Endoscopic Resection for Vascular Anomalies in Children: A New Standard.

OBJECTIVE: To report an innovative endoscopic surgery for subcutaneous vascular malformations and intramuscular fibro-adipose vascular anomaly (FAVA) at our center. BACKGROUND: Historically, open surgical resection has been the treatment of choice. Recent advances in minimally invasive surgery have led to the successful application of endoscopic resection techniques for the surgical management of diseases of soft tissue. METHODS: Patients who underwent endoscopic resection of vascular anomalies were included in this retrospective review. Data were extracted from our Vascular Anomalies Center database between September 2019 and October 2022, including sex, age, symptoms, diagnosis, sites of surgery, previous treatment, surgery, and follow-up. RESULTS: There were 13 females and 15 males in the current study, with ages ranging from 1 to 17 years. The diagnoses included microcystic lymphatic malformation (LM) (n = 8), Klippel-Trénaunay syndrome (n = 7), venous malformation (n = 6), FAVA (n = 6), and mixed cystic LM (n = 1). Surgical sites included the lower extremity (n = 24), abdominal wall (n = 2), upper extremity (n = 1), and thoracic wall (n = 1). Five patients had an intramuscular lesion (FAVA). The endoscopic technique used 2 or 3 small ports in a gas inflation manner. Surgery included thrombectomy, radical resection, and debulking of vascular anomalies. Postoperative sclerotherapy with bleomycin was performed through a drainage tube in 6 patients with microcystic LM. Technical success was obtained in 27 patients. The conversion to open surgery was performed in one patient owing to the deep location of the lesion. No wound-related complication was observed. CONCLUSIONS: Endoscopic surgery is a minimally invasive, effective, and safe treatment for subcutaneous vascular malformations and intramuscular FAVA. This approach can set a new standard that minimizes wound complications and reduces recovery time in patients undergoing resection for benign soft-tissue lesions.

Curettage and sclerotherapy technique: A hybrid approach to superficial lymphatic malformation.

OBJECTIVE: To describe the curettage and sclerotherapy technique, a hybrid approach to treatment for superficial lymphatic malformations. METHODS: A retrospective analysis of a lymphatic malformation data base was performed. Patients with superficial lymphatic malformation treated by curettage and sclerotherapy technique with bleomycin were included in this study. Safety and efficacy of the curettage and sclerotherapy technique with bleomycin were evaluated. RESULTS: Between September 2019 and October 2021, 10 consecutive patients (male/female ratio: 4:6; mean age, 10.9 years; range, 3-35 years) presented with superficial lymphatic malformations that were subsequently treated by curettage and sclerotherapy technique with bleomycin. All lesions were located on the trunk and extremities. Each patient received one treatment session and a mean follow-up of 12 months. We observed minor complications. No postoperative infections occurred in this series. No patient developed skin ulceration or necrosis. Scarring and recurrence occurred in one patient. Complete regression was confirmed for all 10 patients by photographic evaluation. CONCLUSION: A curettage and sclerotherapy technique is proposed to treat superficial lymphatic malformation in this study. This technique seems to be safe and highly effective.

Polysaccharides from Holothuria leucospilota Relieve Loperamide-Induced Constipation Symptoms in Mice.

A vital bioactive component of marine resources is Holothuria leucospilota polysaccharides (HLP). This study examined whether HLP could regulate intestinal flora to treat loperamide-induced constipation. Constipated mice showed signs of prolonged defecation (up by 60.79 min) and a reduced number of bowel movements and pellet water content (decreased by 12.375 and 11.77%, respectively). The results showed that HLP treatment reduced these symptoms, reversed the changes in related protein expression levels in the colon, and regulated the levels of active peptides associated with the gastrointestinal tract in constipated mice, which significantly improved water-electrolyte metabolism and enhanced gastrointestinal motility. Meanwhile, it was found that intestinal barrier damage was reduced and the inflammatory response was inhibited through histopathology and immunohistochemistry. As a means to further relieve constipation symptoms, treatment with low, medium, and high HLP concentrations increased the total short-chain fatty acid (SCFA) content in the intestine of constipated mice by 62.60 µg/g, 138.91 µg/g, and 126.51 µg/g, respectively. Moreover, an analysis of the intestinal flora's gene for 16S rRNA suggested that the intestinal microbiota was improved through HLP treatment, which is relevant to the motivation for the production of SCFAs. In summary, it was demonstrated that HLP reduced loperamide-induced constipation in mice.

Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model.

Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT4 receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT4 receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75NTR and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT4 receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model.

Sirolimus as initial therapy for kaposiform hemangioendothelioma and tufted angioma.

BACKGROUND: Sirolimus has been used to manage various complex vascular anomalies. Kaposiform hemangioendothelioma and tufted angioma may develop Kasabach-Merritt phenomenon in infancy. METHODS: We retrospectively reviewed the clinical and laboratory data of eight patients with kaposiform hemangioendothelioma and tufted angioma who were initially treated using oral sirolimus in our center, including six with Kasabach-Merritt phenomenon. RESULTS: Five girls and three boys seen between September 2012 and March 2015 were included. Age at initiation of sirolimus ranged from 30 days to 14 weeks (mean±SD 8.6 ± 3.5 weeks). Six of these eight patients had kaposiform hemangioendothelioma, and two had a tufted angioma. Platelet count before start of oral sirolimus ranged from 5 × 109 /L to 189 × 109 /L ((78.8 ± 65.2)×109 /L) and fibrinogen level from 68 to 215 mg/dL (123.1 ± 50.5 mg/dL). All patients received standard doses of sirolimus (0.05 mg/kg orally, twice daily) as initial therapy. All patients with thrombocytopenia or hypofibrinogenemia reached a normal platelet count and a normal fibrinogen level within 3 to 4 weeks after sirolimus treatment. Length of treatment ranged from 12 to 79 weeks (39.9 ± 15.3 weeks). Two patients developed grade 2 oral mucositis during treatment. CONCLUSION: Sirolimus as first-line therapy shows great promise in the treatment of kaposiform hemangioendothelioma and tufted angioma.

Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro.

A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin(+) cells decreased whilst the percentage of GFAP(+) cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies.

Sirolimus for Vincristine-Resistant Kasabach-Merritt Phenomenon: Report of Eight Patients.

BACKGROUND: The use of sirolimus for patients with multidrug-resistant Kasabach-Merritt phenomenon (KMP) has been reported in recent years. We present the experience of a single center in treating vincristine-resistant KMP using sirolimus alone. METHODS: Children with vincristine-resistant KMP who were treated with oral sirolimus alone were eligible for inclusion in the study. We evaluated responses according to graded response criteria and acute toxicities according to the National Cancer Institute Common Toxicity Criteria. RESULTS: Between March 2012 and October 2014, eight patients underwent sirolimus treatment. The response rate of hematologic parameters was 100% (8/8). Three tumors shrank enough to allow excision. The tumors were resected after hematologic parameters normalized. Of the five patients with unresectable vascular lesions, three had complete response, and two had partial response of their tumors at the completion of long-term (39.7 ± 24.4 wks) sirolimus treatment. Grade 3 or 4 adverse events were not documented during treatment or follow-up. No recurrence or progression of the disease was observed during follow-up. CONCLUSION: In this small case series, we found sirolimus to be highly effective, with minimal side effects, for vincristine-resistant KMP. A larger study to compare sirolimus and vincristine for KMP is warranted.

A Time-Limited and Partially Reversible Model of Hypoganglionosis Induced by Benzalkonium Chloride Treatment.

Serosal application of benzalkonium chloride (BAC) has been previously applied to produce a model of aganglionosis; however, confusion remains regarding the extent of chemical ablation of enteric myenteric plexus after BAC treatment. The time sequence of BAC-induced effects on the myenteric plexus of the rat colon was determined and followed the morphologic changes. After sacrifice of animals 7, 14, 28, 56, 84 or 168 days postintervention, colonic tissue samples were removed, fixed in formalin, and cut into 5-µm longitudinal sections for histological analysis. The neural analysis was used to re-evaluate BAC treatments for the appropriate model. Compared with rats in sham groups, rats in 0.1 %-30-min BAC group maintained only 15.27 ± 4.80 % of ganglia per section in a 1-cm/5-µm slice and 11.76 ± 2.30 % of ganglionic cells after 28 days, the lower and stable number of ganglionic cells between Day 7 and 84 (from 11.67 ± 2.10 to 19.05 ± 5.10 %). Although an increase, ganglionic cell numbers did not recover at Day168 when compared with the numbers in sham groups. The results showed that characteristics of rats in the 0.1 %-30-min BAC group between Day 7 and 84 most closely kept in stable state, suggesting that these treatment parameters are ideal for producing a hypoganglia model of hypoganglionosis.

Clinical prognostic significance of xeroderma pigmentosum group C and IFN­Î³ in non­small cell lung cancer.

Lung cancer is the most common cancer in the world due to its high incidence and recurrence. Genetic instability is one of the main factors leading to its occurrence, development and poor prognosis. Decreased xeroderma pigmentosum group C (XPC) expression notably enhances the stem cell properties of lung cancer cells and increases their proliferation and migration. Additionally, patients with lung cancer and low XPC expression had a poor prognosis. The purpose of the present study was to analyze the effect of XPC and IFN-γ on the clinical prognosis of patients with non-small cell lung cancer (NSCLC). Lung adenocarcinoma specimens were collected from a total of 140 patients with NSCLC. Additionally, from these 140 patients, 48 paracarcinoma tissue specimens were also collected, which were later used to construct tissue microarrays. The expression of XPC and IFN-γ in cancer tissues and in paraneoplastic tissues was detected using immunohistochemistry. The prognosis and overall survival of patients were determined through telephone follow-up. The results showed a positive correlation between expression of XPC and IFN-γ in NSCLC. Additionally, high expression of both markers was associated with a favorable prognosis in patients with NSCLC. The aforementioned findings suggest that the expression of XPC and IFN-γ has prognostic value in clinical practice and is expected to become a marker for clinical application.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

Fibro-adipose vascular anomaly (FAVA) - diagnosis, staging and management.

BACKGROUND: The diagnosis and treatment of fibro-adipose vascular anomaly (FAVA) of the limb remains challenging since this entity is rare and complex. This paper is aimed to describe the clinical and imaging features, staging and management of this underrecognized disease of the limb. MATERIAL AND METHOD: Patients diagnosed with FAVA and managed between September 2019 and May 2022 in department of pediatric surgery & vascular anomalies of Xi'an international medical center hospital were retrospectively reviewed. Data extracted include age at presentation, previous diagnosis, affected muscles, symptoms, previous treatment, our management, and follow-up. RESULTS: Thirty-two patients with FAVA were diagnosed and managed in our center. There was a female sex predominance, with 23 female (72%) and 9 male (28%) in the cohort. Only one lesion was noticed during infancy; the remaining presented at age 1 to 20 years (median, 7 years). The most commonly involved muscles were gastrocnemius (14/32, 44%) and soleus (13/32, 40%). Swelling (mass), pain and contractures were the most common presentations. MRI featured a heterogeneous and ill-defined intramuscular high signal intensity. Diseases were staged according to clinical features: stage I (pain stage, n = 4), stage II (contracture stage, n = 20) and stage III (deformity stage, n = 8). Patients with stage I disease underwent radical resection and obtained a cure. Patients with stage II disease received radical resection and possible Achilles lengthening, having an outcome of cure. Personalized treatment was required in patients with stage III disease, including radical/partial/staged resection, Achilles lengthening/tenotomy, joint capsulotomy, neurolysis/neurectomy, tendon transfer, stretching exercises, and oral sirolimus/alpelisib. Significant improvement of symptoms was achieved in most. CONCLUSION: The most distinct features of FAVA include enlarging mass, severe pain and contracture. Based on distinct clinical and radiologic features, it is not difficult to make the diagnosis of FAVA. Earlier awareness of this disease can reduce misdiagnoses. Surgery-based comprehensive management can typically improve pain and contracture. Oral sirolimus or alpelisib plays an important role in treatment of unresectable lesions and major nerve involvement. Surgery alone can be curative in early stage FAVA.

Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management.

Klippel-Trénaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. Gastrointestinal involvement is not infrequent in Klippel-Trénaunay syndrome. Rectal bleeding is the most common complication. In recent years, this condition has been increasingly reported. However, most authors simply described extreme manifestations or various combinations of clinical observations. The underlying pathophysiology of gastrointestinal involvement in Klippel-Trénaunay syndrome has been underrecognized. Pathophysiologically, some seemingly adequate managements are pitfalls in treatment. Anorectosigmoid vascular malformations in KTS have distinct and more complicated pathophysiologies than anorectal vascular malformation. Once understanding the pathophysiology, some patients can be successfully managed with a staged plan in our practice. Therefore, recognizing the pathophysiologies of gastrointestinal involvement is needed to evaluate, prevent pitfalls, and determine adequate managements for practitioners. Because of the complexity and rarity of this condition, prospective controlled study or a large cohort of patients is impossible. Based on literature review and our practice, we discuss pathophysiologies, evaluation, pitfalls, and treatment strategies for gastrointestinal involvement in Klippel-Trénaunay syndrome.

Liposuction-Like Sclerotherapy Technique for Microcystic Lymphatic Malformation.

Background The treatment for microcystic lymphatic malformation (LM) remains challenging. We describe the liposuction-like sclerotherapy technique, a new treatment for extensive microcystic LM. Methods LM data was retrospectively reviewed. This study included patients with a microcystic LM component treated by liposuction-like technique with bleomycin sclerotherapy. Results Between June 2016 and October 2019, 39 consecutive patients (male/female ratio: 21:18; mean age, 33.6 months; range: 5 months to 15 years) with microcystic LM were treated by liposuction-like sclerotherapy (LS-LS) technique. Fifty-six sessions of LS-LS were performed (mean of 1.44 sessions per patient; range: one to four sessions). Follow-up ranged 6-30 months (mean of 21 months). We observed no major complications. Transient minor complications included: postoperative noninfectious fever, vomiting, temporary skin edema, pigmentation, mild local depressions, and/or irregularities, and a small hyperpigmented scar at the incision. No postoperative infection, skin ulcer, or necrosis occurred. The patients' symptoms were successfully resolved or stable. A sub-complete response and partial response were observed for 26 (76%) and 13 patients (33%), respectively. Conclusion The LS-LS technique for microcystic LMs is safe, feasible, and effective. This technique is an effective intervention with which it is possible to manage and potentially cure microcystic LM clinically.

Internal Iliac Vein Reflux: An Underrecognized Pathophysiology in Klippel-Trénaunay Syndrome With Pelvis Involvement.

Background and objective Internal iliac vein reflux (IIVR) has been underrecognized in Klippel-Trénaunay syndrome (KTS) with pelvis involvement. In this study, our aim was to report clinical and radiological characteristics, modified phlebography technique, and diagnostic and treatment algorithm and outcomes of IIVR in KTS patients with pelvis involvement. Materials and methods KTS patients diagnosed between May 2014 and January 2021 were retrospectively analyzed. The medical records and imaging studies of all patients with KTS of the lower extremities were included and reviewed. KTS was defined as the triad of capillary malformation, venous malformation, and limb overgrowth. Pelvis involvement was evaluated with MRI. Phlebography was performed if IIVR was suspected. IIVR ablation and sclerotherapy were performed if IIVR was confirmed in KTS patients with external genitalia/perineum manifestation and bleeding. Patients were followed up via outpatient consultations. Episodes of gross bleeding were specifically investigated. Results A total of 211 patients with lower limb KTS diagnosed by our team were included in the study. Unilateral IIVR was diagnosed in 97 patients, and bilateral IIVR in two patients; 117 KTS patients were managed with radiological intervention and/or hybrid surgery by our team. Eleven patients underwent an IIVR ablation procedure due to recurrent bleeding from pelvic organs. Postprocedural complications included transient fever (n=2) and mild anaphylactic reaction (n=1). A small hyperpigmented scar at the incision and/or accessing site was noticed in patients receiving bleomycin during the procedure (n=6). Bleeding episodes and anemia resolved in all patients during the follow-up period. Correspondingly, the involved IIV and its tributaries were found to have disappeared on imaging during the follow-up. Conclusion IIVR is common in KTS patients, and it can cause bleeding from pelvic organs. Bleeding can be managed with IIVR ablation and sclerotherapy in KTS with pelvis involvement.

The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

Role of Proximal Intestinal Glucose Sensing and Metabolism in the Blood Glucose Control in Type 2 Diabetic Rats After Duodenal Jejunal Bypass Surgery.

BACKGROUND: Although gastric surgery can significantly improve blood glucose homeostasis in type 2 diabetes mellitus (T2DM), its mechanism remains unclear. This study evaluated the role of intestinal glucose sensing, glucose transport, and metabolism in the alimentary limb (A limb) of T2DM rats after duodenal jejunal bypass (DJB) surgery. METHODS: A T2DM rat model was induced via a high-glucose high-fat diet and low-dose streptozotocin injection. The diabetic rats were divided into two groups: the DJB surgery (T2DM-DJB) group and the sham surgery (T2DM-Sham) group. Wistar rats were used as wild-type control (Control). Small animal PET was used to assess the change in glucose metabolic status in the intestine. The intestinal villi height and the number of EECs after DJB were evaluated. The expressions of sweet taste receptors (T1R2/T1R3), glucose transporters (SGLT1/GLUT2), and key enzymes involved in glucose metabolism (HK2, PFK2, PKM2, G6Pase, and PCK1) in the A limb after DJB was detected by Western blot and qRT-PCR. RESULTS: Small animal PET analysis showed the intestinal glucose metabolism increased significantly 6 weeks after DJB surgery. The intestinal villi height and the number of EECs in the A limb 6 weeks after surgery increased significantly in T2DM-DJB rats comparing to T2DM-Sham rats. The mRNA and protein expression of T1R1/T1R3 and SGLT1/GLUT2 were downregulated in DJB-T2DM rats, while enzymes involved in glucose metabolism was upregulated in the A limb in T2DM-DJB rats. CONCLUSION: Proximal intestinal glucose sensing and metabolism play an important role in blood glucose homeostasis by DJB.