Extracellular matrix-cell interactions: Focus on therapeutic applications.

Extracellular matrix (ECM) macromolecules together with a multitude of different molecules residing in the extracellular space play a vital role in the regulation of cellular phenotype and behavior. This is achieved via constant reciprocal interactions between the molecules of the ECM and the cells. The ECM-cell interactions are mediated via cell surface receptors either directly or indirectly with co-operative molecules. The ECM is also under perpetual remodeling process influencing cell-signaling pathways on its part. The fragmentation of ECM macromolecules provides even further complexity for the intricate environment of the cells. However, as long as the interactions between the ECM and the cells are in balance, the health of the body is retained. Alternatively, any dysregulation in these interactions can lead to pathological processes and finally to various diseases. Thus, therapeutic applications that are based on retaining normal ECM-cell interactions are highly rationale. Moreover, in the light of the current knowledge, also concurrent multi-targeting of the complex ECM-cell interactions is required for potent pharmacotherapies to be developed in the future.

Incidence of fistulas after drainage of acute anorectal abscesses.

PURPOSE: The aim of this study was to assess the incidence of anal fistulas and factors related to this incidence after incision and drainage of acute cryptoglandular anorectal abscesses. METHODS: Of 170 patients without previous anal fistulas, 146 were followed up for an average of 99 (range, 22-187) months after abscess drainage or until a fistula appeared. RESULTS: Fifty-four (37 percent) patients developed a fistula, and 15 (10 percent) patients developed a recurrent abscess. The incidence of fistulas was higher in females than in males (50 vs. 31 percent; P = 0.0403), especially regarding anterior abscesses (88 vs. 33 percent). Abscesses growing Escherichia coli were more prone to fistula formation than those growing other bacteria (46 vs. 27 percent; P = 0.0368). CONCLUSION: Incision and drainage alone of acute anorectal abscesses is recommended, because an unnecessary primary fistulotomy can be avoided in more than half of the patients by this approach. For superficial anterior abscesses in females, however, primary fistulotomy may be considered.

Cutting seton for anal fistulas: high risk of minor control defects.

PURPOSE: Long-term results of cutting seton in the treatment of anal fistulas were studied. METHODS: Of the 44 patients with anal fistulas, mainly of the high variety, managed with this method, 35 (25 men) attended a clinical and manometric follow-up examination on average 70 (range, 28-184) months after operation. Fistula distribution was high transsphincteric (25), low transsphincteric (5), extrasphincteric (3), and suprasphincteric (2). The seton was tightened at one-week to two-week intervals to achieve gradual sphincter division. RESULTS: Time required to achieve complete fistula healing ranged from 37 to 557 (mean, 151) days. Two (6 percent) of the 35 patients re-examined had recurrence of fistula and 22 (63 percent) reported symptoms of minor impairment in anal control, which in four patients had existed already before operation. Anal resting pressures were similar for defective and normal control, but other manometric variables were inferior in incontinence, although total squeeze pressure only showed statistically significant difference from normal continence (P = 0.0345). Incontinence was likely associated with hard and gutter-shaped operation scars in the anal canal, but the difference from normal continence was not statistically significant. CONCLUSION: Cutting seton yields fairly good results in regard to cure of fistula, but the risk of anal incontinence, despite its minor degree, seems to be too high to recommend its routine use for all high fistulas. The suprasphincteric fistulas and some extrasphincteric fistulas are difficult to treat otherwise, but especially for high transsphincteric fistulas, other methods of treatment (preferably those in which sphincter division can be avoided and the risk of anal canal deformity and incontinence are minimized) are advocated.

Factors related to frequency, type, and outcome of anal fistulas in Crohn's disease.

PURPOSE: Relation of clinical factors to frequency, type, and, in particular, outcome of anal fistulas in Crohn's disease was studied. METHODS: One hundred twelve patients seen in this hospital between January 1972 and June 1993 who suffered from Crohn's disease were included in the study. Those 35 (31 percent) with anal fistulas were re-examined or interviewed and asked about their perianal symptoms and anal control. RESULTS: Rectal involvement of Crohn's disease was associated with an increased incidence of anal fistula (49 vs. 17 percent; P < 0.01), especially high ones (82 vs. 17 percent; P < 0.01). Ten of 18 patients with low fistulas underwent fistulotomy; all 10 fistulas healed, but slowly (mean healing time, 7.5 months), and 4 of them recurred. Of eight low fistulas managed by drainage alone, four healed. Finally, 11 of 18 patients with low fistulas had their fistulas heated. Fourteen of 17 patients with high fistulas were primarily treated by drainage and 3 by local surgery. Finally, only three patients had healed fistulas--two after simple drainage and one after local surgery, and seven patients had to undergo proctectomy. Only two patients with low fistulas required proctectomy. Eight patients (33 percent) of those 24 with fistulas in whom anal continence could be assessed, 5 with local surgery and 3 with drainage alone, reported minor defects in anal control. CONCLUSIONS: Fistulotomy is a justifiable option with satisfactory results for low symptomatic anal fistulas associated with Crohn's disease, although healing may be delayed and some fistulas will recur. Outcome of high fistulas is less satisfactory, and proctectomy is ultimately required in a number of patients; therefore, for high fistulas a conservative approach is primarily recommended.

Anal encirclement with polypropylene mesh for rectal prolapse and incontinence.

Seventeen selected patients (mean age, 74 years)--14 with rectal prolapse and 3 with persisting anal incontinence after previous operations--underwent high anal encirclement with polypropylene mesh. There was no operative mortality. Prolapse recurred in 2 (15 percent) of the 13 patients followed up for 6 months or more (mean, 3.5 years). Three (27 percent) of the 11 patients with associated anal incontinence improved functionally, as did the three operated on for persisting incontinence, but only one patient regained normal continence. No breakage, cutting out, or infection related to the mesh was observed. Because of the risk of fecal impaction encountered in three of our patients, the procedure is not advocated for severely constipated patients. Despite the somewhat disappointing results regarding restoration of continence, we find this method useful in patients with rectal prolapse who are unfit for more extensive surgery, in controlling the prolapse to an acceptable degree.

Recovery of anal sphincter function following transabdominal repair of rectal prolapse: cause of improved continence?

Twenty-eight patients with complete rectal prolapse underwent anorectal manometry before and 6 months and 1-2 years after abdominal rectopexy and sigmoid resection in a study of the mechanisms responsible for postoperatively improved anal continence. Preoperatively, 22 patients reported defective and control. Seven patients (all with minor incontinence) regained normal control and eight other patients achieved improved continence after surgery. Anal resting, squeeze, and voluntary contraction pressures were significantly lower for defective than for normal control, with a significant rise in these pressures at 6 months after the operation, except for those incontinent patients in whom continence was not improved. No further pressure rise was seen later. Improvement of continence was not accompanied by changes in rectal sensation or reflexive functions of the internal anal sphincter. These results suggest that recovery of the resting and voluntary contraction functions of the sphincter muscles was the cause of continence improvement observed after surgery. Anal manometry was unable to predict outcome of function. Therefore, supplementary procedures for restoration of continence are not advisable, although patients with only minor incontinence are likely to regain full continence after rectopexy alone.