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.

Mucosal Schwann cell hamartoma: a benign and little-known entity.

Dear editor, 50 years-old female with personal history of mutation of the gene BRCA1 and previous prophylactic double anexectomy consulted for rectal bleeding without pain since two weeks. A blood test was performed, with hemoglobin levels of 13.1g/dl and without iron deficiency. In the anal inspection there were neither external hemorrhoids nor anal fistulas, so a colonoscopy was requested. In the colonoscopy, all the colon mucosa was normal but, in the rectal retroflexion, apart from internal engorged hemorrhoids, surrounding the 50% of the anal opening an erythematous and indurated mucosa was found (figure 1). Biopsies were taken. The pathology report informed of proliferation of spindle-shaped cells exclusively in the lamina propria with eosinophilic cytoplasm and unclear cell borders (figure 2). Not nuclear atypia or mitotic activity were observed. On immunohistochemistry, S-100 protein was strongly positive (figure 3) and CD34, SMA, EMA and c-kit were negative. These results are concordant with the diagnosis of Schwann cells in the context of a mucosal Schwann cell hamartoma (MSCH). Given that these lesions seem to not have malignant potential, the patient was discharged without control colonoscopies. The episodes of rectorrhagia were attributed to the presence of internal hemorrhoids. Discussion: MSCH are benign and intramucosal tumors with a mesenchymal origin. They are most commonly located in the distal colon, but they were also found in the gallbladder, the esophagogastric union and in the antrum. They are observed most frequently in middle aged women (around 60 years-old) and they are generally asymptomatic. They are presented as polyps between 1 and 6mm, but in other cases they appeared as small whitish nodules, protruding lesions with normal superficial mucosa or even they were found in random biopsies of the colon. The MSCH are a rare entity with an unknown prevalence. Less than 100 cases are described in the literature. It is essential the differentiation between this entity and the Schwanomas or the gastrointestinal stromal tumors (GIST). Schwanomas are rare in the colon, they are well circumscribed (in contrast with the MSCH) and they are not limited to the lamina propria. GIST are more frequently located in the stomach and they are positive for c-kit. MSCH are not associated with hereditary syndromes such as neurofibromatosis and, in contrast with Schwanomas or GIST, they do not require surveillance because they are benign.

[Usefulness and safety of observing anorectal lesions by colon capsule endoscopy].

We investigated the findings of rectoanal lesions in 190 patients who underwent colon capsule endoscopy (CCE) at our hospital. Internal hemorrhoids were observed in 70 (36.8%) patients and rectal polyps in 19 (10%) patients. When conventional endoscopy (colonoscopy and double balloon endoscopy) was considered the gold standard, the sensitivity and specificity of rectal polyps were 75% and 93.4%, respectively, and those of internal hemorrhoids were 88.9% and 92.7%, respectively. The prevalence of constipation was significantly higher in the false-negative group for internal hemorrhoids, and the colonic transit time was significantly shorter in the false-negative and false-positive groups for rectal polyps. No adverse events occurred in any of the patients. CCE might be a useful and safe examination method for rectoanal lesions.

A morphometric analysis of pathological alterations in hemorrhoidal disease versus normal controls: a controlled trial

Objective: Until today, the true pathophysiology of hemorrhoidal disease (HD) has not yet been unraveled. More and more evidence guides us towards the hypothesis that reduced connective tissue stability is associated with a higher incidence of hemorrhoids. The present study aimed to compare the quantity and quality of collagen, and vessel morphometrics, in patients with symptomatic HD compared with normal controls. Methods: Twenty-two samples of grade III and grade IV HD tissue from patients undergoing a hemorrhoidectomy between January 2004 and June 2015 were included in the study group. Samples of 15 individuals without symptomatic HD who donated their body to science and died a natural death served as controls. The quantity and quality of anal collagen, and anal vessel morphometrics were objectified. The quality of collagen was subdivided in young (immature) and old (mature) collagen. Results: Patients with HD had an increased percentage of total anal collagen (62.1 ± 13.8 versus 18.7 ± 14.5%; p = 0.0001), a decreased percentage of young collagen (0.00009 ± 0.00008 versus 0.0008 ± 0.0008%; p = 0.001), and a smaller surface area of the anal vessels (795.1 ± 1215.9 micrometre2 versus 1219.0 ± 1976.1; p = 0.003) compared with controls. The percentage of old collagen did not differ between the control and study groups (0.588 ± 0.286% versus 0.389 ± 0.242%; p = 0.06). Conclusion: The outcomes of the present study suggest that alterations in anal collagen composition may play a role in the formation of hemorrhoids. (AU)

Anorectal Melanoma-Brownish Black Mass Not Always a Hemorrhoid.

The non-specific clinical symptoms of anorectal brownish-black mass do not help to differentiate colorectal cancer, hemorrhoids, rectal ulcers which result in a delayed diagnosis or lead to inadequate management of lethal anorectal melanoma. Primary malignant melanoma of the anorectal region is an uncommon tumor, constituting approximately 1% of anal canal tumors which may be misdiagnosed clinically as hemorrhoids. Because of aggressive behavior and poor prognosis, efficient and prompt diagnosis is required in these cases. We report 2 cases of this rare tumor.

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.

Prevalence and associated factors of hemorrhoids among adult patients visiting the surgical outpatient department in the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

INTRODUCTION: Hemorrhoidal disease is a very common benign anorectal disease. It affects millions of people around the world, and represent a major medical and socioeconomic problem. However, studies that determine the magnitude and risk factors are limited. Therefore, the aim this study is to assess the prevalence and associated factors of hemorrhoid among adult patients visiting the surgical outpatient department at the University of Gondar Comprehensive Specialized Hospital (UoGCSH) Northwest Ethiopia. METHODS: An institution-based cross-sectional study was conducted from February to May 2020. A systematic random sampling technique was used to select a total of 403 participants. The data were collected then entered using EPI DATA version 3.1 and exported to the STATA 14 for analysis. Bivariable and multivariable logistic regression analysis were performed. Adjusted odds ratio (AOR) with 95% confidence interval was used as a measure of association. Variables having P-value < 0.05 from the multivariable analysis were considered to have a significant association with the outcome. RESULT: Out of the 403 study participants, 13.1% (95%CI; 10.1, 16.8) had hemorrhoids. Constipation (AOR = 4.32, 95% CI; 2.20, 8.48) and BMI ≥25kg/m2 (AOR = 2.6, 95% CI; 1.08, 6.23) had a statistically significant association with hemorrhoid. CONCLUSION: The overall prevalence of hemorrhoid was high and its prevalence was higher in male subjects. Constipation and being overweight were found to increase the odds of having hemorrhoids. Screening for early identification and intervention of hemorrhoids, especially for risk groups is better to be practiced by health professionals.

From nutrition to medicine: Assessing hemorrhoid healing activity of Solanum melongena L. via in vivo experimental models and its major chemicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum melongena L. (eggplant) is used for treatment of rheumatism, beriberi, itching, toothache, bleeding, asthma, bronchitis, cholera, neuralgia and hemorrhoids in traditional medicine (Turkish, Chinese, and Indian). Hemorrhoids from these diseases, are common illness in all over the world, which are treated with various approaches including ethnobotanicals. AIM OF THE STUDY: This study aimed to evaluate the anti-hemorrhoidal activity of eggplant, an edible plant, which is commonly utilized around the world. MATERIALS & METHODS: In vivo anti-hemorrhoidal activity of the methanolic extract prepared from eggplant was evaluated by experimental hemorrhoid model, subsequently histological and biochemical analysis. Hemorrhoid, which was induced by applying croton oil to the anal area of the rats. Furthermore, the extract was screened for anti-inflammatory activity which is based on the inhibition of acetic acid-induced increase in capillary permeability. The healing potential was comparatively assessed with a reference Pilex® tablet and cream. Phytochemical analysis performed by HPLC. The amount of the major phenolic compound (chlorogenic acid) in extract was found by using HPLC method. RESULTS: Histological and biochemical analysis demonstrated that eggplant extract is highly effective against hemorrhoid in comparison to the controls and the commercial preparation. In addition, the methanolic extract demonstrated significant inhibitory effect on acetic acid-induced increase in capillary permeability. The phytochemical studies identified major compound as chlorogenic acid (2.86%) by liquid chromatography. CONCLUSION: The eggplant calyxes, not edible, are easy to reach, by products/vast from the food sources. This is the first scientific evidence revealing that the eggplant extract has significant anti-hemorrhoidal and anti-inflammatory activity.

Routine pathology examination in the era of value-based healthcare: the case of haemorrhoids specimens.

Routine pathologic examination of specimens is a common practice with ill-defined value. The present study is the first to investigate the incidence and cost of incidental microscopic lesions in both haemorrhoidectomy and stapled haemorrhoidopexy specimens. Pathological reports of specimens obtained from haemorrhoidectomy and stapled haemorrhoidopexy procedures performed from January 2003 to May 2017 were analysed. Specimens resulting from patients treated for any disease other than haemorrhoids alone were excluded from the study. Unexpected diagnoses in the pathological report were defined as incidental diagnoses. A cost analysis was then performed. In the considered period we performed a total of 3017 procedures complying with our criteria. We found 65 (2.15%) unexpected lesions. Of the incidental diagnosis, 30 (0.99%) altered either the follow-up or the treatment. The incidences of both findings were extremely higher in haemorrhoidectomies specimens (p < 0.0001). We estimated that the cost of 14 years of routine pathological examination of haemorrhoids specimens was 133,351.4 euros, each consequential incidental diagnosis costing 4445.03 euros. The incidence of unexpected lesions in routine pathologic examination of haemorrhoidectomy and haemorrhoidopexy specimens is low but not negligible. The vast majority of incidental findings were found among haemorrhoidectomy specimens. Even though the real value of routine pathological examination of haemorrhoids specimens is still uncertain, from a clinical standpoint we were glad to suggest each patients the best follow-up and/or treatment. Future studies should assess preoperative patient's risk stratification and careful intraoperative macroscopic inspection strategies for selective pathology examination of haemorrhoids specimens.

Regional Distribution of Nitric Oxide Synthase in Human Anorectal Tissue: A Pilot Study on the Potential Role for Nitric Oxide in Haemorrhoids.

OBJECTIVE: To study the distribution of nitric oxide synthase (NOS) isoforms and protein levels in human haemorrhoids and rectal tissue. METHODS: Protein expression of NOS1, NOS2 and NOS3 was compared between haemorrhoids (n=14) and normal rectal submucosa (n=6) using Western blot analysis. The localisation of all NOS isoforms to specific structures was determined by immunohistochemistry. RESULTS: Western blot analysis showed median (interquartile range) protein levels of all NOS isoforms were 1.5-2.4 times higher in haemorrhoids than rectal tissue; 121.4 (55.2-165.5) vs 50.0 (25.5-73.7) for NOS1 (p=0.020), 32.2 (23.8-140.6) vs 14.8 (9.6-34.0) for NOS2 (p=0.109), and 80.1 (62.0-139.5) vs 54.3 (48.7 -61.7) for NOS3 (p=0.015). Immunohistochemistry revealed a different distribution and location of all NOS isoforms in vascular and non-vascular structure of haemorrhoids and rectal tissues. The number of haemorrhoid specimens showing positive immunoreactivity of NOS in the vascular endothelium was significantly higher than that in rectal tissue for NOS1 (11/14 (79%) vs 1/6 (17%); p=0.018) and NOS3 (8/14 (57%) vs 0/6 (0%); p=0.042), but not for NOS2 (6/14 (43%) vs 4/6 (67%); p=0.63). CONCLUSION: Haemorrhoids have significantly higher protein levels of NOS1 and NOS3 than rectal tissue. The vascular endothelium of haemorrhoids also has significantly higher positive immunoreactivity of NOS1 and NOS3 than rectal tissue suggesting that blood vessels in haemorrhoids are exposed to higher NO concentrations than those of rectal tissue. Since haemorrhoids exhibit marked vascular dilatation and present with bleeding or swelling, a reduction in NOS - by applying NOS inhibitors - may potentially improve the symptoms of haemorrhoids.

Comparison of surgical procedures implemented in recent years for patients with grade III and IV hemorrhoids: a network meta-analysis.

PURPOSE: This study aimed to investigate the complications and recurrence rates of the different surgical procedures implemented in recent years for the treatment of grade III and IV hemorrhoids using a network meta-analysis approach. METHODS: A systematic literature search was conducted for randomized clinical trials (RCTs) published from January 2013 to August 2018, via PubMed, Embase, the Cochrane Library, and Web of Science. Data related to anal stenosis, fecal incontinence, hemorrhoids thrombosis, and recurrence rates were extracted from the included studies, which were selected based on associations with surgical procedures for grade III and IV hemorrhoids. A network meta-analysis was conducted by using the automated software Aggregate Data Drug Information System (ADDIS) 1.16.8 to evaluate and rank the safety and efficacy of the different surgical methods. RESULTS: Twenty-one studies with 2799 participants involving nine surgical procedures for grade III and IV hemorrhoids were ultimately analyzed. Transanal hemorrhoidal dearterialization (THD) and stapled hemorrhoidectomy (SH) exhibited fewer anal stenosis than open hemorrhoidectomy (OH) and Harmonic scalpel (Harmonic). SH presented the highest fecal incontinence rates. OH and Harmonic presented lower hemorrhoids thrombosis than SH and THD. Importantly, SH and THD exhibited the highest recurrence rates, when compared with the other hemorrhoidectomy surgical procedures. CONCLUSIONS: In summary, THD and SH were found to be associated with more complications and higher recurrence rates. In addition, the use of OH treatments resulted in less hemorrhoids thrombosis rate but higher recurrence rate. The use of Harmonic resulted in higher anal stenosis rate but lower recurrence rate.

Rethinking What We Know About Hemorrhoids.

Although hemorrhoids are responsible for considerable economic cost and personal suffering, they have received surprisingly little research attention. In the United States, hemorrhoids are the third most common outpatient gastrointestinal diagnosis with nearly 4 million office and emergency department visits annually. The etiology of hemorrhoids is speculative. A low-fiber diet and constipation have historically been thought to increase the risk for hemorrhoids, but not proven. Symptoms commonly attributed to hemorrhoids include bleeding, pain, pruritus, fecal seepage, prolapse, and mucus discharge. Research has found that these symptoms were equally reported by patients with and without hemorrhoids. Medical therapies for hemorrhoids have not been formally studied except for fiber where the results have been inconsistent. A number of office-based interventions such as rubber band ligation and infrared coagulation are widely used and economically favorable for practitioners. Surgical procedures are effective at eliminating hemorrhoids but may be painful. Given the burden of disease and numerous gaps in our understanding, the time has come for targeted research to understand the cause, symptoms, and best treatment for patients with symptomatic hemorrhoids.

Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease.

Vein segmentation is a vascular remodeling process mainly studied in experimental conditions and linked to hemodynamic factors, with clinical implications. The aim of this work is to assess the morphologic characteristics, associated findings, and mechanisms that participate in vein segmentation in humans. To this end, we examined 156 surgically obtained cases of hemorrhoidal disease. Segmentation occurred in 65 and was most prominent in 15, which were selected for serial sections, immunohistochemistry, and immunofluorescence procedures. The dilated veins showed differently sized spaces, separated by thin septa. Findings associated with vein segmentation were: (a) vascular channels formed from the vein intima endothelial cells (ECs) and located in the vein wall and/or intraluminal fibrin, (b) vascular loops formed by interconnected vascular channels (venous-venous connections), which encircled vein wall components or fibrin and formed folds/pillars/papillae (FPPs; the encircling ECs formed the FPP cover and the encircled components formed the core), and (c) FPP splitting, remodeling, alignment, and fusion, originating septa. Thrombosis was observed in some nonsegmented veins, while the segmented veins only occasionally contained thrombi. Dense microvasculature was also present in the interstitium and around veins. In conclusion, the findings suggest that hemorrhoidal vein segmentation is an adaptive process in which a piecemeal angiogenic mechanism participates, predominantly by intussusception, giving rise to intravascular FPPs, followed by linear rearrangement, remodeling and fusion of FPPs, and septa formation. Identification of other markers, as well as the molecular bases, hemodynamic relevance, and possible therapeutic implications of vein segmentation in dilated hemorrhoidal veins require further studies.

Evaluation of the effectiveness and patients' contentment with transanal haemorrhoidal artery dearterialisation and mucopexy (THD) for treatment of haemorrhoidal disease: a 6-year study.

INTRODUCTION: With high incidence of haemorrhoidal disease and significant complication rates of traditional haemorrhoidectomy procedures, transanal haemorrhoidal artery ligation and mucopexy (THD) emerges as a minimally invasive procedure with superior results. However, it is crucial that effectiveness of results and patient satisfaction be gauged based on post-operative experience, symptomology and recurrence. AIM: Our aim is to provide a long-term analysis of efficacy and patient's satisfaction for the procedure, for the largest patient population, in correlation to presenting symptoms and degree of haemorrhoids. METHOD: A prospective study was conducted for all the patients (324) that underwent THD between 2011 and 2016 in Naas General Hospital. The assessment was done for postoperative complications, symptoms pre- and postoperatively and patients' satisfaction rating. Clinical follow-up was done after 6 weeks and long-term follow-up by standardized questionnaire filled by telephonic clinic. RESULTS: Of the 324 patients who underwent surgery, 256 (79.0%) participated in the study. There were 119 (46.5%) males and 137 (53.5%) females. The average age of patients was 48.40 years (17-82). Two hundred and fifteen (84.0%) patients had no recurrence. Forty-one (16.0%) had recurrence requiring further treatment. There was statistically significant higher recurrence in patients with grade 3 and 4 haemorrhoids and per-rectal bleeding (p < 0.05) while there was no statistically significant recurrence for age, gender, sedentary lifestyle and constipation/pruritus. Two hundred and twenty-four (87.5%) patients were completely satisfied from the procedure and highly recommend the procedure. CONCLUSION: THD is a comparably pain-free procedure with improved results that prides in higher long-term satisfaction, minimal recurrence and fewer complications, in comparison to other surgical modalities.

Diagnosis and Management of Anorectal Disorders in the Primary Care Setting.

Anorectal disorders are very common among a wide population of patients. Because patients may be embarrassed about the anatomic location of their symptoms, they may present to care late in the course of their illness. Care should be taken to validate patient concerns and normalize fears. This article discusses the diagnoses and management of common anorectal disorders among patients presenting to a primary care physician.

Typical MR imaging findings of perianal infections in patients with hematologic malignancies.

OBJECTIVE: We aimed to investigate the MR imaging findings of patients with hematologic malignancies who have symptoms suggesting perianal infection and to demonstrate the importance of imaging. SUBJECTS AND METHODS: The study included 36 patients with hematologic malignancies who underwent anorectal MR imaging in our department between September 2011-May 2016. Two radiologists experienced in abdominal radiology viewed the MR images in consensus. Abscesses, fistulous or sinus tracts, signal alterations and contrast enhancement in keeping with an inflammation and edema in the perianal region were recorded. RESULTS: Perianal abscess was found in 16 of the 36 patients. In 10 of these 16 patients there was also extensive inflammatory signal alterations in perianal and/or perineal soft tissues. In six of the 36 patients perianal fistula was detected. A sinus tract was seen at the level of subcutaneous external anal sphincter in one patient. Inflammatory signal alterations in the surrounding soft tissues were present in three of these seven patients. There were abscesses in labium majus in two patients and in one patient there were perineal abscesses with accompanying inflammatory signal alterations. In six of the 36 patients no abscess or fistula/sinus tract was seen. There were only inflammatory signal alterations with contrast enhancement in perianal or subcutaneous tissues. In two patients presenting with perianal pain and hemorrhoids, minimal inflammatory changes were detected on MR images. There were two patients with normal MR imaging findings. CONCLUSION: As digital examination of the anorectum and rectoscopy are avoided in neutropenic patients, MR imaging, which clearly demonstrates the perianal pathology should be preferential.