Effectiveness and safety of 3% polidocanol foam sclerotherapy in hemorrhoidal disease: a multicenter, prospective study

Abstract

Aim

To evaluate the effectiveness and safety of 3% polidocanol foam sclerotherapy (PFS) injection under anoscopy in the treatment of hemorrhoidal disease (HD) compared with rubber band ligation (RBL).

Method

This was a multicenter, open-label, prospective, observational study that enrolled 222 patients with Goligher grade I, II, or III HD (internal or mixed), who were treated with 3% PFS or RBL, which depended on the physician’s assessment and the patient’s willingness. The primary endpoint was the clinical cure rate under anoscopy and clinical symptoms assessment at 4 weeks post-treatment.

Results

A total of 222 patients from 14 centers participated in the study, with 127 patients receiving PFS and 95 patients receiving RBL. Among the effectiveness analysis set (EAS), the clinical cure rate was 74.19% (69/93) in the PFS group and 83.13% (69/83) in the RBL group (P > 0.05). The PFS group showed quicker and better improvement in hemorrhage score post-treatment than the RBL group, with the mean (SD) changes from baseline in hemorrhage score of the two groups (P < 0.001) at 1, 4, and 12 weeks being −3.44 (1.99) vs. −1.70 (2.19), −3.85 (1.80) vs. −2.75 (2.02), and −3.81 (1.84) vs. −2.89 (2.10), respectively. The incidences of adverse events (AEs) were 2.36% (3/127) in the PFS group and 3.16% (3/95) in the RBL group, respectively, and no serious adverse events (SAEs) occurred in both groups.

Conclusion

Patients treated with PFS showed similar effectiveness and safety as those treated with RBL under anoscopy, and a quick improvement trend in hemorrhage score post-treatment was observed in patients treated with PFS, but it needs further verification.

Trial registration

This study has been registered on the website of Chinese Clinical Trial Registry (https://www.chictr.org.cn/), registration number: ChiCTR2200060325.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00384-025-05057-8.

Introduction

Hemorrhoidal disease (HD) is one of the most common anorectal diseases. It has been estimated that more than 50% of people over 50 years present at least one episode of symptomatic haemorrhoids during their life. A large-scale survey from the USA reported a prevalence of 4.4% in the general population, with no difference between sexes and a peak prevalence between 45 and 65 years [1].Among hemorrhoid cases, internal HD was the most common, accounting for 59.86% of all cases of HD, while external HD accounted for 16.01%, and mixed HD accounted for 24.13% [2].

For symptomatic internal HD, the therapeutic approaches include conservative therapy, outpatient procedures (device therapy), and surgical therapy [3, 4]. Outpatient procedures refer to the treatment of internal HD with devices such as anoscope and colonoscope, including rubber band ligation (RBL), sclerotherapy (SCL), or infrared coagulation (IRC). Compared with other therapies, endoscopic injection sclerotherapy is less invasive and has a lower incidence of post-treatment symptoms such as pain and bleeding. As a result, sclerotherapy has better patient acceptance [4]. In a prospective, single-center study [5], which included 2000 patients who were treated with 2% polidocanol foam sclerosant (PFS), the results showed that 1957 (98%) patients were “very satisfied” with the treatment outcome at 4 weeks post-treatment, reporting reduction/resolution of bleeding and prolapse; 1112 patients underwent follow-up visits, of whom 954 (86%) were diagnosed with reduced prolapse by the investigator.

Mixed HD main clinical manifestation is co-presence of internal HD and external HD, with relapse of circular HD in severe cases. Early mixed HD can be treated conservatively, while severe cases generally require surgical intervention. Hemorrhoidectomy may be applicable to patients with grade III–IV internal HD, external, or mixed HD with prolapse. Sclerotherapy can also be used for the internal or mixed HD [3]. However, there is a lack of large-scale clinical studies.

Therefore, this prospective, observational real-world study was designed to evaluate the effectiveness and safety of anoscopy injection of the sclerosant 3% PFS versus RBL in the treatment of internal HD and mixed HD, to provide evidence for anoscopy treatment of HD with PFS.

Materials and methods

Checklist for the reporting of observational studies

This article was written in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies [6].

Study design and participants

This multicenter, open-label, prospective, observational study was conducted in 14 hospitals in China (see Supplementary material). The aim of the study was to evaluate the effectiveness and safety of injection of PFS versus RBL in the treatment of HD under anoscopy. Patients with Goligher grade I–III internal HD or mixed HD were enrolled. Inclusion and exclusion criteria are described in Table 1.

Table 1.

Inclusion/exclusion criteria

Inclusion criteria	Exclusion criteria
1) Male or female aged 18 to 75 years	1. Patients with any coagulation dysfunction
2) Patients with grade I (failure of conservative treatment), grade II, or grade III internal HD, or mixed HD (irrespective of prior conservative therapy)	2. Patients with perianal abscesses, anal fistula, rectal polyps, intestinal tumor, or any intestinal infectious disease
3) Patients who are scheduled to receive treatment with injection of 3% PFS or RBL	3. Patients with anal papillary hypertrophy or any other intestinal disease that would interfere with disease evaluation
4) Sign the informed consent form	4. Previous history of low rectal or anal surgery
	5. Patients with any severe systemic disease (especially untreated)
	6. Patients who cannot move
	7. Patients with thromboembolic diseases, patients at high risk of thrombosis (for example, patients with known genetic thrombosis tendency or patients with multiple risk factors, such as hormonal contraceptives or hormone replacement therapy, obesity, smoking and long-term infertility active patient)
	8. Patients with severe anemia (hemoglobin 30–60 g/L)
	9. History of sclerotherapy within 1 month
	10. Pregnant and lactating women
	11. Mentally disabled persons
	12. Those who have participated in clinical research of other drugs in the past three months
	13. Poor compliance and unable to cooperate to complete the test
	14. Other conditions that the doctor thinks are not suitable for enrollment

Procedures

Patients who fulfilled all inclusion criteria and did not fulfill any exclusion criteria were treated with 3% PFS or RBL in a non-interventional manner depending on the physician’s assessment and the patient’s willingness. All patients were followed up for 12 weeks following the end of treatment and advised to visit the surgery outpatient department or electronic Patient Reported Outcomes (e-PRO) at week 1, week 4, and week 12 post-treatment. At the follow-up visit, clinical effectiveness evaluation under anoscopy, clinical symptoms assessments, hemorrhage score, the grade of anorectal stenosis, the 36-Item Short Form Survey (SF-36), and safety indicators such as laboratory tests and vital signs were documented.

Outcomes

The primary effectiveness endpoint was the clinical cure rate based on anoscopy and clinical symptoms assessments at 4 weeks post-treatment. Clinical effectiveness evaluations related to the primary effectiveness endpoint included three categories: cured, improved, and ineffective. Cured was defined as complete resolution of hemorrhoid-related symptoms, disappearance of inflammation and edema at the anoscopy bulge site, normal shape and size of the bulge site, hemorrhoid atrophy, and normal repair of mucosa; improved was defined as improvement in hemorrhoid-related symptoms, marked relief of edema at the anoscopy bulge site or prolapse, hemorrhoid atrophy, and generally normal repair of mucosa; ineffective was defined as no improvement or even worsening of hemorrhoidal prolapse and bleeding. Clinical cure rate = number of patients cured/(total number of patients cured + improved + ineffective).

The secondary effectiveness endpoint measures included changes in hemorrhage score at 1, 4, and 12 weeks post-treatment. The scores at the time of the most severe bleeding were observed and recorded based on the following grading criteria as shown in Table 2.

Table 2.

Hemorrhage score grading used in the study

0 point	No bleeding after defecation
2 points:	Blood on toilet paper after defecation
4 points	Dripping blood during defecation
6 points:	Spraying blood during defecation, stopping after defecation
8 points	Major bleeding after defecation, with shock presentation requiring suture hemostasis

Anorectal stenosis was graded according to Table 3 based on Practical Anorectal Surgery [7].

Table 3.

Anorectal stenosis grading used in the study

Grade I	No stenosis, index finger can pass through the anal canal smoothly
Grade II	Mild stenosis, anal diameter 1.5 to 2 cm, but allows index finger to pass through
Grade III	Moderate stenosis, anal diameter 1.0 to 1.5 cm, index finger cannot pass through the anal canal but little finger can pass through
Grade IV	Severe stenosis, anal diameter smaller than 1.0 cm, little finger cannot enter the anal canal

Statistical analysis

A retrospective analysis of 39 studies involving 8060 patients undergoing RBL showed that 14% of the patients experienced complications after RBL, including severe pain (5.8%), bleeding (1.7%), infection (0.05%), and anal fissure and fistula (0.4%) [7]. In estimating the sample size based on Poisson distribution assuming a 95% confidence to detect AEs with the incidence ≥ 1.5%, a sample size of 200 patients would be required. Considering a 20% dropout rate, a total sample size of 250 patients would be required.

The baseline characteristics in the two groups were described. The balance of baseline characteristics was assessed by chi-square test for categorical variables and by t-test for continuous variables. A characteristic with P-value < 0.2 was considered unbalanced and was included in the analysis model. Effectiveness analysis was based on the effectiveness analysis set (EAS). EAS includes patients who used the medication at least once and had at least one baseline measurement and at least one post-baseline assessment of effectiveness. Safety analysis was based on the safety analysis set (SS).

Given that this study is a real-world analysis, we controlled for confounding bias by employing multivariable regression to adjust for baseline imbalances in factors such as hemorrhoid type, Goligher classification, hemorrhage score, and anorectal stenosis. For analysis of clinical cure rate (primary endpoint), logistic regression was used to correct for imbalance between groups at baseline, and the 95% confidence interval was calculated. For change in hemorrhage score (secondary endpoint), a general linear model was used to correct for the score and other imbalanced factors between groups at baseline. Other effectiveness variables were analyzed using appropriate methods. For continuous data, an independent samples t-test or Wilcoxon test was used for between-group comparisons. For categorical data, the chi-square test was used for between-group comparisons and Fisher’s exact test when necessary. No imputation for missing data was performed.

As random allocation was not used in this study, imbalances in baseline characteristics between groups were inevitable. Therefore, multivariate analyses were used to adjust for these imbalances in the analysis of effectiveness.

All statistical analyses were performed using SAS 9.3 software, of which a P < 0.05 was statistically significant.

Results

Generally, 261 patients from 14 hospitals in China from July 2022 to October 2023 signed Informed Consent Form (ICF) were screened, and 222 patients were enrolled (consisting of the SS). After being enrolled in the study, the subjects received PFS or RBL treatment. Follow-up visits were conducted at the 4 and 12 weeks after the operation. Primary efficacy outcome as symptom evaluation and anoscopy was performed during baseline and follow-up visit, as well as other efficacy outcomes and safety outcomes. One hundred twenty-seven patients were included in the PFS group, and 95 patients were included in the RBL group. Twenty-nine patients in the PFS group and 6 patients in the RBL group were missing data on anoscopy at 4 weeks and 12 weeks, respectively. The detailed patients’ disposition and analysis set distribution are presented in Fig. 1.

Fig. 1.

Detailed flow chart for patient screening, enrollment, and data analysis in the study

Patient demographics and baseline characteristics

For the EAS (N = 176), 93 and 83 patients were in the PFS group and the RBL group, respectively. Baseline patient characteristics were shown in Table 4. Most patients in both groups were male. 44.09% (41/93) patients in the PFS group, and 63.86% (53/83) patients in the RBL group had mixed HD. 48.39% (45/93) patients in the PFS group had Goligher grade II and 46.99% (39/83) patients in the RBL group had Goligher grade III.

Table 4.

Patient demographics and baseline characteristics (EAS)

Items	PFS (n = 93)	RBL (n = 83)	P
Gender			0.625
Male	67 (72.04)	57 (68.67)
Female	26 (27.96)	26 (31.33)
Age (years)	40.18 ± 12.46	43.10 ± 11.40	0.108
BMI (kg/m2)	23.71 ± 3.82	23.86 ± 3.49	0.794
Smoking			0.986
Never smoker	66 (70.97)	59 (71.08)
Smoker	27 (29.03)	24 (28.92)
Alcohol use			0.838
Non-drinker	74 (79.57)	65 (78.31)
Drinker	19 (20.43)	18 (21.69)
Hemorrhoid type			0.009
Internal HD*	52 (55.91)	30 (36.14)
Mixed HD*	41 (44.09)	53 (63.86)
Goligher classification#			0.000
Grade I	32 (34.41)	14 (16.87)
Grade II	45 (48.39)	30 (36.14)
Grade III	16 (17.20)	39 (46.99)
Anorectal stenosis			0.071
Grade I	83 (89.25)	80 (96.39)
III/IV	10 (10.75)	3 (3.61)
Hemorrhage score	2.88 ± 1.05	2.24 ± 1.38	0.002

BMI  body mass index

^*Internal HD: soft venous cushions formed by the dilation of submucosal hemorrhoidal veins above the dentate line. Key clinical manifestations include bleeding, prolapse, perianal moisture, pruritus, and complications such as thrombosis, incarceration, strangulation, or defecation difficulty

^*Mixed HD involves the fusion of internal and external hemorrhoidal vascular plexuses across the dentate line, presenting concurrent symptoms of both internal and external hemorrhoids. Severe cases may manifest as circumferential prolapse

^#Goligher classification: Grade I: Hemorrhoidal bleeding (dripping or spraying blood) during defecation, with bleeding ceasing spontaneously post-defecation; no prolapse. Grade II: Recurrent bleeding; prolapse during defecation that spontaneously reduces post-defecation. Grade III: Occasional bleeding; prolapse during defecation, prolonged standing, coughing, or exertion, requiring manual reduction. Grade IV: Occasional bleeding; persistent prolapse or prolapse that reoccurs immediately after reduction, potentially accompanied by infection, edema, necrosis, or severe pain

Majority of patients were with grade I anorectal stenosis in two groups, with 89.25% in the PFS group and 96.39% in the RBL group. At baseline, the mean (standard deviation [SD]) hemorrhage scores were 2.88 (1.05) in the PFS group and 2.24 (1.38) in the RBL group, respectively.

Effectiveness results

At 4 weeks post-treatment, all patients met the criteria for improvement or cure in clinical effectiveness evaluation. 74.19% (69/93) and 25.81% (24/93) patients of the PFS group were cured and improved, respectively. 83.13% (69/83) and 16.87% (14/83) patients of the RBL group were cured and improved, respectively. After correcting the imbalanced factors between groups at baseline, e.g., age, hemorrhoid type, Goligher grade, anorectal stenosis grade, and baseline hemorrhage score (P < 0.2), with being cured or not being the dependent variable, there was no statistically significant difference between the two groups (P > 0.05), and the odds ratio (OR) for PFS versus RBL was 0.691 (0.299–1.599) (Table 5).

Table 5.

Multivariate analysis of clinical cure rate

Factor	Coefficient	Standard error	Wald	P	OR (95%CI)
PFS vs. RBL	−0.370	0.428	0.747	0.388	0.691 (0.299–1.599)
Age (years)	0.021	0.017	1.613	0.204	1.021 (0.989–1.055)
Hemorrhoid type (internal vs. mixed)	0.040	0.403	0.010	0.921	1.041 (0.472–2.294)
Goligher grade I vs. grade III	0.038	0.568	0.005	0.946	1.039 (0.341–3.166)
Goligher classification (grade II vs. grade III)	−0.395	0.468	0.712	0.399	0.674 (0.269–1.686)
Anorectal stenosis grade (grade I vs. grade II–IV)	−0.434	0.850	0.261	0.610	0.648 (0.122–3.428)
Hemorrhage score	−0.193	0.173	1.241	0.265	0.824 (0.587–1.158)

The mean (SD) changes of hemorrhage score from baseline to postoperative visits were greater in the PFS group than in the RBL group at 1, 4, and 12 weeks, with −3.44 (1.99) vs. −1.70 (2.19), −3.85 (1.80) vs. −2.75 (2.02), and −3.81 (1.84) vs. −2.89 (2.10), respectively. The statistically significant differences after correcting for baseline were P < 0.001 (Fig. 2).

Fig. 2.

Hemorrhage score change from baseline to postoperative visits

Analysis results of proportion of patients with a hemorrhage score of 0

At baseline, the proportion of patients with a hemorrhage score of 0 in the RBL group was significantly higher than the PFS group (22.89% vs. 6.45%). At 12 weeks post-treatment, the proportions of patients with a hemorrhage score of 0 in the RBL group were similar in the PFS group (97.59% vs. 95.70%). At 1 and 4 weeks post-treatment, the proportions of patients with a hemorrhage score of 0 in the PFS group were all higher than in the RBL group (79.57% vs. 79.57%; 97.85% vs. 90.36%). These indicated that the PFS group showed quicker and better improvement in hemorrhage score post-treatment than the RBL group (Fig. 3).

Fig. 3.

Changes in proportion of patients with a hemorrhage score of 0

Anorectal stenosis

The proofreader removed the data from the PFS group in week 12,98.92%(92/93). The translation means that the proportion of patients with grade I rectal stenosis in the PFS group in weeks 4 and 12 was 98.92% (92/93) and 98.92% (92/93), respectively, while the corresponding proportions in the RBL group were 93.98% and 100%, respectively. There were no statistically significant differences between both groups in the proportions of patients with grade I stenosis (P > 0.05) (Fig. 4).

Fig. 4.

Proportions of patients with grade I hemorrhoid stenosis in both groups

SF-36

No statistically significant differences were shown between both groups in SF-36 total scores or change from baseline in SF-36 total scores at 12 weeks (P > 0.05), with 80.55 (133.95) points in PFS group and 76.86 (131.97) points in RBL group (Table 6).

Table 6.

Analysis of 36-Item Short Form Survey

Items	PFS	RBL	P-value
SF-36 total score at baseline			0.489
Mean ± SD	662.23 ± 138.89	648.52 ± 121.68
Median (Q1, Q3)	719.00 (578.00, 760.50)	670.00 (583.67, 735.50)
Min, Max	306.50,825.00	260.50,817.00
SF-36 total score at 12 weeks			0.106
Mean ± SD	742.78 ± 64.88	725.38 ± 76.96
Median (Q1, Q3)	758.00 (719.00, 785.00)	748.50 (664.50, 789.00)
Min, Max	478.50,825.00	497.33,816.00
ΔSF-36 total score			0.106
Mean ± SD	80.55 ± 133.95	76.86 ± 131.97
Median (Q1, Q3)	46.00 (0.00, 144.50)	61.00 (−7.50, 152.50)
Min, Max	−206.00,472.50	−213.50,432.50

Safety results

For SS (N = 222), all patients tolerated the treatment. None experienced AEs leading to discontinuation. 2.7% (6/222) patients experienced 7 cases of AEs, and most of them were grade I (CTCAE V5.0); only 1 case of hemorrhagic anemia was grade III, which occurred in the RBL group, and at 12 weeks, the level of hemoglobin had returned to normal. In the PFS group, 2.36% (3/127) patients experienced three cases of AEs, including investigations (PT (preferred terms), urine leukocyte esterase positive), cardiac disorders (PT, right bundle branch block), and blood and lymphatic system disorders (PT, postoperative anemia). In the RBL group, 3.16% (3/95) patients experienced four cases of AEs, including infections and infestations (PT, infection), investigations (PT, electrocardiogram high voltage), and blood and lymphatic system disorders (PT, hemorrhagic anemia). All the AEs were unrelated to the study treatment assessed by the investigator, and no SAEs occurred.

Discussion

In this multicenter prospective clinical evaluation, we found that PFS in treating grade I, II, or III internal HD and mixed HD is effective and safe, even when assessed objectively under anoscopy.

As previous studies [8] indicated, the patients undergoing sclerotherapy had a 93% (151/163) therapeutic success rate compared to 75% (68/91) in the RBL group (OR 3.39, 95% CI 1.48–7.74, P < 0.01), and the overall success rate after 3 years was over 90% [9]. However, the primary effectiveness endpoint showed no statistically significant differences between the PFS group and the RBL group in our study. In fact, a randomized controlled trial (RCT) has reported that no significant difference in the rate of treatment success among HD patients with grade I–III was seen between RBL and PFS [10].

Patients treated with PFS showed similar effectiveness and safety as those treated with RBL under anoscopy. A quick improvement trend in hemorrhage score post-treatment was observed in patients treated with PFS, but it needs further verification. In our study, 79.57% of patients with grade I–III internal HD and mixed HD experienced complete bleeding resolution at 1 week post-treatment, compared to 68.3% in a previous study [9] with grade II HD. A previous study [11] reported a bleeding rate of 4.8% following treatment with PFS, comparing with the bleeding rates ranging from 3.5% to 50% with RBL. The findings suggest that PFS may be more efficacious than RBL in terms of accelerating the process of bleeding. Additionally, patients taking anti-platelet and/or anti-coagulant medication seem to have a higher risk, with some reports of massive life-threatening hemorrhage after RBL [12]; nevertheless, PFS does not increase hemorrhage score post-treatment in patients receiving anticoagulant treatment [13, 14].

The rapid hemostatic effect observed in the PFS group may be attributed to its unique pharmacological properties and mode of action. Polidocanol, a detergent-type sclerosing agent, induces endothelial damage through direct chemical interaction with cell membranes, leading to rapid vascular occlusion via protein denaturation and thrombus formation [9, 15]. The foam formulation further enhances this effect by increasing the surface area of contact between the sclerosant and the hemorrhoidal vasculature [16–18] promoting uniform distribution and prolonged retention within the target tissue to provide adequate therapeutic effects from relatively short times=[19]. This dual mechanism—direct vascular obliteration and subsequent anti-inflammatory modulation—explains the significant reduction in hemorrhage scores observed as early as 1 week post-treatment.

In contrast, RBL relies on mechanical compression of the hemorrhoidal plexus, inducing ischemia and necrosis of the ligated tissue [20]. The delayed clinical response (e.g., slower resolution of bleeding) may reflect the time required for tissue sloughing and secondary inflammatory processes to resolve. While RBL achieves long-term efficacy through fibrosis and tissue fixation, its initial phase is characterized by localized trauma, which may exacerbate transient inflammation and prolong symptomatic relief. The immediate hemostatic advantage of PFS aligns with its non-ischemic mechanism, minimizing tissue injury and enabling faster mucosal repair—a critical factor for patients prioritizing rapid symptom relief.

The disparate outcomes observed between PFS and RBL may be attributed to their distinct pathophysiological mechanisms. PFS exerts its therapeutic effect primarily at the microvascular level, inducing sclerosis of the submucosal veins and consequently reducing blood flow to the hemorrhoidal cushions. Importantly, this targeted intervention does not result in macroscopic tissue destruction, thereby preserving mucosal integrity. This preservation of mucosal integrity is crucial, as it accelerates the healing process and mitigates post-procedural discomfort.

In contrast, the effectiveness of RBL depends on macroscopic tissue necrosis. This process elicits a robust inflammatory response, which subsequently leads to fibrosis and secure fixation of the mucosa. Although RBL is effective in treating HD, the inherent nature of this procedure involves a longer recovery period. This is evidenced by the slower improvement in bleeding scores observed in the RBL group compared to those treated with PFS.

These results suggest that PFS may be of some benefit to HD patients who need urgent control of bleeding or coagulation dysfunction; these have been preliminarily confirmed by some studies that injection sclerotherapy can be considered as a potential treatment option for HD patients who are at a high risk of thromboembolic disease requiring anticoagulation, and PFS is just as effective and safe for the treatment of HD in patients with bleeding disorders as in those without bleeding dyscrasia [21, 22]. However, its reliance on operator-dependent injection techniques highlights the need for standardized protocols to optimize foam preparation and dosing. However, patients suffering from coagulation disorders and those undergoing anticoagulant therapy were excluded from the study, thus limiting the inference that PFS has some advantage for people with bleeding disorders or requiring long-term anticoagulant therapy. It is imperative to exercise caution when extending these findings to high-risk populations, such as those undergoing anticoagulation therapy, or to regions of the country with divergent medical practices. Future studies should investigate the molecular pathways underlying the anti-inflammatory effects of PFS and explore synergies with adjunctive therapies (e.g., topical analgesics) to improve patient comfort. For RBL, innovations in bandaging devices or combined regimens (e.g., RBL with targeted sclerotherapy) may fill the gap in early symptom control.

In the discussion, attention should be given to the current dissemination of sclerobanding, a technique that integrates sclerotherapy and RBL. The spreading of the 3% polidocanol after the ligation of the nodule by the rubber band represents a barrier to the diffusion of the foam in the submucosa, a potential cause of severe pain, mucosal ulceration, abscess, and acute prostatitis reported in some series; at the same time, sclerotherapy increases the inflammatory response and the “lifting effect” on mucosal prolapse, avoiding delayed hemorrhage [23]. Sclerobanding is significantly more efficient in treating second-degree hemorrhoidal disease than sclerotherapy alone. The complication rate was low at 4.1%, involving only minor self-limiting complications. Sclerobanding is a safe and low-cost technique for treating second- and third-degree hemorrhoidal disease. The procedure can be performed in an outpatient clinic and is repeatable [23, 24]. The adoption of sclerobanding is expected to continue expanding in clinical practice for hemorrhoidal disease management.

The incidence of AEs was 2.36% (3/127) and 3.16% (3/95) in the PFS group and RBL group, respectively, and no SAEs were in the study. In a study of 2000 patients treated with 2% PFS [5], AEs were rare and mostly mild, with only 0.15% of patients experiencing significant bleeding, 0.7% of patients experiencing SAEs, and 92% of patients reporting no pain/mild pain. Other studies reported 3% to 18.8% AEs in RBL, with pain and bleeding being the most common [25]. In summary, both PFS and RBL are safe for HD treatment.

Limitations

There are also some limitations affecting study quality and interpretation. Initially, the non-randomized allocation (based on operator or patient preference only) resulted in a baseline imbalance, with a higher proportion of grade III HD in the RBL group and a higher proportion of grade I–II HD in the PFS group. The higher proportion of patients in the RBL group and the higher proportion of patients with grade I–II HD in the PFS group may reflect a clinical preference for mechanical interventions for advanced prolapse. Patients diagnosed with grade II HD and exhibiting less severe symptoms were found to be more inclined towards PFS, a procedure that boasts cost-effectiveness, repeatability, and virtually painless surgical procedures [25–27]. Despite the implementation of statistical adjustments, residual confounders may influence the generalizability of the findings to populations with distinct baseline characteristics.

Secondly, although multicenter participation increased diversity, all were in China. It is acknowledged that variations in medical resources, operator expertise, and patient preferences may influence the interpretation of results. For instance, the outcomes of RBL may be subject to variation in settings where procedures are less standardized. Furthermore, the recurrence rate is a more significant aspect for assessing hemorrhoidal therapy; however, in this study, the 12-week follow-up period was insufficient to assess long-term efficacy, therefore leaving the question of long-term efficacy unanswered.

Finally, despite the development of a standardized protocol in our study, differences in surgical operative technique across centers may have affected the results. For instance, the efficacy of PFS may have been subject to variation due to the injection technique, which was not adequately quantified. Despite the rigorous application of the Goligher grading method, variations in operator experience may lead to inconsistencies in the grading process. Despite the provision of standardized training, subjective interpretations of prolapse severity (e.g. manual versus spontaneous decompensation) may compromise the accuracy of grading. This is consistent with criticisms of Goligher reproducibility in heterogeneous cohorts [28]. Objective imaging or centralized adjudication may reduce this bias.

These limitations can be addressed by further studies: firstly, the implementation of a well-designed randomized controlled trial (RCT) would serve to reduce bias. Secondly, interventions could be trailed with a combination of PFS and RBL, which may observe more therapeutic benefit. Thirdly, the enrolment population could consider patients requiring oral antiplatelet therapy or anticoagulant medication to validate the benefit of PFS in this group of patients.

In summary, while the study provides some evidence for the effectiveness and safety of PFS and RBL in selected populations, its external validity is constrained by exclusions and design limitations. Addressing these shortcomings through inclusive RCTs will enhance the generalizability of findings.

Conclusion

In conclusion, this study observed the effectiveness and safety of PFS for the treatment of grade I, II, or III internal and mixed HD. Based on the combined assessment of anoscopy and clinical symptoms at 4 weeks postoperatively, 74.19% and 83.13% of patients treated with PFS and RBL, respectively, met the criteria for cure. In this study, patients treated with PFS showed similar effectiveness and safety as those treated with RBL under anoscopy; a quick improvement trend in hemorrhage score post-treatment was observed in patients treated with PFS, but it needs further verification. Sclerotherapy with 3% polidocanol foam is a safe procedure and may provide a new therapeutic option for grade I–III HD patients. However, more randomized control trials are needed to further validate the effectiveness of PFS.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Y.D. Y and T.Y. Zh contributed to the Study design; Y.D. Y and T.Y.Zh contributed to the data analysis and manuscript writing; Y.D. Y, T.Y. Zh, Z.T. Y, X.G.T, S.X. Zh, l. P, Z.M.G, Z.A. G, X.A. Zh, Y.D.L, X.J. S, Y. X, W.Y, R. W, X.D.H, J.H. G, S.Y. X and X.J. L contributed to the data collection. All authors read and approved the final draft of the manuscript.

Funding

The study was supported by Shenzhen Kangzhe Pharmaceutical Co., Ltd.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval

This study was conducted in accordance with local legislations and approved by the Ethics Committee of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and the independent ethics committees of the other study sites, and all patients signed the Informed Consent Form (leading site approval number: 2022010CS (KT)-007-01).

Consent to participate

Written consent was obtained from all patients participating in the evaluation.

Competing interests

The authors declare no competing interests.