Miguel Minguez

Therapeutic Effects of Different Doses of Botulinum Toxin in Chronic Anal Fissure

PURPOSE: The aim of this study was to evaluate the clinical and manometric results of three different doses of botulinum toxin and two methods of injection for the treatment of chronic idiopathic anal fissure. METHODS: Sixty-nine patients with chronic anal fissure were included in a nonrandomized, prospective trial of intrasphincteric injection of botulinum toxin. All patients reported postdefecatory anal pain lasting more than two months. Scoring systems were developed for anal pain, bleeding, and defecatory difficulty. Maximum resting and squeeze anal pressures were determined before and one month after treatment. Twenty-three patients undergoing a 5-U injection of diluted botulinum toxin A (BOTOX®) on each side of the anal sphincter (total dose, 10 U) constituted the first group. In a second group 27 patients were injected as previously described, with an additional 5-U injection below the fissure (total dose, 15 U). The 19 patients constituting the third group received a 7-U injection on each side of the anus and below the fissure (total dose, 21 U). All patients were followed up for at least six months. RESULTS: Pain relief one month after treatment was more evident in the second and the third group (48 percent of patients in the first group, 74 percent in the second group, and 100 percent in the third group). A significant reduction of the mean resting pressure was demonstrated only in Groups II and III (P<0.05), whereas the mean squeeze pressure significantly decreased in the three groups (P<0.01 in Group I andP<0.001 in Groups II and III). Fifty-two percent of the patients in the first group, 30 percent in the second group, and 37 percent in the third group were reinjected during the follow-up period, because of persistence of symptomatology or early relapse. The need for surgery was similar in the first and the second group (17 and 19 percent, respectively) and clearly lower in the last group (5 percent). No serious complications or incontinence attributable to this therapeutic modality developed in any patient. CONCLUSIONS: Intrasphincteric injection of botulinum toxin is a reliable new option in the treatment of uncomplicated chronic anal fissure. The healing rate is related to the dose and probably to the number of puncture sites. No permanent damage to the continence mechanism was detected in these patients.

Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy

Background There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus (HCV). Aim To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD. Methods Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome. Results 162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg. Conclusion Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.

Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy volunteers

OBJECTIVES To assess the salivary flow rate, pH, and buffer capacity of healthy volunteers, and their relationships with age, gender, obesity, smoking, and alcohol consumption, and to establish the lower-end value of normal salivary flow (oligosialia). METHODS A prospective study was conducted in 159 healthy volunteers (age > 18 years, absence of medical conditions that could decrease salivary flow). Unstimulated whole saliva was collected during ten minutes, and salivary flow rate (ml/min), pH, and bicarbonate concentration (mmol/l) were measured using a Radiometer ABL 520. The 5 percentile of salivary flow rate and bicarbonate concentration was considered the lower limit of normality. RESULTS Median salivary flow rate was 0.48 ml/min (range: 0.1-2 ml/min). Age younger than 44 years was associated with higher flow rates (OR 2.10). Compared with women, men presented a higher flow rate (OR 3.19) and buffer capacity (OR 2.81). Bicarbonate concentration correlated with salivary flow rate. The lower-end values of normal flow rate and bicarbonate concentration were 0.15 ml/min and 1.800 mmol/l, respectively. The presence of obesity, smoking, and alcohol consumption did not influence salivary parameters. CONCLUSIONS In healthy volunteers, salivary flow rate depends on age and gender, and correlates with buffer capacity. Obesity, smoking, and alcohol use do not influence salivary secretion.

Dental and periodontal lesions in patients with gastro-oesophageal reflux disease

OBJECTIVE Dental erosion has been considered an extraesophageal manifestation of gastro-oesophageal reflux disease, but few reports have studied the relationship between this disease and other periodontal or dental lesions. The aim of this study was to investigate the prevalence of dental and periodontal lesions in patients with gastro-oesophageal reflux disease. PATIENTS AND METHODS A total of 253 subjects were prospectively studied between April 1998 and May 2000. Two study groups were established: 181 patients with gastro-oesophageal reflux disease and 72 healthy volunteers. Clinical assessment, including body mass index and consumption of tobacco and alcohol, was performed in all subjects, as well as a dental and periodontal examination performed by a dentist physician, blind as to the diagnosis of subjects. Parameters evaluated were: (a) presence and number of dental erosion, location and severity, according to the Eccles and Jenkins index [Prosthet Dent 1979;42:649-53], modified by Hattab [Int J Prosthes 2000;13:101-71; (b) assessment of dental condition by means of the CAO index; and (c) periodontal status analysed by the plaque index, the haemorrhage index, and gingival recessions. RESULTS Clinical parameters were similar in both groups (p > 0.05). Age was statistically associated with the CAO index, presence of dental erosion, and gingival recession (p < 0.001, Students t-test). Compared with the control group, the percentage of dental erosion was significantly higher in the gastro-oesophageal reflux disease group (12.5 vs. 47.5%, p < 0.001, chi2-test), as was the number and severity of dental erosions (p < 0.001, Students t-test). Location of dental erosion was significantly different between groups. Age was not statistically related to either the amount or severity of dental erosion. CAO and periodontal indices were similarly distributed between groups. CONCLUSIONS Dental erosion may even be considered as an extraesophageal manifestation of gastro-oesophageal reflux disease. The fact that the prevalence of caries and periodontal lesions is similar in patients with gastro-oesophageal reflux disease and in healthy volunteers suggests a lack of relationship with gastro-oesophageal reflux disease.

Gastroesophageal reflux in diabetes mellitus

OBJECTIVE:Although abnormal gastroesophageal (GE) reflux is the most frequent alteration of the gastrointestinal tract, its prevalence in diabetes mellitus (DM) is not widely known. The objective of this study was to analyze both the presence of abnormal GE reflux in diabetic patients with no esophageal symptoms and the influence of cardiovascular autonomic neuropathy (CVAN) in the development of abnormal GE reflux.METHODS:Fifty insulin-dependent diabetic patients, averaging 29.2 ± 9.0 yr of age, who had had diabetes for > 5 yr and showed no symptoms or history of gastroesophageal disease, were compared with a control group composed of 36 healthy volunteers (18 men, 18 women) whose average age was 35.9 ± 10.1 yr. The cardiovascular autonomic nervous system was examined in the diabetics and control subjects who complied with inclusion criteria. Long-term (24-h) ambulatory esophageal pH monitoring was performed, as well as a manometric study of the lower esophageal sphincter.RESULTS:The parameters obtained from the monitoring showed significant differences (p < 0.01) between DM and control subjects. Abnormal GE reflux, defined as any percentage of time with esophageal pH < 4 exceeding 3.5% of total time (8.7 ± 5.6%; range, 4.1–24.4%), was detected in 14 patients. Diabetic subjects were classified according to cardiovascular autonomic neuropathy tests (without CVAN [n = 19, 38%] and with abnormal CVAN tests [n = 31, 62%]). The pH monitoring parameters showed significant differences between these two groups (p < 0.05).CONCLUSIONS:A higher prevalence (28%) of abnormal GE reflux appeared among asymptomatic diabetic patients than among the general population. The presence of abnormal GE reflux in diabetic patients was associated with the existence of cardiovascular autonomic neuropathy (abnormal GE reflux = 38.7% in diabetic patients with abnormal CVAN tests vs 10.5% in diabetic patients without CVAN).

Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy.

OBJECTIVES:To determine the prevalence of recurrence of gallstone pancreatitis, its clinical features, and the presence of prognostic factors of recurrence.METHODS:From January 1, 2000 to August 31, 2003, 233 patients admitted with acute gallstone pancreatitis (AGP) were prospectively studied. Patients were divided into two groups: recurrent and nonrecurrent group. Clinical, analytical, radiological, prognostic parameters, and severity (Atlanta criteria) were assessed, along with the performance of cholecystectomy or endoscopic sphincterotomy (ES). Clinical features of recurrence were analyzed. Univariate (χ2, Students t-test) and multivariate tests were performed. Statistical significance was assumed if p < 0.05.RESULTS:Two hundred and eighty-six attacks were identified. Forty-two patients (18.2%) recurred, suffering 53 recurrent attacks, which took place within 30 days in 23.3%. Patients who did not undergo surgery after the first attack had 31-fold risk of recurrence (OR = 31.5%, CI = 95%[7.22–137.84], p < 0.001). In patients not operated, recurrence was more frequent if ES was not performed (37.04%vs 0%, p= 0.019). Among patients with surgical risk, none who recurred underwent ES, compared with 27.9% of those who did not recur. Patients in the nonrecurrent group underwent cholecystectomy within the first 30 days or ES more frequently (31.2%vs 7.3%, p= 0.001).CONCLUSIONS:Recurrence of gallstone pancreatitis is a frequent event. Delay of cholecystectomy implies an increased risk of recurrence. ES could be an acceptable option to prevent recurrence in patients who are not candidates for surgery or who do not desire to undergo cholecystectomy.

Elevated serum eotaxin levels in patients with inflammatory bowel disease

OBJECTIVE:Eotaxin is a recently characterized chemokine with potent and selective chemotactic activity for eosinophils. Previous studies indicating that eosinophils accumulate and become activated in inflammatory bowel disease (IBD) led us to hypothesize that eotaxin is potentially involved in the pathophysiology of IBD and, therefore, that eotaxin would be increased in the serum of patients with IBD. The objective of this study was to test those assumptions.METHODS:We investigated 72 patients with IBD, 35 with ulcerative colitis, and 37 with Crohns disease. A total of 27 patients had active and 45 inactive disease; 26 were receiving corticosteroids. Eotaxin serum levels were determined by solid phase sandwich ELISA. Lymphocytes, monocytes, and granulocyte subpopulations were determined in fresh blood samples with an automated autoanalyzer.RESULTS:Serum eotaxin levels were significantly higher in patients with Crohns disease and in those with ulcerative colitis than in the control subjects (p < 0.0001). Patients with inactive Crohns disease had significantly higher levels of eotaxin than patients with inactive ulcerative colitis (p < 0.05). We did not find significant differences for activity or inactivity of disease, nor for treatment with prednisone. A negative correlation (p < 0.05) was found between eotaxin serum level and eosinophil counts in peripheral blood in patients with Crohns disease.CONCLUSIONS:There is an increased expression of eotaxin in IBD patients, suggesting that eotaxin may be involved in the pathogenesis of IBD. This increase is more accentuated in Crohns disease and negatively correlates with the eosinophil number in peripheral blood. Our data support the increasing evidence that eosinophil are functionally involved in the pathophysiology of IBD.

Adaptation to Spanish Language and Validation of the Fecal Incontinence Quality of Life Scale

PurposeThe aim of this study was to perform a psychometric evaluation of the Fecal Incontinence Quality of Life Scale in the Spanish language.MethodsEleven hospitals in Spain participated in the study, which included 118 patients with active fecal incontinence. All the patients filled out a questionnaire on the severity of their incontinence, a general questionnaire of health (Medical Outcomes Survey Short Form), and a Spanish translation of the Fecal Incontinence Quality of Life Scale (Cuestionario de Calidad de Vida de Incontinencia Anal), which consists of 29 items in four domains: lifestyle, behavior, depression, and embarrassment. On a second visit, patients repeated the Fecal Incontinence Quality of Life Scale. For each domain, an evaluation was made of temporal reliability, internal reliability, the convergent validity with the generic questionnaire of health, and the discriminant validity correlating the domains of Cuestionario de Calidad de Vida de Incontinencia Anal with the severity of fecal incontinence.ResultsFor cultural adaptation, the answer alternatives for 14 items were modified. A total of 111 patients (94 percent) completed the study adequately. Temporal reliability (test–retest) was good for all domains except for embarrassment, which showed significant differences (P < 0.02). Internal reliability was good/excellent for all domains (Cronbach alpha >0.80, between 0.84 and 0.96). The four domains of Cuestionario de Calidad de Vida de Incontinencia Anal significantly correlated with the domains of the generic questionnaire on health (P < 0.01) and with the scale of severity of fecal incontinence (P < 0.001). All domains of Cuestionario de Calidad de Vida de Incontinencia Anal correlated negatively with the need to wear pads (P < 0.01) and with the presence of complete fecal incontinence.ConclusionsThe Cuestionario de Calidad de Vida de Incontinencia Anal incorporates sufficient requirements of reliability and validity to be applied to patients with fecal incontinence.

Anal endosonographic evaluation after closed lateral subcutaneous sphincterotomy.

PURPOSE: The present study was undertaken to evaluate anal endosonographic results of the transverse and longitudinal extent of internal anal sphincter division after closed lateral subcutaneous sphincterotomy and its relationship to outcome with respect to anal fissure recurrence and postoperative anal incontinence. METHODS: Ten patients selected for symptomatic anal fissure recurrence (mean follow-up, 10.9 months) and 41 asymptomatic control patients (mean follow-up, 15.5 months) were reviewed by anal endosonography after closed lateral subcutaneous sphincterotomy. Clinical evaluation was focused on anal fissure recurrence and postoperative anal incontinence. The anal endosonographic study involves serial radial images of the distal, proximal, and midanal canal. RESULTS: In 32 patients in whom a complete internal sphincter defect was identified, 31 (75.6 percent) were from the control group and only 1 patient (10 percent) was from the recurrence group (P<0.001). In 19 patients, an incomplete internal sphincter defect was identified; 10 (24.4 percent) were from the control group (residual median size, 1.8 mm; contralateral, 2.5 mm) and 9 patients (90 percent) were from the recurrence group (P=0.001; residual median size, 1.4 mm; contralateral, 2.2 mm). Ten patients (19.6 percent) were incontinent for gas and three patients (5.9 percent) for liquid feces, without significant differences between groups. CONCLUSIONS: Anal endosonography is a useful method for evaluating the anatomic effectiveness of closed lateral subcutaneous sphincterotomy. An incomplete sphincterotomy is associated with significant symptomatic anal fissure recurrence.

Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study

Background:Psoriasis induced by anti–tumor necrosis factor-&agr; (TNF) therapy has been described as a paradoxical side effect. Aim:To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Methods:Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Results:Anti-TNF–induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4–2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4–0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3–2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4–3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. Conclusions:The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.