Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice.

Angiopoietin-like protein (ANGPTL)4 regulates plasma lipids, making it an attractive target for correcting dyslipidemia. However, ANGPTL4 inactivation in mice fed a high fat diet causes chylous ascites, an acute-phase response, and mesenteric lymphadenopathy. Here, we studied the role of ANGPTL4 in lipid uptake in macrophages and in the above-mentioned pathologies using Angptl4-hypomorphic and Angptl4-/- mice. Angptl4 expression in peritoneal and bone marrow-derived macrophages was highly induced by lipids. Recombinant ANGPTL4 decreased lipid uptake in macrophages, whereas deficiency of ANGPTL4 increased lipid uptake, upregulated lipid-induced genes, and increased respiration. ANGPTL4 deficiency did not alter LPL protein levels in macrophages. Angptl4-hypomorphic mice with partial expression of a truncated N-terminal ANGPTL4 exhibited reduced fasting plasma triglyceride, cholesterol, and NEFAs, strongly resembling Angptl4-/- mice. However, during high fat feeding, Angptl4-hypomorphic mice showed markedly delayed and attenuated elevation in plasma serum amyloid A and much milder chylous ascites than Angptl4-/- mice, despite similar abundance of lipid-laden giant cells in mesenteric lymph nodes. In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice.

Chylous ascites, anti-interferon-gamma autoantibody, and angioimmunoblastic T-cell lymphoma: a rare but intriguing connection over Mycobacterium avium.

We report a case of non-AIDS (acquired immunodeficiency syndrome), non-CAPD (Continuous Ambulatory Peritoneal Dialysis), non-cirrhotic, Mycobacterium avium peritonitis, which is a rare form of mycobacterial infection. A 66-year-old Japanese man who had been treated previously for angioimmunoblastic T-cell lymphoma (AITL), had developed disseminated M. avium infection. Antimycobacterial regimen improved his symptoms; however, following an interruption in treatment, he developed chylous ascites. The patient died of uncontrolled peritonitis despite intensive treatment. Anti-interferon-γ autoantibody was positive, and AITL was presumed to be involved in autoantibody production. A rare coexistence of chylous ascites, autoantibody, and AITL taught us an intriguing lesson on the pathogenesis of M. avium infection. Particularly, we conclude that treatment strategies for M. avium infection should aim to restore immunity.

Chylous ascites following laparoscopic live donor nephrectomy: A new improved treatment paradigm.

Chylous ascites is a difficult, albeit uncommon complication of laparoscopic live donor nephrectomy (LLDN). Lymphatic leak is believed to be a result of injury to the cisterna chyli, regional lymph nodes, or other peri-aortic lymphatics intraoperatively. Recommended management with dietary modifications can result in malnutrition and immunodeficiency. We present four patients who developed chylous ascites following LLDN. Approach to these patients evolved over time. Our initial two patients were successfully treated with a combination of surgical intervention followed by drain placement, after the failure of conservative management. The latter two cases were successfully treated with prompt intra-abdominal drain placement, without dietary modifications. Our cohort challenges the standard of care for treatment of chylous ascites after LLDN. We believe that prompt diagnosis and placement of an intra-abdominal drain can be used safely in select patients that develop this complication. We hypothesize that continuously draining the lymphatic leak, thus avoiding the re-accumulation of ascites, allows bowel and mesentery to make contact and adhere to the retroperitoneal tissue. We believe that prompt, initial, percutaneous drain placement is a viable alternative to both conservative and reoperative management in the treatment of chylous ascites after LLDN and should be considered as a reasonable first-line therapy.

3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice.

TCDD-inducible poly-ADP-ribose polymerase (TIPARP) is an aryl hydrocarbon receptor (AHR) target gene that functions as part of a negative feedback loop to repress AHR activity. Tiparp-/- mice exhibit increased sensitivity to the toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including lethal wasting syndrome. However, it is not known whether Tiparp-/- mice also exhibit increased sensitivity to other AHR ligands. In this study, we treated male Tiparp-/- or wild type (WT) mice with a single injection of 100 mg/kg 3-methylcholanthrene (3MC). Consistent with TIPARP's role as a repressor of AHR signaling, 3MC-treated Tiparp-/- mice exhibited increased hepatic Cyp1a1 and Cyp1b1 levels compared with WT mice. No 3MC-treated Tiparp-/- mice survived beyond day 16 and the mice exhibited chylous ascites characterized by an accumulation of fluid in the peritoneal cavity. All WT mice survived the 30-day treatment and showed no signs of fluid accumulation. Treated Tiparp-/- mice also exhibited a transient and mild hepatotoxicity with inflammation. 3MC-treated WT, but not Tiparp-/- mice, developed mild hepatic steatosis. Lipid deposits accumulated on the surface of the liver and other abdominal organs in the 3MC-Tiparp-/- mice. Our study reveals that Tiparp-/- mice have increased sensitivity to 3MC-induced liver toxicity, but unlike with TCDD, lethality is due to chylous ascites rather than wasting syndrome.

Feeding Angptl4-/- mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites.

Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting LPL. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces the risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in the mesenteric lymph nodes (MLNs). In mice these pathological events exclusively unfold upon feeding a high saturated FA diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here, we show that Angptl4-/- mice fed a diet rich in trans FAs develop numerous lipid-filled giant cells in their MLNs, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a saturated FA-rich diet. In RAW264.7 macrophages, the saturated FA, palmitate, markedly increased markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate had the opposite effect. In conclusion, trans and saturated FAs have very distinct biological effects in macrophages. Furthermore, lipid accumulation in MLNs is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.

Multifocal Kaposiform Hemangioendothelioma Causing Massive Fetal Chylous Ascites.

Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that usually occurs in soft tissues of the extremity and rarely in the retroperitoneum. We report a unique case of isolated massive fetal ascites attributed to KHE, involving the retroperitoneum and multiple visceral organs, along with the Kasabach-Merritt phenomenon. We suspect that retroperitoneal KHE might have caused massive fetal ascites because of its high potential to invade the lymphatic vessels aggressively in the retroperitoneal space, which possibly permits intestinal lymph leakage into the peritoneal cavities.

[CONGENITAL CHYLOUS ASCITES: A CASE REPORT].

Congenital chylous ascites is a rare polietiologic entity, requiring close study of the infant's organism by visualization methods in order to diagnose the bening or malignant underlying pathology. In the article is given a report on case of congenital chylous ascites in infant, caused by lymphangioma in the peritoneal cavity. Atypical clinic and the lack of diagnostic standards led to the later detection of the ascite's origin.

Choloperitoneum causes extensive coloring of the abdominal wall skin.

Laparoscopic cholecystectomy, because it is the less invasive surgical procedure, has been established as the procedure of choice for the treatment of patients with symptomatic gallbladder stones. However, bile leakage after laparoscopic cholecystectomy should not be overlooked. It is generally due to a minor biliary complication, although it can sometimes herald a major duct injury. Bile leakage rates of 1.2% to 4.0% in laparoscopic cholecystectomies have been reported, which are higher than the incidence with open cholecystectomies.

Chylous ascites in a hedgehog (Atelerix albiventris).

An African pygmy hedgehog (Atelerix albiventris) was diagnosed as chylous ascites with biliary cirrhosis. Abdomenocentesis revealed a milky fluid with a 324 mg/dl triglyceride level. On serum biochemical examination, the hedgehog had hypoalbuminemia, hypoglycemia, and high blood urea nitrogen. There was no cytologic or genomic evidence of infection, and a blood culture was negative. Histopathologic examination revealed a liver with proliferative bile ducts that were often surrounded by prominent septa of fibrous connective tissue. In the area of ductular reaction, proliferative cells positive for CD66, an embryogenic antigen of epithelial cells, were revealed. The potential association between chylous ascites and liver cirrhosis is undetermined but could be an aspect of future study. This is the first description of chylous ascites in a hedgehog.

Ultrasonographic characteristics of the cisterna chyli in eight dogs and four cats.

Ultrasonography of the cisterna chyli has been used in humans to diagnose increased lymphatic flow or lymph flow obstruction and to guide percutaneous embolization of the thoracic duct via the cisterna chyli. The aim of this study was to describe the ultrasonographic characteristics of the dorsal portion of cisterna chyli in dogs and cats with chylous ascites or chylothorax and in a group of healthy dogs and cats. The aorta and the cranial mesenteric artery were used as anatomic landmarks. Ultrasonography was performed before and 2 h after a fatty meal in healthy dogs and cats. The visualized structure was confirmed to be a dilated cisterna chyli at necropsy in a dog with chylous ascites. The confirmed or presumed cisterna chyli was consistently detected using ultrasonography in nonfasted healthy animals and clinically affected animals and appeared as an anechoic tubular structure, without detectable flow, at the right dorsolateral aspect of the aorta. It had a similar ultrasonographic appearance in patients with chyloabdomen and in nonfasted healthy dogs and cats. There was considerable overlap in diameters of the cisterna chyli for affected and healthy animals. The shape and size of the cisterna chyli in an individual animal were variable during the same ultrasound examination and between different examinations. This study demonstrated the appearance of the presumed dorsal portion of the cisterna chyli by ultrasonography and might provide useful preliminary data for further studies into the feasibility of ultrasound-guided injections or aspirations of the cisterna chyli in dogs and cats.

Chylous ascites: analysis of 24 patients.

OBJECTIVES: Chylous ascites is the pathologic accumulation of lymphatic fluid in the peritoneal cavity. Patients who underwent surgery for gynecologic malignancy and had postoperative chylous ascites were evaluated retrospectively. METHODS: We reviewed 1514 patients who had staging surgery for gynecologic malignancy at our institution from January 2003 to February 2012. We analyze the patients who develop chylous ascites and who didn't. RESULTS: Twenty-four (2%) patients had postoperative chylous ascites. In the patients with chylous ascites, the median number of removed para-aortic lymph nodes was 26 (range 8-54), while this number was 17 (range 1-76) for the patients who didn't develop chylous ascites (p=0.001). Among the patients with chylous ascites, nine patients took chylous diet and 15 patients took TPN as the initial treatment. Totally seven (29%) patients required surgical correction, since 17 (71%) responded to conservative treatment. In the TPN group, the time from staging surgery to the diagnosis of chylous ascites was significantly longer in the group who required surgery compared with the group who did not (20 days vs 8 days, p:0.037). In addition this time wasn't statistically different from the patients' time in the diet group who didn't require surgery. CONCLUSION: The aggressiveness of para-aortic lymphadenectomy should be individualized and the lymphatics should be controlled with suture ligation or hemoclips, since the extent and method of para-aortic lymphadenectomy has a determinative role in the development of chylous ascites. It may be logical to treat chylous ascites with diet rather than TPN initially in case the symptoms occur later.

Chyle leak after major pancreatic surgery. Is this an underestimated complication? A narrative review of the literature.

PURPOSE: Postoperative chyle leak, termed 'chylous ascites', is a rare complication with a reported frequency of only one in 20464 abdominal operations. The purpose of this study was to summarize the available scientific data reviewing the most relevant studies for this type of postoperative complication after pancreatic surgery, highlighting at the same time the necessity for pancreatic surgeons to retain a high level of clinical suspicion for the early diagnosis and its therapeutic management. METHODS: A thorough literature search in Pubmed and Google Scholar, under the terms' chylous ascites OR chyle leak AND pancreas OR pancreatic', since the year of inception until 19th of February 2021 was conducted by the authors and the associated results are presented in this narrative review. RESULTS: Chyle leak is a rare complication following pancreatic surgery. Patients may suffer from exudative enteropathy and malnutrition leading to repeated infections and impaired wound healing or even death secondary to sepsis. Several studies have highlighted the issue of increased hospital stay, while others failed to reach statistical significance as far as hospital stay or survival are concerned. Researchers found that patients with diffuse chyle leak tended to have a worse 3-year survival rate (18.8%), which can be attributed to postoperative complications and early demise due to immunosuppression associated with the leak, or delayed adjuvant chemotherapy Conclusion: Further clinical research is needed to enhance prevention, diagnosis, treatment and long-term prognosis of this relevant surgical problem that shows trends of increase due to the great number of major operations which are performed nowadays.

Resolution of chyloperitoneum in a preterm with octreotide, diet and cessation of dialysis.

The diagnosis of chyloperitoneum (CP) is based on the presence of high levels of triglycerides (TGs) in the dialysate. It is a rare complication of peritoneal dialysis (PD) and even rarer in neonates. We report here the case of CP in a 1700-g male baby delivered at the 30th gestational week due to posterior urethral valve and associated oligohydramnios. On postnatal day 2, the serum creatinine (Scr) was 1.6 mg/dL, and he was anuric. PD was instituted via a Tenckhoff catheter. At the end of the second week, after the initiation of enteral feeding, the ultrafiltrate became cloudy, with a leukocyte count of 900/mm(3). A treatment regimen consisting of intraperitoneal vancomycin and ceftazidime was then started. Five days later, the fluid became milky, with a TG level of 251 mg/dL. The patient was then placed on a diet based on medium-chain triglycerides and octreotide (1 microg/kg/h; increasing up to 2 microg/kg/h over 15 days). Although the TG and leukocyte levels decreased, the milky appearance persisted. PD was stopped for 2 days when the Scr decreased to 1.7 mg/dL. When it was resumed, the fluid was totally clear, with a TG level of 7 mg/dL. The infant was discharged with a nightly intermittent peritoneal dialysis program and has had no recurrence. In summary, we report a preterm infant who developed CP during PD and recovered following treatment that included diet modification, octreotide, and temporary discontinuation of the PD.

[Chylous ascites after trans-peritoneal laparoscopic adrenalectomy: anatomical distribution of lymph nodes and management]. / Ascite chyleuse post-surrénalectomie laparoscopique transpéritonéale : distribution anatomique des lymphonoeuds et prise en charge thérapeutique.

We report the case of a chylous ascites after transperitoneal laparoscopic adrenalectomy. This complication is known after surgery in urology but remains rare and was not described after laparoscopic adrenalectomy. Anatomy for lymph nodes distribution was described to understand the occurrence of this complication. The diagnosis of chylous ascites is referred to clinical signs of peritoneal irritation and confirmed by puncture, the treatment is initially conservative.

Cytomorphology of Mycobacterium avium intracellulare-associated ascites.

Ascites due to Mycobacterium avium intracellulare (MAI) infection is extremely rare and associated with a poor outcome. The cytomorphology of this condition has not been previously reported. We present a unique case of a 45-year-old woman with iatrogenic immunodeficiency who developed MAI-associated chylous ascites. The ascitic fluid cytology showed numerous lymphocytes and foamy histiocytes with abundant intracytoplasmic MAI organisms. The diagnosis was confirmed by tissue biopsy showing MAI mesenteritis. It is important to consider MAI-associated ascites in the differential diagnosis whenever ascitic fluid shows a predominant population of lymphocytes and macrophages, especially in immunocompromised patients.

Successful Conversion Surgery Following Chylous Ascites After Nivolumab for Advanced Gastric Cancer.

CASE REPORT: A 75-year-old man who underwent nivolumab as the third-line chemotherapy for advanced gastric cancer had chylous ascites (CA) after the primary tumor shrank remarkably. Total parenteral nutrition and subcutaneous octreotide were initiated, and CA disappeared. Nivolumab was continued for a total of 23 courses. Computed tomography showed lymph node swelling; however, staging laparoscopy showed that peritoneal metastasis had disappeared. Therefore, conversion surgery and distal gastrectomy with D1+ dissection were performed. RESULTS: The pathological diagnosis was type IV, poorly differentiated adenocarcinoma (por2) with signet ring cells, ypT2 (muscularis propria), without lymphatic or venous invasion, and no involvement of the proximal and distal margins. After the operation, no recurrence was observed over 7 months with no adjuvant chemotherapy. CONCLUSION: Nivolumab has the potential to lead to R0 resection for patients with peritoneal carcinomatosis gastric cancer. To our knowledge, this is the first report of successful conversion surgery after nivolumab-related chylous ascites.

Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1.

VEGF and Angiopoietin-1 requisitely collaborate during blood vessel development. While Angiopoietin-1 obligately activates its Tie2 receptor, Angiopoietin-2 can activate Tie2 on some cells, while it blocks Tie2 activation on others. Our analysis of mice lacking Angiopoietin-2 reveals that Angiopoietin-2 is dispensable for embryonic vascular development but is requisite for subsequent angiogenic remodeling. Unexpectedly, mice lacking Angiopoietin-2 also exhibit major lymphatic vessel defects. Genetic rescue with Angiopoietin-1 corrects the lymphatic, but not the angiogenesis, defects, suggesting that Angiopoietin-2 acts as a Tie2 agonist in the former setting, but as an antagonist in the latter setting. Our studies define a vascular growth factor whose primary role is in postnatal angiogenic remodeling and also demonstrate that members of the VEGF and Angiopoietin families collaborate during development of the lymphatic vasculature.

Histiocytic sarcoma presenting with chylous ascites in a 7-month-old infant: a case report.

We describe in this report what we believe to be the first report of a rare presentation of a very rare tumor, especially in this age group. We highlight the importance of early consideration of malignancy as a cause of chylous ascites in infancy and we discuss different causes of chylous ascites.