-
Circulation Research Aug 2023Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell...
BACKGROUND
Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood.
METHODS
We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries.
RESULTS
By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction.
CONCLUSIONS
Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.
Topics: Mice; Animals; Vascular Endothelial Growth Factor A; Endothelial Cells; Phosphatidylinositol 3-Kinases; Chylomicrons; Lymphatic Vessels; Monomeric GTP-Binding Proteins; Capillary Permeability
PubMed: 37462027
DOI: 10.1161/CIRCRESAHA.123.322607 -
Porto Biomedical Journal 2023Gastrostomies can be performed percutaneously by interventional radiology (PRG) or endoscopy (PEG).
INTRODUCTION
Gastrostomies can be performed percutaneously by interventional radiology (PRG) or endoscopy (PEG).
METHODS
Retrospective analysis of patients with advanced cancer who underwent a gastrostomy in 2017 in an oncology center.
RESULTS
In 2017, 164 patients underwent gastrostomies, and 137 (84%) were male. The median age was 60 years (range: 38-91). The predominant Eastern Cooperative Oncology Group (ECOG) performance status stage was 1, with 73 (45%) patients. Head and neck cancer was the most common diagnosis, with 127 (77%) cases. The most frequent reason for performing a gastrostomy was dysphagia, 132 (81%). Most gastrostomies were PEG, 121 (74%), followed by PRG, 41 (25%), and surgery, 2 (1%). Early complications occurred in 86 (52%) patients, and the most frequent of them were local pain in 69 (80%) patients and minor local bleeding in 13 (15%). Late complications occurred in 90 (55%) patients, and the most frequent was also local pain in 57 (63%) patients, followed by local infection in 8 (9%), tube extrusion in 7 (8%), and stomal leakage in 7 (8%). In the multivariable analysis, the factors associated with survival were lymph node metastases and the ECOG performance status. Until June 30th, 2022, 123 (75%) patients had died, and 41 (25%) were still alive.
CONCLUSION
Gastrostomies were performed predominantly in ECOG performance stage 1 patients with head and neck cancer and symptoms of dysphagia, and PEG was the most common procedure.
PubMed: 38093796
DOI: 10.1097/j.pbj.0000000000000238 -
Clinical Science (London, England :... Sep 2023Resolution of edema remains a significant clinical challenge. Conditions such as traumatic shock, sepsis, or diabetes often involve microvascular hyperpermeability,... (Review)
Review
Resolution of edema remains a significant clinical challenge. Conditions such as traumatic shock, sepsis, or diabetes often involve microvascular hyperpermeability, which leads to tissue and organ dysfunction. Lymphatic insufficiency due to genetic causes, surgical removal of lymph nodes, or infections, leads to varying degrees of tissue swelling that impair mobility and immune defenses. Treatment options are limited to management of edema as there are no specific therapeutics that have demonstrated significant success for ameliorating microvascular leakage or impaired lymphatic function. This review examines current knowledge about the physiological, cellular, and molecular mechanisms that control microvascular permeability and lymphatic clearance, the respective processes for interstitial fluid formation and removal. Clinical conditions featuring edema, along with potential future directions are discussed.
Topics: Humans; Edema; Capillary Permeability; Kinetics; Sepsis
PubMed: 37732545
DOI: 10.1042/CS20220314 -
Frontiers in Immunology 2023Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the...
Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic () and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host's inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral treatment but was deteriorated by antibiotics. , butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.
Topics: Mice; Animals; Fatty Acids, Volatile; Gastrointestinal Microbiome; Mucocutaneous Lymph Node Syndrome; Propionates; Butyrates; Inflammation; Bacteria; Anti-Bacterial Agents
PubMed: 37398673
DOI: 10.3389/fimmu.2023.1124118 -
Current Opinion in Urology Jul 2023Although lymph node dissection (LND) during radical nephroureterectomy (RNU) is recommended for high-risk nonmetastatic upper tract urothelial carcinoma (UTUC),... (Review)
Review
PURPOSE OF REVIEW
Although lymph node dissection (LND) during radical nephroureterectomy (RNU) is recommended for high-risk nonmetastatic upper tract urothelial carcinoma (UTUC), adherence to guidelines remains insufficient in clinical practice. Therefore, this review aims to comprehensively summarize the current evidence regarding the diagnostic, prognostic, and therapeutic impact of LND during RNU in UTUC patients.
RECENT FINDINGS
Clinical nodal staging using conventional CT scan has low sensitivity (25%) and diagnostic accuracy [area under the curve (AUC): 0.58] in UTUC, suggesting the importance of LND for obtaining accurate N-staging. Patients with pathological node-positive (pN+) disease have poor disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) compared with those with pN0. In addition, population-based studies showed that patients who underwent LND improved CSS and OS than those who did not, even in patients who received adjuvant systemic therapy. The number of lymph nodes removed has also been shown to be associated with improved CSS and OS, even in pT0 patients. Template-based LND should be performed as the extent of lymph node is more important than the number of lymph nodes. Robot-assisted RNU may facilitate performing a meticulous LND compared with a laparoscopic approach. Postoperative complications such as lymphatic and/or chylous leakage are increased but adequately manageable. However, the current evidence is not supported by high-quality studies.
SUMMARY
Based on the published data, LND during RNU is a standard procedure for high-risk nonmetastatic UTUC, owing to its diagnostic, staging, prognostic, and, potentially, therapeutic benefits. Template-based LND should be offered to all patients who are planned for RNU for high-risk nonmetastatic UTUC. Patients with pN+ disease are optimal candidates for adjuvant systemic therapy. Robot-assisted RNU may facilitate meticulous LND compared with laparoscopic RNU.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Lymph Node Excision; Lymph Nodes; Nephroureterectomy; Retrospective Studies; Ureteral Neoplasms
PubMed: 37014743
DOI: 10.1097/MOU.0000000000001097 -
World Journal of Gastrointestinal... Mar 2024In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the W. The authors present an interesting review on the use of...
In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the W. The authors present an interesting review on the use of indocyanine green fluorescence in different aspects of abdominal surgery. They also highlight future perspectives of the use of indocyanine green in mini-invasive surgery. Indocyanine green, used for fluorescence imaging, has been approved by the Food and Drug Administration and is safe for use in humans. It can be administered intravenously or intra-arterially. Since its advent, there have been several advancements in the applications of indocyanine green, especially in the surgical field, such as intraoperative mapping and biopsy of sentinel lymph node, measurement of hepatic function prior to resection, in neurosurgical cases to detect vascular anomalies, in cardiovascular cases for patency and assessment of vascular abnormalities, in predicting healing following amputations, in helping visualization of hepatobiliary anatomy and blood vessels, in reconstructive surgery, to assess flap viability and for the evaluation of tissue perfusion following major trauma and burns. For these reasons, the intraoperative use of indocyanine green has become common in a variety of surgical specialties and transplant surgery. Colorectal surgery has just lately begun to adopt this technique, particularly for perfusion visualization to prevent anastomotic leakage. The regular use of indocyanine green coupled with fluorescence angiography has recently been proposed as a feasible tool to help improve patient outcomes. Using the best available data, it has been shown that routine use of indocyanine green in colorectal surgery reduces the rates of anastomotic leak. The use of indocyanine green is proven to be safe, feasible, and effective in both elective and emergency scenarios. However, additional robust evidence from larger-scale, high-quality studies is essential before incorporating indocyanine green guided surgery into standard practice.
PubMed: 38577071
DOI: 10.4240/wjgs.v16.i3.641 -
Gastroenterology Report 2023Gastrointestinal cancers have become an important cause of cancer-related death in humans. Improving the early diagnosis rate of gastrointestinal tumors and improving... (Review)
Review
Gastrointestinal cancers have become an important cause of cancer-related death in humans. Improving the early diagnosis rate of gastrointestinal tumors and improving the effect of surgical treatment can significantly improve the survival rate of patients. The conventional diagnostic method is high-definition white-light endoscopy, which often leads to missed diagnosis. For surgical treatment, intraoperative tumor localization and post-operative anastomotic state evaluation play important roles in the effect of surgical treatment. As a new imaging method, near-infrared fluorescence imaging (NIRFI) has its unique advantages in the diagnosis and auxiliary surgical treatment of gastrointestinal tumors due to its high sensitivity and the ability to image deep tissues. In this review, we focus on the latest advances of NIRFI technology applied in early diagnosis of gastrointestinal tumors, identification of tumor margins, identification of lymph nodes, and assessment of anastomotic leakage. In addition, we summarize the advances of NIRFI systems such as macro imaging and micro imaging systems, and also clearly describe the application process of NIRFI from system to clinical application, and look into the prospect of NIRFI applied in the theranostics of gastrointestinal tumors.
PubMed: 37781571
DOI: 10.1093/gastro/goad055 -
Life Sciences Aug 2023Chronic alcohol consumption in rodents induces mesenteric collecting lymphatic vessel hyperpermeability, lymph leakage, and consequent immunometabolic dysregulation of...
Chronic alcohol consumption in rodents induces mesenteric collecting lymphatic vessel hyperpermeability, lymph leakage, and consequent immunometabolic dysregulation of the perilymphatic adipose tissue (PLAT). The specific lymphatic components mediating PLAT immunometabolic dysregulation remain to be identified. Specifically, whether alcohol impacts lymph composition is unknown. This study aimed to determine alcohol associated changes in lymph and plasma proteome. Adult male rats were fed a Lieber-DeCarli liquid diet containing 36 % of calories from alcohol for 10 weeks. Time-matched control animals were pair-fed. At sacrifice lymph was collected for 2 h using the lymph-fistula technique and plasma was collected prior to sacrifice. Quantitative discovery-based proteomics identified a total of 703 proteins. An integrative approach combining Ingenuity Pathway Analysis (IPA) and an unbiased network analysis using WGCNA (Weighted Gene Co-expression Network Analysis) was used to analyze the proteomics data. IPA results identified significant upregulation of a cluster of apolipoproteins in lymph from alcohol-fed animals compared with pair-fed controls and a downregulation of 34 proteins in the plasma from alcohol-fed animals. WGCNA analysis identified several candidate hub proteins in the lymph that were also significantly differentially expressed in lymph from alcohol-fed animals compared to that of pair-fed controls. WGCNA analysis of plasma identified a module without significant enrichment of differentially expressed proteins. Of the 59 proteins contained within this module, only 2 were significantly differentially expressed in plasma from alcohol-fed rats compared to plasma of pair-fed controls. Future studies will investigate further the functionality of the hub proteins affected by alcohol feeding in both lymph and plasma.
Topics: Rats; Male; Animals; Proteome; Rodentia; Ethanol; Lymph; Lymphatic Vessels
PubMed: 37268288
DOI: 10.1016/j.lfs.2023.121818 -
Journal of Plastic Surgery and Hand... Dec 2023In this report, we describe a super microsurgical technique that enables rapid and accurate anastomosis while adjusting for caliber differences when anastomosing a...
In this report, we describe a super microsurgical technique that enables rapid and accurate anastomosis while adjusting for caliber differences when anastomosing a small-caliber lymphatic vessel and a vein with a larger caliber, which is frequently encountered in surgeries such as lymphaticovenous anastomosis (LVA). The suture size adjustment technique was performed in 30 anastomoses of lymphatic vessels and veins, whose diameter of lymph duct was at least two times smaller than that of the vein. The type of lymphedema, caliber of lymphatic vessels and veins anastomosed, caliber ratio, vein wall thickness, modified caliber ratio after vein wall thickness subtracted, presence of additional anastomosis, and anastomosis time were examined. On average, the lymphatic vessels had a diameter of 0.61 mm, while the veins were 1.43 mm in diameter. The mean caliber ratio of vein to lymphatic vessel was 2.3, while the modified caliber ratio of vein-to-lymphatic vessel was 1.5 on average. The average venous wall thickness was 0.51. The average anastomosis time was 9.1 min and no additional anastomosis due to leakage was necessary in any case. We successfully performed an anastomosis of lymphatic vessels and veins with different calibers, which can maintain long-term patency while adjusting the caliber difference and suppressing leakage at the anastomosis site. Finally, the caliber of the vein is commonly larger than that of the lymphatic vessel to be anastomosed in many cases of LVA surgery, indicating that the proposed anastomosis method could be of therapeutic use in many cases.
Topics: Humans; Veins; Lymphedema; Lymphatic Vessels; Anastomosis, Surgical; Lymphography; Microsurgery
PubMed: 38130209
DOI: 10.2340/jphs.v58.18384 -
Langenbeck's Archives of Surgery Jul 2023The aim of this systematic review and meta-analysis is to summarize the current scientific evidence regarding the impact of the level of inferior mesenteric artery (IMA)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this systematic review and meta-analysis is to summarize the current scientific evidence regarding the impact of the level of inferior mesenteric artery (IMA) ligation on post-operative and oncological outcomes in rectal cancer surgery.
METHODS
We conducted a systematic review of the literature up to 06 September 2022. Included were RCTs that compared patients who underwent high (HL) vs. anterior (LL) IMA ligation for resection of rectal cancer. The literature search was performed on Medline/PubMed, Scopus, and the Web of Science without any language restrictions. The primary endpoint was overall anastomotic leakage (AL). Secondary endpoints were oncological outcomes, intraoperative complications, urogenital functional outcomes, and length of hospital stay.
RESULTS
Eleven RCTs (1331 patients) were included. The overall rate of AL was lower in the LL group, but the difference was not statistically significant (RR 1.43, 95% CI 0.95 to 2.96). The overall number of harvested lymph nodes was higher in the LL group, but the difference was not statistically significant (MD 0.93, 95% CI - 2.21 to 0.34). The number of lymph nodes harvested was assessed in 256 patients, and all had a laparoscopic procedure. The number of lymph nodes was higher when LL was associated with lymphadenectomy of the vascular root than when IMA was ligated at its origin, but there the difference was not statistically significant (MD - 0.37, 95% CI - 1.00 to 0.26). Overall survival at 5 years was slightly better in the LL group, but the difference was not statistically significant (RR 0.98, 95% CI 0.93 to 1.05). Disease-free survival at 5 years was higher in the LL group, but the difference was not statistically significant (RR 0.97, 95% CI 0.89 to 1.04).
CONCLUSIONS
There is no evidence to support HL or LL according to results in terms of AL or oncologic outcome. Moreover, there is not enough evidence to determine the impact of the level of IMA ligation on functional outcomes. The level of IMA ligation should be chosen case by case based on expected functional and oncological outcomes.
Topics: Humans; Mesenteric Artery, Inferior; Rectal Neoplasms; Rectum; Lymph Node Excision; Lymph Nodes; Anastomotic Leak; Ligation; Laparoscopy
PubMed: 37493853
DOI: 10.1007/s00423-023-03022-z