Length-tension relationship of the external anal sphincter muscle: implications for the anal canal function

The length at which a muscle operates in vivo (operational length) and the length at which it generates maximal force (optimal length) may be quite different. We studied active and passive length-tension characteristics of external anal sphincter (EAS) in vivo and in vitro to determine the optimal and operational length of rabbit EAS. For the in vitro studies, rings of EAS (n = 4) were prepared and studied in a muscle bath under isometric conditions. For in vivo studies, female rabbits (n = 19) were anesthetized and anal canal pressure was recorded by use of a sleeve sensor placed in the custom-designed catheter holders of 4.5-, 6-, and 9-mm diameters. Measurements were obtained at rest and during EAS electrical stimulation. Sarcomere length of EAS muscle was measured by laser diffraction technique with no probe and three probes in the anal canal. In vitro studies revealed 2,054 mN/cm(2) active tension at optimal length. In vivo studies revealed a probe size-dependent increase in anal canal pressure and tension. Maximal increase in anal canal tension with stimulation was recorded with the 9-mm probe. Increases in anal canal tension with increase in probe size were completely abolished by pancuronium bromide. EAS muscle sarcomere length without and with 9-mm probe in the anal canal were 2.11 +/- 0.08 and 2.99 +/- 0.07 microm, respectively. Optimal sarcomere length, based on the thin filament length measured by thin filament analysis, is 2.44 +/- 0.10 microm. These data show that the operational length of EAS is significantly shorter than its optimal length. Our findings provide insight into EAS function and we propose the possibility of increasing anal canal pressure by surgical manipulation of the EAS sarcomere length.     

Endocrine cells and melanin-containing cells in the anal canal epithelium

Summary The epithelium of the anal canal from 22 humans was studied in order to demonstrate the possible presence of endocrine cells and melanin-containing cells. Histochemical methods aimed at demonstrating reducing substances, biogenic amines, argyrophilia and melanin, were used. Enterochromaffin cells, and possibly other types of endocrine cells, were demonstrated above the dentate line both in colo-rectal type epithelium and in the anal transitional zone. Melanin-containing cells could also occasionally be found in the anal transitional zone. The presence of endocrine cells in the anal canal epithelium opens up the possibility that carcinoids can originate in this region. Further, the presence of melanin-containing cells might explain the occurrence of malignant melanomas arising above the dentate line.     

Gastrointestinal stromal tumor of the anal canal: an unusual presentation

Background

Gastrointestinal stromal tumors (GIST) of the stomach are the most frequent followed by those of the intestinal tract, while colon and rectum represent rare sites. GIST of the anal canal are extremely rare. They have been studied along with GIST of the rectum, as a single entity, and along with them they represent 5% of GIST. GIST arising from the anal canal account for only 2%–8% of the anorectal GIST. Thus anal GIST must be considered an exceptional case.

Case presentation

A 78-year-old man was referred to our Institution for an anal mass, in absence of any symptom. The patient was treated by local excision. An histological diagnosis of a low grade GIST was made. No further treatment was necessary. No local recurrence of distant metastases were found at follow-up.

Conclusion

At the moment, only ten cases of c-kit positive anal GIST are reported in the literature. These few data are not sufficient to establish a widely accepted approach for this neoplasia.We recommend to perform an initial local excision, to define the risk of aggressive behavior and the resection margins and proceed to a more aggressive treatment, if the GIST belongs to high or very high risk group. The role of adjuvant therapy is still uncertain. Although inhibitors of tyrosine-kinase receptor needs further studies before their routine use, their role in case of distant or local recurrence has been accepted. Patients' close follow up is mandatory to disclose as soon as possible local recurrences or metastases.

     

Mucin histochemistry of the anal canal epithelium. Studies of normal anal mucosa and mucosa adjacent to carcinoma

Summary The epithelial lining of the anal canal is of colo-rectal type in the upper part and squamous in the lower part, while the middle zone is called the anal transitional zone (ATZ). This zone is characterized by an epithelium which bears a resemblance to that of the anal glands and shows little mucus secretion. The histochemical properties of the mucins in the epithelium of 39 anal canals, resected for ano-rectal adenocarcinoma, basaloid carcinoma, squamous carcinoma and malignant melanoma were investigated. The study reveals that (1) the mucin composition of the ATZ epithelium corresponds to that of the anal glands, being characterized by a mixture of sulpho- and sialomucins with scarcity or absence ofO-acylated sialic acids; and (2) cases with carcinomas located near the dentate line show changes in the mucin composition of the adjoining anal canal epithelium, regardless of tumour type. In colo-rectal type mucosa, these mucins consist of increasing amounts of sialomucins with a predominance ofN-acyl derivatives, and in the anal could be detected in the ATZ epithelium. It is concluded that rectal and anal glands in the anal canal are exposed to stimuli which alter the normal process of glycoprotein synthesis and secretion. The changes seem to be secondary to tumour growth and independent of the histological type of tumour.     

Activation-dependent descending reflex evacuation motority of anal canal in rat model

The evacuative motor responses of the anal canal and recto-anal reflexes during defecation were studied in an isolated rat recto-anal model preparation using (i) partitioned organ bath, (ii) electrical stimulation, (iii) balloon distension and (iv) morphological techniques. Electrical field stimulation applied to the anal canal or to the distal part of the rectum elicited tetrodotoxin (10(-7) M)-sensitive frequency-dependent local or descending contractions of the anal canal and the local responses were bigger in amplitude (14.9 ± 1.35 mN) than the descending contractions (5.3 ± 0.7 mN at frequency of 5 Hz, p < 0.05). The balloon-induced distension of the distal rectum evoked descending responses of the anal canal consisting of a short contraction (1.50 ± 0.18 mN) followed by deep relaxation (3.12 ± 0.34 mN). In the presence of atropine (3 x 10(-7) M) the electrically-elicited (5 Hz) local or descending contractions of the anal canal were suppressed and a relaxation revealed. The initial contraction component of the distension-induced response was decreased while the relaxation was not changed. During atropine treatment, spantide (10(-7) M) lowered even more the contractile component of the anal canal response. NG-nitro-L-arginine (5 x 10(-4) M) enhanced the contraction, prevented the atropine-dependent relaxation of the electrically-elicited response and inhibited the distension-induced relaxation. L-Arginine (5 x 10(-4) M) suppressed the contraction and extended the relaxation. ChAT-, substance P- and NADPH-diaphorase-positive perikarya and nerve fibers were observed in myenteric ganglia of the anal canal. The results suggest activation-dependent descending reflex motority of the anal canal involving electrical stimulation-displayed cholinergic and tachykininergic and distension manifested nitrergic neuro-muscular communications.     

Effects of pelvic floor muscle contraction on anal canal pressure

The role of pelvic floor muscle contraction in the genesis of anal canal pressure is not clear. Recent studies have suggested that vaginal distension increases pelvic floor muscle contraction. We studied the effects of vaginal distension on anal canal pressure in 15 nullipara asymptomatic women. Anal pressure, rest, and squeeze were measured using station pull-through manometry techniques with no vaginal probe, a 10-mm vaginal probe, and a 25-mm vaginal probe in place. Rest and squeeze vaginal pressures were significantly higher when measured with the 25-mm probe compared with the 10-mm probe, suggesting that vaginal distension enhances pelvic floor contraction. In the presence of the 25-mm vaginal probe, rest and squeeze anal pressures in the proximal part of the anal canal were significantly higher compared with no vaginal probe or the 10-mm vaginal probe. On the other hand, distal anal pressures were not affected by any of the vaginal probes. Ultrasound imaging of the pelvic floor revealed that vaginal distension increased the anterior-posterior length of the puborectalis muscle. Atropine at 15 micro g/kg had no influence on the rest and squeeze anal pressures with or without vaginal distension. Our data suggest that pelvic floor contractions increase pressures in the proximal part of the anal canal, which is anatomically surrounded by the puborectalis muscle. We propose that pelvic floor contraction plays an important role in the fecal continence mechanism by increasing anal canal pressure.     

Identification of epithelial label-retaining cells at the transition between the anal canal and the rectum in mice

In certain regions of the body, transition zones exist where stratified squamous epithelia directly abut against other types of epithelia. Certain transition zones are especially prone to tumorigenesis an example being the anorectal junction, although the reason for this is not known. One possibility is that the abrupt transition of the simple columnar epithelium of the colon to the stratified squamous epithelium of the proximal portion of the anal canal may contain a unique stem cell niche. We investigated whether the anorectal region contained cells with stem cell properties relative to the adjacent epithelium. We utilized a tetracycline-regulatable histone H2B-GFP transgenic mice model, previously used to identify hair follicle stem cells, to fluorescently label slow-cycling anal epithelial cells (e.g. prospective stem cells) in combination with a panel of putative stem cell markers. We identified a population of long-term GFP label-retaining cells concentrated at the junction between the anal canal and the rectum. These cells are BrdU-retaining cells and expressed the stem cell marker CD34. Moreover, tracking the fate of the anal label-retaining cells in vivo revealed that the slow-cycling cells only gave rise to progeny of the anal epithelium. In conclusion, we identified a unique population of cells at the anorectal junction which can be separated from the other basal anal epithelial cells based upon the expression of the stem cell marker CD34 and integrin a6, and thus represent a putative anal stem cell population.     

Identification of epithelial label-retaining cells at the transition between the anal canal and the rectum in mice

In certain regions of the body, transition zones exist where stratified squamous epithelia directly abut against other types of epithelia. Certain transition zones are especially prone to tumorigenesis an example being the anorectal junction, although the reason for this is not known. One possibility is that the abrupt transition of the simple columnar epithelium of the colon to the stratified squamous epithelium of the proximal portion of the anal canal may contain a unique stem cell niche. We investigated whether the anorectal region contained cells with stem cell properties relative to the adjacent epithelium. We utilized a tetracycline-regulatable histone H2B-GFP transgenic mice model, previously used to identify hair follicle stem cells, to fluorescently label slow-cycling anal epithelial cells (e.g., prospective stem cells) in combination with a panel of putative stem cell markers. We identified a population of long-term GFP label-retaining cells concentrated at the junction between the anal canal and the rectum. These cells are BrdU-retaining cells and expressed the stem cell marker CD34. Moreover, tracking the fate of the anal label-retaining cells in vivo revealed that the slow-cycling cells only gave rise to progeny of the anal epithelium. In conclusion, we identified a unique population of cells at the anorectal junction which can be separated from the other basal anal epithelial cells based upon the expression of the stem cell marker CD34 and integrin α6, and thus represent a putative anal stem cell population.Key words: stem cells, transitional epithelium, keratinocyte, slow-cycling, label retaining cell     

Ectopic Cushing's syndrome in cloacogenic carcinoma of the anal canal: a case demonstrating APUD characteristics

A patient found to have ectopic Cushing's syndrome three months after surgical resection of cloacogenic carcinoma of the anal canal was studied with serial plasma cortisol and ACTH measurements. The effects of therapy on plasma ACTH and cortisol levels were noted. An autopsy was performed immediately after death and liver metastatic tumor tissue was assayed for "small" ACTH, "big" ACTH, PTH, and alpha sub-unit of hCG, Clinical Cushing's syndrome was observed along with nonsuppressible plasma cortisol level. Plasma ACTH only reached the highest normal level but tumor ACTH ("small"), "big" ACTH, alpha sub-unit and PTH were markedly elevated. It was concluded that a case of classic cloacogenic carcinoma of the anal canal produced ectopic Cushing's syndrome. Elevated tumor alpha sub-unit and PTH were not associated with appreciable biologic activity. Ectopic Cushing's syndrome in this disease may imply poorer prognosis.     

Structure of the sensory innervation of the anal canal in the pig. A light- and electron-microscopical study

The sensory innervation of the anal canal of the pig was investigated by light and electron microscopy. The distribution of the different types of sensory nerve endings correlates with the histology of different zones: (1) After the rectal mucosa there was a zone lined with nonkeratinized stratified squamous epithelium. (2) A middle zone was lined with keratinized stratified squamous epithelium. Here the dermis already showed a papillary and reticular layer. (3) The last zone showed hairy skin with a high hair density. The following nerve endings were found: Free nerve endings reached the stratum superficiale in nonkeratinized squamous epithelium and the stratum granulosum in the keratinized squamous epithelium. Dermal free nerve endings were found in all zones near the epithelium and two different types were identified as those derived from C-fibers and those from A-delta-fibers. Merkel nerve endings showed different features depending on their location. Few Merkel-like cells were found in the epithelium of the anal crypts. Typical Merkel Tastscheiben were located at the base of epithelial ridges or pegs in zones 2 and 3. The number of Merkel cells varied up to 200. The myelinated afferent fiber supplied 10-15 Merkel cells. Merkel cells were also found regularly in the outermost layer of the external rooth sheath of hair follicles at about the same level as perifollicular nerve endings. Lamellated corpuscles were found in the dermis of all zones except the cranial part of zone 1, where the anal crypts are located. Generally they consisted of a central nerve terminal which may be branched. Each terminal was surrounded by an inner core of concentrically arranged lamellae of the terminal Schwann cell and one or several inner cores were included in a capsule of perineural cells. The size of the corpuscle, the regularity of the inner core and the number of capsular layers depended on the location of the corpuscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Roentgeno-functional study of the talocrural joint in the long-term follow-up of a fracture of the crural bone

On the basis of the results of clinicoroentgenological and tensographic investigations of 119 patients after traumas of the crural bones and ankle joint (2-36 yrs. ago) the authors showed the importance of roentgenofunctional investigation of the ankle joint, a patient being in a standing position with maximum flexion and extension of the foot. A specially designed footing was proposed. Of 77 patients after intra-articular fractures of the ankle bones various disorders in articular proportions, undetectable on routine roentgenography, were diagnosed in 29 by functional roentgenography. Articular changes on roentgenofunctional investigation were revealed in one patient only out of 42 patients with extra-articular fractures of the crural bones. Tensography showed disorders of foot biomechanics in all patients with subluxations in the ankle.