptysis and shunting, causing hypoxia and high-output cardiac failure. They can also permit paradoxical embolism. Some such lesions are due to hereditary hemorrhagic telangiectasia (HHT). HHT is an autosomal dominant disorder with manifestations that include visceral arteriovenous malformations seen in the GI tract, lungs, and liver. Mucosal involvement is common with epistaxis being the most frequent symptom. In a recent study, about 20% of children with HHT were noted to have pulmonary AVMs.14 These lesions are also often diffuse, and generally, surgical resection is not usually possible or indicated.
Fig. 1. A T2-weighted MR image demonstrating a large retroperitoneal lymphatic malformation.
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before the age of 3 years.18 It can also be associated with lymphedema of the extremities and chylous ascites and chylothorax. Etiology of the disease is unknown. There are rare familial cases. Diagnosis is made with the endoscopic visualization of intestinal lymphangeictasia and dilation of the lymphatics seen on intestinal biopsy. Associated abnormalities such as lymphoma, lymphopenia, impaired neutrophil function, and impaired cellmediated immunity, splenic atrophy, diarrhea, steatorrhea, failure to thrive, and growth retardation are also seen in these patients. The primary treatment of intestinal lymphangiectasia is supportive, consisting of the correction of fluid and electrolyte imbalance and dietary manipulation. A low-fat, high-protein diet supplemented with medium-chain triglycerides is recommended. The absence of fat prevents engorgement of intestinal lymphatic vessels and helps prevent rupture of the lacteals.18 Other treatments that have been used include corticosteroid, octreotide, and anti-plasmin. Surgical resection of localized disease can be helpful in controlling disease while ensuring adequate length of remaining bowel.19 Small bowel transplantation may also have some long-term promise in patients who are resistant to medical management.20 Venous malformations
Fig. 2. A retroperitoneal lymphatic malformation mimicking inguinal hernia: (A) a ballotable groin mass, (B) a CT scan demonstrates a microcystic retroperitoneal malformation extending through the inguinal canal, and (C) inguinal dissection reveals LM intertwined within the spermatic cord. (Color version of figure is available online.)
cord, and the reoperation will be much more difficult with scarring around the testicular vessels and vas deferens. Intestinal lymphangiectasia or Waldmann's disease is a rare disorder that can be congenital or secondary to other disorders. It is characterized by the presence of dilated intestinal lacteals and lymphatic channels involving all layers of the bowel and can also include mesentery. It presents with abdominal pain, nausea, vomiting, and hypocalcemic seizures. It is generally diagnosed
Venous malformations in the abdomen most commonly present with gastrointestinal bleeding.21 Treatment options depend on the anatomic distribution of the lesions. Venous anomalies in the abdomen can be focal, multifocal, or diffuse. Large focal lesions can generally be excised along with the involved segment of the bowel. Multifocal lesions are present in the blue rubber bleb nevus syndrome. Blue rubber bleb nevus syndrome was first described by Gascoyen in 1860 and in more detail by William Bean in 1958, and it was given the eponym Bean syndrome.22 This syndrome is characterized by multifocal discrete venous malformations that most frequently occur on the skin and within the gastrointestinal (GI) tract (Figure 3A). Lesions typically vary in size between several millimeters and 2 cm. Some patients will have one very large dominant soft tissue lesion. The morbidity associated with this syndrome depends on the extent of visceral organ involvement. Lesions within the GI tract may cause significant bleeding. These patients do not have large volume spontaneous hemorrhage, but rather chronic melena and/or hematochezia, causing chronic anemia. If patients are requiring multiple transfusions, this is an indication for multifocal surgical resection.23 It is not generally possible to identify specific lesions bleeding. Thus, an attempt should be made to remove all lesions with luminal contact. We perform total intra-operative endoscopy from mouth to anus to identify all lesions. When lesions are sparsely distributed, their locations are marked with serosal sutures to facilitate removal. Enterotomies are performed around transmural lesions. Nearby mucosal lesions can be accessed by intussuscepting and inverting adjacent segments of bowel through the enterotomies (Figure 3B). In cases where lesions are densely distributed, serosal marking is not necessary, since the entirety of the mucosal surface will be examined with sequential segmental inversion intussusceptions. We avoid segmental bowel resection, limiting its use to short segments with many adjacent lesions precluding closure of multiple nearby enterotomies. There is early data that bleeding from lesions may be controlled with the use of sirolimus therapy. The experience with this drug is small and there is virtually no data as to whether bleeding recurs with cessation of the medication. Diffuse VM in the abdomen can encompass large segments of the bowel in addition to mesentery, retroperitoneum, and pelvic spaces. Surgical procedures must focus on eradicating bleeding rather than removing the entirety of abnormal tissues. One relatively common pattern is a colorectal venous malformation.
R. Dasgupta, S.J. Fishman / Seminars in Pediatric Surgery 23 (2014) 216–220
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lesion, injection sclerotherapy may be effective. Direct injection of foamed 1.5% sodium tetradecyl sulfate can be performed with a spinal needle advanced submucosally beginning above the dentate line with anoscopic exposure. Care should be taken to avoid ulceration of the mucosa. With one or several sclerotherapy sessions, bleeding can be minimized or arrested. However, permanent success should not be anticipated. Many patients will choose repeated sclerotherapy over coloanal pull-through, understanding the more extensive procedure may become desirable at some future time. Patients with colorectal venous malformations may have congenital ectatic major mesenteric veins. These patients are at risk for portomesenteric thrombosis.25 All patients with a known rectal venous malformation, or suspicion thereof due to the presence of a vascular stain of the perineum, should be investigated for a potential ectatic inferior mesenteric vein. If this pattern is present, we recommend anticoagulation followed by ligation of the inferior mesenteric vein immediately adjacent to the splenic vein. Extensive life-threatening VMs may require individual creative solutions. Circumferential duodenal VMs including the retroperitoneum and the mesenteric root and portal vein are most challenging. We have found that portal decompressive procedures can deflate the duodenal lesion and stop bleeding. In one case, multivisceral autotransplantation with “back table” pancreaticoduodenectomy and central mesenteric resection and reconstruction was successful.26 Arteriovenous malformations True arteriovenous malformations in the abdomen are exceedingly rare. The term AVM is commonly mis-applied to venous lesions in the hollow viscera. When proven by selective arteriography, intestinal AVM is usually limited in extent and amenable to segmental bowel resection.27 Hepatic AVMs are uncommon but can be seen sporadically and in patients with HHT. Lesions in HHT are generally not symptomatic in childhood.14 To the contrary, congenital arterioportal shunts cause dramatic and dangerous portal hypertension in infancy.28 References
Fig. 3. Blue rubber bleb nevus syndrome: (A) the endoscopic appearance of mucosal-based intestinal venous malformation and (B) a segment of the small bowel intussuscepted through enterotomy, providing access to excise mucosal lesions. (Color version of figure is available online.)
This typically extends from the splenic flexure or left colon down to the anus. The VM involves the full-thickness of the colon and may extend throughout the pelvis. Particularly in patients with Klippel–Trenaunay (capillary-lymphaticovenous malformation) and CLOVES syndromes, the malformation may encompass the pelvic floor, buttocks, vagina, and bladder. Extirpation of the entire lesion is not indicated and would carry a significant risk of uncontrollable hemorrhage. We have found that the submucosal plane of the rectum is preserved, allowing for left colectomy, mucosal proctectomy, and coloanal pull-through.24 The dissection is more difficult and certainly entails greater blood loss than a rectal mucosectomy for Hirschsprung disease or ulcerative colitis. For more limited anorectal lesions or those demonstrated or suspected to be bleeding from the most distal portions of the
1. Fishman SJ. Truncal, visceral and genital vascular malformations. In: Mulliken JB, Burrows PE, Fishman SJ, editors. Vascular Anomalies: Hemangiomas and Malformations. 2nd ed. New York: Oxford University Press; 2013. p. 966–1016. 2. Schulman JM, Christison-Lagay ER, Kozakewich HP, et al. Macrocystic lymphatic malformation in the pulmonary parenchyma. Ann Thorac Surg. 2009;87: 1607–1609. 3. Mettauer N, Agrawal S, Pierce C, et al. Outcome of children with pulmonary lymphangiectasis. Pediatr Pulmonol. 2009;44:351–357. 4. Yao LC, Testini C, Tvorogov D, et al. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circ Res. 2014;114:806–822. 5. Bouchard S, Di Lorenzo M, Youssef S, et al. Pulmonary lymphangiectasia revisited. J Pediatr Surg. 2000;35:796–800. 6. Moerman P, Vandenberghe K, Devlieger H, et al. Congenital pulmonary lymphangiectasis with chylothorax: a heterogeneous lymphatic vessel abnormality. Am J Med Genet. 1993;47:54–58. 7. Kuriyama DK, McElligott SC, Glaser DW, Thompson KS. Treatment of Gorham– Stout disease with zoledronic acid and interferon-alpha: a case report and literature review. J Pediatr Hematol Oncol. 2010;32:579–584. 8. Kose M, Pekcan S, Dogru D, et al. Gorham–Stout syndrome with chylothorax: successful remission by interferon alpha-2b. Pediatr Pulmonol. 2009;44: 613–615. 9. Chen W, Adams D, Patel M, et al. Generalized lymphatic malformation with chylothorax: long-term management of a highly morbid condition in a pediatric patient. J Pediatr Surg. 2013;48:e9–e12. 10. Heyd R, Micke O, Surholt C, et al. Radiation therapy for Gorham–Stout syndrome: results of a national patterns-of-care study and literature review. Int J Radiat Oncol Biol Phys. 2011;81:e179–e185. http://dx.doi.org/10.1016/j. ijrobp.2011.01.006. 11. Nadolski GJ, Itkin M. Thoracic duct embolization for nontraumatic chylous effusion: experience in 34 patients. Chest. 2013;143:158–163.
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12. Fishman SJ, Burrows PE, Upton J, Hendren WH. Life-threatening anomalies of the thoracic duct: anatomic delineation dictates management. J Pediatr Surg. 2001;36:1269–1272. 13. Tie ML, Poland GA, Rosenow EC 3rd. Chylothorax in Gorham's syndrome. A common complication of a rare disease. Chest. 1994;105:208–213. 14. Giordano P, Lenato GM, Suppressa P, et al. Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children. J Pediatr. 2013;163:179–186. (e171–e173). 15. Kosir MA, Sonnino RE, Gauderer MW. Pediatric abdominal lymphangiomas: a plea for early recognition. J Pediatr Surg. 1991;26:1309–1313. 16. Chaudry G, Burrows PE, Padua HM, et al. Sclerotherapy of abdominal lymphatic malformations with doxycycline. J Vasc Interv Radiol. 2011;22:1431–1435. 17. Burrows PE, Mitri RK, Alomari A, et al. Percutaneous sclerotherapy of lymphatic malformations with doxycycline. Lymphat Res Biol. 2008;6:209–216. 18. Vignes S, Bellanger J. Primary intestinal lymphangiectasia (Waldmann's disease). Orphanet J Rare Dis. 2008;3:5. 19. Kim NR, Lee SK, Suh YL. Primary intestinal lymphangiectasia successfully treated by segmental resections of small bowel. J Pediatr Surg. 2009;44:e13–e17. 20. Campbell DI, Beath SV, deVille de Goyet J, et al. Severe intestinal lymphangiectasia complicated by nephrotic syndrome treated by small bowel, liver, and kidney transplantation. J Pediatr Gastroenterol Nutr. 2003;36:278–282.
21. Fishman SJ, Burrows PE, Leichtner AM, Mulliken JB. Gastrointestinal manifestations of vascular anomalies in childhood: varied etiologies require multiple therapeutic modalities. J Pediatr Surg. 1998;33:1163–1167. 22. Boente MD, Cordisco MR, Frontini MD, Asial RA. Blue rubber bleb nevus (Bean syndrome): evolution of four cases and clinical response to pharmacologic agents. Pediatr Dermatol. 1999;16:222–227. 23. Fishman SJ, Smithers CJ, Folkman J, et al. Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal bleeding. Ann Surg. 2005;241:523–528. 24. Fishman SJ, Shamberger RC, Fox VL, Burrows PE. Endorectal pull-through abates gastrointestinal hemorrhage from colorectal venous malformations. J Pediatr Surg. 2000;35:982–984. 25. Kulungowski AM, Fox VL, Burrows PE, et al. Portomesenteric venous thrombosis associated with rectal venous malformations. J Pediatr Surg. 2010;45: 1221–1227. 26. Tzakis AG, Pararas NB, Tekin A, et al. Intestinal and multivisceral autotransplantation for tumors of the root of the mesentery: long-term follow-up. Surgery. 2012;152:82–89. 27. Fremond B, Yazbeck S, Dubois J, et al. Intestinal vascular anomalies in children. J Pediatr Surg. 1997;32:873–877. 28. Burrows PE, Dubois J, Kassarjian A. Pediatric hepatic vascular anomalies. Pediatr Radiol. 2001;31:533–545.
Contents lists available at ScienceDirect
Seminars in Pediatric Surgery journal homepage: www.elsevier.com/locate/sempedsurg
Management of visceral vascular anomalies Roshni Dasgupta, MD, MPHa,n, Steven J. Fishman, MDb a b
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Medical Center, University of Cincinnati, 3333 Burnett Ave, Cincinnati, Ohio 45229 Department of Pediatric Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
a r t i c l e in f o
abstract
Keywords: Visceral vascular anomalies Blue rubber bleb nevus syndrome Klippel–Trenaunay syndrome CLOVES syndrome
Vascular malformations affect the viscera less commonly than the head and neck, extremities, and extracavitary soft tissues. They present with a wide spectrum of symptoms and findings including pain, respiratory compromise, hemoptysis, chylothorax, ascites, gastrointestinal bleeding, and obstruction. Management options depend upon the subtype of malformation and anatomic extent and may include sclerotherapy, embolization, surgical extirpation, coloanal pull-through, and occasionally more innovative individualized surgical approaches. & 2014 Elsevier Inc. All rights reserved.
Management of visceral vascular malformations Vascular malformations can affect all regions of the body. Visceral involvement can be extensive and problematic. Presentation, complications, and management options are determined by the type of lesion, the organ systems affected, and extent of involvement. Vascular malformations are anomalies that occur during the morphological development of the vascular system. These lesions are present at birth, generally growing with the child, but often undetected until symptoms occur. Some are associated with or are direct extensions of more visible cutaneous and soft tissue lesions. These malformations can be exacerbated by trauma, infection, or hormonal changes. Herein we present an overview of some of the types of visceral vascular malformations and management options. For more comprehensive descriptions and discussion of more rare entities, the reader is referred to Chapter 25 of Mulliken and Young's Vascular Anomalies, 2nd Edition.1
Thoracic vascular malformations Lymphatic malformations Most vascular malformations in the thoracic cavities and mediastinum are lymphatic malformations (LMs). Mass lesions can be macrocystic, microcystic, or combined. Microcystic malformations are sponge-like masses with individual cysts that are too small to drain. Macrocystic lesions are almost always multicystic n
Corresponding author. E-mail address: [email protected] (R. Dasgupta).
http://dx.doi.org/10.1053/j.sempedsurg.2014.07.003 1055-8586/& 2014 Elsevier Inc. All rights reserved.
masses similar in appearance to compressed bunches of variably sized grapes. Thoracic LMs are most commonly in the mediastinum or retropleural space. They can be in contiguity with lesions in the thoracic inlet, neck, retroperitoneum, or torso soft tissues. Small asymptomatic lesions can be followed without intervention. Lesions causing or threatening airway compression or that are so large as to impact pulmonary development should be treated. Macrocystic lesions are generally best ameliorated with imageguided intralesional sclerotherapy, as described in detail by Elluru and Padua elsewhere in this monograph. Large predominantly microcystic lesions require resection. These lesions are not malignant, so vital structures should not be sacrificed; however, leaving large amounts of residual LMs will generally lead to re-expansion of the lesion. Reoperation to remove residual scarred mass is very challenging and creates significant increased risk for neurovascular injury. Thus, the surgeon undertaking such a resection should be prepared to meticulously remove nearly the entirety of the lesion in a defined anatomic region regardless of operative duration. LM masses in the lung parenchyma are extremely rare. Lobectomy cured life-threatening hemoptysis in one case.2 The most common intrapulmonary lymphatic anomaly is congenital pulmonary lymphangiectasia (CPL). CPL is a rare disorder that is thought to result from a diffuse dysplasia of the lymphatic network. It is characterized by dilation of the pulmonary lymphatics that drain the subpleural and interstitial spaces of the lung. Autopsy results suggest that CPL has an incidence of 0.5–1% in infants who die in the neonatal period.3 Cases are thought to be sporadic although associations with Noonan's, Downs, and Ullrich–Turner syndromes are known. There are preliminary reports that VEGF-C overexpression can induce pulmonary lymphangiectasia during development.4 Patients can present in utero as a hydrops fetalis with pleural effusions.5 It appears at birth with intractable respiratory
R. Dasgupta, S.J. Fishman / Seminars in Pediatric Surgery 23 (2014) 216–220
distress in the newborn, often associated with chylous pleural effusions.6 It may also present as part of generalized lymphangiectasias, as secondary to pulmonary venous hypertension or venous obstruction, or as isolated lesions. Diagnosis is made with a combination of radiologic, pathologic studies in conjunction with the clinical presentation. A chest radiograph has increased interstitial markings, hyperexpansion, and may have pleural effusions. Chest computerized tomography (CT) scans show ground glass infiltrates, interstitial densities, and pleural effusions. Lung biopsy is the most definitive means of diagnosing these patients. Biopsy reveals dilated lymphatics within the interstitium of the lung. Treatment of this disease is supportive with gentle ventilation strategies, extra-corporeal membrane oxygenation (ECMO), and nutritional support, all playing important roles. Localized lesions are sometimes amenable to surgery. The overall prognosis, however, remains poor when patients present in the neonatal period despite advances in neonatal intensive care.3 Particularly problematic lymphatic conditions in the chest include those resulting in pleural effusion and/or chylothorax. These include generalized lymphatic anomaly, Gorham–Stout disease,5 and poorly characterized central conducting lymphatic anomalies. Medical management for chylothorax has included octreotide, interferon,7,8 and, more recently, sirolimus therapy has been utilized.9 There is also some preliminary data that radiation therapy may effectively prevent bony disease progression and may also aid in management of resistant chylothoraces, using total doses ranging from 30 to 45 Gy.10 The long-term outcome of radiation treatment is still unclear in these patients. Surgical management of chylothorax secondary to lymphatic disease can be quite challenging and is often unsuccessful. Pleurodesis, ligation of the thoracic duct, and pleurectomy have all been reported with some success in the management of effusions. Recently, there have been reports of the use of embolization of the thoracic duct to treat chylothorax.11 Reconstruction of the thoracic duct by lymphovenous anastomosis has been performed successfully, but its general applicability remains to be established.12 Often, a combination of both medical and surgical treatment is the best means of management of these difficult problems.13
217
Abdominal vascular malformations Lymphatic malformations Abdominal lymphatic malformations often arise from the mesentery, omentum, or retroperitoneum. These may remain asymptomatic for long durations and thus sometimes do not become apparent until adulthood. Intra-abdominal LM is more commonly macrocystic than microcystic. Children tend to present acutely with abdominal pain, distention, nausea, diarrhea, or constipation.15 The cysts are generally anechoic or contain echogenic debris. Imaging studies reveal a uni- or multi-septated mass with thin walls (Figure 1). Initial study should be ultrasonography, and for those in whom sonography does not provide enough anatomic information, MR imaging should be undertaken. Treatment of symptomatic or large intra-abdominal LMs is indicated. Traditionally, surgical resection was the primary treatment of choice; however, this may involve significant risk of bowel injury, persistent chylous ascites, and re-enlargement of residual lesion. Segmental bowel resection is only justified for a limited regional lesion that can be completely excised. Macrocystic lesions can usually be easily substantially reduced with percutaneous imageguided intralesional sclerotherapy. Doxycycline is the most commonly used agent.16,17 Lymphatic cysts are aspirated under US guidance and the sclerosant is injected into the cyst, under fluoroscopic guidance to ensure proper distribution of the agent. In larger malformations, a closed suction drain may be placed to aspirate ongoing fluid drainage and perform repeated doxycycline instillations. Microcystic lesions are more commonly asymptomatic. Surgical resection is occasionally required for large lesions causing mass effect, such as urinary tract obstruction. Occasionally a LM, either macrocystic or microcystic, can mimic an inguinal hernia, sometimes extending fully into the scrotum (Figure 2). Macrocystic lesions can be sclerosed. Microcystic lesions require meticulous dissection since they are usually intimately associated with the vital structures of the spermatic cord. Partial resection will result in re-expansion of the residual malformation in the
Venous malformations Endothoracic venous malformations (VMs) of significance are uncommon and are usually extensions of chest wall or neck lesions. Treatment is rarely necessary, and image-guided endovascular techniques are almost always preferred. Although subtotal surgical resection of large chest wall VMs can be performed without exsanguination by closing skin over residual lesion, this is not possible inside the chest. Thus, endothoracic surgical resection of a poorly circumscribed VM is almost never indicated. Arteriovenous malformations Arteriovenous malformations (AVMs) in the thorax are also uncommon. Most are best managed, if not cured, with endovascular obliterative techniques, discussed by Richter and Alomari elsewhere in this issue. Intrapulmonary arteriovenous malformations can cause hemoptysis and shunting, causing hypoxia and high-output cardiac failure. They can also permit paradoxical embolism. Some such lesions are due to hereditary hemorrhagic telangiectasia (HHT). HHT is an autosomal dominant disorder with manifestations that include visceral arteriovenous malformations seen in the GI tract, lungs, and liver. Mucosal involvement is common with epistaxis being the most frequent symptom. In a recent study, about 20% of children with HHT were noted to have pulmonary AVMs.14 These lesions are also often diffuse, and generally, surgical resection is not usually possible or indicated.
Fig. 1. A T2-weighted MR image demonstrating a large retroperitoneal lymphatic malformation.
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R. Dasgupta, S.J. Fishman / Seminars in Pediatric Surgery 23 (2014) 216–220
before the age of 3 years.18 It can also be associated with lymphedema of the extremities and chylous ascites and chylothorax. Etiology of the disease is unknown. There are rare familial cases. Diagnosis is made with the endoscopic visualization of intestinal lymphangeictasia and dilation of the lymphatics seen on intestinal biopsy. Associated abnormalities such as lymphoma, lymphopenia, impaired neutrophil function, and impaired cellmediated immunity, splenic atrophy, diarrhea, steatorrhea, failure to thrive, and growth retardation are also seen in these patients. The primary treatment of intestinal lymphangiectasia is supportive, consisting of the correction of fluid and electrolyte imbalance and dietary manipulation. A low-fat, high-protein diet supplemented with medium-chain triglycerides is recommended. The absence of fat prevents engorgement of intestinal lymphatic vessels and helps prevent rupture of the lacteals.18 Other treatments that have been used include corticosteroid, octreotide, and anti-plasmin. Surgical resection of localized disease can be helpful in controlling disease while ensuring adequate length of remaining bowel.19 Small bowel transplantation may also have some long-term promise in patients who are resistant to medical management.20 Venous malformations
Fig. 2. A retroperitoneal lymphatic malformation mimicking inguinal hernia: (A) a ballotable groin mass, (B) a CT scan demonstrates a microcystic retroperitoneal malformation extending through the inguinal canal, and (C) inguinal dissection reveals LM intertwined within the spermatic cord. (Color version of figure is available online.)
cord, and the reoperation will be much more difficult with scarring around the testicular vessels and vas deferens. Intestinal lymphangiectasia or Waldmann's disease is a rare disorder that can be congenital or secondary to other disorders. It is characterized by the presence of dilated intestinal lacteals and lymphatic channels involving all layers of the bowel and can also include mesentery. It presents with abdominal pain, nausea, vomiting, and hypocalcemic seizures. It is generally diagnosed
Venous malformations in the abdomen most commonly present with gastrointestinal bleeding.21 Treatment options depend on the anatomic distribution of the lesions. Venous anomalies in the abdomen can be focal, multifocal, or diffuse. Large focal lesions can generally be excised along with the involved segment of the bowel. Multifocal lesions are present in the blue rubber bleb nevus syndrome. Blue rubber bleb nevus syndrome was first described by Gascoyen in 1860 and in more detail by William Bean in 1958, and it was given the eponym Bean syndrome.22 This syndrome is characterized by multifocal discrete venous malformations that most frequently occur on the skin and within the gastrointestinal (GI) tract (Figure 3A). Lesions typically vary in size between several millimeters and 2 cm. Some patients will have one very large dominant soft tissue lesion. The morbidity associated with this syndrome depends on the extent of visceral organ involvement. Lesions within the GI tract may cause significant bleeding. These patients do not have large volume spontaneous hemorrhage, but rather chronic melena and/or hematochezia, causing chronic anemia. If patients are requiring multiple transfusions, this is an indication for multifocal surgical resection.23 It is not generally possible to identify specific lesions bleeding. Thus, an attempt should be made to remove all lesions with luminal contact. We perform total intra-operative endoscopy from mouth to anus to identify all lesions. When lesions are sparsely distributed, their locations are marked with serosal sutures to facilitate removal. Enterotomies are performed around transmural lesions. Nearby mucosal lesions can be accessed by intussuscepting and inverting adjacent segments of bowel through the enterotomies (Figure 3B). In cases where lesions are densely distributed, serosal marking is not necessary, since the entirety of the mucosal surface will be examined with sequential segmental inversion intussusceptions. We avoid segmental bowel resection, limiting its use to short segments with many adjacent lesions precluding closure of multiple nearby enterotomies. There is early data that bleeding from lesions may be controlled with the use of sirolimus therapy. The experience with this drug is small and there is virtually no data as to whether bleeding recurs with cessation of the medication. Diffuse VM in the abdomen can encompass large segments of the bowel in addition to mesentery, retroperitoneum, and pelvic spaces. Surgical procedures must focus on eradicating bleeding rather than removing the entirety of abnormal tissues. One relatively common pattern is a colorectal venous malformation.
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lesion, injection sclerotherapy may be effective. Direct injection of foamed 1.5% sodium tetradecyl sulfate can be performed with a spinal needle advanced submucosally beginning above the dentate line with anoscopic exposure. Care should be taken to avoid ulceration of the mucosa. With one or several sclerotherapy sessions, bleeding can be minimized or arrested. However, permanent success should not be anticipated. Many patients will choose repeated sclerotherapy over coloanal pull-through, understanding the more extensive procedure may become desirable at some future time. Patients with colorectal venous malformations may have congenital ectatic major mesenteric veins. These patients are at risk for portomesenteric thrombosis.25 All patients with a known rectal venous malformation, or suspicion thereof due to the presence of a vascular stain of the perineum, should be investigated for a potential ectatic inferior mesenteric vein. If this pattern is present, we recommend anticoagulation followed by ligation of the inferior mesenteric vein immediately adjacent to the splenic vein. Extensive life-threatening VMs may require individual creative solutions. Circumferential duodenal VMs including the retroperitoneum and the mesenteric root and portal vein are most challenging. We have found that portal decompressive procedures can deflate the duodenal lesion and stop bleeding. In one case, multivisceral autotransplantation with “back table” pancreaticoduodenectomy and central mesenteric resection and reconstruction was successful.26 Arteriovenous malformations True arteriovenous malformations in the abdomen are exceedingly rare. The term AVM is commonly mis-applied to venous lesions in the hollow viscera. When proven by selective arteriography, intestinal AVM is usually limited in extent and amenable to segmental bowel resection.27 Hepatic AVMs are uncommon but can be seen sporadically and in patients with HHT. Lesions in HHT are generally not symptomatic in childhood.14 To the contrary, congenital arterioportal shunts cause dramatic and dangerous portal hypertension in infancy.28 References
Fig. 3. Blue rubber bleb nevus syndrome: (A) the endoscopic appearance of mucosal-based intestinal venous malformation and (B) a segment of the small bowel intussuscepted through enterotomy, providing access to excise mucosal lesions. (Color version of figure is available online.)
This typically extends from the splenic flexure or left colon down to the anus. The VM involves the full-thickness of the colon and may extend throughout the pelvis. Particularly in patients with Klippel–Trenaunay (capillary-lymphaticovenous malformation) and CLOVES syndromes, the malformation may encompass the pelvic floor, buttocks, vagina, and bladder. Extirpation of the entire lesion is not indicated and would carry a significant risk of uncontrollable hemorrhage. We have found that the submucosal plane of the rectum is preserved, allowing for left colectomy, mucosal proctectomy, and coloanal pull-through.24 The dissection is more difficult and certainly entails greater blood loss than a rectal mucosectomy for Hirschsprung disease or ulcerative colitis. For more limited anorectal lesions or those demonstrated or suspected to be bleeding from the most distal portions of the
1. Fishman SJ. Truncal, visceral and genital vascular malformations. In: Mulliken JB, Burrows PE, Fishman SJ, editors. Vascular Anomalies: Hemangiomas and Malformations. 2nd ed. New York: Oxford University Press; 2013. p. 966–1016. 2. Schulman JM, Christison-Lagay ER, Kozakewich HP, et al. Macrocystic lymphatic malformation in the pulmonary parenchyma. Ann Thorac Surg. 2009;87: 1607–1609. 3. Mettauer N, Agrawal S, Pierce C, et al. Outcome of children with pulmonary lymphangiectasis. Pediatr Pulmonol. 2009;44:351–357. 4. Yao LC, Testini C, Tvorogov D, et al. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circ Res. 2014;114:806–822. 5. Bouchard S, Di Lorenzo M, Youssef S, et al. Pulmonary lymphangiectasia revisited. J Pediatr Surg. 2000;35:796–800. 6. Moerman P, Vandenberghe K, Devlieger H, et al. Congenital pulmonary lymphangiectasis with chylothorax: a heterogeneous lymphatic vessel abnormality. Am J Med Genet. 1993;47:54–58. 7. Kuriyama DK, McElligott SC, Glaser DW, Thompson KS. Treatment of Gorham– Stout disease with zoledronic acid and interferon-alpha: a case report and literature review. J Pediatr Hematol Oncol. 2010;32:579–584. 8. Kose M, Pekcan S, Dogru D, et al. Gorham–Stout syndrome with chylothorax: successful remission by interferon alpha-2b. Pediatr Pulmonol. 2009;44: 613–615. 9. Chen W, Adams D, Patel M, et al. Generalized lymphatic malformation with chylothorax: long-term management of a highly morbid condition in a pediatric patient. J Pediatr Surg. 2013;48:e9–e12. 10. Heyd R, Micke O, Surholt C, et al. Radiation therapy for Gorham–Stout syndrome: results of a national patterns-of-care study and literature review. Int J Radiat Oncol Biol Phys. 2011;81:e179–e185. http://dx.doi.org/10.1016/j. ijrobp.2011.01.006. 11. Nadolski GJ, Itkin M. Thoracic duct embolization for nontraumatic chylous effusion: experience in 34 patients. Chest. 2013;143:158–163.
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12. Fishman SJ, Burrows PE, Upton J, Hendren WH. Life-threatening anomalies of the thoracic duct: anatomic delineation dictates management. J Pediatr Surg. 2001;36:1269–1272. 13. Tie ML, Poland GA, Rosenow EC 3rd. Chylothorax in Gorham's syndrome. A common complication of a rare disease. Chest. 1994;105:208–213. 14. Giordano P, Lenato GM, Suppressa P, et al. Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children. J Pediatr. 2013;163:179–186. (e171–e173). 15. Kosir MA, Sonnino RE, Gauderer MW. Pediatric abdominal lymphangiomas: a plea for early recognition. J Pediatr Surg. 1991;26:1309–1313. 16. Chaudry G, Burrows PE, Padua HM, et al. Sclerotherapy of abdominal lymphatic malformations with doxycycline. J Vasc Interv Radiol. 2011;22:1431–1435. 17. Burrows PE, Mitri RK, Alomari A, et al. Percutaneous sclerotherapy of lymphatic malformations with doxycycline. Lymphat Res Biol. 2008;6:209–216. 18. Vignes S, Bellanger J. Primary intestinal lymphangiectasia (Waldmann's disease). Orphanet J Rare Dis. 2008;3:5. 19. Kim NR, Lee SK, Suh YL. Primary intestinal lymphangiectasia successfully treated by segmental resections of small bowel. J Pediatr Surg. 2009;44:e13–e17. 20. Campbell DI, Beath SV, deVille de Goyet J, et al. Severe intestinal lymphangiectasia complicated by nephrotic syndrome treated by small bowel, liver, and kidney transplantation. J Pediatr Gastroenterol Nutr. 2003;36:278–282.
21. Fishman SJ, Burrows PE, Leichtner AM, Mulliken JB. Gastrointestinal manifestations of vascular anomalies in childhood: varied etiologies require multiple therapeutic modalities. J Pediatr Surg. 1998;33:1163–1167. 22. Boente MD, Cordisco MR, Frontini MD, Asial RA. Blue rubber bleb nevus (Bean syndrome): evolution of four cases and clinical response to pharmacologic agents. Pediatr Dermatol. 1999;16:222–227. 23. Fishman SJ, Smithers CJ, Folkman J, et al. Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal bleeding. Ann Surg. 2005;241:523–528. 24. Fishman SJ, Shamberger RC, Fox VL, Burrows PE. Endorectal pull-through abates gastrointestinal hemorrhage from colorectal venous malformations. J Pediatr Surg. 2000;35:982–984. 25. Kulungowski AM, Fox VL, Burrows PE, et al. Portomesenteric venous thrombosis associated with rectal venous malformations. J Pediatr Surg. 2010;45: 1221–1227. 26. Tzakis AG, Pararas NB, Tekin A, et al. Intestinal and multivisceral autotransplantation for tumors of the root of the mesentery: long-term follow-up. Surgery. 2012;152:82–89. 27. Fremond B, Yazbeck S, Dubois J, et al. Intestinal vascular anomalies in children. J Pediatr Surg. 1997;32:873–877. 28. Burrows PE, Dubois J, Kassarjian A. Pediatric hepatic vascular anomalies. Pediatr Radiol. 2001;31:533–545.