Comparative study of one-step and four-step injection combined with external stripping and internal ligation for mixed hemorrhoids

Abstract

BACKGROUND

Mixed hemorrhoids are a common anorectal condition with a high incidence, significantly impacting patients’ quality of life due to bleeding, pain, and prolapse. While external stripping and internal ligation is a definitive surgical treatment, postoperative complications such as pain, edema, and prolonged recovery remain clinical challenges. Although combining this surgery with Xiaozhiling sclerotherapy is common, the optimal injection technique—the comprehensive four-step method vs the simplified one-step method—lacks systematic comparison. Therefore, this study aims to compare the clinical efficacy and safety of these two combined approaches.

AIM

To determine the safety and efficacy of four-step vs one-step sclerotherapy in Milligan-Morgan hemorrhoidectomy.

METHODS

Eighty patients with mixed hemorrhoids between August 2021 and April 2025 were randomly divided into control (n = 40) and observation (n = 40) groups. All patients underwent Milligan-Morgan hemorrhoidectomy, during which the observation group received a four-step Xiaozhiling injection, whereas the control group received a one-step injection. The two groups were compared regarding operative time, postoperative pain [assessed by Visual Analogue Scale (VAS) on days 1 and 5], recovery parameters (hemorrhoid sloughing time and hospital stay), complication rates, and six-month recurrence.

RESULTS

No statistically significant difference was observed in operative time between the two groups (P > 0.05). The observation group exhibited significantly lower VAS scores on postoperative days 1 and 5 compared to the control group (P < 0.05). While the time to hemorrhoid sloughing was comparable between groups (P > 0.05), the total hospital stay was significantly shorter in the observation group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P > 0.05), although a trend towards fewer complications was noted in the observation group. No recurrences were observed in either group during the six-month follow-up period.

CONCLUSION

The four-step Xiaozhiling injection method offers superior short-term outcomes over the one-step method by reducing pain and hospital stay, without prolonging operative time, though long-term efficacy requires further study.

Key Words: Mixed hemorrhoids; External stripping and internal ligation; Sclerotherapy; Four-step injection method; One-step injection method

Core Tip: This retrospective study compared one-step vs four-step Xiaozhiling injection combined with external stripping and internal ligation for mixed hemorrhoids. The four-step method significantly reduced postoperative pain on days 1 and 5 and shortened hospital stays compared to the one-step method, with comparable surgical time and no recurrence at 6 months. These findings suggest the four-step injection technique offers superior postoperative recovery and represents a clinically valuable optimization for mixed hemorrhoid surgery.

INTRODUCTION

In the clinical diagnosis and treatment of anorectal diseases, mixed hemorrhoids represent a common and frequently occurring condition. Its primary clinical manifestations include rectal bleeding, prolapse of anal masses, and a sensation of distension and discomfort, all of which significantly impair patients’ physical and psychological well-being[1,2]. Epidemiological studies indicate that the overall prevalence of hemorrhoids is high across numerous countries and regions, with mixed hemorrhoids accounting for a substantial proportion. Furthermore, its incidence is increasing with advancing age and lifestyle changes[3,4]. In 2018, the standardized prevalence of hemorrhoids among Chinese women reached 43.7%[5]. For symptomatic mixed hemorrhoids, surgery is widely recognized as an effective treatment. A traditional surgical procedure, external dissection and internal ligation, involves ligating the base of the internal hemorrhoids while simultaneously excising the external components. This method offers a definitive curative effect and remains widely utilized in clinical practice[6,7]. However, conventional external dissection and internal ligation still face challenges in achieving thorough treatment of extensive internal hemorrhoids and in managing postoperative complications such as pain, edema, and bleeding[8]. To optimize therapeutic outcomes and minimize surgical trauma, injection therapy is frequently employed as an important adjunctive measure. Xiaozhiling, a commonly used sclerosing agent in Chinese clinical practice, induces hemorrhoidal shrinkage through its inflammatory and fibrotic effects. It has been demonstrated that combining Xiaozhiling injection with surgery can enhance therapeutic efficacy and reduce recurrence rates[9]. Currently, the primary injection technique for Xiaozhiling is the four-step method, which targets the superior rectal artery area, the submucosa of the hemorrhoidal zone, the lamina propria of the hemorrhoidal zone, and the anal sinus vein area, aiming to achieve comprehensive vascular occlusion and tissue fixation[10]. In clinical practice, to pursue operational simplicity and efficiency, a simplified one-step method involving injection of the sclerosant into the submucosa of the hemorrhoids has also been adopted. However, systematic comparative studies on the differences in overall efficacy between this one-step method and the traditional four-step method, when both are combined with external dissection and internal ligation for treating mixed hemorrhoids, remain lacking.

Therefore, this study aims to systematically compare and evaluate the clinical efficacy of the four-step method vs the one-step method, both combined with external dissection and internal ligation, for the treatment of mixed hemorrhoids. The investigation will focus on assessing the differences between the two combination regimens in terms of surgical-related indicators, postoperative pain levels, postoperative recovery, complication rates, and six-month recurrence rates. The goal is to provide a more advanced evidence-based reference for selecting the optimal injection technique in clinical practice. The results are reported below.

MATERIALS AND METHODS

General information

Eighty patients with mixed hemorrhoids, admitted to our institution between August 2021 and April 2025, were included in this retrospective study. They were divided into two groups of 40 patients each: An observation group and a control group, based on the intraoperative technique used for injecting the hemorrhoid-reducing medication.

Exclusion and inclusion criteria

Inclusion criteria: (1) The Clinical Practice Guidelines for the Treatment of Hemorrhoids’ diagnostic standards for mixed hemorrhoids[11]; (2) Age ≥ 18 years; (3) Meeting the indications for external stripping and internal ligation and sclerotherapy; (4) Having no serious underlying diseases; (5) Having normal communication and no mental illness; and (6) Having the patient or family members voluntarily sign the form for informed consent.

Exclusion criteria: (1) Colorectal tumors or other anorectal diseases; (2) History of anorectal surgery; (3) Contraindications to the drugs used in this study; (4) Significant problems with the kidneys and liver; and (5) Coagulation dysfunction.

Elimination criteria: Loss to follow-up or incomplete follow-up data.

Methods

Both groups of patients ate liquid food the night before the operation to prepare their bowels.

Control group: Patients in the control group received a one-step injection of hemorrhoid-reducing medication combined with external stripping and internal ligation. Before surgery, patients were first given an enema to promote bowel movements and cleanse the intestines, followed by the establishment of an intravenous access. After successful sacral anesthesia, the patient takes the lithotomy site, and the surgical area is routinely disinfected and covered with sterile sheets. The specific surgical procedures are as follows: Determine the position of each hemorrhoid nucleus in mixed hemorrhoids through visual examination, digital examination, and anoscopy examination. For mixed hemorrhoids that need to be treated, a shuttle shaped incision is made in the external hemorrhoid area, and an electric knife or tissue shear is used to bluntly peel off the external hemorrhoid venous mass and hypertrophic connective tissue to about 0.5 cm along the dentate line. The base of the internal hemorrhoid mucosa is clamped with vascular forceps, and a 7-gauge silk thread is used to suture and ligate with figure-of-eight suture under the forceps. After moderate tightening, most of the hemorrhoid nucleus tissue is cut off at the distal end of the ligature line, and the remaining end is sent for pathological examination. For each ligated stump of internal hemorrhoids, according to the size of the hemorrhoids, select 1-2 injection points in the center of the base of the stump, and stab it into the submucosa at an angle of 15°-30° with the rectal wall, with a depth of about 0.5-1.0 cm. After confirming that there was no blood, Xiaozhiling injection (Beijing China Resources high tech Natural Medicine Co., Ltd., gyzz z11020605) was prepared with 1% lidocaine in the ratio of 1:1, and was injected into the base of the hemorrhoids by one-step method. Slowly inject the liquid until the mucosa in the injection area was evenly raised and the color was slightly pale, so as to achieve the purpose of hardening and atrophy. After checking for no stenosis in the anus and complete hemostasis of the wound, place a Vaseline gauze strip, cover it with dressing, and fix it.

Observation group: Patients in the observation group received a four-step injection of hemorrhoid-reducing medication combined with external stripping and internal ligation. The preoperative preparation, anesthesia method, patient position, surgical area disinfection, hemorrhoid assessment and classification, and specific procedures of external stripping and internal ligation were exactly the same as those in the control group. Subsequently, hemorrhoid-reducing medication (same as the control group, Beijing Huarun Gaoke Natural Medicine Co., Ltd., National Drug Approval Number Z11020605) was administered. The specific steps were as follows: (1) Injection into the superior rectal artery area: At the point where the rectal mucosal artery pulsation was obvious, the needle was inserted at a 45° angle into the submucosa. After aspiration, 1-2 mL of medication was injected; (2) Injection into the submucosa of the hemorrhoid: The surface mucosa of the hemorrhoid was exposed, and the needle was inserted along its long axis into the submucosa. After aspiration, the medication was slowly injected under pressure. Depending on the size of the hemorrhoid, the injection was continued until the hemorrhoid was uniformly and fully swollen, the surface mucosa turned pale white, and the vascular texture was clearly visible. The injection volume for each internal hemorrhoid is controlled at 6-13 mL; (3) Injection into the inferior pole of sinus vein: After completing the submucosal layer injection, withdraw the needle tip to the surface of the muscularis mucosae and perform small-volume injections at different points on the surface of the hemorrhoid. Inject 1-2 mL of medication at each point to allow the medication to diffuse within the mucosal layer until the mucosa around the injection point shows obvious “bubble-like” or “orange peel-like” changes; and (4) Injection into the area around the dentate line: Insert the needle into the lower pole area of the hemorrhoid about 0.5 cm above the dentate line, with the needle tip penetrating into the superficial part of the submucosal layer. After aspirating and confirming no blood, slowly inject 1-2 mL of medication. During injection, closely observe the color of the perianal skin to ensure that the medication does not penetrate below the dentate line to avoid causing severe pain. After checking for no stenosis in the anus and complete hemostasis of the wound, place a Vaseline gauze strip, cover it with dressing, and fix it. The surgery was completed.

Observation indicators

Surgical-related indicators: The duration of the procedure both groups of patients.

Comparison of pain intensity: The Visual Analogue Scale (VAS) was used preoperatively, 1 day postoperatively, and 5 days postoperatively. VAS (visual analogues)[12] assesses the patient’s pain level. The total score is 0-10. The 0 represents no pain, and 10 represents unbearable pain.

Postoperative recovery: The recovery time for both groups of patients after surgery was recorded, including the time for hemorrhoids to fall off and the total length of hospital stay.

Occurrence of complications: The incidence of postoperative edema, bleeding, anal tenesmus, and defecation difficulties was statistically analyzed in both groups of patients. Complication rate = (number of cases with edema + number of cases with bleeding + number of cases with anal tenesmus + number of cases with defecation difficulties)/total number of cases × 100%.

Recurrence rate: Postoperative follow-up was conducted for six-month, with monthly telephone follow-ups. If the patient experienced discomfort, they were told to come back to the hospital for a second assessment. The recurrence rate was assessed based on the examination results and calculated as follows: Recurrence rate = (number of recurrent cases/total number of cases) × 100%.

Statistical analysis

The statistical program SPSS 21.0 was used to analyze the data. The mean ± SD was utilized to express normally distributed continuous data, and independent samples t-tests were employed to compare groups. The median and interquartile range (P25, P75) were utilized to express non-normally distributed data, and Mann-Whitney U tests were employed to compare groups. The n (%) was utilized to describe categorical data, and group comparisons were performed using χ² tests. Statistical significance was defined as a P value of less than 0.05.

RESULTS

Comparison of the two sets of baseline data

The general information of the two groups of patients was comparable (P > 0.05), as shown in Table 1.

Table 1 Comparison of baseline data between the two groups.

Project	Category	Control group (n = 40)	Observation group (n = 40)	Test statistic	P value
Age (year)		50.50 ± 16.70	50.68 ± 14.59	-0.050	0.960
Gender	Male	24 (60.00)	18 (45.00)	1.805	0.179
	Female	16 (40.00)	22 (55.00)
Disease duration (year)		1 (1, 1.75)	1 (1, 8)	-1.182	0.237

The mean ± SD was utilized to express normally distributed continuous data, and independent samples t-tests were employed to compare groups. The median and interquartile range (P25, P75) were utilized to express non-normally distributed data, and Mann-Whitney U tests were employed to compare groups. The n (%) was utilized to describe categorical data, and group comparisons were performed using χ² tests.

Comparison of surgical-related indicators between the two groups

According to Table 2, the difference in surgical time between the two groups did not show statistical significance (P > 0.05).

Table 2 Comparison of surgical-related indicators between the two groups [median (P25, P75)].

Group	Number of cases	Operation time (minute)
Control group	40	35.00 (25.00,43.75)
Observation group	40	30.00 (25.00,45.00)
Z value		-0.286
P value		0.775

Comparison of VAS scores before and after surgery between the two groups

Before surgery, the two patient groups’ VAS ratings were comparable (P > 0.05). As indicated in Table 3, the observation group’s VAS ratings were lower than the control group's on postoperative days 1 and 5 (P < 0.05).

Table 3 Comparison of Visual Analogue Scale scores before and after surgery in the two groups (n = 40).

Group	Preoperative	1 day after surgery	5 days post-surgery
Control group	0.33 ± 0.66	3.40 ± 1.06	2.48 ± 0.72
Observation group	0.50 ± 0.93	2.83 ± 0.96	1.90 ± 0.50
t value	-0.970	2.549	4.176
P value	0.335	0.013	< 0.001

Comparison of the two groups' postoperative recuperation

Table 4 shows that the observation group’s overall hospital stay was shorter than the control group’s (P < 0.05), but there was no statistically significant difference in the time it took for hemorrhoids to fall off between the two groups (P > 0.05).

Table 4 Comparison of the two groups’ postoperative recuperation (n = 40).

Group	Hemorrhoid shedding time (day)	Total length of stay (day)
Control group	10.90 ± 3.88	15.03 ± 5.23
Observation group	10.80 ± 3.07	12.55 ± 4.29
t value	0.128	2.315
P value	0.899	0.023

Comparing the two groups' incidence of complications

There was no statistically significant difference in postoperative complications between the two groups (P > 0.05), as shown in Table 5.

Table 5 Comparison of complication rates between the two groups [n (%)].

Group	Edema	Bleeding	Anal pressure	Pharmacological laxative intervention	Overall incidence
Control group	0 (0.00)	0 (0.00)	0 (0.00)	20 (50.00)	20 (50.00)
Observation group	0 (0.00)	0 (0.00)	0 (0.00)	12 (30.00)	12 (30.00)
χ2 value					3.333
P value					0.068

Comparison of recurrence rates between the two groups

No recurrence was observed in either group during the six-month follow-up period.

DISCUSSION

Efficient removal of hemorrhoids and precise preservation of anal function are the primary objectives in the surgical treatment of mixed hemorrhoids[13]. While the procedure of internal ligation and external excision effectively removes the lesion, it can disrupt the architecture of the anal canal, often leading to postoperative discomfort, edema, and other complications that impede recovery[14]. In this context, sclerotherapy has emerged as a key adjunctive technique to improve both efficacy and prognosis[15]. Xiaozhiling injection achieves its therapeutic effect by inducing fibrosis and adhesion within the hemorrhoidal tissue. The one-step injection method is simpler to perform; however, because its injection points are relatively concentrated and target a single anatomical level, the comprehensiveness and consistency of its clinical effect require systematic evaluation. In contrast, the four-step injection method is based on three-dimensional anatomical principles and involves multi-level injection. Theoretically, this approach allows for more comprehensive treatment of the vascular areas of the hemorrhoids[16]. Nevertheless, the procedure is more complex, and its impact on overall patient outcomes when combined with external excision and internal ligation warrants further investigation. This study aims to provide empirical evidence for refining clinical surgical techniques by comparing these two injection methods, focusing on surgical efficiency, postoperative rehabilitation, complication control, and long-term efficacy.

The results of this study showed no statistically significant difference in operative time between the two groups (P > 0.05). Although the four-step method might theoretically require more time due to its involvement with multiple anatomical planes and more precise injection sites, this was not observed in practice. With standardized procedures and proficient teamwork, the actual time consumption did not increase significantly. This finding may be attributed to the following factors. First, the four-step method provides a three-dimensional, multi-level treatment of the vascular structures within the hemorrhoid. This systematic approach can comprehensively address the target area in a single session, avoiding the need for repeated adjustments that may be necessary when a simplified injection incompletely covers the lesion[17]. Second, with the widespread clinical application of this technique and the standardization of its procedures, surgical teams have become highly proficient in each step of the four-step method. This proficiency effectively minimizes the transition time between steps, ensuring the overall smoothness and efficiency of the surgery[18]. Therefore, in routine clinical practice, the adoption of the systematically taught four-step injection method does not necessarily lead to a significant extension of the total operative time.

Regarding postoperative pain and recovery, the study's findings demonstrated that on postoperative days 1 and 5, VAS scores in the observation group were significantly lower than those in the control group (P < 0.05). This result suggests that the four-step method may help alleviate postoperative pain. The aluminum potassium sulfate and tannic acid sclerotherapy used in the study by Takada et al[19] was also based on the four-step injection method. Their findings demonstrated that the degree of postoperative pain in patients was significantly lower than that in the traditional surgery group, and the duration of pain was significantly shortened[19]. The study by Niu et al[20] on wound healing suggests that the local concentration and distribution pattern of the injected substance are key factors in determining its efficacy and side effects. Under the same total dose, excessively high concentration or improper injection can lead to local accumulation of the drug solution, which may cause unexpected severe inflammatory reactions and is not conducive to tissue repair. By optimizing the concentration and injection interval, the continuous and uniform distribution of the drug can effectively promote healing and structural remodeling[20]. The four-step method disperses the volume of the drug solution and inflammatory stimulation by injecting appropriate amounts at different levels, which may reduce excessive concentrated stimulation of nerve endings in the anorectal region, thereby alleviating the postoperative inflammatory pain response[21]. Regarding postoperative recovery, the observation group had a significantly shorter total hospital stay compared to the control group (P < 0.05), while there was no significant difference in hemorrhoid sloughing time between the two groups. This further indicates that the four-step method, while ensuring the core treatment effect, may promote the overall rehabilitation process and shorten the patient's hospitalization time due to its more comprehensive hardening and fixation effect and lower incidence of postoperative complications.

In terms of postoperative complications, there was no statistically significant difference between the two groups (P > 0.05), but the P value was 0.068. As the sample size of each group in this study was only 40 cases, the statistical power may be insufficient. This result cannot rule out the clinical benefit of the observation group in reducing postoperative complications. The incidence of complications in the observation group showed a trend lower than that in the control group, indicating that this intervention may have potential clinical advantages and needs to be further validated in future studies with larger sample sizes. However, the research results suggest that the difference in complications between the two groups is mainly reflected in pharmacological laxative intervention, with a higher proportion of medication-assisted defecation in the control group. Possible reasons include: The one-step method involves injecting a concentrated and high-dose hardening agent into the base of the hemorrhoids. Although this operation is intended to treat major blood vessels, it is prone to strong inflammatory stimulation due to high local drug concentration and large volume[22]. More importantly, high-pressure and large-volume injections can easily cause the medication to diffuse into surrounding tissues. The study by Najjar et al[23] suggests that the nerve innervation in the vicinity of the dentate line is sensitive. Therefore, injection in this area can easily lead to postoperative anal sensory abnormalities. Diffuse drugs may nonspecifically infiltrate or stimulate this area, causing local tissue edema and abnormal excitation of nerve endings, leading to abnormal defecation sensation and spastic pain, clinically manifested as significant difficulty in defecation. In contrast, the four-step injection method does not simply increase the injection volume, but achieves spatial optimization distribution of the drug solution through a precise injection strategy of layering, targeting, and small doses. Even when injection is performed in the sinus vein area above the dentate line, the injection depth and range should be strictly controlled to prevent the drug from penetrating into the skin side of the anal canal. This strategy effectively treats lesions while minimizing chemical and physical stimuli to the dentate line sensitive area[24]. In addition, early injection of the four-step method into the upper rectal artery and submucosal layer may help improve local microcirculation and venous reflux, reduce overall congestion and edema in the perianal area after surgery, and thus reduce the risk of postoperative anal dysfunction from multiple aspects[25].

Furthermore, no recurrence was observed in either patient group six months after surgery. This finding suggests that, despite utilizing different injection techniques, both methods—when combined with external stripping and internal ligation—can achieve reliable long-term efficacy. The core mechanism of action of Xiaozhiling lies in the aseptic inflammation and subsequent secondary fibrosis induced by its components[26]. The injection technique used in the observation group, guided by three-dimensional anatomy, allows for more comprehensive coverage of the hemorrhoidal vascular supply. This includes the branches of the superior rectal artery, the vessels within the submucosa and lamina propria of the hemorrhoidal area, and the sinus veins, thereby achieving more extensive vascular occlusion and tissue fixation[27]. Through this multi-level, precise injection approach, the four-step method creates ideal conditions for the uniform spatial distribution of the therapeutic solution and the formation of effective fibrosis.

However, this study also has limitations. First, this study is a single center design, and the sample size is relatively limited. In addition, the grouping of the two groups of patients is based on the intraoperative injection method, that is, the grouping is not achieved by randomization, but determined by the surgeon according to the clinical situation. Although Table 1 shows that the two groups are comparable in age, gender, course of disease and other baseline data, this non randomized design still cannot completely eliminate potential selection bias and confounding factors, such as the surgeon’s operation proficiency, subtle differences in perioperative management, etc., which may affect the research results. Secondly, this study mainly focused on the recurrence of hemorrhoids in half a year after operation, lacking longer-term follow-up data, and unable to fully evaluate the impact of the two injection methods on the long-term recurrence risk of hemorrhoids. Finally, this study did not analyze the subgroups with different hemorrhoids size, shape and anal pad prolapse. Therefore, it is necessary to carry out prospective, multicenter, large sample randomized controlled trials with rigorous design in the future to further verify the long-term efficacy of the two injection methods and their applicability in different subtypes of hemorrhoids, and provide higher-level evidence-based medicine for clinical practice.

CONCLUSION

To sum up, this study preliminarily shows that when combined with external dissection and internal ligation in the treatment of mixed hemorrhoids, the four-step injection method of Xiaozhiling can more effectively reduce the postoperative pain and shorten the hospitalization time of patients without prolonging the operation time. In terms of postoperative complications, although there was no significant difference in the total incidence between the two groups, the observation group showed a lower trend, and its potential clinical benefits were worthy of attention. However, limited by the 6-month follow-up period, this study can only confirm the recurrence of the two groups in the short term, and its long-term efficacy remains to be further observed. Therefore, the conclusion of this study is mainly applicable to the short-term efficacy evaluation of perioperative period.