Neonatal perspective on central lymphatic disorders.

Lymphatic disorders presenting in the first year of life are difficult to identify and manage given the broad range of underlying etiologies. Neonatal lymphatic disease arising from congenital or acquired conditions results in the abnormal accumulation of lymph fluid in the pleura (chylothorax), peritoneum (chylous ascites) and skin (edema/anasarca). There is also increasing recognition of lymphatic losses through the intestine resulting in protein-losing enteropathy (PLE). While the incidence of lymphatic disorders in neonates is unclear, advances in genetic testing and lymphatic imaging are improving our understanding of the underlying pathophysiology. Despite these advancements, medical management of neonatal lymphatic disorders remains challenging and variable among clinicians.

Anesthetic challenges in patients with multicompartmental lymphatic failure after Fontan palliation undergoing transcatheter thoracic duct decompression.

Lymphatic flow abnormalities are central to the development of protein losing enteropathy, plastic bronchitis, ascites and pleural effusions in patients palliated to the Fontan circulation. These complications can occur in isolation or multicompartmental (two or more). The treatment of multicompartmental lymphatic failure aims at improving thoracic duct drainage. Re-routing the innominate vein to the pulmonary venous atrium decompresses the thoracic duct, as atrial pressure is lower than systemic venous pressure in Fontan circulation. Transcatheter thoracic duct decompression is a new minimally invasive procedure that involves placing covered stents from the innominate vein to the atrium. Patients undergoing this procedure require multiple general anesthetics, presenting challenges in managing the sequelae of disordered lymphatic flow superimposed on Fontan physiology. We reviewed the first 20 patients at the Center for Lymphatic Imaging and Intervention at a tertiary care children's hospital presenting for transcatheter thoracic duct decompression between March 2018 and February 2023. The patients ranged in age from 3 to 26 years. The majority had failed prior catheter-based lymphatic intervention, including selective embolization of abnormal lympho-intestinal and lympho-bronchial connections to treat lymphatic failure in a single compartment. Fourteen had failure in three lymphatic compartments. Patients were functionally impaired (ASA 3-5) with significant comorbidities. Concurrent with thoracic duct decompression, three patients required fenestration closure for the resultant decrease in oxygen saturation. Ten patients had improvement in symptoms, seven had no changes and three have limited follow up. Five (25%) of these patients were deceased as of January 2024 due to non-lymphatic complications from Fontan failure.

Understanding the next circulation: lymphatics and what the future holds.

PURPOSE OF REVIEW: The lymphatic system was previously considered the forgotten circulation because of an absence of adequate options for imaging and intervention. However, recent advances over the last decade have improved management strategies for patients with lymphatic disease, including chylothorax, plastic bronchitis, ascites, and protein-losing enteropathy. RECENT FINDINGS: New imaging modalities have enabled detailed visualization of lymphatic vessels to allow for a better understanding of the cause of lymphatic dysfunction in a variety of patient subsets. This sparked the development of multiple transcatheter and surgery-based techniques tailored to each patient based on imaging findings. In addition, the new field of precision lymphology has added medical management options for patients with genetic syndromes, who have global lymphatic dysfunction and typically do not respond as well to the more standard lymphatic interventions. SUMMARY: Recent developments in lymphatic imaging have given insight into disease processes and changed the way patients are managed. Medical management has been enhanced and new procedures have given patients more options, leading to better long-term results.

Percutaneous fractionated radiotherapy of the groin to eliminate lymphatic fistulas after vascular surgery.

BACKGROUND: Vascular surgery of the inguinal area can be complicated by persistent lymphatic fistulas. Rapid and effective treatment is essential to prevent infection, sepsis, bleeding, and possible leg amputation. Current data on irradiation of lymphatic fistulas lack recommendation on the appropriate individual and total dose, the time of irradiation, and the target volume. Presumably, a dose of 0.3-0.5 to 1-12 Gy should be sufficient for the purpose. Currently, radiotherapy is a "can" recommendation, with a level 4 low evidence and a grade C recommendation, according to the DEGRO S2 guidelines. As part of a pilot study, we analyzed the impact and limitations of low-dose radiation therapy in the treatment of inguinal lymphatic fistulas. PATIENTS AND METHODS: As a part of an internal quality control project, patients with lymphatic fistulas irradiated in the groin area after vascular surgery for arterial occlusive disease (AOD) III-IV, repair of pseudo aneurysm or lymph node dissection due to melanoma were selected, and an exploratory analysis on retrospectively collected data performed. RESULTS: Twelve patients (10 males and 2 females) aged 62.83 ± 12.14 years underwent open vascular reconstruction for stage II (n = 2), III (n = 1), and IV (n = 7) arterial occlusive disease (AOD), lymph node dissection for melanoma (n = 1) or repair of a pseudoaneurysm (n = 1). Surgical vascular access was obtained through the groin and was associated with a persistent lymphatic fistula, secreting more than 50 ml/day. Patients were irradiated five times a week up to a maximum of 10 fractions for the duration of the radiation period. Fraction of 0.4 Gy was applied in the first 7 cases, while 5 patients were treated with a de-escalating dose of 0.3 Gy. There was a resolution of the lymphatic fistula in every patient without higher grade complications. CONCLUSION: Low-dose irradiation of the groin is a treatment option for persistent lymphatic fistula after inguinal vascular surgery.

Intranodal Glue Embolization for Postoperative Lymphatic Leaks in the Groin and Pelvis: Comparison with Sclerotherapy.

PURPOSE: To compare the effectiveness of and adverse events related to intranodal glue embolization (IGE) with those of intracavitary sclerotherapy for the treatment of postoperative groin and pelvic lymphatic leaks. MATERIALS AND METHODS: From November 2015 to July 2021, IGE for postoperative pelvic or groin lymphocele or lymphorrhea was performed in 33 patients. From January 2010 to July 2021, 28 patients with postoperative pelvic or groin lymphocele were treated with sclerosis alone. Clinical success was defined as resolution of drainage within 3 weeks of the last intervention performed without recurrence. Patients presenting >1 year after surgery or with <30 days of follow-up were excluded. Patients with lymphorrhea treated with IGE were not statistically compared with those in the sclerosis group because they were not eligible for sclerosis. RESULTS: Clinical success was similar between the groups (lymphocele IGE, 15/18, 83.3%, vs sclerosis, 15/23, 65.2% [P = .29]; lymphorrhea IGE, 8/9, 88.9%). The mean number of interventions performed to successfully treat a lymphocele was significantly higher in the sclerosis group (2.5 for sclerosis vs 1.3 for IGE; P = .003; lymphorrhea IGE, 1.0). The mean time to resolution was significantly longer for sclerosis than for IGE (27 vs 7 days; P = .002; 4 days for lymphorrhea IGE). There were no sclerosis-related adverse events and 2 IGE-related adverse events: (a) 1 case of mild lymphedema and (b) 1 case of nontarget embolization resulting in deep vein thrombosis. CONCLUSIONS: For treatment of postoperative pelvic and groin lymphoceles, IGE results in faster resolution with fewer interventions compared with sclerosis. IGE is also an effective treatment for postoperative groin lymphorrhea.

Breast-implant Related Silicone Lymphadenopathy: Asteroid Bodies do not Always Equal Sarcoidosis!

Silicone breast implants are frequently used for breast augmentation for cosmetic purposes, as well as for breast reconstruction after prophylactic or therapeutic mastectomy. Silicone lymphadenopathy is a well-known complication of silicone breast implants. Silicone droplets are present in the breast tissue through 'silicone bleeding' of the implant or because of implant rupture. These silicone particles can migrate from the breast to the regional lymph nodes. Silicone lymphadenopathy is caused by a substantial foreign body reaction against these silicone particles, and is frequently associated with asteroid body-containing multinucleated giant cells. Similar multinucleated giant cells are often observed in the capsule surrounding the silicone breast implant, and the number of associated asteroid bodies is highly variable. Here, we discuss a series of twelve women with breast implant-related asteroid bodies in their lymph nodes and/or breast tissue. This pictorial essay illustrates that the presence of asteroid bodies in a lymph node does not necessarily suggests a diagnosis of sarcoidosis. Clinical information about the patient having (or having had) silicone breast implants is often lacking. The encounter of asteroid body-containing giant cells in lymph node cytology, biopsies or resections should therefore lead to reflex clinical-pathological correlation, before establishing a final diagnosis.

[Fluorescence-guided Lymph Vessel Sealing in Systematic Nodal Dissection: a New Surgical Technique to Prevent Lymphorrhea and Lymphocele.] / Fluoreszenzgesteuerte Lymphgefäßversiegelung bei der systematischen Lymphknotendissektion zur Vermeidung von Lymphfisteln und Lymphozelen.

INTRODUCTION: The primary morbidities of inguinal and axillary systematic nodal dissection are lymphatic fistulas and seromas. Intraoperative fluorescence imaging-guided sealing of lymph vessels may prevent these postoperative complications. METHODS: Indocyanine dye was injected intracutaneously into the distal limb before the beginning of the lymphadenectomy. Systematic nodal dissection was performed according to standard protocols. Near-infrared imaging was applied throughout the procedure and real-time fluorescence-guided lymph vessel sealing was performed. RESULTS: Fluorescence-guided lymph vessel sealing was implemented in three patients undergoing axillary systematic lymph node dissection. No adverse events occurred following fluorescence dye injection. All patients could be discharged free of wound complications. CONCLUSION: Fluorescence-guided lymph vessel sealing might be a promising new technique for preventing lymphatic fistulas and lymphocele after systematic lymphadenectomy.

Lymphoscintigraphic Investigations for Axillary Web Syndromes.

Background: Axillary web syndrome (AWS) is a frequent complication after surgery for breast cancer, but its lymphatic involvement is not definitively established. Here we report the results of lymphoscintigraphic investigations in patients with AWS. Methods and Results: We conducted a retrospective, single-center review of lymphoscintigraphic investigations performed in 46 patients with AWS that was either clinically obvious or suspected. Of this group, 23 patients had two investigations with a mean interval of 19 weeks between them (range, 6-98 weeks). Results of the lymphoscintigraphic investigations, which were performed according to a well-standardized protocol, were classified into four patterns: normal; functional lymphatic insufficiency only (no lymphatic vascular morphologic abnormality); lymphovascular blockade without collateralization; and vascular collateralization and/or dermal backflow. Of the 46 patients, on the first lymphoscintigraphic investigation, four (8.6%) had a normal pattern, seven (15.2%) had functional lymphatic insufficiency only, four (8.6%) had lymphovascular blockade without collateralization, and 31 (67.3%) had vascular collateralization and/or dermal backflow. Among patients who underwent two investigations, four of the five who had only functional lymphatic insufficiency at the first investigation had developed vascular collateralization and/or dermal backflow by the second. The three patients who had lymphovascular blockade without collateralization at the first examination had also progressed to collateralization and/or dermal backflow at the second. None of the 15 patients who initially had vascular collateralization and/or dermal backflow showed any reversal at the second examination. Conclusions: Our analysis confirms the lymphatic nature of AWS and shows the lymphoscintigraphic patterns and evolutions of the lymphatic lesions with potential therapeutic implications. The retrospective review of our database is approved by the institutional ethics committee under number 2048.

Lymphatic leakage after pelvic lymphadenectomy for cervical cancer: a retrospective case-control study.

BACKGROUND: The study aims to evaluate the clinical features and management of postoperative lymphatic leakage (PLL) in patients with cervical cancer who received pelvic lymphadenectomy. METHODS: This retrospective study screened consecutive patients with cervical cancer (stage Ia2-IIb). RESULTS: Among 3427 cases screened, 63 patients (1.8%) were diagnosed with PLL, which manifested as persistent abdominal drainage (42/63, 66.7%), chylous ascites (12/63, 19.0%) or vaginal drainage (9/63, 14.3%). Median time from surgery to onset of PLL was 6 days (range, 4-21 days). All cases resolved in a median 10 days (range, 3-56 days) after conservative treatment; although one case experienced recurrence of vaginal drainage after 26 days, this also resolved after conservative therapy. Multivariate analysis showed that two cycles of neoadjuvant chemotherapy (odds ratio [OR], 3.283; 95% confidence interval [95%CI], 1.289-8.360; P = 0.013), a decrease in hemoglobin level of ≥20 and < 30 g/L (OR, 6.175; 95%CI, 1.033-10.919; P = 0.046) or ≥ 30 g/L (OR, 8.467; 95%CI, 1.248-17.426; P = 0.029), and postoperative albumin level ≥ 30 and < 35 g/L (OR, 2.552; 95%CI, 1.112-5.857; P = 0.027) or < 30 g/L (OR, 5.517; 95%CI, 2.047-18.148; P = 0.012) were associated with PLL. CONCLUSION: Neoadjuvant chemotherapy, postoperative anemia and postoperative hypoproteinemia are risk factors for PLL.

Children with cervical lymphadenopathy: reactive or not?

BACKGROUND: This study aims to evaluate the etiology of cervical lymphadenopathies in children and to define the significance of demographic, clinical, and laboratory features in the prediction of malignancy. METHODS: Medical records of 527 patients were reviewed retrospectively between 2015 and 2019. The patients were examined in terms of demographics, clinical, radiologic, and serologic findings. A lymph node biopsy was performed in selected patients. The risk factors for malignancy were evaluated. RESULTS: Out of 527 children, 26 had neck masses mimicking lymphadenopathy; 501 had lymphadenopathy. The most common location was the anterior cervical region and the median age was 5.7 years. Thirty-nine patients had malignancy (lymphoma in 34, nasopharyngeal carcinoma in 3, leukemia in 1 and neuroblastoma in 1). The risk of malignancy was associated with older age, duration of > 4 weeks, lymph node size > 3 cm, supraclavicular location, presence of systemic symptoms, and hepatosplenomegaly (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001). On laboratory evaluation, anemia, leukocytosis, and increased erythrocyte sedimentation rate were found to be associated with malignancy (p < 0.001, p=0.003, p < 0.001). CONCLUSIONS: Cervical lymphadenopathies in children are generally benign but patients with persisting cervical lymphadenopathy, adolescent age, accompanying systemic symptoms and abnormal laboratory findings should be considered for an early biopsy.

Infection-Associated Thymic Atrophy.

The thymus is a vital organ of the immune system that plays an essential role in thymocyte development and maturation. Thymic atrophy occurs with age (physiological thymic atrophy) or as a result of viral, bacterial, parasitic or fungal infection (pathological thymic atrophy). Thymic atrophy directly results in loss of thymocytes and/or destruction of the thymic architecture, and indirectly leads to a decrease in naïve T cells and limited T cell receptor diversity. Thus, it is important to recognize the causes and mechanisms that induce thymic atrophy. In this review, we highlight current progress in infection-associated pathogenic thymic atrophy and discuss its possible mechanisms. In addition, we discuss whether extracellular vesicles/exosomes could be potential carriers of pathogenic substances to the thymus, and potential drugs for the treatment of thymic atrophy. Having acknowledged that most current research is limited to serological aspects, we look forward to the possibility of extending future work regarding the impact of neural modulation on thymic atrophy.

Functional lymphatic reserve capacity is depressed in patients with a Fontan circulation.

BACKGROUND: Lymphatic abnormalities play a role in effusions in individuals with a Fontan circulation. Recent results using near-infrared fluorescence imaging disclosed an increased contraction frequency of lymphatic vessels in Fontan patients compared to healthy controls. It is proposed that the elevated lymphatic pumping seen in the Fontan patients is necessary to maintain habitual interstitial fluid balance. Hyperthermia has previously been used as a tool for lymphatic stress test. By increasing fluid filtration in the capillary bed, the lymphatic workload and contraction frequency are increased accordingly. Using near-infrared fluorescence imaging, the lymphatic functional reserve capacity in Fontan patients were explored with a lymphatic stress test. METHODS: Fontan patients (n = 33) were compared to a group of 15 healthy individuals of equal age, weight, and gender. The function of the superficial lymphatic vessels in the lower leg during rest and after inducing hyperthermia was investigated, using near-infrared fluorescence imaging. RESULTS: Baseline values in the Fontan patients showed a 57% higher contraction frequency compared to the healthy controls (0.4 ± 0.3 min-1 vs. 0.3 ± 0.2 min-1 , p = 0.0445). After inducing stress on the lymphatic vessels with hyperthermia the ability to increase contraction frequency was decreased in the Fontan patients compared to the controls (0.6 ± 0.5 min-1 vs. 1.2 ± 0.8 min-1 , p = 0.0102). CONCLUSIONS: Fontan patients had a higher lymphatic contraction frequency during normal circumstances. In the Fontan patients, the hyperthermia response is dampened indicating that the functional lymphatic reserve capacity is depressed. This diminished reserve capacity could be part of the explanation as to why some Fontan patients develop late-onset lymphatic complications.

Combined internal and external negative pressure wound therapy: breakthrough treatment for lymphocutaneous intractable fistula.

PURPOSE: Lymphocutaneous fistula after lymph node dissection is intractable, yet there is no established treatment strategy. This study demonstrates the wound closure time achieved by a new method of combined internal and external negative pressure wound therapy (CIEN) in patients with lymphocutaneous fistula. METHODS: The subjects of this study were six consecutive patients with lymphocutaneous fistula after lymphatic surgery, who were treated with CIEN between 2018 and 2020. The CIEN technique can be summarized as follows: first, internal foam is inserted into the fistula from the opening of the fenestration. Next, a slightly larger area of external foam is applied above the fistula flap outside the external margin of the foam-filled fistula. After bridging the internal foam and external foam, negative-pressure wound therapy is carried out on this bridging foam block. RESULTS: CIEN led to rapid and complete wound healing in all six patients. Fistula flap margin ischemia developed in one patient, but adjusting the mode and pressure settings resulted in improvement. Three patients suffered contact dermatitis. There were no signs of tumor or fistula recurrence in any patients after at least 3 months of follow-up. CONCLUSION: CIEN is an effective and less invasive treatment modality than the conventional method of managing lymphocutaneous fistula.

Disparities in Cardiovascular Disease Risk Among Hispanic Breast Cancer Survivors in a Population-Based Cohort.

Background: Breast cancer is the leading cause of cancer death among Hispanic women. The aim of our study was to estimate cardiovascular disease (CVD) risk among Hispanic and non-Hispanic White (NHW) breast cancer survivors compared with their respective general population cohorts. Methods: Cohorts of 17 469 breast cancer survivors (1774 Hispanic and 15 695 NHW) in the Utah Cancer Registry diagnosed between 1997 and 2016, and 65 866 women (6209 Hispanic and 59 657 NHW) from the general population in the Utah Population Database were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CVD. Results: The risk of diseases of the circulatory system was higher in Hispanic than NHW breast cancer survivors 1-5 years after cancer diagnosis, in comparison with their respective general population cohorts (HRHispanic = 1.94, 99% confidence interval [CI] = 1.49 to 2.53; HNHW = 1.38, 99% CI = 1.33 to 1.43; 2-sided P heterogeneity = .01, respectively). Increased risks were observed for both Hispanic and NHW breast cancer survivors for diseases of the heart and the veins and lymphatics, compared with the general population cohorts. More than 5 years after cancer diagnosis, elevated risk of diseases of the veins and lymphatics persisted in both ethnicities. The CVD risk due to chemotherapy and hormone therapy was higher in Hispanic than NHW breast cancer survivors but did not differ for distant stage, higher baseline comorbidities, or baseline smoking. Conclusions: We observed a risk difference for diseases of the circulatory system between Hispanic and NHW breast cancer survivors compared with their respective general population cohorts but only within the first 5 years of cancer diagnosis.

Abdominal Imaging of Children and Young Adults With Fontan Circulation: Pathophysiology and Surveillance.

OBJECTIVE. The Fontan procedure has significantly improved the survival in children with a functional single ventricle, but it is associated with chronically elevated systemic venous pressure that leads to multisystemic complications. Imaging plays an important role in assessing these complications and guiding management. The pathophysiology, imaging modalities, and current surveillance recommendations are discussed and illustrated. CONCLUSION. Significant improvement in survival of patients with Fontan circulation is associated with ongoing cardiac and extracardiac comorbidities and multisystemic complications. The liver and intestines are particularly vulnerable to damage. In addition, this patient population has been shown to be at increased risk of certain malignancies such as hepatocellular carcinoma and neuroendocrine tumors. Familiarity with imaging findings of Fontan-associated liver disease and other abdominal complications of the Fontan circulation is essential for radiologists because we are likely to encounter these patients in our general practice.

Aponeurotic-Cutaneous Tract Exeresis in Patients With Persistent Lymphorrhea After Kidney Transplantation: A Valid Approach in a Day Surgery Setting.

BACKGROUND: Lymphatic disorders (LDs) are the most common minor complications after kidney transplantation (KT), with an incidence rate between 0.6% and 33.9%, which appears to be related to both surgical and medical factors. LDs mostly resolve spontaneously, but occasionally a surgical approach may be required. MATERIALS AND METHODS: We report our experience with 7 KT recipients who developed persistent lymphorrhea (>150 mL/24 h) between October 2017 and March 2019. All cases were treated as outpatients with parietal fistulectomy (PF). The fibrotic aponeurotic-cutaneous tract was thoroughly excised, and the residual aponeurotic defect was closed by watertight suturing. Serial abdominal ultrasounds (US) were carried out after the procedure. RESULTS: A small perirenal graft lymphocele of <2 cm was detected by US in all patients after 48 to 72 hours, without any evidence of either vascular or ureteral compression. During the subsequent scheduled US follow-up, lymphoceles did not increase in size, and additional interventions were not needed. Neither superficial nor deep surgical-site infections were recorded in such patients. CONCLUSIONS: PF was found to be a safe and effective minimally invasive approach for persistent lymphorrhea after KT. It could be easily performed with local anesthesia in a day surgery setting and did not require patient hospitalization.