• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of annsurgLink to Publisher's site
Ann Surg. Jul 2005; 242(1): 29–35.
PMCID: PMC1357701

Stapled Hemorrhoidopexy Versus Milligan-Morgan Hemorrhoidectomy

A Prospective, Randomized, Multicenter Trial With 2-Year Postoperative Follow Up

Abstract

Purpose:

The purpose of this study was to compare the outcome of stapled hemorrhoidopexy (SH group) performed using a circular stapler with that of the Milligan-Morgan technique (MM group). The goals of the study were to evaluate the efficacy and reproducibility of stapled hemorrhoidopexy and define its place among conventional techniques.

Methods:

A series of 134 patients were included at 7 hospital centers. They were randomized according to a single-masked design and stratified by center (with balancing every 4 patients). Patients were clinically evaluated preoperatively and at 6 weeks, 1 year, and a minimum of 2 years after treatment. Patients completed a questionnaire before and 1 year after surgery to evaluate symptoms, function, and overall satisfaction.

Results:

The mean follow-up period was 2.21 years ± 0.26 (1.89–3.07). Nine patients (7%) could not be monitored at 1 or 2 years, but 4 of these 9 nevertheless filled in the 1-year questionnaire. The patients in the SH group experienced less postoperative pain/discomfort as scored by pain during bowel movement (P < 0.001), total analgesic requirement over the first 3 days (according to the World Health Organization [WHO] class II analgesics [P = 0.002]; class III [P = 0.066]), and per-patient consumption frequency of class III analgesics (P = 0.089). A clear difference in morphine requirement became evident after 24 hours (P = 0.010). Hospital stay was significantly shorter in the SH group (SH 2.2 ± 1.2 [0; 5.0] versus MM 3.1 ± 1.7 [1; 8.0] P < 0.001). At 1 year, no differences in the resolution of symptoms were observed between the 2 groups, and over 2 years, the overall incidence of complications was the same, specifically fecaloma (P = 0.003) in the MM group and external hemorrhoidal thrombosis (P = 0.006) in the SH group. Impaired sphincter function was observed at 1 year with no significant difference between the groups for urgency (12%), continence problems (10%), or tenesmus (3%). No patient needed a second procedure for recurrence within 2 years, although partial residual prolapse was detected in 4 SH patients (7.5%) versus 1 MM patient (1.8%) (P = 0.194).

Conclusion:

Stapled hemorrhoidopexy causes significantly less postoperative pain. The technique is reproducible and can achieve comparable outcomes as those of the MM technique as long as the well-described steps of the technique are followed. Like with conventional surgery, anorectal dysfunction can occur after stapled hemorrhoidopexy in some patients. Its effectiveness in relieving symptoms is equivalent to conventional surgery, and the number of hemorrhoidal prolapse recurrences at 2 years is not significantly different. Hemorroidopexy is applicable for treating reducible hemorrhoidal prolapse.

Stapled hemorrhoidopexy, as developed by Dr. Antonio Longo with use of a circular stapler, has emerged as a possible alternative to open hemorrhoidectomy.1 According to a recently published consensus among experts, the technique has been standardized and is widely accepted in different countries.2 The indications, contraindications, and operative technique have been defined. Numerous controlled studies have already demonstrated that this technique is associated with less postoperative pain and a quicker recovery.3–10 However, certain issues remain unsolved.11 Most of these studies were conducted in highly specialized centers. Long-term outcomes have not been reported. Our goals were to find out if the results of the stapled hemorrhoidopexy are the same as those reported in the literature when the operation is performed at independent centers. After a preliminary study,12 we decided to perform a controlled study focused on long-term results.

METHODS

A total of 134 patients were randomized over a 15-month period at 7 different centers (both teaching hospitals and private hospitals). Inclusion began in January 1999 and ended in April 2000. Patients were randomized to undergo either the stapled hemorrhoidopexy technique or the Milligan-Morgan technique. Two groups were constituted: a stapled hemorrhoidopexy (SH) group (63 patients), operated on using the PPH 01 kit (Ethicon Endo-Surgery); and a Milligan-Morgan (MM) group (63 patients), operated on using a standard open hemorrhoidectomy technique.13 The protocol was approved by an ethics committee. After patients had given their written consent, they were informed of the result of randomization. Four rejected the result of the randomization and 4 others were not operated on for personal reasons.

The main inclusion criterion was symptomatic hemorrhoidal disease, which could be treated by either surgical technique. Each center had had previous experience in treating at least 30 patients using the stapled hemorrhoidopexy technique. Exclusion criteria were acute hemorrhoidal episodes with thrombosis, prior hemorrhoidectomy, and intercurrent anal pathology (ie, fistula and/or fissure). The main end point was a comparison of the 2 groups with respect to postoperative pain. Secondary end points included outcome in the mid- and long-term (after a minimum of 2 years).

Postoperative pain was managed according to the guidelines of the French Anesthesiology Society.14 Pain was assessed using a visual analog scale (VAS) in which 0 corresponds to “no pain” and 10 to “maximum pain.” The aim was to keep the pain down to a VAS score of less than 3 at all times. Prescribed analgesics were classified using the World Health Organization (WHO) system. During the operation and immediately after patient recovery, the analgesic regimen included a systematic antiinflammatory medication and subcutaneous morphine in case of pain. While the patient was hospitalized, analgesics were administered on the basis of the VAS score in the following way: VAS <3, a WHO class I analgesic (paracetamol); between 3 and 5, a WHO class II analgesic (paracetamol codeine, dextropropoxyphene–paracetamol); or VAS >5, a WHO class III analgesic (morphine administered systematically with paracetamol). If a given analgesic was having an inadequate but partial effect, an analgesic of the next class up was prescribed. Type of anesthesia was left up to the investigating center. While hospitalized, patients were systematically administered an antiinflammatory drug (300 mg ketoprofen per day), but other medications (laxatives, topical treatments, and so on) were left up to the care-providing team. Patients were discharged once their pain was being effectively managed with oral analgesics.

Other parameters evaluated were length of hospital stay, the time to return to normal activities (both professional and social), postoperative complications, effectiveness in symptom control, and whether there was recurrence.

Patient monitoring included a series of clinical examinations by the surgeon: prior to the operation, then after 6 weeks, after 1 year, and finally after a minimum of 2 years. Preoperatively and 1 year postoperatively, patients were asked to fill out a 53-item patient questionnaire about symptoms, sphincter function, defecation, and quality of life. This allowed the assessment of the effectiveness in symptom control, functional outcome, and the patient's overall satisfaction.

Statistical Analysis

Randomization was stratified according to the center and balanced every 4 patients. The main analysis covered all patients. The 2 different groups were compared using a chi-squared test for qualitative variables and a parametric t test to compare means for quantitative variables. Performance and safety were evaluated using a chi-squared test. Statistical testing was carried out on the basis of the following hypotheses: bilateral test and a first degree α error risk of 0.05 (α = 5%). The software used was SPSS version 11.0 for Windows. Some of the results are expressed in the text as a mean ± standard deviation (SD) (minimum; maximum).

RESULTS

A total of 126 patients (63 for each group) were included, randomized, and received treatment. There were no significant differences between the 2 groups with respect to sex, weight, history, or risk factors. The mean age in the SH group was higher than in the MM group (51 versus 44 years; P = 0.003).

Clinical data were comparable in both groups except for skin tags before the operation (MM group 65% versus SH group 33%; P = 0.001). The most common problem reported by the patients before the operation was the impression of a mass at the anus (90%). Other problems included frequent bleeding (47%), itching (35%), discharge and soiling (31%), and pain (15%).

Prolapse of internal hemorrhoids was the most common reason for the decision to operate. In 85% of cases, the prolapse was reducible and only 5% had a bulky prolapse that could not be reduced. In 10% of cases, patients did not complain of prolapse. The preoperative examination failed to detect hemorrhoidal prolapse in only 2 patients in the SH group (3.2%) and 3 in the MM group (4.8%). The same types of anesthesia were used in both groups.

No particular event occurred in any of the operations. In the SH group, associated procedures included: excision of 1 or more skin tags (7 patients), excision of an isolated hemorrhoidal pile (3 patients), and removal of a fibrous anal polyp (1 patient). In the SH group, the mean distance of the staple line above the dentate line was 2.96 ± 0.94 cm, although this parameter varied between different centers, in some cases significantly (between 1.5 and 4.0 cm).

Stapled hemorrhoidopexy was significantly faster than the Milligan-Morgan technique (21 minutes versus 31 minutes; P < 0.001), as was the time spent in the operating room (46 minutes versus 53 minutes; P = 0.035).

Postoperative Follow Up During the First 6 Weeks

The first defecation occurred sooner in the SH group: SH 1.6 day ± 1.0 (0; 5.0) versus MM 2.1 day ± 1.1 (0; 5.0) (P = 0.006).

Comparable degrees of pain were experienced in both groups (mean VAS <3) at all times of the day (given varying analgesics prescriptions depending on pain level). The only differences observed concerning VAS scores were during defecation. Patients in the MM group experienced significantly more pain during defecation for the first 10 days after the surgery (P < 0.001) (Fig. 1). VAS scores were comparable in both groups at all other times of the day, but there was a significant difference in analgesic consumption. To obtain an equivalent VAS score over the first 3 days, patients in the MM group had to be administered 50% to 100% more class II and class III analgesics than did those in the SH group. The difference in class II analgesics was significant (P=0.002), although it was small over the first 24 hours (Table 1). Regarding morphine consumption in the first 3 days, patients in the MM group consumed more but not to a significant extent: SH 1.3 ± 1.9 (0; 7) versus MM 2.0 ± 2.6 (0; 13) (P = 0.089). However, after 24 hours, the number of patients who no longer required morphine was significantly different: SH 52 (82%) versus MM 39 (62%) (P = 0.010).

figure 5FF1
FIGURE 1. Mean pain (visual analog scale [VAS]) during bowel movement.
Table thumbnail
TABLE 1. Total Consumption of Analgesics After 24 and 72 Hours, Class I (mg); Class II (Tablets or Capsules); Class III (mg)

Regarding total analgesic consumption over the 3 days after the operation, no difference was observed within the SH group between those patients who had had tags removed (7 patients) or isolated piles removed (3 patients) and the rest of the group. None of the 11 patients in this group (18%) who needed morphine after more than 24 hours had had any extra procedure performed during the operation. Nevertheless, pain during defecation over the first 10 days was directly correlated with the presence of an open wound in the anal canal in that the difference between mean pain in the MM group (4.20±2.24) and that in those of the SH group who had not undergone any extra procedure (2.36 ± 2.07) was significant (P < 0.001). This difference was not observed in the patients in SH group who had undergone an extra procedure (3.85 ± 2.36). No correlation was observed between the degree of pain and the location of the stapling, regardless of the center (P = 0.977) (n = 54).

The mean hospital stay was shorter (P < 0.001) for the SH group (Table 2). Significant differences were also observed between centers with the mean length of stay varying from 1.00 to 3.50 days in the SH group and from 1.67 to 5.00 days in the MM group. At 2 centers, the mean length was longer for the SH group.

Table thumbnail
TABLE 2. Data on Patients Over the First 6 Weeks

At the 6-week postoperative visit, collected data showed that normal activity was restored earlier in the SH group (P < 0.001). In addition, postoperative topical treatment and wound management at home was significantly less for the SH group (P < 0.001) (Table 2).

Results at 1 and 2 Years

A total of 17 patients (11 SH and 6 MM) failed to return to the 2-year follow-up clinic. There were no details for 9 patients (7%) at either 1 or 2 years. Of the latter, 4 refused to return for the follow-up clinic but nevertheless filled out the 1-year patient questionnaire. Concerning these dropouts, there is no significant difference between the 2 groups. The mean overall follow-up time was 2.21 ± 0.26 years (1.89–3.07).

Regarding control of symptoms after 1 year, no difference was detected between the 2 groups: 94% of the patients who had felt a mass at the anus before the operation no longer had this complaint, 84% had no more pain and discomfort, 92% had no more bleeding, 92% had no more itching, 100% had no more discharge, 65% had no more incontinence problems, 92% had no more tenesmus, 56% had no more urgency, and 58% had no more constipation.

Anatomic assessment at 1-and 2-year physical examination revealed no differences between the 2 groups. The 2 techniques were effective against both skin tags and external, hypertrophic hemorrhoids. This was normal in 92% and 89% of patients in SH group at 1 and 2 years, respectively, the corresponding figures for the MM group being 100% and 95% (Table 3).

Table thumbnail
TABLE 3. Impact of Surgery on Skin Tags and Hypertrophic External Hemorrhoids

Complications and Side Effects

No significant difference was observed in the incidence of complications in the 2 groups (P = 0.871). Specific complications were observed in each group, namely fecaloma (P = 0.003) in the MM group and external hemorrhoidal thrombosis in the SH group (P = 0.006) (Table 4). One patient in the SH group withdrew from the study 2 days after the operation to undergo traditional hemorrhoidectomy to reduce major external thromboses. Five patients (2 SH, 3 MM) had to be readmitted into the hospital within 2 months: 2 patients (MM) for fecaloma evacuation, 2 patients for spontaneous reactive bleeding (necessitating in 1 case of emergency treatment and a blood transfusion), and the last (MM) for symptomatic stenosis.

Table thumbnail
TABLE 4. Incidence of Complications During the Follow-up Period

After 1 year, anorectal function assessed by the patient questionnaire showed the occurrence of impaired fecal continence, although there was no difference between the 2 techniques: 12% reported urgency, 10% continence problems, 3% tenesmus, and 3% loss of discrimination between gas and stool (Table 5). Most of the continence problems reported by the patients were occasional and did not affect their social life, but 1 patient in the MM group had to wear protective incontinence pads. Of the 8 patients, 3 reported experiencing gas leaks (3 MM), 4 had experienced accidents with liquid stools (1 SH, 3 MM), and 2 had had problems with solid stools (1 SH, 1 MM).

Table thumbnail
TABLE 5. Adverse Effects of Surgery on Anorectal Function After 1 Year

Recurrence

None of the patients needed a second operation within the 2-year follow-up period. After 1 year, there was no difference in satisfaction between the 2 groups (as evaluated in the questionnaire). All patients declared themselves as either satisfied or very satisfied, and considered themselves cured no matter what their responses were to other items in the questionnaire.

Recurrence was based on the findings of the surgeon's physical examination of the patient 1 and 2 years after the procedure. At 1 year, prolapse recurrence was 3% (2 patients) and 0%, respectively, in the SH group and the MM group (P=0.498). At 2 years, prolapse recurrence was 7.5% in the SH group (4 patients) versus 1.8% in the MM group (1 patient) (P=0.194). All 4 patients in the SH group had incomplete recurrent prolapse, in most cases positioned on the anterior pile.

DISCUSSION

Until now, only 1 controlled study has been conducted at different types of centers, namely a proctology unit, a general surgery department, and a department of general surgery and transplantation.3 Our results also come from various surgical units and similarly show no difference in outcomes at participating centers. The only observed differences concern the length of the postoperative hospital stay and the distance of the staple line from the dentate line. Although this distance varies from one center to another, it was never greater than 4 cm. All patients in the SH group were treated according to the same basic protocol involving reduction of the hemorrhoidal prolapse, resection of the glandular mucosa and/or the transitional epithelium while preserving internal hemorrhoidal piles, and placing a staple line above the internal piles reinforced by sutures as necessary.2 Similarly, the indications for surgical treatment at the various centers were identical with most of patients being operated on for reducible prolapse considered as not amenable by banding or that have failed to respond to previous banding. Only a few patients—less than 5%—without prolapse were submitted to surgery as a result of failure of either drug-based or instrument-based treatments.

Like those of the other controlled studies reported in the literature,3–10 the results reported here show that stapled hemorrhoidopexy is associated with significantly less postoperative discomfort. In our study, this manifested as a shorter delay before the first bowel movement, a significantly lower degree of pain during defecation, a shorter hospital stay, the absence of any need for topical treatment (wound care), and quicker return to normal social and/or professional activities. Whichever technique is under consideration, the amount of morphine consumed was considerably higher than what is reported in the literature. The reason for this is the inclusion in the study protocol of a requirement to keep pain levels to a minimum, even in the days immediately after the operation. Although the SH group consumed lower levels of analgesics (by a factor of 50%), the difference is not significant. However, a statistically significant difference emerged after 24 hours with the SH group requiring less analgesic drugs than the MM group.

In contrast to what other investigators have shown,10 we detected little difference in pain between the 2 groups on day 1. It is also worth noting that a small number of patients in the SH group (approximately 10%) needed prolonged analgesic relief with high doses of morphine, as high as those demanded by certain patients in the MM group (Table 1). We did not find any correlation in the SH group between the intensity of pain (total analgesic dose administered and frequency of administration) and the height of the staple line. Similarly, the removal of either a skin tag or an isolated pile at the same time as stapled hemorrhoidopexy did not seem to exacerbate pain (apart from that felt during defecation). In this group of patients, no local complications were observed by the investigators that might account for this pain.

Both types of treatment were equally effective in curing the symptoms because both resolved the prolapse that was causing them. Both groups were equally positive about the procedure with no patients declaring themselves less than satisfied. The main inconvenience reported by the patients in the MM group was the length of time it took for anal wounds to heal (Table 2). The presence of large hypertrophic, external hemorrhoids does not seem to contraindicate stapled hemorrhoidopexy because we observed regression of external piles in 90% of cases at 1 year, an effect that persisted through 2 years in 85% of cases (Table 3).

Most of the complications arose within the first few weeks after the operation. The incidence of complications was similar in both groups, and no serious adverse event occurred apart from 1 case of bleeding 3 days after the patient's discharge, which necessitated local hemostasis and blood transfusion. Immediate postoperative bleeding as reported elsewhere did not occur, probably because of careful hemostatic control at the staple line during the procedure.15 In our study, external hemorrhoidal thrombosis was a complication specific to stapled hemorrhoidopexy. It may be delayed by several months and is usually medically controlled. Therefore, patients with a history of external thrombosis and, more generally, those in whom the hemorrhoidal disease is predominantly external, are less suitable candidates for stapled hemorrhoidopexy. Major, persistent, debilitating pain as others have observed did not occur in our series.16 However, it emerged from the patient questionnaire that hemorrhoidal surgery, whatever the technique, can compromise sphincter function (with 12% reporting urgency within 1 year and 10% reporting continence problems) (Table 5). These adverse effects were minor and patients still reported themselves as satisfied. However, we were unable to predict, explain, or prevent them. These were probably the result of postoperative anatomic remodeling of the anal canal. Numerous manometric and ultrasound studies have detected such modifications to the sphincter, although no correlation has ever been defined in terms of clinical outcome.17,18

The follow-up period in this study allowed the long-term comparison of efficacy between stapled hemorrhoidopexy and the Milligan-Morgan technique. The Milligan-Morgan is currently the reference technique because it is reputed to be the most effective when it comes to correcting hemorrhoidal prolapse. However, in this study, it was not significantly more effective than stapled hemorrhoidopexy.

Stapled hemorrhoidopexy is probably more dependent on operator skills than previously believed. The practical difficulty is in identifying the amount of mucosa to be removed because this parameter varies according to the extent of prolapse.19 This explains why most instances of residual prolapse in stapled hemorrhoidopexy within our study have involved anterior hemorrhoids. This observation justifies a strategy of compensating for the imperfection of the technique, as done in 3 of our cases, by complementary resection of the pile in case of insufficient reduction after stapling.

CONCLUSION

This study confirms that stapled hemorrhoidopexy is associated with less postoperative pain and is not associated with any greater morbidity than conventional techniques. The procedure is reproducible, and different operators can achieve comparable outcomes as long as they follow the underlying principles and have a minimum of experience.

Long-term outcome is good, although in some cases, anorectal function can be somewhat compromised, as is also true with conventional techniques. Stapled hemorrhoidopexy would seem to be the most suitable for reducible hemorrhoidal prolapse in that it repositions internal hemorrhoids and induces the regression of external hemorrhoids. It is as effective at curing symptoms as conventional techniques as long as the symptoms are directly related to the prolapse. According to the results of this study, we consider stapled hemorrhoidopexy as the preferred technique for hemorrhoidal prolapse given the appropriate indications.

ACKNOWLEDGMENTS

The authors thank the following for their contributions to this work: K. Aït Ali, B. Laurent, I. Migueres, G. Piel, M. Sodji, G. Staumont, and F. Varcus.

Footnotes

Reprints: Jean-Pierre Arnaud, MD, Centre Hospitalo-Universitaire, Service de chirurgie digestive, 4 rue Larrey, 49933 ANGERS cedex9, France. E-mail: rf.sregna-uhc@duanrapj.

REFERENCES

1. Longo A. Treatment of haemorrhoids disease by reduction of mucosa and hemorrhoidal prolapse with circular suturing device: a new procedure. 6th World Congress of Endoscopic Surgery; Rome; 1998:777–784.
2. Corman ML, Gravié JF, Hager T, et al. Stapled hemorrhoidopexy: a consensus position paper by an international working party—indications, contraindications and technique. Colorectal Disease. In press. [PubMed]
3. Ganio E, Altomare F, Gabrielli F, et al. Prospective randomized multicentre trial comparing stapled with open haemorrhoidectomy. Br J Surg. 2001;88:669–674. [PubMed]
4. Mehingan BJ, Monson JR, Hartley JE. Stapling procedure for haemorrhoids versus Milligan-Morgan haemorrhoidectomy: randomised controlled trial. Lancet. 2000;355:782–785. [PubMed]
5. Rowsell M, Bello M, Hemingway DM. Circumferential mucosectomy (stapled haemorrhoidectomy) versus conventional haemorrhoidectomy: randomised controlled trial. Lancet. 2000;355:779–781. [PubMed]
6. Ho YH, Cheong WK, Tsang C, et al. Stapled hemorrhoidectomy—cost and effectiveness. Randomized, controlled trial including incontinence score, anorectal manometry, and endoanal ultrasound assessments at up to three months. Dis Colon Rectum. 2000;43:1666–1675. [PubMed]
7. Shalaby R, Desoky A. Randomized clinical trial of stapled versus Milligan-Morgan haemorrhoidectomy. Br J Surg. 2001;88:1049–1053. [PubMed]
8. Boccasanta P, Capretti PG, Venturi M, et al. Randomised controlled trial between stapled circumferential mucosectomy and conventional circular hemorrhoidectomy in advanced hemorrhoids with external mucosal prolapse. Am J Surg. 2001;182:64–68. [PubMed]
9. Wilson MS, Pope V, Doran HE, et al. Objective comparison of stapled anopexy and open hemorrhoidectomy: a randomised, controlled trial. Dis Colon Rectum. 2002;45:1437–1444. [PubMed]
10. Pavlidis T, Papaziogas B, Souparis A, et al. Modern stapled Longo procedure vs. conventional Milligan-Morgan hemorrhoidectomy: a randomized controlled trial. Int J Colorectal Dis. 2002;17:50–53. [PubMed]
11. Lehur PA, Gravié JF, Meurette G. Circular stapled anopexy for haemorrhoidal disease: results. Colorectal Disease. 2001;3:374–379. [PubMed]
12. Papillon M, Arnaud JP, Descottes B, et al. Le traitement de la maladie hémorroïdaire par la technique de Longo. Résultats préliminaires d'une étude prospective portant sur 94 cas. Chirurgie. 1999;124:666–669. [PubMed]
13. Milligan ETC, Morgan CN, Jones LE, et al. Surgical anatomy of the anal canal and operative treatment of haemorrhoids. Lancet. 1937;1:1119–1124.
14. Delbos A. Management of post-operative pain on surgical wards. Ann Fr Anesth Réanim. 1998;17:649–662. [PubMed]
15. Arnaud JP, Pessaux P, Huten N, et al. Treatment of hemorrhoids with circular stapler, a new alternative to conventional methods: a prospective study of 140 patients. J Am Coll Surg. 2001;193:161–165. [PubMed]
16. Cheetham MJ, Mortensen NJ, Nystrom PO, et al. Persistent pain and faecal urgency after stapled haemorrhoidectomy. Lancet. 2000;356:730–733. [PubMed]
17. Altomare DF, Rinaldi M, Sallustio L, et al. Long-term effects of stapled haemorrhoidectomy on internal anal function and sensitivity. Br J Surg. 2001;88:1487–1491. [PubMed]
18. Ho YH, Seow-Choen F, Tsang C, et al. Randomized trial assessing anal sphincter injuries after stapled haemorrhoidectomy. Br J Surg. 2001;88:1449–1455. [PubMed]
19. Kairaluoma M, Nuorva K, Kellokumpu I. Day-case stapled (circular) vs. diathermy hemorrhoidectomy. A randomised, controlled trial evaluating surgical and functional outcome. Dis Colon Rectum. 2003;46:93–99. [PubMed]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...