Overview numero 6.doc

Anal Fistula
Endosonography in anal fistulae and abscesses
Sudol-Szopinska and coIs assessed the reliability of anal endosonography (AES) in the
diagnosis of anal fistulae and abscesses in 86 patients. In 66 cases with permeable
external opening, hydrogen peroxide solution was introduced into the fistula tract.
Reliability of AES was defined after surgical treatment of all cases and found that 74
anal fistulae (86%) were found on AES. In 10 patients a coexisting abscess was found;
the remaining 12 abscesses were without any fistula. Surgery confirmed the type of
anal fistula in 64 patients (86.5%), and location of internal openings in 60 cases
(81.1%). All abscesses were confirmed. They concluded that AES showed high
accuracy in diagnosing anal fistulae and abscesses.
Radiation proctitis
Sucralfate and late radiation proctitis
O'Brien and cols assessed the potential for sucralfate administered rectally to reduce
the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy
(RT) for carcinoma of the prostate and to study the variables related to acute and late
toxicity. Eighty-six patients with localized prostate carcinoma were randomized in a
double-blind, placebo-controlled study to a daily enema of sucralfate suspension or
the same suspension without sucralfate. The enema began the first day of RT and was
continued for 2 weeks after treatment completion. With a median follow-up of 5 years,
the probability of late Grade 2 RTOG/EORTC toxicity was 12% for placebo and 5%
for sucralfate (p = 0.26). The probability of late rectal bleeding was 59% for placebo
and 54% for sucralfate. No statistically significant difference was found between the
treatment arms for the peak incidence of any of the other patient self-assessment
variables. Rectal pain of a moderate or severe grade during RT was the best predictor
of the subsequent development of late toxicity. They concluded that the results of this
study do not support the use of sucralfate administered rectally as a method for
reducing the late toxicity of nonconformal RT for prostate cancer.
Rectal prolapse
No relevant papers were found in the present review.
Topical nifedipine
Perrotti and cols undertook a prospective, randomized, double-blind study including
110 patients treated for chronic anal fissure. Patients treated with nifedipine (n = 55)
used topical 0.3 percent nifedipine and 1.5 percent lidocaine ointment every 12 hours
for 6 weeks. The control group (n = 55) received topical 1.5 percent lidocaine and 1
percent hydrocortisone acetate ointment during therapy. Healing of fissure was
achieved after 6 weeks of therapy in 94.5% of the nifedipine-treated patients (P <
0.001) as opposed to 16.4% of the controls. Mean anal resting pressure had a 11%
reduction (P = 0.002). They concluded that the therapeutic use of topical nifedipine
and lidocaine ointment should be extended to the conservative treatment of chronic
anal fissure.
Oral lacidipine
Ansaloni and cols assessed the effectiveness in healing anal fissure (AF) of lacidipine, a
calcium channel blocker with a better tolerability in comparison to other calcium
antagonists. Twenty-one consecutive patients with AF were treated with oral
lacidipine (6 mg daily) and warm sitz baths for 28 days. Seven patients (33.3%)
developed side effects, but only one, who developed dyplopia, withdrew from the study
at the 14-day control. Three fissures (14.3%) healed by 14 days and a total of 19
(90.4%) after 28 days. They concluded that oral lacedipine is quite well tolerated and
may offer a promising alternative treatment for AF.
Nitroglycerin ointment dose
Bailey and cols undertook a study to determine the optimal dose and dosing interval
of nitroglycerin ointment to heal chronic anal fissures. A randomized, double-blind
study of intra-anally applied nitroglycerin ointment (Anogesic) was conducted in 17
centers in 304 patients with chronic anal fissures. The patients were randomly
assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin
ointment applied twice or three times per day), for up to eight weeks. A dose-
measuring device standardized the delivery of 374 mg ointment. There were no
significant differences in fissure healing among any of the treatment groups; all
groups, including placebo had a healing rate of approximately 50 percent. Treatment
with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P <
0.0002) decrease in average pain intensity compared with vehicle as assessed by
patients with a visual analog scale. Treatment was well tolerated, with only 3.29
percent of patients discontinuing treatment because of headache. They concluded that
nitroglycerin ointment did not alter healing but significantly and rapidly reduced the
pain associated with chronic anal fissures.
Artificial anal sphincter
Devesa and cols evaluated results after implantation of Acticon Neosphincter in 53
patients with total anal incontinence not amenable to sphincter repair or after failed
sphincteroplasty in a mean follow-up was 26.5 months. Perioperative events occurred
in 26% patients including abnormal bleeding, vaginal perforation, rectal perforation,
and unobserved urethral perforation. Late complications were cuff and/or pump
erosion (18%), infection (6%), impaction (22%), pain (8%) and mechanical failures
(4%). There were 10 (19%) definitive explants caused by septic or skin complications.
Only 60% of patients with the device in action use the pump (patients' decision).
Normal continence was achieved in 65% and continence to solid stool in 98%. They
concluded that the artificial anal sphincter restores continence to solid stool in almost
all severely incontinent patients and two-thirds achieve practically normal continence.
No predictable factors of functional success could be found in this study.
Wong and cols published the results of a multicenter, prospective, nonrandomized
clinical trial including 112 patients with artificial bowel sphincter. A total of 384
device-related or potentially device-related adverse events were reported in 99
enrolled patients. Of these events, 246 required no intervention or only noninvasive
intervention. Seventy-three revisional operations were required in 46% of the 112
implanted patients. Infection rate necessitating surgical revision was 25%. Forty-one
patients (37 percent) have had their devices completely explanted, of which 7 have had
successful reimplantations. In patients with a functioning neosphincter, improvement
in quality of life and anal continence was documented. A successful outcome was
achieved in 85 percent of patients with a functioning device. Intention to treat success
rate was 53 percent. They concluded that although morbidity and the need for
revisional surgery are high, the artificial bowel sphincter can improve anal
incontinence and quality of life in patients with severe fecal incontinence.
Anal Fissure
Botulinum toxin
Wollina and cols compared traditional Botulinum toxin A (BTXA) treatment in anal
fissures with combined treatment of spasticity and focal hyperhidrosis of the anal fold
and perianal skin. Ten patients with chronic anal fissures associated with focal
hyperhidrosis as assessed by Minor's sweat test were investigated in an open, two-
armed trial. Intramuscular injections of 20-25 U BTXA (Botox) were performed in
group A (n = 5). In group B (n = 5) those injections were combined with
intracutaneous injection of 30-50 U BTXA to treat focal hyperhidrosis. In a mean
follow-up of 5 months, all five patients in group B but only two of five patients in
group A experienced a complete remission despite the fact that relief of pain was
evident in eight of 10 patients within 2 weeks. This open trial suggests that combined
therapy of both muscular spasticity and focal hyperhidrosis may provide better
results than intramuscular injections alone in anal fissure therapy with BTXA.
Anal sphincter tests after childbirth
Damon and cols assessed 100 consecutive incontinent patients and found that 38%
had a normal sphincter and 62% had a defect detected by ultrasonography: The
radial size of the defects was positively correlated with the severity of clinical
symptoms. This study confirms the high prevalence of anal sphincter defects detected
by ultrasonography in a population of incontinent parous females. Anal vector
manometry was a useful tool to confirm the relation between echographic anal
sphincter lesions and fecal incontinence.
Nazir and cols investigated 132 females obstetric sphincter rupture by transanal
ultrasound, manometry, and scoring of bowel symptoms five months after delivery.
They found that although both anal sphincter rupture and transanal ultrasound grade
correlated with soiling grade and with manometry variables, in both cases only the
transanal ultrasound grade was a significant independent variable.
Graciloplasty
Bresler and cols assessed the safety and efficacy of dynamic graciloplasty involved in a
total of 24 patients treated with dynamic graciloplasty for fecal incontinence in 5
French surgical centers. No death occurred. A successful functional outcome was
reported for 19 patients (79%) during the follow up period. Twenty-two complications
occurred. One patient presented with an infected anal erosion leading to material
explantation. They concluded that dynamic graciloplasty is an effective procedure for
patients with refractory fecal incontinence but carries a significant morbidity which
seems to be correlated with the surgeons' experience.
Anterior anal sphincter repair
Elton and cols evaluated the results of overlapping anterior anal sphincter repair in
20 patients. In 12 of the patients, a polypropylene mesh was inserted in the repair to
act as re-inforcement. At a median follow-up of 13 months 80% of patients said that
surgery had improved their symptoms. There was a significant improvement in the
continence score after operation (P < 0.01). They concluded that overlapping anterior
anal sphincter repair is successful in relieving symptoms in patients with faecal
incontinence due to an anterior sphincter defect but this improvement is not
associated with any significant changes in anorectal manometric parameters.
Procon device
Giamundo and cols evaluated 7 patients who used the Procon device for fecal
incontinence for 14 consecutive days. This device consists of a disposable, pliable
rubber catheter with an infrared photo-interrupter sensor and flatus vent holes on the
distal tip that is connected to a pager (or "beeper"). They reported an overall
significant improvement in the quality of life (p < 0.05) and a significant reduction in
incontinence scores with the Procon device (p < 0.05) and concluded that this is a
promising device for patients with severe fecal incontinence who are unfit to undergo
surgery, those in whom previous surgical treatments have failed.
Polyps and polyposis
Results in FAP after pancreatoduodenal surgery
Adenomatous polyps and adenocarcinomas of the periampullary region are the most
common upper gastrointestinal neoplasms encountered in familial adenomatous
polyposis (FAP) patients. Ruo and cols reviewed the clinical outcome of FAP patients
after pancreaticoduodenal surgery for periampullary neoplasms. Of the 61
individuals participating in our prospective FAP registry, 8 underwent surgical
resection of periampullary neoplasms. Seven of these had pancreaticoduodenectomy
and 1 had duodenotomy with ampullectomy. The indications for surgery were
periampullary cancer (3), severe dysplasia within a duodenal villous tumor (4), and
solid- pseudopapillary tumor of the pancreas (1). At a median follow-up of 70.5
months 2 patients had died, neither from their periampullary neoplasm. The patient
treated by local excision subsequently developed gastric cancer arising from a polyp
and went on to gastrectomy. They concluded that pancreaticoduodenectomy is a safe
and appropriate surgical option for FAP patients with duodenal villous tumors
containing severe dysplasia or carcinoma.
Surveillance following colorectal polypectomy
Nusko and cols undertook a multivariate analysis of 1159 patients who had a
polipectomy on long term follow up to identify risk factors for metachronous
adenomas. Two risk groups were identified: (1) patients with no parental history of
colorectal carcinoma with only small (< or = 10 mm) tubular adenomas have an
estimated chance of 10% to develop advanced metachronous adenomas after 10 years;
(2) the high risk group contained all other patients, 10% of whom will show
metachronous adenomas of advanced pathology at follow up after only three years.
They concluded that surveillance intervals can be scheduled for low risk (10 years)
and high risk (three years) patients.
Fecal incontinence
Childbirth factors
Subpubic arch angle
Frudinger and cols assessed the relationship between the subpubic arch angle, anal
sphincter and perineal trauma, and anal incontinence after childbirth in 134 low risk
nulliparous women. Thirty-two women with a subpubic arch angle of less than 90
degrees had significantly prolonged first and second stages of labour when compared
with 102 women whose subpubic arch was wider. Following delivery, anal continence
deteriorated in more women with a narrow subpubic angle (69% vs 21%, P < 0.001)
but this was unrelated to the incidence of anal sphincter and perineal trauma. They
concluded that a narrow subpubic arch is strongly associated with prolonged labour
and postpartum anal incontinence in nulliparous women but no relationship was
found to perineal and anal sphincter trauma as assessed by ultrasound.
Martinez-Borra and cols investigated the effect of infliximab on circulating cytokines
and acute phase proteins to determine the clinical response to anti-TNF-alpha in 36
patients with fistulizing Crohn's disease. Elevated TNF-alpha, IL-1beta, IL-6, and
acute phase proteins were observed in patients with Crohn's disease. Of the patients
with fistulas, 22 (61.1%) responded to treatment. Before receiving infliximab, higher
levels of serum TNF-alpha were found in patients who did not respond to infliximab
compared with those who did. So, circulating levels of TNF-alpha are associated with
the response to infliximab and could help to identify patients who would benefit from
anti-TNF-alpha treatment.
Parsi and cols evaluated 100 patients with either inflammatory or fistulous Crohn's
disease in a at least 3 months of follow-up after infliximab infusion to identify
predictors of response to therapy. For inflammatory disease, 73% of nonsmokers,
compared with 22% of smokers, responded to infliximab (P < 0.001). Among patients
taking concurrent immunosuppressives, 74% responded to infliximab compared with
39% not taking any immunosuppressives (P = 0.007). Prolonged response (duration
>2 months) was achieved in 59% of nonsmokers compared with 6% of smokers (P <
0.001) and in 65% of patients on immunosuppressives compared with 18% not on
immunosuppressives (P < 0.001). For fistulous disease, overall response rates were not
different between nonsmokers and smokers, but nonsmokers had a longer duration of
response (P = 0.046). They concluded that in patients with inflammatory disease,
nonsmoking and concurrent immunosuppressive use are associated with higher rates
of response and longer duration of response to infliximab. In patients with fistulous
Crohn's disease, nonsmoking is associated with longer duration of response to
infliximab.
Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)
Treatment for Crohn's disease is aimed at immunosuppression. Dieckgraefe and cols
performed an open-label dose-escalation trial (4-8 microg/kg per day) to investigate
the safety and possible benefit of granulocyte-macrophage colony-stimulating factor
(GM-CSF) in the treatment of 15 patients with moderate to severe Crohn's disease.
No patients had worsening of their disease. Adverse events were negligible and
included minor injection site reactions and bone pain. Patients had a significant
decrease in mean Crohn's disease activity index (CDAI) score during treatment
(p<0.0001). Overall, 12 patients had a decrease in CDAI of more than 100 points, and
eight achieved clinical remission. Retreatment was effective, and treatment was
associated with increased quality-of-life measures. GM-CSF may offer an alternative
to traditional immunosuppression in treatment of Crohn's disease.
Probiotics
Some articles regarding the role of probiotic agents in the treatment of Crohn’s
disease have been published by Gionchetti and cols, Shanahan and cols and Prantera
and cols. None of these reports and reviews showed evidences of benefits with this
therapeutic approach and further studies are required to assess its role in Crohn’s
disease.
Overview on
Colorectal papers
Nº 6 -- February 2003
A ProctoSite's e-publication
September / October / November 2002
Crohn’s disease
Infliximab
To evaluate the results of infliximab therapy, Doubremelle and cols reviewed the
results obtained with 69 patients treated with a total of 170 infusions of infliximab, 32
patients being treated for refractory Crohn's disease and 37 for fistulas. In a median
follow-up of 8 months an objective response was observed in 79% of refractory
Crohn's disease patients and 78% of fistulazing patients. Forty-five percent of
patients had relapsed within 4 months and a steroid-sparing effect was obtained in
73% of patients. The authors concluded that infliximab is very effective in steroid-
dependent and fistulazing Crohn's disease although long term safety remains to be
established by further studies.
de Ridder and cols described the clinical experience of infliximab treatment in 23
children and adolescents with refractory Crohn's with an average follow-up of 14.5
months. Four from 10 patients with refractory Crohn's disease showed good long-
term response. Five from 12 patients with severe fistulas showed good long-term
response.
Ljung and cols reviewed the results obtained with 8 patients with pyoderma
gangrenosum associated with Crohn disease treated with infliximab. Complete
healing of the pyoderma gangrenosum was observed in 3 cases, partial healing in 3
and temporary improvement in 2. Adverse effects such as skin rash, pneumonia and
diarrhoea were seen in three patients. They concluded that infliximab has a
therapeutic potential on skin manifestations associated with inflammatory bowel
disease, even though successful treatment may require repeat courses of infliximab
infusions.
Vermeire and cols assessed whether demographic or clinical parameters influence
short-term response to infliximab. They studied the response to infliximab in 240
Crohn’s disease patients of the Belgian Infliximab Expanded Access Program after
the first infusion. They found 73.5% responders and 26.5% nonresponders to
treatment. Young age, Crohn's colitis, and concomitant immunosuppressive
treatment were identified as independent variables favoring short-term response to
infliximab.

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