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1.
Colorectal Dis ; 12(3): 254-60, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19220375

ABSTRACT

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.


Subject(s)
Fecal Incontinence/etiology , Rectal Fistula/complications , Rectal Fistula/surgery , Adult , Digestive System Surgical Procedures , Fecal Incontinence/diagnosis , Fecal Incontinence/surgery , Female , Humans , Male , Middle Aged , Patient Selection , Recurrence
2.
Colorectal Dis ; 11(5): 502-7, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18637925

ABSTRACT

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.


Subject(s)
Anal Canal/surgery , Endosonography/methods , Fissure in Ano/surgery , Sphincterotomy, Endoscopic/methods , Adult , Anal Canal/diagnostic imaging , Fecal Incontinence/etiology , Female , Fissure in Ano/diagnostic imaging , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Recurrence , Sphincterotomy, Endoscopic/instrumentation
3.
Rev. esp. enferm. dig ; 100(10): 652-658, oct. 2008. ilus
Article in Es | IBECS | ID: ibc-71056

ABSTRACT

La pancreatitis autoinmune es una enfermedad recientementecaracterizada y que en la actualidad constituye un reto diagnósticoespecialmente su diferenciación con el cáncer de páncreas. Suevolución a largo plazo es poco conocida, presentándose un casoestudiado a lo largo de 14 años y mostrando su evolución clínica,bioquímica y morfológica.Paciente mujer de 54 años que debuta con un cuadro de ictericiaobstructiva y molestias abdominales inespecíficas y constataciónen la TAC de un aumento de la cabeza del páncreas, todoello sugestivo de neoplasia de páncreas. Fue intervenida evidenciándoseun aumento difuso de todo el páncreas descartándosemalignidad intraoperatoriamente, realizando únicamente colecistectomíay coledocoduodenostomía, quedando diagnosticada entoncescomo pancreatitis crónica. Durante los años posterioresfueron apareciendo diferentes procesos autoinmunes como asma,sialoadenitis y colangitis esclerosante secundaria, así como episodiosrecurrentes de ictericia e insuficiencia pancreática endocrinay exocrina. La aparición de estas complicaciones y la detección deniveles séricos elevados de IgG4 y de anticuerpos antianhidrasacarbónica II condujo a la reevaluación de la histología inicial concluyendofinalmente con el diagnóstico de pancreatitis autoinmuneal evidenciarse una infiltración linfocitaria y plasmacitariaIgG4+, así como fibrosis y flebitis obliterativa. En los últimos añosse ha añadido a las anteriores complicaciones una fibrosis retroperitonealcon hipertensión portal, varices esofágicas y esplenomegalia


Autoimmune pancreatitis is a recently characterized diseasethat still constitutes a diagnostic challenge, especially regarding differentialdiagnosis from neoplasia. Long-term outcome is poorlyknown. We herein report a case of a patient with autoimmunepancreatitis and 14 years of follow-up, and show its clinical, biochemical,and morphological characteristics.A 54-year-old female presented with obstructive jaundice andabdominal tenderness, as well as a mass at the pancreatic head ona CT scan, suggestive of pancreatic neoplasia. Surgery showed anincrease of the whole pancreas, malignancy was intraoperativelyruled out, and a cholecystectomy and choledochoduodenostomywere carried out. The diagnosis was chronic pancreatitis. Over thefollowing years different autoimmune complications developed, includingasthma, salivary gland swelling, and sclerosing cholangitis,as well as recurrent episodes of jaundice, and exocrine and endocrinepancreatic failure. The development of these complicationscombined with the demonstration of high serum levels ofIgG4 and carbonic anhydrase II led to a re-evaluation of the initialhistology of the pancreas, leading to a final diagnosis of autoimmunepancreatitis: IgG4+ lymphoplasmacytic infiltrates, fibrosis,and obliterative phlebitis. New complications developed during thelast few years: retroperitoneal fibrosis with portal hypertension,esophageal varices, and splenomegaly


Subject(s)
Autoimmune Diseases/complications , Granuloma, Plasma Cell/complications , Hypertension, Portal/complications , Retroperitoneal Fibrosis/complications , Autoimmune Diseases/diagnosis , Autoimmune Diseases , Autoimmune Diseases/surgery , Splenomegaly/etiology , Time Factors , Tomography, X-Ray Computed , Cholangiography , Cholangitis, Sclerosing/etiology , Cholecystectomy , Chronic Disease , Diagnosis, Differential , Esophageal and Gastric Varices/etiology , Follow-Up Studies
4.
Colorectal Dis ; 10(3): 298-302, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18257849

ABSTRACT

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.


Subject(s)
Fascia/anatomy & histology , Pelvis/surgery , Rectum/anatomy & histology , Cadaver , Female , Humans , Male , Pelvic Floor/anatomy & histology , Pelvic Floor/surgery , Pelvis/anatomy & histology , Retroperitoneal Space/anatomy & histology , Retroperitoneal Space/surgery , Sensitivity and Specificity
5.
Rev Esp Enferm Dig ; 100(10): 652-8, 2008 Oct.
Article in Spanish | MEDLINE | ID: mdl-19119794

ABSTRACT

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.


Subject(s)
Autoimmune Diseases/complications , Granuloma, Plasma Cell/complications , Hypertension, Portal/complications , Pancreatitis, Chronic/complications , Retroperitoneal Fibrosis/complications , Autoimmune Diseases/diagnosis , Autoimmune Diseases/diagnostic imaging , Autoimmune Diseases/pathology , Autoimmune Diseases/surgery , Cholangiography , Cholangitis, Sclerosing/etiology , Cholecystectomy , Chronic Disease , Diagnosis, Differential , Esophageal and Gastric Varices/etiology , Female , Follow-Up Studies , Humans , Liver/pathology , Middle Aged , Pancreas/pathology , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/diagnostic imaging , Pancreatitis, Chronic/pathology , Pancreatitis, Chronic/surgery , Radiography, Abdominal , Splenomegaly/etiology , Time Factors , Tomography, X-Ray Computed
6.
Rev Esp Enferm Dig ; 99(6): 320-4, 2007 Jun.
Article in Spanish | MEDLINE | ID: mdl-17883294

ABSTRACT

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.


Subject(s)
Diverticulitis, Colonic/diagnostic imaging , Tomography, X-Ray Computed , Acute Disease , Adult , Aged , Barium Sulfate , Diagnosis, Differential , Disease Management , Diverticulitis, Colonic/complications , Diverticulitis, Colonic/surgery , Early Diagnosis , Female , Humans , Male , Middle Aged , Peritonitis/etiology , Predictive Value of Tests , Prospective Studies , Severity of Illness Index , Unnecessary Procedures
7.
Rev. esp. enferm. dig ; 99(6): 320-324, jun. 2007. tab
Article in Es | IBECS | ID: ibc-058221

ABSTRACT

Objetivo: valorar el uso precoz de la tomografía computarizada (TC) para el diagnóstico, estadificación y manejo de la diverticulitis aguda. Material y métodos: realizamos un estudio prospectivo de 102 pacientes con el diagnóstico clínico de diverticulitis aguda de colon izquierdo. La diverticulitis aguda fue inicialmente dividida en tres estadios. Los pacientes fueron reestadiados en los estadios I, IIa, IIb y III de acuerdo a los hallazgos encontrados en la TC. El diagnóstico se confirmó después intraoperatoriamente, por colonoscopia o estudio con bario. Resultados: fueron incluidos 102 pacientes (52 mujeres y 50 hombres) con una edad media de 59,4 (DS ± 14,96). En 84 (82,35%) pacientes con el diagnóstico clínico de diverticulitis aguda se confirmó este diagnóstico con un error diagnóstico del 17,65% (n = 18). La diverticulitis aguda se diagnosticó con la TC en el 84,3% (n = 86). La TC tuvo una sensibilidad del 100% y especificidad del 88,9%. La TC cambió la estadificación clínica en un 38% debido a una infraestadificación del 13% y una sobreestadificación del 25%, que llega al 60 y al 50% en los estadios clínicos II y III, respectivamente. La reclasificación o reestadificación de los pacientes de acuerdo con los hallazgos en la TC tiene una consecuencia importante en la indicación quirúrgica. Conclusiones: la estadificación clínica precoz de la diverticulitis con la TC evita errores de diagnóstico clínico en el 17,65%. La TC modifica la estadificación clínica de severidad en el 38% evitando la cirugía innecesaria y el retraso en el tratamiento quirúrgico


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


Subject(s)
Humans , Tomography, X-Ray Computed , Diverticulitis/diagnosis , Prospective Studies , Sensitivity and Specificity , Early Diagnosis , Severity of Illness Index
8.
Br J Surg ; 94(7): 894-902, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17335124

ABSTRACT

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.


Subject(s)
Anal Canal/drug effects , Muscle Relaxation , Muscle, Smooth/drug effects , Phosphodiesterase Inhibitors/pharmacology , Piperazines/pharmacology , Sulfones/pharmacology , Adult , Aged , Aged, 80 and over , Anal Canal/physiology , Cyclic GMP/metabolism , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , Male , Middle Aged , Muscle, Smooth/physiology , Purines/pharmacology , Sildenafil Citrate
9.
Colorectal Dis ; 8(9): 777-80, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17032324

ABSTRACT

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.


Subject(s)
Abscess/surgery , Anal Canal/pathology , Anus Diseases/surgery , Digestive System Surgical Procedures/methods , Abscess/classification , Abscess/diagnostic imaging , Anal Canal/surgery , Anus Diseases/classification , Anus Diseases/diagnostic imaging , Catheterization , Drainage , Female , Humans , Male , Retrospective Studies , Treatment Outcome , Ultrasonography
10.
Br J Surg ; 93(6): 698-706, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16703624

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/surgery , Oxygen Inhalation Therapy/methods , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical/methods , Blood Gas Monitoring, Transcutaneous , Female , Humans , Hydrogen-Ion Concentration/drug effects , Male , Middle Aged , Perioperative Care/methods , Prospective Studies , Treatment Outcome , Wound Healing/drug effects
11.
Rev Esp Enferm Dig ; 97(7): 472-80, 2005 Jul.
Article in English, Spanish | MEDLINE | ID: mdl-16262526

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/therapy , Genes, ras/genetics , Oligodeoxyribonucleotides, Antisense/therapeutic use , Telomerase/antagonists & inhibitors , Cell Line, Tumor , Colorectal Neoplasms/genetics , Genetic Therapy , Humans , Oligodeoxyribonucleotides, Antisense/genetics , Software
12.
Rev. esp. enferm. dig ; 97(7): 472-480, jul. 2005. tab, graf
Article in Es | IBECS | ID: ibc-041833

ABSTRACT

Objetivo: evaluar la eficacia de oligonucleótidos anti k-ras yantitelomerasa para detener el crecimiento tumoral en el cáncercolorrectal.Material y métodos: se ha empleado una línea celular establecidade cáncer colorrectal humano (SW 480, ATTC®). Los oligodesoxirribonucleótidos(ODN) utilizados en el presente trabajo presentanmodificación fosforotioato con el fin de mejorar su estabilidad enpresencia de fluidos biológicos. Hemos utilizado un ODN antitelomerasa(Telp5), y dos ODN anti k-ras (AS-KRAS e ISIS). AS-KRAS actúaen el exón 1 e ISIS actúa a nivel de la unidad terminal de transcripción5’ del oncogen k-ras. Telp5 se une a la subunidad hTR de latelomerasa. Se han aplicado en concentraciones 1, 5, 10 y 20 micromolar,midiendo la viabilidad celular a las 48 y 72 horas de tratamiento.El análisis estadístico y el diseño de los gráficos se han realizadomediante el programa “Analyzing Data with GraphPadPrism-1999”. GraphPad Sofware Inc., San Diego CA©. Para el tratamientoestadístico se ha utilizado el test t de Student.Resultados: la dosis mínima (1 µM) no fue efectiva ni a 48 nia 72 horas postratamiento. Con la dosis máxima (20 µM durante48 horas) y utilizando la combinación de AS-KRAS y Telp5 obtuvimosuna reducción de la viabilidad celular del 99,67%. El restode resultados fueron intermedios, dependiendo del tipo de oligonucleótidoempleado, la dosis y el tiempo de exposición.Conclusiones: los oligonucleótidos antisentido probados detienenel crecimiento celular en el cáncer colorrectal, siendo larespuesta más eficaz la combinación de ambos y aumentando dichaeficacia con mayor dosis y tiempo de exposición


Aim: to test the efficacy of anti-k-ras and antitelomeraseoligonucleotides for disabling colorectal cancer cell growth.Material and methods: an established human colorectalcancer cell line (SW 480, ATTC®) was used. Oligodeoxiribonucleotides(ODNs) have a phosphorotioate modification to ensureintracellular intake. We used an antitelomerase ODN (Telp5) andtwo anti-k-ras ODNs (AS-KRAS and ISIS). AS-KRAS is designedto join the k-ras oncogene’s exon 1. ISIS links to the terminaltranscription unit 5’ of k-ras. Telp5 joins the template region ofthe hTR telomerase subunit. ODNs have been tested in differentconcentrations (1, 5, 10, 20 micromolar). Cell viability has beentested at 48 and 72 hours. Statistical analysis and graphic designwere made with the statistical package “Analyzing Data withGraphPad Prism-1999”, GraphPad Sofware Inc., San DiegoCA©. We used the Student’s t test for statistical analysis.Results: the lowest dose (1 µM) was not effective. Using thehighest dose (20 µM for 48 hours) of combined AS-KRAS andTelp5 cell viability decreased to 99.67%. The rest of results varieddepending on ODN type, dose, and exposure time.Conclusions: tested antisense ODNs stop colorectal cancercell growth, and a combination of anti-telomerase and anti-k-ras isthe most useful treatment. Efficacy is best with a higher dose andlonger treatment period


Subject(s)
Humans , Genes, ras/genetics , Oligodeoxyribonucleotides, Antisense/genetics , Oligodeoxyribonucleotides, Antisense/therapeutic use , Telomerase/antagonists & inhibitors , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , Cell Line, Tumor , Genetic Therapy , Software
13.
Colorectal Dis ; 6(4): 236-42, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15206965

ABSTRACT

BACKGROUND: Increased telomerase activity can be found in almost 90% of colorectal tumours. We aim to describe the preliminary results for quantification in plasma of hTERT mRNA in colorectal cancer patients. MATERIALS AND METHODS: Fifty patients undergoing surgery for colorectal cancer and a control group of 50 healthy volunteers were prospectively studied. Pre-operative venous blood samples were taken from all cancer patients and volunteers. Plasma hTERT expression was determined from peripheral blood based on real-time quantitative RT-PCR (qRT-PCR) method normalized to the amount of RNA input using 18S rRNA gene expression. Plasma pre-operative CEA levels were also determined. RESULTS: Median values for normalized hTERT (hTERT(N)) gene expression were higher in colorectal cancer patients (11.62, range 0.23-47.67) than healthy volunteers (0.29, range 0.00-4.63) (P < 0.001). Individual data showed that 82% of colorectal cancer patients had hTERT(N) expression values superior to the maximum value observed in the control group. Sensitivity and specificity of the assay for colorectal cancer detection were 98% and 64%, respectively. No significant differences in hTERT(N) expression between gender or with age (P > 0.05). No significant correlation was found between hTERT(N) expression and CEA values (Spearman's rank test = 0.136, P = 0.348). CONCLUSIONS: These results show that detection of mRNA based on the qRT-PCR of the telomerase hTERT(N) gene in plasma clearly differentiates between healthy and colorectal cancer patients and that hTERT(N) can be detected and quantified in plasma. This opens up a new field as a noninvasive blood test for colorectal cancer diagnosis.


Subject(s)
Carcinoembryonic Antigen/blood , Colorectal Neoplasms/blood , RNA, Messenger/blood , Telomerase/blood , Adolescent , Adult , Aged , Aged, 80 and over , Colectomy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/surgery , DNA-Binding Proteins , Female , Humans , Male , Middle Aged , Preoperative Care , Prospective Studies , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Telomerase/biosynthesis , Telomerase/genetics
14.
Pancreas ; 28(1): 65-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14707732

ABSTRACT

OBJECTIVES: To investigate the recovery of pancreatic function after severe acute biliary pancreatitis (ABP), especially the influence of necrosectomy on endocrine and exocrine functions. METHODS: Prospective cohort study including 39 patients with severe ABP. According to need or no need for surgical necrosectomy, patients were further subdivided into 2 groups. Functional pancreatic evaluation was carried out 12 months after the ABP episode. Endocrine function was evaluated by an oral glucose tolerance test and exocrine function by fecal fat excretion, fecal chymotrypsin (FQ), and secretin-cerulein tests (SCT). RESULTS: Most of the patients with necrosectomy had an abnormal exocrine pancreatic function, with steatorrhea in 25%. In the group without surgery, exocrine function was pathologic in only 13.3% and there were no cases of steatorrhea. Endocrine function was pathologic in 75% of patients undergoing necrosectomy versus 26.7% in the nonoperated group. In this latter group, the patients with abnormal endocrine function did not require insulin therapy, while in 33.3% of patient in the necrosectomy group insulin was necessary. CONCLUSIONS: In our homogeneous series of severe ABP, necrosectomy impaired significantly pancreatic endocrine and exocrine function. On the other hand, most patients with the same origin and severity index, but without surgical debridement, maintained normal pancreatic function.


Subject(s)
Biliary Tract Diseases/complications , Pancreas/physiopathology , Pancreatitis, Acute Necrotizing/physiopathology , Aged , Blood Glucose/metabolism , Cohort Studies , Female , Glucose Tolerance Test , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatectomy , Pancreatic Function Tests , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/surgery , Prospective Studies , Severity of Illness Index
15.
Dig Surg ; 21(5-6): 440-6, 2004.
Article in English | MEDLINE | ID: mdl-15665539

ABSTRACT

AIM: A prospective review of the complications of ileostomy construction and takedown. MATERIALS AND METHODS: One hundred twenty-seven consecutive patients undergoing construction of a loop ileostomy were included in a prospective nonrandomized computer database. Complications of the loop ileostomy were assessed prior to and after closure. Three closure techniques were performed [enterotomy suture (25.7%), resection and hand sewn (31.2%) or stapled anastomosis (43.1%)] and compared. RESULTS: One hundred twenty-seven (73 male, 54 female) patients, mean age 54 years were included from 1992 to 2002. Seventy-two patients underwent anterior resection for low rectal carcinoma, 30 an ileoanal pouch for ulcerative colitis and 25 for miscellaneous conditions. Fifty-nine pre-takedown complications occurred in 50 (39.4%) patients. The most common were dermatitis (12.6%) and erythema (7.1%). The most severe were dehydration in 1 patient and stomal prolapse in 4 patients. Closure was associated with a complication rate of 33.1% and a mortality rate of 0.9%. Wound infection occurred in 18.3% and small bowel obstruction in 4.6%. Anastomotic leak requiring reanastomosis occurred in 2.8% and enterocutaneous fistula treated conservatively in 5.5%. There were no statistically significant differences in morbidity between closure techniques (p = 0.892). There were no statistically significant differences in complications (p = 0.516) between patients with ulcerative colitis and those with neoplasia (39.29% vs. 32.2%). CONCLUSIONS: Loop ileostomy construction and takedown is associated with considerable morbidity, mostly minor. No differences exist between technique used for closure or the baseline pathology of the patient.


Subject(s)
Colonic Pouches , Ileostomy/adverse effects , Rectal Neoplasms/surgery , Female , Humans , Ileostomy/methods , Male , Middle Aged , Prospective Studies
16.
Dig Surg ; 20(3): 222-8, 2003.
Article in English | MEDLINE | ID: mdl-12759502

ABSTRACT

OBJECTIVES: To develop an experimental model to assess the parietal perfusion pressure (PPP) of the digestive tract using photoplethysmography. MATERIALS AND METHODS: Twenty-two mongrel dogs were used. Progressive external compression was applied to the intestinal wall and the PPP was assessed with photoplethysmography. The study group was divided into two groups. In group 1 PPP was measured at the levels of the stomach, duodenum, jejunum and transverse colon. In group 2 PPP was measured after temporary occlusion of the truncal and marginal circulation of the jejunum to provide further variables. RESULTS: The PPP decreased significantly for each successive distal section. Correlation coefficients and indices for PPP and mean arterial pressures were statistically significant (p < 0.005). Truncal occlusion provoked a drop in PPP whereas marginal occlusion scarcely modified the basal results. CONCLUSIONS: Photoplethysmography, through measurements of the residual arterial wave amplitude, is a valid method of determining quantitatively the PPP of the digestive tract and could be useful in a clinical environment.


Subject(s)
Blood Circulation/physiology , Blood Pressure , Digestive System Surgical Procedures , Photoplethysmography/methods , Animals , Blood Pressure Determination/methods , Digestive System/blood supply , Dogs , Manometry/methods , Models, Animal , Monitoring, Intraoperative , Perfusion , Regional Blood Flow
17.
Fundam Clin Pharmacol ; 15(1): 47-54, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11468013

ABSTRACT

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.


Subject(s)
Budesonide/pharmacokinetics , Liver/metabolism , Skin/metabolism , Administration, Topical , Anti-Inflammatory Agents/pharmacokinetics , Biotransformation , Bronchi/metabolism , Budesonide/analogs & derivatives , Cell Line , Cells, Cultured , Colon/metabolism , Culture Techniques , Glucocorticoids , Hepatocytes/metabolism , Humans , Intestinal Mucosa/metabolism , Stereoisomerism
18.
Dig Surg ; 18(3): 235-7, 2001.
Article in English | MEDLINE | ID: mdl-11464022

ABSTRACT

Multiple strictures of the small bowel are relatively rare. In many cases, a distinct cause can be defined, but some strictures are unexplainable by any specific mechanism and have been termed 'idiopathic' small bowel strictures. We present 3 cases of multiple small bowel strictures in which the affected segments were studied with perioperative photoplethysmography, in vivo specimen angiography and pathology. Neither photoplethysmographic alterations nor structural vascular lesions were found.


Subject(s)
Intestine, Small/pathology , Intestine, Small/surgery , Adult , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/surgery , Fatal Outcome , Female , Humans , Male , Middle Aged , Photoplethysmography , Radiography , Recurrence
20.
Colorectal Dis ; 3(3): 179-84, 2001 May.
Article in English | MEDLINE | ID: mdl-12790986

ABSTRACT

PURPOSE: The present study was designed to assess the differences in the outcome of patients with rectal cancer treated by a group of surgeons before and after being organized as a Coloproctology Unit at the same University Department of Surgery. METHODS: Comparison of two periods of rectal cancer surgery: I (1986-91) and II (1992-95). Period I: 94 patients were operated on by 14 general surgeons. Period II: 108 patients were operated on by only 4 surgeons of the same group organized as a Colorectal Surgery Unit after visiting referral centres abroad, adopting techniques such as total mesorectal excision (TME) for middle and low rectal cancer and washout of rectal stump. Mean follow-up during periods I and II was 69.1 and 42.0 months, respectively. A prospective data base analysis was used. Survival and local recurrence rates were calculated by the actuarial method. For comparison between groups the log rank method was used. RESULTS: The two groups were comparable with respect to mean age, gender, TNM and rectal tumour location. A significant increase in radical resectability and a decrease of the Abdominoperineal resection (APR)/Low anterior resection (LAR) ratio were observed in the second period. The overall pelvic recurrence rate was 25% in the first period and 11 in the second (P < 0.01). Significant differences were also found when the patients with LAR were compared between both periods, 30% vs 9% (P < 0.01) and specially when the 10 cm anal verge distance was considered to divide the LAR groups. No differences were found regarding the APR procedures in both periods. There was improved cancer-specific survival for the LAR group in the second period (P=0.03). CONCLUSION: Specialization and centralization influence the quality of rectal cancer surgery, mainly local recurrence rates and survival after low anterior resection.

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