Risk factors for recurrence and incontinence after anal fistula surgery.

OBJECTIVE: Fistula-in-ano continues to raise problems that require important therapeutic decisions. Our aim was to evaluate its recurrence and incontinence risk factors. METHOD: We analysed a series of 279 patients who had undergone anal fistula surgery with long-term follow-up. RESULTS: 42.7% of the fistulae were considered complex and 46% had been referred from other institutions. There was delayed healing or recurrence in 7.2% patients, which appeared at a median of 4 months. The factors associated with recurrence were the type of fistula (extrasphincteric/suprasphincteric), nonidentification of internal opening (IO), recurrent or complex fistulae (CF), and associated chronic abscess. Only CF and nonidentification of IO were statistically significant in the multivariate analysis. Preoperative incontinence was a risk factor for postoperative incontinence, as were suprasphincteric, recurrent and CF. The age and gender of the patient did not influence postoperative continence, nor did the surgeon or surgical technique appear as a risk factor, although after excluding preoperative incontinent patients, fistulotomy was the technique that showed a higher risk of incontinence. Multivariate analysis only confirmed previous incontinence as a RF. CONCLUSION: The overall recurrence rate is acceptable, but high fistulae continue to be difficult to treat. IO identification is also essential for obtaining good results. It is important to identify the patients with preoperative incontinence as they are at a greater risk of deterioration after surgery.

The ideal lateral internal sphincterotomy: clinical and endosonographic evaluation following open and closed internal anal sphincterotomy.

OBJECTIVE: To evaluate the relationship between extent of internal sphincter division following open and closed sphincterotomy, as assessed by anal endosonography, with fissure persistence/recurrence and faecal incontinence. METHOD: A total of 140 consecutive patients undergoing lateral internal sphincterotomy (LIS) for idiopathic chronic anal fissure were prospectively studied. Preoperative clinical assessment was performed together with a postoperative clinical and endosonographic examination. Three zones of the internal sphincter, identifiable by endosonography, were used to describe the uppermost extent of LIS. Primary end-points were fissure persistence/recurrence and faecal incontinence. RESULTS: A total of 140 patients, median age 49.5 years (IQR: 38-56 years) were included. Seventy-five (53.6%) and 65(46.4%) patients underwent percutaneous LIS (PLIS) and open LIS (OLIS) respectively. Median follow-up was 21 months (IQR: 14-29 months). Persistence and recurrence rates were 2.9% (4/140) and 5.7% (8/140) respectively. 7.9% (11/140) patients scored > 3 on the Jorge and Wexner Faecal Incontinence scale. PLIS was associated with a trend towards higher fissure persistence/recurrence rates than OLIS (12.0%vs 4.6%, P = 0.141). OLIS was significantly associated with a higher proportion of complete sphincterotomies (CS) than PLIS (56/65 vs 48/75, P = 0.003). A CS was associated with a lower fissure persistence or recurrence rate (1/104 vs 11/36, P < 0.001) but higher incontinence scores (11/104 vs 0/36 cases with Wexner scores > 3, P = 0.042) than following incomplete sphincterotomy. There was a strongly significant increase in incontinence scores (P < 0.001) and decrease in recurrence rates (P < 0.001) with increasing length of sphincterotomy. CONCLUSION: We recommend a short and CS using either PLIS or OLIS for the treatment of idiopathic anal fissure.

Review of the anatomic concepts in relation to the retrorectal space and endopelvic fascia: Waldeyer's fascia and the rectosacral fascia.

OBJECTIVE: A precise anatomical study of the fascias within the retrorectal space is reported, analyzing and clarifying the anatomical concepts previously employed to describe Waldeyer's and the rectosacral fascia. METHOD: The pelvis was dissected in 15 cadavers (10 males and five females). All specimens were divided in the median sagittal plane including the middle axis of the anal canal, to allow a correct visualization of and access to the retrorectal space. RESULTS: The retrorectal space was limited anteriorly by the rectum and posterior mesorectum covered by a fine visceral fascia, and posteriorly by the sacrum covered by the parietal presacral fascia. The rectosacral fascia divided the retrorectal space into inferior and superior portions in 80% of the male and 100% of the female specimens. It originated from the presacral parietal fascia at the level of S2 in 15%, S3 in 38% and S4 in 46% of specimens. In all cases it passed caudally to join the rectal visceral fascia 3-5 cm above the anorectal junction. As described by Waldeyer, the floor of the retrorectal space is formed by the fusion of the presacral parietal fascia and the rectal visceral fascia and lies above the levator ani muscle at the level of the anorectal junction. CONCLUSION: The rectosacral fascia divides the retrorectal space into inferior and superior portions. This must be differentiated from Waldeyer's description of the fascia lying in the inferior limit of the retrorectal space, formed by the fusion of the rectal visceral and parietal fascias.

[Autoimmune pancreatitis: inflammatory pseudotumor, multifocal fibrosclerosis, portal hypertension, and long-term outcome]. / Pancreatitis autoinmune: pseudotumor inflamatorio, afectación multifocal, hipertensión portal y evolución a largo plazo.

Autoimmune pancreatitis is a recently characterized disease that still constitutes a diagnostic challenge, especially regarding differential diagnosis from neoplasia. Long-term outcome is poorly known. We herein report a case of a patient with autoimmune pancreatitis and 14 years of follow-up, and show its clinical, biochemical, and morphological characteristics. A 54-year-old female presented with obstructive jaundice and abdominal tenderness, as well as a mass at the pancreatic head on a CT scan, suggestive of pancreatic neoplasia. Surgery showed an increase of the whole pancreas, malignancy was intraoperatively ruled out, and a cholecystectomy and choledochoduodenostomy were carried out. The diagnosis was chronic pancreatitis. Over the following years different autoimmune complications developed, including asthma, salivary gland swelling, and sclerosing cholangitis, as well as recurrent episodes of jaundice, and exocrine and endocrine pancreatic failure. The development of these complications combined with the demonstration of high serum levels of IgG4 and carbonic anhydrase II led to a re-evaluation of the initial histology of the pancreas, leading to a final diagnosis of autoimmune pancreatitis: IgG4+ lymphoplasmacytic infiltrates, fibrosis, and obliterative phlebitis. New complications developed during the last few years: retroperitoneal fibrosis with portal hypertension, esophageal varices, and splenomegaly.

[Early use of CT in the management of acute diverticulitis of the colon]. / El uso precoz de la tomografía computarizada en el manejo de la diverticulitis aguda.

OBJECTIVE: To assess the early use of CT for the diagnosis, staging, and management of acute diverticulitis. MATERIAL AND METHODS: A prospective study of 102 patients with a clinical diagnosis of acute diverticulitis of the left colon. Acute diverticulitis was initially divided into 3 clinical stages. Patients were restaged according to CT findings into stages I, IIa, IIb, and III. Diagnosis was subsequently confirmed intraoperatively or by colonoscopy or barium studies. RESULTS: 102 patients (52 females and 50 males, mean age of 59.4 (SD + 14.96 years)) were included; 84 (82.35%) patients with a clinical diagnosis of acute diverticulitis were confirmed to suffer this disease for a diagnostic error of 17.65% (n=18). Acute diverticulitis was diagnosed by CT in 84.3% (n=86). CT had a sensitivity of 100% and a specificity of 88.9%. CT changed clinical stage for 38% of patients because of understaging in 13% and of overstaging in 25%. When stages II and III were analyzed separately, 60 and 50% were overstaged, respectively. The reclassification of patients according to CT results had a significant impact on treatment. CONCLUSIONS: Early clinical staging with CT avoids diagnostic clinical errors in 17.65% of patients. CT changes the initial clinical staging of acute episodes in 38% of cases, thus avoiding unnecessary delays in surgery for severe cases, and unnecessary surgeries for mild cases.

Antisense gene therapy using anti-k-ras and antitelomerase oligonucleotides in colorectal cancer.

AIM: To test the efficacy of anti-k-ras and antitelomerase oligonucleotides for disabling colorectal cancer cell growth. MATERIAL AND METHODS: An established human colorectal cancer cell line (SW 480, ATTC) was used. Oligodeoxiribonucleotides (ODNs) have a phosphorotioate modification to ensure intracellular intake. We used an antitelomerase ODN (Telp5) and two anti-k-ras ODNs (AS-KRAS and ISIS). AS-KRAS is designed to join the k-ras oncogene s exon 1. ISIS links to the terminal transcription unit 5 of k-ras. Telp5 joins the template region of the hTR telomerase subunit. ODNs have been tested in different concentrations (1, 5, 10, 20 micromolar). Cell viability has been tested at 48 and 72 hours. Statistical analysis and graphic design were made with the statistical package "Analyzing Data with GraphPad Prism-1999", GraphPad Sofware Inc., San Diego CA. We used the Student's t test for statistical analysis. RESULTS: The lowest dose (1 microM) was not effective. Using the highest dose (20 microM for 48 hours) of combined AS-KRAS and Telp5 cell viability decreased to 99.67%. The rest of results varied depending on ODN type, dose, and exposure time. CONCLUSIONS: Tested antisense ODNs stop colorectal cancer cell growth, and a combination of anti-telomerase and anti-k-ras is the most useful treatment. Efficacy is best with a higher dose and longer treatment period.

Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin.

The pharmacological effects of glucocorticoids are greatly influenced by their pharmacokinetic properties. In the present report, the in vitro biotransformation of the 22R and 22S epimers of the topical steroid budesonide was studied in the S-9 fraction of human liver, bronchus, skin and colonic mucosa. The disappearance of unchanged epimers of budesonide was measured during 90 min of incubation by high performance liquid chromatography. The rate of disappearance was high in human liver while little biotransformation occurred in bronchial tissue and colonic mucosa, and none was detected in the skin. A marked decay of the initial concentration of unchanged budesonide epimers was noticed after 2 h incubation in cultured human hepatocytes, while only a small decrease was observed after 24 h incubation in cultured human airway smooth muscle cells and BEAS-2B cells. The 22R epimer of budesonide suffered greater in vitro biotransformation than the 22S epimer in human hepatic, bronchial and colonic tissues. These findings extend those of other studies, and confirm that the high therapeutic ratio of budesonide is due to negligible local biotransformation combined with high level of liver metabolism for locally absorbed budesonide.

Transmucosal potential difference in experimental colitis in rats.

Colon transmucosal potential difference (TPD), macro- and microscopic lesions, myeloperoxidase activity, and leukotriene levels were studied after the induction of experimental colitis in the rat. Forty-three male Wistar rats were subjected to the instillation of 200 mg/ml 2,4,6-trinitrobenzenesulfonic acid (TNB) solution through a rectal cannula. TPD measurements were made at different distances from the anus before and 24 h and one, two, three, and four weeks after lesion induction. Leukotriene B4 levels were assayed by intracolonic dialysis 24 h and one, two, three and four weeks after lesion induction. Macro- and microscopic evaluations were made of the bowel lesions, and myeloperoxidase activity was assayed. The mean basal TPD was -46.06 mV at 1 cm from the anus, and +10.86 mV in the proximal colon. Twenty-four hours after lesion induction the values proved markedly positive. This was correlated with an abrupt increase in LTB4 levels and myeloperoxidase activity. After one week the TPD values exhibited a greater electronegativity, returning to basal values by the fourth week after lesion induction. This coincided with an improved macroscopic lesion index, LTB4 levels, and myeloperoxidase activity. In conclusion, TPD is a useful indicator of acute colonic lesions and correlates well with LTB4 and myeloperoxidase assays. Moreover, the parameter is able to delimit lesion evolution, reflecting possible ad integrum restoration of the bowel mucosa.

Intraoperative photoplethysmographic diagnosis of ischemic colitis.

Intraoperative evaluation of ischemic colitis presents several problems related to diagnosis, severity, and extension. The aim of this study was to determine the usefulness of photopletysmography (PPG) to detect colonic arterial wave amplitude changes in patients operated on for ischemic colitis, comparing the affected area with a control area on the transverse colon. Four patients were studied, two with gangrenous colitis, and two with protracted "transient" ischemic colitis. All four patients survived. PPG is a useful method for intraoperative diagnosis and surgical assessment of ischemic colitis.

[Incidence of inflammatory bowel disease in Sagunto]. / Incidencia de enfermedad inflamatoria de intestino en Sagunto.

The incidence and prevalence of inflammatory bowel disease in the population served by the Sagunto Hospital during 1983-1989 is reported. The global incidence of IBD is 9.07 cases/100,000 inhabitants. The mean incidence of ulcerative colitis has been 4 +/- 2.15; a peak incidence of 8.2 was observed in 1985. It was 3.3 in 1989. Prevalence was 28.87/100,000 inhabitants. The mean incidence of Crohn' disease is 3.06 +/- 1.76/100,000 inhabitants/year, with an increase from 0.8 in 1983 to 5.7 in 1989. Prevalence of Crohn's disease is 21.4/100,000 inhabitants.

Evolutive study of the functional results after restorative proctocolectomy for ulcerative colitis.

AIM: Evolutive study of the functional results after restorative proctocolectomy for ulcerative colitis. PATIENTS AND METHODS: Prospective study in 24 patients with an ileoanal "J" pouch (n = 8: mucosectomy and hand-sewn anastomosis; n = 16: stapled anastomosis without mucosectomy). A clinical survey was carried out during two evolutive follow-ups of the functional pouch (medians: 14.5 and 39.0 months) as well as an anorectal manometry study during the preoperative period and in two follow-ups after the creation of the pouch (medians: 6.0 and 35.5 months). RESULTS: The mean frequency of defecation per 24 hours and per night was significantly reduced in the first follow-up (5.5 [24 h]; p < 0.003 and 1.0 [per night]; p < 0.009) compared with the postoperative period (7.9 [24 h] and 1.4 [per night]), with no significant changes in the second follow-up (5.5 [24 h] and 0.9 [per night]). At the same time, it has been significantly lower in patients with stapled anastomosis in the different evolutive follow-ups. One patient (4.2%) had major fecal incontinence in the two evolutive follow-ups and 7 (29.2%) and 6 (25%) patients had minor incontinence in the first and second follow-up respectively. The mean maximum resting anal pressure in the first follow-up was significantly lower (p = 0.002) in patients with mucosectomy than the values observed in patients with stapled anastomosis (35.4 vs 68.0 mmHg). In the second follow-up increased significantly (p = 0.046) only in patients with mucosectomy (55.1 mmHg). Recto-anal inhibitory reflex was present in 2 (10%) and 9 (45%) patients in the first and second follow-up respectively. CONCLUSIONS: The functional results improve significantly with the follow-up time, fundamentally during the first year of the functional pouch.

[Morphological, histochemical and immunochemical characteristics of the terminal ileum of patients with ulcerative colitis. Relationship with the development of pouchitis]. / Características morfológicas, histoquímicas e inmunohistoquímicas del íleon terminal de los pacientes con colitis ulcerosa. Relación con el desarrollo de reservoritis.

UNLABELLED: Pouchitis is the most frequent long-term complication of the ileoanal reservoirs. Its etiology is unknown and it is currently believed to be a recurrence of ulcerative colitis in the mucosa of the ileal reservoir. AIM: To evaluate whether the mucosa of the terminal ileum of patients with ulcerative colitis is different from that of patients free of this disease and whether there are morphological and immunological alterations which might predispose to inflammation of the reservoir. PATIENTS AND METHODS: Colectomy samples from the terminal ileum of 20 patients (12 women, 8 men) with ulcerative colitis who had undergone restorative proctocolectomy with ileoanal reservoir and of 10 controls who had undergone right hemicolectomy for other causes were studied. During follow-up (46.9 months) seven patients were diagnosed with pouchitis (Sandborn > 7). In all patients, morphometric histopathologic, histochemical and immunohistochemical studies of the ileal mucosa were performed. RESULTS: Chronic inflammatory infiltrate and the degree of villous atrophy and of global chronic inflammation were significantly higher in the terminal ileum of patients with ulcerative colitis than in the control group. There were no differences in the mucin content between the two groups and IgA, IgG and B lymphocyte expression was significantly higher in the terminal ileum of patients with ulcerative colitis. Chronic inflammatory infiltrate, degree of atrophy, villous atrophy and of global chronic infiltration, macrophage and CD8 lymphocyte expression were higher in the terminal ileum of patients with pouchitis, but differences was not significant. CONCLUSIONS: The terminal ileum of patients with ulcerative colitis has histopathologic, morphometric and immunohistochemical characteristics that are different from those of patients without this disease. These results may eventually lead to an association between alterations in the ileum and the subsequent development of pouchitis.

[Intestinal complications from vascular prostheses]. / Complicaciones intestinales de las prótesis vasculares.

Secondary FAE is a rare complication, usually located at the duodenum. The typical clinical presentation is like a digestive hemorrhage or a sepsis. We report two cases of FAE with atypical manifestations. The first case presented a lower digestive hemorrhage produced by the fistulization to the sigma. The second case appeared like an intestinal obliteration caused by the full emigration of a prosthesis to the jejunum. We wish to remark the importance of the clinical suspicion of a FAE (Key of diagnosis), and the sparing relevance of the complementary examinations and the urgency of a surgical treatment in order to avoid the high rate of morbi-mortality associated with this complication.

Relaxation of the isolated human internal anal sphincter by sildenafil.

BACKGROUND: Hypertonicity of the internal anal sphincter (IAS) appears to be involved in the pathogenesis of anal fissure. The relaxant effects of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on isolated human IAS were investigated. METHODS: The efficacy (maximal effect, E(max)) and potency (-log IC(50), where IC(50) is half-maximal inhibitory concentration) of the PDE5 inhibitors, sildenafil and zaprinast, and of nitric oxide donors, sodium nitroprusside and glyceryl trinitrate, as relaxants of histamine (0.1 mmol/l)-induced tone were examined in IAS strips under isometric contraction. The presence of PDE5 isoenzymes and changes in intracellular calcium and cyclic nucleotide levels in IAS muscle were tested by real-time reverse transcriptase-polymerase chain reaction, epifluorescence microscopy and enzyme immunoassay respectively. RESULTS: Sildenafil produced a concentration-related inhibition of the mean(s.e.m.) histamine-induced tone (E(max) 83(2) per cent, - log IC(50) 7.04(0.05); n = 12). Zaprinast produced relaxation to similar degree, but with lower potency. Nitric oxide donors also relaxed IAS. Sildenafil (1 micromol/l) produced a 1.8-fold increase in guanosine 3',5'-cyclic monophosphate content, with no change in adenosine 3',5'-cyclic monophosphate levels. Sildenafil markedly depressed the peak intracellular calcium increase evoked by histamine. PDE5A1, PDE5A2 and PDE5A3 transcripts were expressed in IAS muscle. CONCLUSION: Sildenafil relaxes the augmented tone of human IAS in vitro. These results support the potential use of this PDE5 inhibitor in the treatment of chronic anal fissure.

Management of intersphincteric abscesses.

OBJECTIVE: Intersphincteric abscesses are relatively rare, and in some cases of upward extensions in the supralevator plane, can be difficult to manage. The aim of this study was to analyse the type of treatment used in these abscesses. METHODS: Twenty-one intersphincteric abscesses treated by endoanal drainage in our colorectal unit between 1992 and 2004 were reviewed from our database; location and extension of the abscess, type of treatment and recurrence rates and the use of endoanal ultrasound were studied. RESULTS: Ninety per cent of patients were male; 10 had a previous history of surgery for perianal abscess and suppuration (48%); 16 (76%) had a posterior location and five were anterolateral. Twelve patients had low intersphincteric abscesses and were treated by laying open the abscess and dividing the internal sphincter. Nine were found to have high extensions into the intermuscular planes and were treated by staged procedures: a temporary transanal mushroom catheter was used in seven patients. Endoanal ultrasound was used initially in seven patients (33.3%) and for the evaluation of definitive treatment in 11 (52%). CONCLUSIONS: Low intersphincteric abscesses should be treated by de-roofing of the abscess and division of the internal sphincter up to a level of the dentate line. High intersphincteric abscesses are relatively frequent and mostly require staged surgery with a temporary mushroom (de Pezzer) catheter. Accurate anatomical ultrasound localization and proper drainage become important to avoid recurrences or extrasphincteric fistulas.

Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis.

BACKGROUND: Perioperative supplemental oxygen therapy may have beneficial effects on wound healing following colorectal surgery. The aim of this study was to evaluate the effects of such therapy on colorectal anastomotic pH and partial pressure of carbon dioxide (PCO(2)) gap. METHODS: Forty-five patients undergoing anterior resection for rectal or sigmoid cancer were randomized to receive 30 or 80 per cent perioperative oxygen. Administration was commenced after induction of anaesthesia and maintained for 6 h after surgery. Intragastric and anastomotic tonometric catheters were placed in each patient and intramucosal pH (pHi) was measured immediately after operation, and 6 and 24 h later. Gastric and anastomotic pHi and PCO(2) gap in each group were compared. RESULTS: There was a significantly lower anastomotic pHi and wider PCO(2) gap for gastric readings in the 30 per cent O(2) group, both 30 min (pHi, P = 0.006; PCO(2) gap, P = 0.006) and 6 h (pHi, P = 0.024; PCO(2) gap, P = 0.036) after surgery. There were no differences 24 h after surgery while breathing room air (pHi, P = 0.131; PCO(2) gap P = 0.139). No difference was found between gastric and anastomotic readings at any time point in the 80 per cent O(2) group. CONCLUSION: Perioperative administration of 80 per cent O(2) both during surgery and for 6 hours afterwards is associated with an improvement in relative anastomotic hypoperfusion as assessed by the measurement of pHi and PCO(2) gap.

Relationship of curative surgery on natural killer cell activity in colorectal cancer.

PURPOSE: Aim of this study has been to evaluate natural killer (NK) activity in patients with colorectal tumors before and after curative surgery. METHODS: Forty colorectal cancer patients without distant metastases were stratified according to American Joint Committee on Cancer/International Union Against Cancer staging system into three categories: Stage I (n = 12), Stage II (n = 15), and Stage III (n = 13). All of them underwent curative resection, and there were no major postoperative complications. Venous blood samples were obtained preoperatively, at surgical wound closure, and on the 1st, 7th, and 21st postoperative days. Mononuclear cells were isolated over Ficoll-Hypaque (Lymphoprep, Nycomed Pharma AS, Oslo, Norway) gradients, and NK activity was assayed by evaluation of cytotoxic response against K562 cells. Normal NK activity was achieved from 15 healthy donors. Percentage relative increments in relation to preoperative levels were calculated for every postoperative sample, and t-test was used for statistical evaluation. RESULTS: Before surgery, Stages II and III patients had lower levels of NK activity than healthy people (P < 0.05 and P < 0.001, respectively). NK activity always fell after surgery (Stage I: -18.48 +/- 11.42; Stage II: -16.93 +/- 13.57; Stage III: -35.29 +/- 12.03, at day 1 postsurgery) and appeared to rise slightly by the 21st postoperative day in Stage I patients (+4.87 +/- 12.41). Stage II, and especially Stage III, patients did show a significant recovery by the 21st postoperative day (+23.63 +/- 9.36 and +43.19 +/- 13.34, respectively). At this time, NK activity in these two groups was not significantly lower than in normal subjects (P > 0.05). CONCLUSION: NK activity is depressed in colorectal cancer patients in relation to progression of illness, even at locoregional stages. Curative resection of tumors at Stages II and III has promoted a recovery of NK activity in patients with uneventful postoperative courses.