Development of phytosterol-loaded silver nanoparticles for ameliorating haemorrhoidal complications via the AMPK pathway-a mechanistic approach.

The aim of the current study was to synthesize silver nanoparticles (PLSNPs) using green technology by means of phytosterol-enriched fractions fromBlumea laceraextracts (EAF) and evaluate their toxicological and anti-haemorrhoidal potential. The average size of the synthesized particles was found to be 85.64 nm by scanning electron microscopy and transmission electron microscopy. Energy dispersive spectroscopy showed the elemental composition of PLSNPs to be 12.59% carbon and 87.41% silver, indicating the capping of phytochemicals on the PLSNPs. The PLSNPs were also standardized for total phytosterol content using chemical methods and high-perfromance liquid chromatography. The PLSNPs were found to be safe up to 1000 mg kg-1as no toxicity was observed in the acute and sub-acute toxicity studies performed as per OECD guidelines. After the induction of haemorrhoids, experimental animals were treated with different doses of EAF, PLSNPs and a standard drug (Pilex) for 7 d, and on the eighth day the ameliorative potential was assessed by evaluating the haemorrhoidal (inflammatory severity index, recto-anal coefficient) and biochemical (tumour necrosis factor-alpha and interleukin-6) parameters and histology of the recto-anal tissue. The results showed that treatment with PLSNPs and Pilex significantly (p< 0.05) reduced haemorrhoidal and biochemical parameters. This was further supported by restoration of altered antioxidant status. Further, a marked reduction in the inflammatory zones along with minimal dilated blood vessels was observed in the histopathological study. The results of molecular docking studies also confirmed the amelioration of haemorrhoids via AMP-activated protein kinase (AMPK)-mediated reduction of inflammation and endothelin B receptor modification by PLSNPs. In conclusion, PLSNPs could be a good alternative for the management of haemorrhoids.

Hemorrhoidal disease among doctors from grade-A tertiary hospitals in big cities of China: results from web-based doctors as patients survey.

BACKGROUND: Doctors are at high risk of developing hemorrhoidal disease (HD), but it is unclear whether doctors are aware of this risk. The OASIS (dOctors AS patIentS) study was performed to examine the prevalence, awareness, diagnosis, and treatment of HD among doctors in big cities in China. METHODS: An online survey consisting of a structured questionnaire was carried out among doctors in grade-A tertiary hospitals in 29 provinces across China from August to October 2020. RESULTS: A total of 1227 questionnaire responses were collected. HD prevalence was 56.8%, with a significant difference between internists and surgeons (P = 0.01). 15.6% of doctors with HD didn't have serious concerns about the recurrence and severity of HD. 91.5% of doctors adopted general treatments, and 83.0% considered oral medications only when topical medications were ineffective. Among the oral medications, Micronized Purified Flavonoid Fraction (MPFF) was most effective based on the scores from three important parameters, but only 17% of doctors received MPFF. CONCLUSIONS: Doctors are at higher risk of developing HD with a high prevalence among Chinese doctors, but they are not fully aware or not concerned about HD. There is a deficiency in treatment recommendations and clinical management of HD even for doctors, including late initiation and inadequate oral drug therapy. Therefore, awareness and standardized treatment of HD should be improved among Chinese doctors, as well as in the general population.

Clinical evidence and rationale of mesoglycan to treat chronic venous disease and hemorrhoidal disease: a narrative review.

Chronic venous disease (CVD) and hemorrhoidal disease (HD) are among the most common vascular diseases in the world, with CVD affecting 22-41% of the population in Europe and HD having a point prevalence of 11-39%. The burden is substantial in terms of the effect of symptoms on patients' health-related quality of life (HRQoL) and direct/indirect medical costs. Treatment begins with lifestyle changes, compression in CVD and topical therapies in HD, and escalates as needed through oral therapies first and eventually to surgery for severe disease. CVD and HD share etiological features and pathological changes affecting the structure and function of the tissue extracellular matrix. Mesoglycan, a natural glycosaminoglycan (GAG) preparation composed primarily of heparan sulfate and dermatan sulfate, has been demonstrated to positively impact the underlying causes of CVD and HD, regenerating the glycocalyx and restoring endothelial function, in addition to having antithrombotic, profibrinolytic, anti-inflammatory, antiedema and wound-healing effects. In clinical trials, oral mesoglycan reduced the severity of CVD signs and symptoms, improved HRQoL, and accelerated ulcer healing. In patients with HD, mesoglycan significantly reduced the severity of signs and symptoms and the risk of rectal bleeding. In patients undergoing excisional hemorrhoidectomy, adding mesoglycan to standard postoperative care reduced pain, improved HRQoL, reduced incidence of thrombosis, and facilitated an earlier return to normal activities/work, compared with standard postoperative care alone. The clinical effects of mesoglycan in patients with CVD or HD are consistent with the agent's known mechanisms of action.

Colonization of multidrug-resistant Gram-negative bacteria increases risk of surgical site infection after hemorrhoidectomy: a cross-sectional study of two centers in southern China.

PURPOSE: The present study aims to determine the rectoanal colonization rate and risk factors for the colonization of present multidrug-resistant bacteria (MDRBs). In addition, the relationship between MDRB colonization and surgical site infection (SSI) following hemorrhoidectomy was explored. METHODS: A cross-sectional study was conducted in the Department of Colorectal Surgery of two hospitals. Patients with hemorrhoid disease, who underwent hemorrhoidectomy, were included. The pre-surgical screening of multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization was performed using rectal swabs on the day of admission. Then, the MDRB colonization rate was determined through the rectal swab. Logistic regression models were established to determine the risk factors for MDRB colonization and SSI after hemorrhoidectomy. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 432 patients met the inclusion criteria, and the MDRB colonization prevalence was 21.06% (91/432). The independent risk factors for MDRB colonization were as follows: patients who received ≥ 2 categories of antibiotic treatment within 3 months (odds ratio (OR): 3.714, 95% confidence interval (CI): 1.436-9.605, p = 0.007), patients with inflammatory bowel disease (IBD; OR: 6.746, 95% CI: 2.361-19.608, p < 0.001), and patients with high serum uric acid (OR: 1.006, 95% CI: 1.001-1.010, p = 0.017). Furthermore, 41.57% (37/89) of MDRB carriers and 1.81% (6/332) of non-carriers developed SSIs, with a total incidence of 10.21% (43/421). Based on the multivariable model, the rectoanal colonization of MDRBs (OR: 32.087, 95% CI: 12.052-85.424, p < 0.001) and hemoglobin < 100 g/L (OR: 4.130, 95% CI: 1.556-10.960, p = 0.004) were independently associated with SSI after hemorrhoidectomy. CONCLUSION: The rectoanal colonization rate of MDRBs in hemorrhoid patients is high, and this was identified as an independent risk factor for SSI after hemorrhoidectomy.

Case Report of Anal Fissures and Hemorrhoids Treated with Compounded Cromolyn Sodium and Naltrexone Hydrochloride in MEDISCA's SPG SUPPOSI-BASE.

The purpose of this case report is to evaluate and demonstrate the benefits of compounded therapy in treating chronic rectal fissures with hemorrhoids using a compounded suppository containing cromolyn sodium and naltrexone hydrochloride in MEDISCA's SPG SUPPOSI-BASE. The primary outcomes of symptomatic improvement and healed fissure were reported and confirmed by the practitioner and, via self-assessment, by the patient, which was observed after a long-troubled history of failed treatments. The case had no side effects or complications, and the patient reported a full recovery after using this compounded therapy for ten days.

Sclerotherapy with 3% polidocanol foam to treat second-degree haemorrhoidal disease: Three-year follow-up of a multicentre, single arm, IDEAL phase 2b trial.

BACKGROUND: Sclerotherapy with 3% polidocanol foam is becoming increasingly popular for the treatment of symptomatic I-II or III degree haemorrhoidal disease (HD). However, there are no studies that have reported a follow-up of more than 1 year. The purpose of this study was to analyse the long-term outcomes of sclerotherapy with 3% polidocanol foam in the treatment of II-degree HD. METHODS: This was an open label, single-arm, phase 2b trial conducted in 10 tertiary referral centres for HD. A total of 183 patients with II-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification and unresponsive to medical treatment, were included in the study and underwent sclerotherapy with 3% polidocanol foam. The efficacy was evaluated in terms of bleeding score, haemorrhoidal disease symptom score (HDSS) and short health scale for HD (SHS-HD) score. Successful treatment was defined as the complete absence of bleeding episodes after 7 days (T1) according to the bleeding score. RESULTS: The overall success rate ranged from 95.6% (175/183) at 1 year to 90.2% (165/183) after the final 3 year follow-up. The recurrence rate, based on the primary outcome, ranged from 12% (15/125) to 28% (35/125). The greatest increase in recurrence (15) was recorded between 12 and 18 months of follow-up, then another five between 18 and 24 months. Both the HDSS and the SHS score remained statistically significant (p < 0.001) from a median preoperative value of 11 (10-13) and 18 (15-20) to 0 (0-2) and 4 (0-4), respectively. Symptom-free (HDSS = 0) patients, excluding patients converted to surgery, increased from 55.5% (101/182) at 1 year to 65.1% at 3 years (110/169). There were no intraoperative complications in redo-sclerotherapy nor additional adverse events (AEs) compared to the first 12 months. CONCLUSIONS: Sclerotherapy with 3% polidocanol foam is gradually establishing itself in the treatment of bleeding HD due to its repeatability, safety, convenience in terms of direct and indirect costs with the absence of discomfort for the patient as well as AEs rather than an excellent overall success rate.

Utility of botulinum toxin injection for post-operative pain management after conventional hemorrhoidectomy: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Botulinum Toxin (BTX) has been found to have anti-spasm and analgesic effects. The utility of BTX after conventional hemorrhoidectomy remains unclear. Thus, a systematic review and meta-analysis are required to find out its utility after conventional hemorrhoidectomy. METHODS: Using specific keywords, we comprehensively go through the potential articles on PubMed, ClinicalTrials.gov, and Europe PMC sources until March 27th, 2022. All published studies on botulinum toxin anal sphincter injection after conventional hemorrhoidectomy were collected. We were using Review Manager 5.4 software to conduct statistical analysis. RESULTS: Five clinical trial studies with a total of 260 patients undergoing hemorrhoidectomy were included in the analysis Our pooled analysis revealed that BTX injection after hemorrhoidectomy was associated with lower VAS at 24 h post-operative [Mean Difference -1.35 (95% CI -1.90, -0.80), p < 0.00001, I2 = 0%] and shorter time to return work [Mean Difference -8.94 days (95% CI -12.57, -5.30), p < 0.00001, I2 = 0%]. However, BTX injection did not differ significantly from placebo in terms of time to first defecation (p = 0.22), fecal incontinence (p = 0.91) and urinary retention incidence (p = 0.18). CONCLUSION: BTX sphincter injection may offer some benefit after conventional hemorrhoidectomy in reducing pain from the first day after the procedure and promoting wound healing without complication. Further randomized clinical trials are still needed to confirm the results of our study.

Recurrence Rates and Pharmacological Treatment for Hemorrhoidal Disease: A Systematic Review.

INTRODUCTION: Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD. METHODS: Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews. RESULTS: The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5% following surgery or phlebotonics, with most (n = 19) reporting rates of 20% or less. In addition to time since treatment, risk factors for recurring disease were similar to those for HD in general. With respect to treatment, micronized purified flavonoid fractions significantly improved the main symptoms of HD compared to other pharmacological treatments. CONCLUSION: The SLRs did not identify any RWE studies reporting recurrence in patients receiving systemic or topical treatments, highlighting the need for future research in this area. Further, more studies are needed to understand the optimum duration of medical treatment to prevent recurrence.

Patients with hemorrhoidal disease (HD) can experience recurring disease following a period of improvement or remission. It is not well established how often this might happen, who is at greatest risk, or which treatments can reduce this risk. In this study, a systematic literature review (SLR) was conducted to summarize evidence on the occurrence and recurrence of HD, as well as treatment effectiveness. Several literature databases were searched for articles that described real-world evidence (RWE) studies reporting the epidemiology or recurrence of HD as well as published SLRs that combined the results of multiple studies (meta-analyses) on treatment for adults with HD. Forty of 2037 articles identified by the search were considered relevant, and four others identified by clinicians were also included (total = 44; 39 RWE, 5 meta-analyses). Review of the RWE articles revealed that HD epidemiology was determined differently between studies. Only 23 reported recurrence rates (up to 56.5%) after surgery or treatment with phlebotonic drugs (drugs that improve blood flow in veins). Most (19/23) reported recurrence rates of 20% or less. Risk factors for recurrence were similar to usual HD risk factors (e.g., constipation, male gender, age) in addition to time since treatment. Phlebotonic agents, including those made from plant extracts (micronized purified flavonoid fractions, MPFFs) improved hemorrhoidal symptoms compared with placebo or no treatment. In one meta-analysis, MPFF was the only phlebotonic to significantly reduce recurrence risk versus no treatment or placebo. Overall, more research is needed to compare treatments and determine optimal treatment duration to prevent recurrence. Author-narrated video abstract.

[Modern trends in combined treatment of hemorrhoids: topical form Tribenoside + Lidocaine and phlebotonic Ginkgo biloba + Troxerutin + Heptaminol]. / Sovremennye trendy v kombinirovannom lechenii gemorroya: primenenie mestnoi formy tribenozid + lidokain i sistemnogo venotoniziruyushchego preparata ginkgo biloba + trokserutin + geptaminol.

Acute hemorrhoids are the most common reason for referring to coloproctologist in people of working age. In the modern world, food culture and lifestyle are the most prominent factors leading to the risk of hemorrhoids. In the 21st century, it is hard to overestimate an importance of potential employability and active social role regarding socio-economic well-being. This thesis applies to patients suffering from proctological diseases, and those with hemorrhoids prevail among these ones. Minimally invasive treatment and pharmacotherapy defined primary needs of patients, i.e. treatment should be quick, safe and effective. Favorable treatment outcomes are possible only in pathogenetic therapy. In this review, we will define the priorities in effective combined treatment of hemorrhoids.

Efficacy and safety of micronized purified flavonoid fractions for the treatment of postoperative hemorrhoid complications: A systematic review and meta-analysis.

BACKGROUND: Hemorrhoids, a common anorectal disease, seriously affects patients' quality of life. Micronized purified flavonoid fractions (MPFF) have been shown to improve hemorrhoid symptoms. PURPOSE: To evaluate the efficacy and safety of MPFF in treating postoperative hemorrhoid complications. STUDY DESIGN: A systematic review and meta-analysis of existing literature on natural compounds for treating postoperative complications of hemorrhoids. METHODS: A literature search was conducted using five databases, namely PubMed, WanFang, CNKI, Embase, and the Cochrane Library, to identify randomized controlled trials (RCTs) on the effects of MPFF treatment on hemorrhoids. Stata 15.1 and Revman 15.4 were used to assess the data, while subgroup and sensitivity analyses were performed to evaluate potential heterogeneity, and trial sequential analysis (TSA) and Egger test were used to evaluate the reliability of each trial. RESULTS: A total of 22 RCTs, including 2,335 participants were included in the analysis. MPFF improved the clinical efficacy of post-hemorrhoidectomy and reduced the bleeding rate, pain score, and edema score, although no substantial effect on adverse reactions was reported. Subgroup analyses showed a significant reduction in pain score and bleeding rate in trials with duration of 4-10 days and an improvement in clinical efficacy. Treatment for ≥ 10 days significantly improved the edema score; a dosage range of 1,800-2,700 mg/day of MPFF significantly reduced edema and pain scores, whereas < 1,800 mg/day significantly improved clinical efficacy. CONCLUSIONS: Based on searching the relevant literatures, this is the first meta-analysis on MPFF treatment of postoperative hemorrhoid complications. Our findings, validated by TSA, suggest that MPFF is safe and effective in reducing postoperative hemorrhoid complications, and that dose and duration are key factors in its efficacy, as illustrated by subgroup analysis. However, due to the small sample size, the standardized treatment regimen of MPFF could not be obtained; therefore, further research is warranted.

Safety and efficacy of topical drug-free cream in subjects with hemorrhoidal disease: a randomized, double blind, clinical trial.

BACKGROUND: Hemorrhoidal disease (HD) is one of the most common anorectal benign disorder affecting millions of people around the world. Grade I-II HD are generally treated with a conservative approach with topical products such as creams and ointments considered a safe and effective option to treat mild symptoms. The aim of the present study was to assess the safety and efficacy of a topical medical device (Lenoid™; International Health Science [IHS] - Biofarma Group, Mereto di Tomba, Udine, Italy) in patients affected by symptomatic HD. METHODS: This study is a randomized, double blind, placebo-controlled, 2-weeks clinical trial. Patients affected by I-II grade symptomatic HD were enrolled in the study and then randomly assigned to Lenoid™ arm (LA) or placebo arm (PA), respectively. Patients were evaluated before and after intervention through clinical examination and disease-specific questionnaires assessing symptoms such as pain, tenesmus, pruritus and anal discharge. RESULTS: A total of 68 patients were screened and 60 (30 in each group) were enrolled into the study. All patients belonging to LA showed a statistically significant improvement of each symptom after 7 and 14 days of treatment when compared to PA (P<0.001). Furthermore, subjective improvement of change in overall assessment of disease was observed in the LA but not in the PA. No serious adverse events were recorded. CONCLUSIONS: The tested product was found safe and effective in improving clinical signs and symptoms in patients with grade I-II HD.

Histomorphometric study of ethanolic extract of Graptophyllum pictum (L.) Griff. leaves on croton oil-induced hemorrhoid mice: A Javanese traditional anti-hemorrhoid herb.

ETHNOPHARMACOLOGY RELEVANCE: Graptophyllum pictum (L.) Griff., known as "handeuleum" in West Java and "Daun Ungu" in Indonesia, is traditionally used to cure hemorrhoids. AIM OF THE STUDY: The purpose of this study is to prove its effectiveness scientifically using anorectal histological parameters in Croton oil-induced hemorrhoid mice. MATERIALS AND METHODS: In vivo tests were performed by observing histomorphologic changes in mice anorectal tissue induced by croton oil. In addition, in vitro assay was performed for evaluating antioxidant activity, astringency property, and hemostasis-associated activity. The antioxidant activity was measured using a DPPH radical scavenging assay. The total flavonoid and phenolic contents were also determined spectrophotometrically. RESULTS: The in vivo assay showed that the oral-topical combination use of the ethanolic extract of G. pictum leaves demonstrated significant improvement on the croton oil-induced anorectal damage better than the single application by oral or topical application. CONCLUSION: These results showed that G. pictum has potent anti hemorrhoid activity, especially for the combinational use of oral and topical administration.

Photodynamic therapy in the treatment of perianal condyloma acuminatum with hemorrhoids: A report of two cases.

In this work, we used photodynamic therapy(ALA-PDT) to treat 2 patients with perianal hemorrhoids combined with condyloma acuminatum. After 4 photodynamic treatments, the condyloma acuminata skin lesions completely disappeared. At the same time, we unexpectedly found that the patient's hemorrhoids skin lesions had mostly faded, and did not reappear during the half-year follow-up. Photodynamic therapy is satisfactory in the treatment of hemorrhoids combined with condyloma acuminatum, and the recurrence rate is low. We also have found that photodynamic therapy is equally effective on hemorrhoid skin lesions. PDT may be adopted as a new strategy in the study and treatment of hemorrhoids. To the best of our knowledge, no such cases have been reported.

Efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and the effect on fibulin protein expression: A study protocol of a randomized controlled trial.

BACKGROUND: Hemorrhoids are a common and seriously disruptive condition that seriously affects people's lives in terms of treatment. Injection therapy is an effective minimally invasive scheme for the treatment of grade II-III hemorrhoids, but its clinical application is limited by the adverse reactions caused by injection drugs. Some clinical studies have confirmed the efficacy and safety of Shaobei injection as a traditional Chinese medicine extract. However, there is no standard randomized controlled study to verify its efficacy and explore its potential mechanism. METHODS: This is a prospective, randomized, single blind, parallel controlled trial to study the efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and its effect on the expression of fibulin-3 and fibulin-5 in fibulin protein family. The patients will be randomly divided into a treatment group and control group. The treatment group will be treated with Shaobei injection, and the control group will be treated with rubber band ligation. The observation indexes include: visual analysis scale, postoperative hospital stay, total use of painkillers, fibulin-3 and fibulin-5, hemorrhoids recurrence, and adverse events. Finally, the data will be statistically analyzed by SPASS 18.0 software. DISCUSSION: This study will compare the efficacy of Shaobei injection with the rubber band ligation method in the treatment of grade II-III haemorrhoids and investigate its effect on the expression of fibulin-3 and fibulin-5 in the fibulin protein family. The results of this study will provide a basis for the clinical use of Paeoniflora injection as an alternative to traditional sclerosing agent in the treatment of grade II-III haemorrhoids.Trial registration: OSF Registration number:DOI 10.17605/OSF.IO/MKVDB.

Polyherbal formulation Anoac­H suppresses the expression of RANTES and VEGF for the management of bleeding hemorrhoids and fistula.

Hemorrhoids and fistula are considered the most common anorectal conditions in the general population. These conditions affect the quality of a patient's life by causing pain and bleeding during defecation or even in the resting state. Lower grades of hemorrhoids may be controlled by traditional measures. However, surgery is an effective treatment option in recurrent­lower and higher­grade hemorrhoids. Surgical procedures are associated with various complications, including pain and delayed wound healing. Recurrence of hemorrhoids is also a major concern in the post­operative period. An anal fistula is the connection between the anus and the skin and causes severe pain, swelling, as well as blood and pus discharge. Fistula has serious social and economic consequences. Hence, it is important to understand the pathophysiology and molecular pathology of hemorrhoids and fistula, to identify the molecular targets and to develop pharmacological­interventions. In a previous study by our group, the polyherbal formulation Anoac­H was developed for the treatment of different stages of hemorrhoids and fistula, and it was demonstrated that Anoac­H is an effective formulation for treating hemorrhoids. However, the molecular mode of action of Anoac­H on hemorrhoids and fistula had remained elusive. In the present study, it was determined that this formulation reduces the migration of mesenchymal (fibroblasts) and immune (RAW 264.7) cells without affecting their viability. It was also observed that Anoac­H suppresses the expression of regulated upon activation, normal T cell expressed and presumably secreted (RANTES) and VEGF in fibroblasts and macrophages. Inflammation and elevated expression of RANTES and VEGF were observed in hemorrhoids and fistula. However, inflammation, as well as the expression of RANTES and VEGF, were significantly reduced in treated human hemorrhoid and fistula tissues as compared to untreated ones, confirming the in vitro results.