Non-excisional laser therapies for hemorrhoidal disease: a systematic review of the literature

Non-excisional laser therapies are emerging treatment for grades II and III hemorrhoidal disease (HD). However, so far, their efficiency is based on low-level evidence. Therefore, we aimed to systematically review the efficiency of non-excisional laser therapies for HD. MEDLINE/Pubmed, Web of science, Embase, and Cochrane were searched from database implementation until the April 17th, 2020. We included studies reporting at least one of surgical indicators of postoperative outcomes of laser therapies, encompassing laser hemorrhoidoplasty (LH) and hemorrhoidal laser procedure (HeLP). Fourteen studies describing LH and HeLP were included, representing 1570 patients. The main intraoperative complication was bleeding (0–1.9% of pooled patients for LH, 5.5–16.7% of pooled patients for HeLP). Postoperative complications occurred in up to 64% of patients after LH and 23.3% after HeLP. Resolution of symptoms ranged between 70 and 100% after LH and between 83.6 and 90% after HeLP. Moreover, four randomized controlled trials included in our review reported similar resolution after LH compared with hemorrhoidectomy or mucopexy and after HeLP compared with rubber band ligation. Recurrence rate was reported to range between 0 and 11.3% after LH and between 5 and 9.4% after HeLP. When compared with hemorrhoidectomy, LH showed conflicting results with one randomized controlled trial reporting similar recurrence rate, but another reporting decreased recurrences associated with hemorrhoidectomy. Laser therapies showed lower postoperative pain than hemorrhoidectomy or rubber band ligation. LH and HeLP are safe and effective techniques for the treatment of grades II and III HD. Electronic supplementary material The online version of this article (10.1007/s10103-020-03142-8) contains supplementary material, which is available to authorized users.


Introduction
Hemorrhoidal disease (HD) is frequent, with an estimated prevalence of 4.4% among the US population [1]. HD is the consequence of an increased inflow into the superior rectal artery, which causes dilatation of the hemorrhoidal plexus. Moreover, degradation of the supportive tissue results in sliding down of hemorrhoids [2]. Hemorrhoids are classified as grade I when they are seen during anoscopy as congested veins, grade II when they prolapse but spontaneously reduce, grade III when they prolapse and need manual reduction, and grade IV when they are irreducible [3]. HD, defined as symptomatic hemorrhoids, can present with pain, itching, bleeding, discharge, or prolapse [4].
Initial treatment of HD consists of lifestyle modifications and administration of phlebotonics. After failure of conservative management, HD is treated with interventional therapies [4]. Open hemorrhoidectomy (HC) was first described in 1937 by Milligan-Morgan [5] and is still considered as the gold standard interventional therapy for advanced stages of HD. However, significant postoperative pain and complications were associated with excision of hemorrhoidal tissue. Therefore, various non-excisional therapies have been developed, such as rubber band ligation (RBL), mucopexy (MP), and more recently laser therapies [4,6].
Non-excisional laser therapy was initially described in 1998 by Barr et al. [7] with an experimental animal study. Administration of a pulsed laser energy to the submucosal pig rectal tissue allowed coagulation of vessels, with limited damage to the surrounding tissue. Latter, non-excisional laser therapy was applied in humans, with laser hemorrhoidoplasty (LH) first described in 2007 by Karahaliloglu et al. [8]. During LH, a laser fiber is introduced through a skin incision at the hemorrhoidal base, and hemorrhoidal cushions are coagulated. Hemorrhoidal laser procedure (HeLP) constitutes another non-excisional laser therapy for the treatment of HD, first described in 2009 by Salfi et al. [9]. During this procedure, a Doppler identifies the terminal branches of the superior rectal artery, which are coagulated with a pulsed laser energy. Both techniques allow obliteration and retraction of the hemorrhoidal plexus. Moreover, they were shown to be safe and effective for the treatment of HD [8,9].
Therefore, non-excisional laser therapies constitute interventional therapies for the treatment of HD. However, their recommendation is based on low level of evidence [4,6]. For the purpose of strengthening the evidence for the benefits of laser therapies, we aimed to systematically review the outcomes of LH and HeLP for the treatment of HD. According to population, intervention, comparison, outcome (PICO) framework, our question was: in patients with HD undergoing nonexcisional laser therapies, what are the postoperative outcomes?

Materials and methods
This systematic review adheres to the recommendations of the Preferred Reporting Items for Systematic Review and Metaanalyses (PRISMA) statement [10] (Supplementary Table 1).

Literature search and study selection
Human studies written in English published before April 17th, 2020 were looked for in MEDLINE/Pubmed, Web of science, Embase, and Cochrane. The search strategy was designed and independently conducted by two authors (GL, EL). The following medical search headings and keywords were used: "hemorrhoids" in MeSH terms; and "haemorrhoid*" OR " h em o r r ho i d*" O R " he morr hoid al d isea se" O R "haemorrhoidal disease" AND "laser" OR "laser hemorrhoidoplasty" OR "hemorrhoidal laser procedure" in non-MeSH terms. The reference lists of included articles were further screened for additional eligible publications.

Outcomes of interest
The aim of the study was to systematically review the outcomes of laser therapies for the treatment of HD, including LH and HeLP.
Primary endpoints were the surgical indicators of postoperative outcomes, including -Improvement, defined as postoperative decrease of HD symptoms or grade adapted from the Goligher classification [3]; -Persistence, defined as postoperative presence of symptoms or prolapse; -Resolution, defined as postoperative absence of symptoms or prolapse; -Recurrence, defined as reappearance of HD, after a resolution; -Reoperation, defined as any procedure performed for HD after the laser therapy.

Secondary endpoints included
-Perioperative characteristics; -Postoperative pain and return to normal activities; -Intraoperative and postoperative complications, defined as any deviation from the normal postoperative course. Therefore pain, tenesmus, and dyschezia that resolved spontaneously without treatment were not considered as complications.

Inclusion criteria
Original publications were eligible only if they fulfilled the following criteria: (i) they reported outcomes of laser therapy for HD and (ii) they reported at least one of the primary endpoint. Articles were included regardless of the design and the size of the study population.

Exclusion criteria
The exclusion criteria were as follows: studies reporting (i) laser hemorrhoidectomy or infrared therapy; (ii) laser therapy performed with an associated procedure or for another anorectal pathology than HD; and (iii) conference abstracts, protocols, and editorials.

Data extraction
Two reviewers (GL, EL) extracted the following data: general and methodological information of the study, baseline characteristics of the study population, surgical indicators of postoperative outcomes, perioperative characteristics, complications, postoperative pain, and return to normal actives. Details of extracted data are reported in the Supplementary Table 2.

Postoperative pain and return to normal activities
Postoperative pain was significantly lower after LH compared with HC [13,15,16] and resulted in a shorter return to normal activities [15,16]. Early postoperative visual analog score (VAS) was also decreased with HeLP compared with RBL [22] (mean 1.1 versus 2.9, p < 0.001, respectively). Details of postoperative pain and return to normal activities are depicted in Table 4.

Surgical indicators of postoperative outcomes
Surgical indicators of postoperative outcomes are detailed in Table 6. The postoperative follow-up duration ranged

Symptom improvement
Improvement of HD symptoms was reported by four studies [9,[17][18][19] after HeLP and ranged from 85% at a median of 15 months [18] to 91.7% at a mean of 5.8 months [17]. No study reported symptom improvement after LH.

Reoperation
Data on reoperation were available in three studies after LH [8,14,15] and in two studies after HeLP [19,21]. In the study by Karahaliloglu et al. [8], 54.7% of patients were reoperated with redo LH, for insufficient treated nodes between 1 and 3 months. Two other studies [14,15] reported no need for reoperation after LH, with a follow-up of 3 to 12 months. After HeLP, up to 7.8% of cases were reoperated within 5 months [19], with redo HeLP, RBL, transanal hemorrhoidal dearterialization, stapled hemorrhoidopexy, or HC [19,21].  17 1.4 ± 1.   Giamundo et al. 17 13.4% (6.7% laser, 6.7% suture) The difference was statistically significant e Additional 11.0% of discharge was described. They were not considered as complications since it did not cause discomfort, and it disappeared within 30 days. Moreover, it was not specified whether the discharge consisted of blood or mucous
Moreover, 64% of bleeding reported after LH [12] consisted of post-defecatory bleeding, which did not require treatment and spontaneously resolved after the 7th postoperative day. Compared with other non-excisional therapy for HD, the RCT by Giamundo et al. [22] showed similar intraoperative bleeding rate associated with HeLP versus RBL (16.6% versus 10%, p = 0.12). Compared with excisional therapy, two RCTs [14,15] showed lower intraoperative blood volume loss associated with LH versus HC. Moreover, postoperative complications were decreased with LH (urinary retention: 0% for LH versus 13.3% for HC, p = 0.038; anal stenosis: 0% for LH versus 13.3% for HC, p = 0.038) [15]. Secondarily, laser therapies are effective for the treatment of grades II and III HD, as shown by surgical indicators of postoperative outcomes. Resolution of symptoms ranged between 70 and 100% after LH and from 83.6 to 90% after HeLP. These rates are similar to the success rate of RBL e Described as persistence in the results section, but as persistence or recurrence in the discussion section reported in the literature. As shown by a retrospective study [23] of 750 patients with grades I to III HD treated with RBL, the success rate was 89%. Moreover, four RCTs included in our review reported similar resolution after LH compared with HC [14][15][16] or MP [16] and after HeLP compared with RBL [22]. Another surgical indicator was the recurrence rate, reported between 0 and 11.3% after LH and between 5 and 9.4% after HeLP. In the literature, recurrence rate at 12 months was reported up to 5% after mucopexy [24] and up to 11.1% [25] after hemorrhoidal artery ligation ± mucopexy. Compared with HC, LH showed conflicting results with one RCT reporting similar recurrence rate [15], but another RCT reporting decreased recurrences associated with HC [16]. Another surgical indicator of postoperative outcome was the reoperation rate, reported in 54% of patients after LH [8]. However, Karahaliloglu et al. [8] were the first to report their experience with LH, and this high reoperation rate seemed to decrease with progress in the learning curve. Moreover, two other studies reported no need for reoperation after LH, at 3 and 6 months of follow-up [14,15]. Nevertheless, a long-term follow-up is mandatory to identify recurrences and the potential need for further intervention. Thirdly, laser therapies conferred the advantages of a quick return to normal activities and low postoperative pain. The latter is explained by the absence of excision of tissue below the dentate line, where pain fibers are present [26]. Compared with HC, two RCTs showed decreased postoperative pain score associated with LH [15,16]. Compared with RBL, another RCT showed decreased postoperative pain associated with HeLP [22]. However, pain comparison between studies is hazardous as postoperative analgesia varied significantly among studies.
The main limitation of the study is the heterogeneity of included studies. Perioperative characteristics, such as preoperative enema, antibioprophylaxis, anesthesia, and laser techniques, varied significantly among studies. Moreover, while grades II and III HD are good candidates for laser therapies, some studies included grades I and IV HD [8,11,20,21]. Another weakness is the small population size of included studies, with the largest cohort composed of 341 patients [11]. This resulted in a decreased statistical power. Moreover, rare complications may be unidentified.
In this review, surgical indicators were used as surrogates of postoperative outcomes. Nevertheless, they were irregularly reported among studies. Moreover, Giamundo et al. [21] reported 9.7% of symptomatic persistence in the results section, but this was latter mentioned as persistence and/or recurrence in the discussion section. Inconsistency with outcomes definition precluded a meticulous analysis. As demonstrated by a recent systematic review [27], assessment of treatment efficiency should emphasize the use of validated scoring systems. However, none of the included study used these scores.
Overall, laser therapies appeared to be safe and effective techniques for the treatment of HD. Moreover, the learning curve is quick and was estimated from three to five cases [14]. These techniques could be alternatives to RBL or hemorrhoidal artery ligation ± mucopexy for the treatment of grade II or III HD. Only one RCT compared HeLP with RBL [21] and future research should focus on the comparison between laser and other non-excisional therapies of HD. Another unanswered question is the utility of the Doppler for the laser procedure. As reported by two RCTs [28,29], the Doppler use did not show benefits for the hemorrhoidal artery ligation technique. Finally, benefits of LH or HeLP should be compared.

Conclusions
To conclude, non-excisional laser therapies, including LH and HeLP, are safe and effective. They should be considered for the treatment of grades II and III HD unresponsive to conservative management.
Authors' contributions GL and EL conceived and designed the study. GL and EL acquired the data. GL, EL, JM, CT, NB, and FR interpreted the data. GL, EL, JM, CT, NB, and FR contributed to the writing of the manuscript and to its critical revision. GL, EL, JM, CT, NB and FR approved the final version of the manuscript. the article.
Funding Open access funding provided by University of Geneva.

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
Ethics approval Not applicable.
Consent to participate Not applicable.

Consent for publication Not applicable.
Code availability Not applicable.
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