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Cell Stem Cell Sep 2023Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate...
Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate the engraftment of the airway epithelial stem cell compartment via intra-airway transplantation of mouse or human primary and pluripotent stem cell (PSC)-derived airway basal cells (BCs). Murine primary or PSC-derived BCs transplanted into polidocanol-injured syngeneic recipients give rise for at least two years to progeny that stably display the morphologic, molecular, and functional phenotypes of airway epithelia. The engrafted basal-like cells retain extensive self-renewal potential, evident by the capacity to reconstitute the tracheal epithelium through seven generations of secondary transplantation. Using the same approach, human primary or PSC-derived BCs transplanted into NOD scid gamma (NSG) recipient mice similarly display multilineage airway epithelial differentiation in vivo. Our results may provide a step toward potential future syngeneic cell-based therapy for patients with diseases resulting from airway epithelial cell damage or dysfunction.
Topics: Humans; Animals; Mice; Pluripotent Stem Cells; Cell- and Tissue-Based Therapy; Epithelial Cells; Epithelium; Mice, Inbred NOD; Mice, SCID
PubMed: 37625411
DOI: 10.1016/j.stem.2023.07.014 -
International Journal of Nanomedicine 2023Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic...
PURPOSE
Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI.
METHODS
A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining.
RESULTS
GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well.
CONCLUSION
The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.
Topics: Humans; Animals; Mice; Hydrogels; Pancreatic Neoplasms; Gemcitabine; Ultrasonography, Interventional
PubMed: 37496690
DOI: 10.2147/IJN.S417445 -
Techniques in Coloproctology Jan 2024This systematic review and meta-analysis aimed to evaluate the safety and efficacy of sclerotherapy methods for hemorrhoidal disease (HD) over the past 40 years. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the safety and efficacy of sclerotherapy methods for hemorrhoidal disease (HD) over the past 40 years.
METHODS
The review followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive literature search was conducted, including studies reporting the use of sclerotherapy in patients with HD. Study eligibility criteria were defined, and data were extracted independently by the authors. Random-effects meta-analyses were performed to assess outcomes of interest.
RESULTS
Out of 1965 records identified, 44 studies met the inclusion criteria, involving 9729 patients. The majority of studies were conducted in Japan, followed by the UK, Italy, and Portugal. The median age of participants was 52 years, and the majority were male. The Goligher grade distribution indicated varying degrees of HD severity. Sclerotherapy was predominantly administered through anoscopy, with polidocanol being the most commonly used agent. The procedure was generally performed without pre-injection analgesia. The meta-analysis of 14 randomized controlled trials (RCTs) revealed that sclerotherapy was not inferior to control interventions in terms of success rate (risk ratio [RR] 1.00, 95% CI 0.71-1.41) and recurrence rate (RR 1.11, 95% CI 0.69-1.77), while resulting in fewer complications (RR 0.46, 95% CI 0.23-0.92).
CONCLUSIONS
This systematic review highlights the safety and efficacy of sclerotherapy for HD, which yields similar success rates and fewer complications compared to other conservative or surgical approaches. Further research is warranted to optimize sclerotherapy techniques and evaluate long-term outcomes.
REGISTRATION
PROSPERO 2023 CRD42023396910.
Topics: Male; Humans; Female; Middle Aged; Sclerotherapy; Hemorrhoids; Italy; Odds Ratio; Polidocanol
PubMed: 38261136
DOI: 10.1007/s10151-023-02908-w -
World Journal of Orthopedics Sep 2023Aneurysmal bone cysts (ABC) are benign cystic bone tumors of an osteolytic and locally aggressive nature. As an alternative to the primary treatment of choice, which...
BACKGROUND
Aneurysmal bone cysts (ABC) are benign cystic bone tumors of an osteolytic and locally aggressive nature. As an alternative to the primary treatment of choice, which consists of curettage with bone grafting, alternative treatment methods with promising results have been described. At our department, we have, in recent years, used percutaneous sclerotherapy with polidocanol. The objective of this study was to identify the healing rate and safety of sclerotherapy with polidocanol.
AIM
To identify the efficacy and safety of sclerotherapy with polidocanol in primary and recurrent ABC.
METHODS
Twenty-two consecutive patients (median age 12.5 years; range 1-27) with 23 ABCs treated with sclerotherapy with polidocanol from 2016-2021 were included retrospectively. Eleven patients (48%) had undergone different forms of previous treatment with recurrence. Under general anesthesia and fluoroscopic guidance, repeated percutaneous injections of 4mg polidocanol/kg body weight were performed. Through review of the electronic medical records, the following were identified: healing and recurrence rate, number of treatments, gender, age, comorbidity, location of the tumor and side effects / complications, as well as any previous surgery for ABC. The median length of radiographic follow-up was 19.5 mo.
RESULTS
All ABCs except one (96%) showed healing or stable disease after a median of 4 (range 1-8) injections. Complete clinical and radiographic healing was observed in 16 cysts (70%), while partial radiographic healing with resolution of pain was seen in 6 cases (26%) and considered as stable disease. The cyst that failed to heal had previously undergone curettage twice with recurrence. One patient with a large pelvic ABC experienced, right after two injections, a sudden drop in blood pressure, which could quickly be reversed. One patient with a juxtaphyseal ABC in the femoral neck showed a minor limb length discrepancy because of deformity. Beyond that, no complications were observed.
CONCLUSION
Percutaneous sclerotherapy with polidocanol appears to be a safe alternative for treatment of aneurysmal bone cysts. In our series of both primary and recurrent cysts, it showed the ability to achieve healing or stable disease in 22 of 23 cases (96%). Further studies are needed to decide if this provides a long-lasting effect.
PubMed: 37744716
DOI: 10.5312/wjo.v14.i9.698 -
Japanese Journal of Radiology Oct 2023This study aimed to evaluate the value of fat-suppressed T2-weighted imaging (FS-T2WI) for predicting short-term pain relief after polidocanol sclerotherapy for painful...
PURPOSE
This study aimed to evaluate the value of fat-suppressed T2-weighted imaging (FS-T2WI) for predicting short-term pain relief after polidocanol sclerotherapy for painful venous malformations (VMs) in the extremities.
MATERIALS AND METHODS
This retrospective study included patients with painful VMs in the extremities between October 2014 and September 2021, had their first sclerotherapy without history of surgical therapy, and underwent magnetic resonance imaging before sclerotherapy. Pain relief was assessed 2 months after 3% polidocanol sclerotherapy and was categorized as follows: progression, no change, partial relief, or free of pain. The associations between pain relief and imaging features on FS-T2WI were analyzed.
RESULTS
The study included 51 patients. The no change, partial relief, and free of pain groups included 6 (11.8%), 25 (49.0%), and 20 (39.2%) patients, respectively. No patient experienced progressive pain. The lesion diameter was ≤ 50 mm in 13 (65.0%) patients in the free of pain group, whereas it was > 50 mm in all patients in the no change group (p = 0.019). The lesions showed well-defined margin in 15 (75.0%) patients in the free of pain group, whereas they showed ill-defined margin in 5 (83.3%) patients in the no change group (p = 0.034). The most common morphological type was cavitary in the free of pain group (14 [70.0%] patients), whereas there was no patient with cavitary type lesion in the no change group (p = 0.003). Drainage vein was demonstrated in 6 (100%), 22 (88.0%), and 11 (55.0%) patients in the no change, partial relief, and free of pain group, respectively (p = 0.011).
CONCLUSION
A lesion size of 50 mm or less, a well-defined margin, a cavitary type, and no drainage vein on FS-T2WI were significant features for predicting short-term pain relief after polidocanol sclerotherapy for painful VMs in the extremities.
Topics: Humans; Sclerotherapy; Polidocanol; Sclerosing Solutions; Retrospective Studies; Vascular Malformations; Pain; Magnetic Resonance Imaging; Extremities; Treatment Outcome
PubMed: 37170024
DOI: 10.1007/s11604-023-01442-x -
Clinics (Sao Paulo, Brazil) 2024Lower limb varicose veins are a prevalent disease associated with several available treatment options, including conventional surgery and polidocanol foam sclerotherapy.... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Lower limb varicose veins are a prevalent disease associated with several available treatment options, including conventional surgery and polidocanol foam sclerotherapy. However, few studies have analyzed therapeutic modality outcomes based on Patient-Reported Outcome Measures (PROMs). This large sample-size study was designed to evaluate the outcomes of polidocanol foam sclerotherapy compared to conventional surgery based on an analysis of PROMs.
METHODS
This was a prospective, observational, and qualitative study of 205 patients who underwent varicose vein treatment with either polidocanol foam sclerotherapy (57 patients, 90 legs) or conventional surgery (148 patients, 236 legs). Patients were preoperatively assessed and re-evaluated 30 days after the procedure using the Venous Disease Severity Score (VCSS) and specific venous disease quality-of-life questionnaires (VEINES-QoL/Sym).
RESULTS
Both treatments significantly improved VCSS and VEINES results 30 days after the procedure (p < 0.05). However, surgery promoted greater improvements in VCSS (on average 4.02-points improvement, p < 0.001), VEINES-QoL (average 8-points improvement, p < 0.001), and VEINES-Sym (average 11.66 points improvement, p < 0.001) than did sclerotherapy. Postoperative pain and aesthetic concerns about the legs were the domains of the questionnaires in which the results varied the most between the treatment modalities, with worse results for sclerotherapy.
CONCLUSION
Both polidocanol foam sclerotherapy and conventional surgery positively impact patients' quality of life after 30 days, but the improvement is more significant for patients who undergo conventional surgery.
Topics: Humans; Polidocanol; Polyethylene Glycols; Prospective Studies; Quality of Life; Saphenous Vein; Sclerosing Solutions; Sclerotherapy; Treatment Outcome; Varicose Veins
PubMed: 38574572
DOI: 10.1016/j.clinsp.2024.100346 -
Journal of Vascular Surgery. Venous and... Mar 2024The objective of this study was to retrospectively evaluate the effectiveness of polidocanol in managing pain, swelling, functional limiting and cosmetic disorders in...
OBJECTIVE
The objective of this study was to retrospectively evaluate the effectiveness of polidocanol in managing pain, swelling, functional limiting and cosmetic disorders in patients with venous malformations (VMs).
METHODS
This retrospective study included patients who underwent sclerotherapy with polidocanol for VMs between 2020 and 2022. Patient records, imaging findings, and evaluation questionnaires used in the preprocedure and follow-up phases were reviewed. After sclerotherapy, patients were followed up at 1, 2, 3, and 6 months. During these visits, the previously used 11-point verbal numerical rating scale (from 0 [no pain] to 10 [worst pain thinkable]) was used to evaluate the severity of symptoms such as pain, swelling, cosmetic discomfort, and functional limitation, and patients were asked to report the number of days per week they experienced these symptoms owing to the VM.
RESULTS
A total of 194 sclerotherapy procedures (mean, 1.6 ± 0.3 procedures) in 84 patients (55 female and 29 male patients; mean age, 22.45 ± 11.83 years) were conducted. The majority of these malformations (81%, or 68 patients) were located in the extremities. We found a significant decrease in pain, swelling, functional limitation, cosmetic appearance, and number of painful days between all time points, except for the comparison between months 3 and 6 (P < .001) CONCLUSIONS: Polidocanol sclerotherapy is a safe and effective treatment for VMs that significantly decreases patient complaints and has a very low complication rate. Particularly, following patients at short intervals and administering additional sclerotherapy sessions when necessary will significantly increase patient satisfaction.
Topics: Humans; Male; Female; Child; Adolescent; Young Adult; Adult; Polidocanol; Sclerotherapy; Retrospective Studies; Sclerosing Solutions; Vascular Malformations; Treatment Outcome; Pain; Polyethylene Glycols
PubMed: 37890587
DOI: 10.1016/j.jvsv.2023.101698 -
Journal of Clinical Medicine Nov 2023Percutaneous treatment for primary aneurysmal bone cysts (ABCs) has been widely accepted. The study aimed to evaluate the efficacy of various sclerotherapy agents on... (Review)
Review
BACKGROUND
Percutaneous treatment for primary aneurysmal bone cysts (ABCs) has been widely accepted. The study aimed to evaluate the efficacy of various sclerotherapy agents on patients with primary ABCs.
METHODS
A meta-analysis of relevant studies. A systematic search was conducted on five databases, resulting in the inclusion of 25 studies with different percutaneous agents.
RESULTS
A total of 729 patients with primary ABCs were included. Patients were administered with Ethibloc, doxycycline, embolization, alcohol, polidocanol, and calcitonin with methylprednisolone, respectively. Overall, 542 (74.3%) patients with ABCs had complete healing, 120 (16.4%) had partial healing, 44 (6%) had no-ossification or failure, and 26 (3.5%) had a recurrence. However, there was a total of 45 (6.1%) patients who had surgical curettage after sclerotherapy. Among the sclerotherapy agents, doxycycline showed highly effective results with minimal complications and recurrence, but it required multiple injections per patient. Ethibloc and embolization also proved to be highly effective with fewer injections required but had a higher rate of complications. Absolute alcohol, polidocanol, and calcitonin with methylprednisolone had similar efficacity and favorable success with fewer complications and fewer injections.
CONCLUSION
Percutaneous treatment showed promising results in treating primary ABCs. However, more robust research is needed to establish the best approach for sclerotherapy in clinical practice and to address the limitations of the current literature.
PubMed: 38068264
DOI: 10.3390/jcm12237213 -
Frontiers in Neurology 2024Although sclerotherapy is widely used to treat vascular malformations (VMs), it is associated with several challenges. One significant issue is the insufficient...
BACKGROUND
Although sclerotherapy is widely used to treat vascular malformations (VMs), it is associated with several challenges. One significant issue is the insufficient understanding of the influence of various factors on the stability of polidocanol (POL) foam used in sclerotherapy.
OBJECTIVE
This study aimed to explore the effect of the catheter needle caliber on foam stability when using POL with or without hyaluronic acid (HA) for the treatment of VMs.
METHODS AND MATERIALS
The Tessari method generated sclerosant foam using POL both with and without HA. We used catheters and syringe needles of various calibers, and the resulting foam was transferred into new syringes to facilitate a comparison of foam stability. Foam half-life (FHT) was utilized as a metric to assess foam stability.
RESULTS
The study found that narrower needle calibers produced a more stable foam when POL was used alone; however, no significant effect was observed when HA was added. Furthermore, when the foam was expelled using catheters and syringe needles of the same size, no noticeable changes in the stability were observed.
CONCLUSION
When choosing needles of varying calibers, their effect on foam stability should be carefully considered, particularly when the foam contains HA.
PubMed: 38841699
DOI: 10.3389/fneur.2024.1417788