Enfermedad Inflamatoria Intestinal de colon de larga ...interactivoendoscopia.atlantacongress.org/userfiles/file/CONGRESOS... · Clasificación e historia natural ... Riesgo de CCR
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Curso interactivo sobre endoscopia avanzada para el seguimiento y tratamiento de los pacientes con alto riesgo de cáncer colorrectal. Barcelona 10-11 febrero 2011 Enfermedad Inflamatoria Intestinal de colon de larga evolución: Bases clínicas evolución: Bases clínicas Dra Elena Ricart Hospital Clínic, Barcelona
Estudios más recientes sugieren una menor incidencia tanto en USA como en europa. Las razones para esta observacion pueden ser: Uso más generalizado de programas de vigilancia endoscópica Quimioprotección atribuible a aminosalicilatos Mejor control de la inflamación. Estudios poblacionales últimos incluyen pacientes más benigna y leve.
-Uso más generalizado de programas de vigilancia endoscópica-Quimioprotección atribuible a aminosalicilatos-Mejor control de la inflamación.-Estudios poblacionales recientes incluyen pacientes más benigna y leve.
Estudios más recientes sugieren una menor incidencia tanto en USA como en europa. Las razones para esta observacion pueden ser: Uso más generalizado de programas de vigilancia endoscópica Quimioprotección atribuible a aminosalicilatos Mejor control de la inflamación. Estudios poblacionales últimos incluyen pacientes más benigna y leve.
Canavan ap&t 2007 an overall pooled estimate for the colorectal cancer RR of 2.5 with a 95% confidence interval 1.3–4.7, which was statistically significant Five papers specified colorectal cancer incidence in patients with colonic disease, 12, 15, 19, 23, 26 the overall pooled estimate for RR of colorectal cancer in these patients is 4.5 with a 95% confidence interval 1.3–14.9, which was statistically significant (P < 0.015; Figure 3). Only three papers specify the incidence of colorectal cancer in patients with ileal disease,12, 15, 26 the combined RR for these patients is 1.1 with 95% confidence interval 0.8–1.5, this risk is not statistically significantly greater than the risk of the general population (P ¼ 0.7).
Displasia y CCR en EII
Frecuencia
Factores de riesgo
FisiopatologíaFisiopatología
Clasificación e historia natural
Tratamiento profiláctico
Tratamiento de la displasia
• Tiempo de evolución• Extensión• Colangitis esclerosante primaria• Hª familiar de CCR esporádico
Factores de riesgo de displasia en la EII
• Hª familiar de CCR esporádico• Edad de inicio• Gravedad de la inflamación• Tratamiento médico
• Tiempo de evolución: 8-10 años. – Iniciar el despistaje antes aumenta costes y reduce
el beneficio
• Extensión:
Factores de riesgo de displasia en la EII
• Extensión:– RR en colitis extensa: 14.8-19.2 (95%CI: 11.4-18.9)– RR en colitis izquierda: 2.8 (95%CI: 1.6-4.4)– RR en proctitis: 1.7 (95%CI: 0.8-3.2)
Ekbom. N Engl J Med 1990
• Colangitis esclerosante primaria
Factores de riesgo de displasia en la EII
CU+CEP
años
CU
Broomé. Hepatology 1995
Metaanálisis: riesgo 4 veces superior comparado con pacientes sin CEP. (Soetniko. Gastrointest Endosc 2002)
CONSEJO: screening desde el diagnóstico, incluso después del trasplante.
• Hª familiar de CCR esporádico– Aumenta 2-3 veces el riesgo: RR 2.5 (95%CI: 1.4-
4.4)– Si <50 años: RR 9.2 (95%CI: 3.7-23)
Askling. Gastroenterology 2001
Factores de riesgo de displasia en la EII
Askling. Gastroenterology 2001
• Edad de inicio– Riesgo acumulado tras 35 años de evolución:
• Diagnóstico<15 años de edad: 35%• Diagnóstico 15-39 años de edad: 25% (Ekbom. NEJM 1990)
– Estudios negativos• Greenstein. Gastroenterology 1979• Friedman. Gastroenterology 2001
Controversias en cuanto a la edad de diagnóstico como factor de riesgo
• Gravedad de la inflamación en CU– Datos iniciales negativos (Eaden. AP&T 2000; Pinczowski.
Gastroenterology 1994)
– Estudios posteriores: • RR: 2.5-5.1 (1.5-11.1) (Rutter. Gastroenterology 2004)
Factores de riesgo de displasia en la EII
• Estenosis: RR 5.7 (1.7-18.9) (Rutter. Gut 2004)
• Colon tubular: RR 28.4 (1.6-512.2) (Rutter. Gut 2004)
• Gravedad de la inflamación en EC– Intestino delgado: RR 66.7 (18.1-170.7) (Ekbom. Lancet
1990)
– Enfermedad perianal
Iniciales neg: colectomía por mayor gravedad y series retrospectivas BACKGROUND & AIMS: Patients with ulcerative colitis are at increased risk of colorectal cancer. It is widely believed that this is secondary to colonic inflammation. However, the severity of colonic inflammation has never been shown to be a risk factor. METHODS: We devised a case-control study of patients with long-standing extensive ulcerative colitis to examine various potential risk factors for neoplasia. All cases of colorectal neoplasia detected from our surveillance program between January 1, 1988, and January 1, 2002, were studied (n = 68). Each patient was matched with 2 control patients from the same surveillance population (n = 136). Matching was for sex, colitis extent, age at onset, duration of colitis, and year of index surveillance colonoscopy. Segmental colonoscopic and histological inflammation was recorded by using a simple score (0, normal; 1, quiescent/chronic inflammation; and 2, 3, and 4, mild, moderate, and severe active inflammation, respectively). Other data collected included history of primary sclerosing cholangitis, family history of colorectal cancer, and smoking and drug history (mesalamine 5-aminosalicylic acid, azathioprine, and folate). RESULTS: Univariate analysis showed a highly significant correlation between the colonoscopic (odds ratio, 2.5; P = 0.001) and histological (odds ratio, 5.1; P < 0.001) inflammation scores and the risk of colorectal neoplasia. No other factors reached statistical significance. On multivariate analysis, only the histological inflammation score remained significant (odds ratio, 4.7; P < 0.001). CONCLUSIONS: In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia. Endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs En EC convincing association between inflmmation and cancer. Small bowel adenoca extremely rare pero en un apoblacion de EC aumento de 60 veces. Tb en enf perianal
• Tratamiento médico:
QUIMIOPROFILAXIS
Factores de riesgo de displasia en la EII
Iniciales neg: colectomía por mayor gravedad y series retrospectivas BACKGROUND & AIMS: Patients with ulcerative colitis are at increased risk of colorectal cancer. It is widely believed that this is secondary to colonic inflammation. However, the severity of colonic inflammation has never been shown to be a risk factor. METHODS: We devised a case-control study of patients with long-standing extensive ulcerative colitis to examine various potential risk factors for neoplasia. All cases of colorectal neoplasia detected from our surveillance program between January 1, 1988, and January 1, 2002, were studied (n = 68). Each patient was matched with 2 control patients from the same surveillance population (n = 136). Matching was for sex, colitis extent, age at onset, duration of colitis, and year of index surveillance colonoscopy. Segmental colonoscopic and histological inflammation was recorded by using a simple score (0, normal; 1, quiescent/chronic inflammation; and 2, 3, and 4, mild, moderate, and severe active inflammation, respectively). Other data collected included history of primary sclerosing cholangitis, family history of colorectal cancer, and smoking and drug history (mesalamine 5-aminosalicylic acid, azathioprine, and folate). RESULTS: Univariate analysis showed a highly significant correlation between the colonoscopic (odds ratio, 2.5; P = 0.001) and histological (odds ratio, 5.1; P < 0.001) inflammation scores and the risk of colorectal neoplasia. No other factors reached statistical significance. On multivariate analysis, only the histological inflammation score remained significant (odds ratio, 4.7; P < 0.001). CONCLUSIONS: In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia. Endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs En EC convincing association between inflmmation and cancer. Small bowel adenoca extremely rare pero en un apoblacion de EC aumento de 60 veces. Tb en enf perianal
INICIO INTERVALO (10-20 AÑOS)
INTERVALO (>20 AÑOS)
ECCO (2008) 8-10 años 2 años 1-2 años
AEG (2009) 8-10 años 3 años 2 años
OMC (2009) 8-10 años 2 años 1 año
AGA (2010) 8 años 1-3 años 1-3 años
Despistaje de displasia
AGA (2010) 8 años 1-3 años 1-3 años
S. Británica (2010) 10 años 3-5 años 3-5 años
GETECCU 10 años 2 años 2 años
*Desde el diagnóstico y anualmente si CEP asociada
Displasia y CCR en EII
Frecuencia
Factores de riesgo
FisiopatologíaFisiopatología
Clasificación e historia natural
Tratamiento profiláctico
Tratamiento de la displasia
Fisiopatología
Mucosa normal
Adenoma incipiente
Adenoma intermedio
Adenoma tardío CARCINOMA
CCR ESPORÁDICO
APC
AneuploidíaMetilación
IMSK-rasCOX-2
C-src DCC/DPC4
P-53
Negativo para
displasia
Indefinido para
displasia
Displasia de bajo grado
Displasia de alto grado CARCINOMA
CANCER ASOCIADO A EII
P53mut
AneuploidíaMetilación
IMSCOX-2
P53PH
DCC C-src K-ras APC
Displasia y CCR en EII
Frecuencia
Factores de riesgo
FisiopatologíaFisiopatología
Clasificación e historia natural
Tratamiento profiláctico
Tratamiento de la displasia
Clasificación Macroscópica
Dysplasia
Flat Raised
Adenoma-like
DALM
Non-adenoma-like
DALMAdenoma
Harpaz. Arch Pathol Lab Med 2010
Grossly adenoma-like DALMs represent well-circumscribed, smooth or papillary, nonnecrotic, sessile, or pedunculated polyps that, similar to sporadic adenomas (Figure 3A and B), are usually readily amenable to removal by routine endoscopic methods (Table 4).79,117 Other synonyms used to describe this lesion include adenoma-like polyp, adenoma-like dysplastic polyp, polypoid dysplasia, and adenoma-like mass. Non–adenoma-like lesions (Figure 4A and B) include velvety patches, plaques, irregular bumps and nodules, wart-like thickenings, stricturing lesions, and broad-based masses.59,60,74,80,82 Non–adenomalike DALMs are not usually amenable to removal by colonoscopic polypectomy. Unfortunately, there are little data on the incidence of cancer as it relates to the different gross subtypes of non–adenoma-like DALMs, and this is an area in need of further research.
Clasificación Microscópica
Negativo para displasia
Positivo para displasia: • Displasia de alto grado
Negativo para displasia
Indefinido para displasia
Displasia de bajo grado
CLASIFICACIÓN DE RIDDELL CLASIFICACIÓN DE VIENNA
• Displasia de alto grado• Displasia de bajo grado
Indefinido para displasia
Adenocarcinoma
(Riddell. Hum Pathol 1983)
(Schlemper. Gut 2000)
Displasia de bajo grado
Displasia de alto grado• Adenoma/displasia de alto grado• Carcinoma in situ• Sospecha de carcinoma invasivo
Neoplasia
Microscopically, dysplastic changes in UC are separated into 3 morphologic categories: negative (regenerating epithelium), indefinite, and positive for dysplasia (low and high grade).75 This microscopic classification system has formed the basis for most retrospective and prospective studies that have evaluated the biologic characteristics, natural history, and treatment of IBD-related precursor lesions. This is a classification system based primarily on observations made by dedicated gastrointestinal pathologists with extensive experience related to IBD. In 1998, an alternative classification system for dysplasia in the gastrointestinal tract was developed with the hope that it would standardize, and help resolve, differences in interpretation and terminology between Western and Japanese pathologists.84 This new classification system was developed in Vienna (termed the “Vienna classification”) and uses 5 diagnostic categories as outlined in Table 2. It is used by pathologists in many European countries, and in Japan, but has yet to be commonly accepted in the United States. In brief, the Vienna classification system84 is similar to the one proposed by Riddell et al in 198375 except that the former uses the term “noninvasive neoplasia” instead of “low- or highgrade dysplasia” and also uses the term “suspicious for invasive carcinoma” for neoplastic lesions that have some cytologic and/or architectural features of invasion but in which the invasive component cannot be demonstrated unequivocally by histologic evaluation. Differences among Western and Japanese pathologists relate to interpretation of nuclear features in neoplastic lesions.85 However, there are no clinically important differences between these 2 classification systems.
LGD: Low-grade dysplasia. A, Surface and superficial crypt epithelium containing uniform, elongated, crowded, basally located nuclei and sparse mucin vacuoles. B, Dysplasia-associated lesion or mass with villous architecture illustrating maturation of dysplastic epithelium at the villous tips. C, Surface and crypt epithelium with hyperchromatic, mildly pleomorphic nuclei. A disorderly pattern of goblet cell vacuoles in the absence of active inflammation serves as a clue to the diagnosis. D, Surface and crypt epithelium with hyperchromatic, pleomorphic, crowded nuclei and no surface maturation. E, Eosinophilic surface and crypt epithelium with striking absence of goblet cells. F, Crypt epithelium with hyperchromatic, enlarged nuclei and numerous dystrophic goblet cells (
High-grade dysplasia (HGD). A, Nuclear stratification, a manifestation of loss of cellular polarity, is a hallmark of HGD. B, Despite preserved epithelial cell polarity in a few of the crypts, most of the epithelium shows nuclear stratification. C, Marked nuclear atypism warrants classification as HGD. D, Another example of HGD featuring nuclear stratification and pleomophism
Indefinite for dysplasia. A, In this inflamed mucosa, the crypt on the right features nuclear atypism and crowding, but there are indications that this may be a regenerative change. First, the atypism and crowding dissipate toward the surface. Second, the crypt left of center is lined by epithelium with regenerative features including low nuclear to cytoplasmic ratios and eosinophilic cytoplasm. Third, the surface epithelium is mature, especially on the left. B, Actively inflamed mucosa with crowded, hyperchromatic nuclei and inconspicuous goblet cells. Maturation cannot be evaluated because the surface epithelium is absent. C, This actively inflamed mucosa features mildly crowded but normochromatic nuclei, small mucin vacuoles throughout, evidence of surface maturation in the crypt on the left, and regenerative surface features. The changes were subclassified as probably negative. D, Atypical regenerative epithelium with several regions of nuclear crowding and hyperchromasia and intervening bland epithelium
Historia naturalLow-grade
tubuloglandularadenocarcinoma
Negative Indefinitedysplasia
Low-grade dysplasia
High-grade dysplasia
Conventionaladenocarcinoma
No siempre es así…ca sin displasia previa, cáncer sin displasia concomitante, no todas la LGD evolucionan a HGD. Recientemente, se ha descrito un tipo de CCR asociado a CU: Understanding the natural history of dysplasia is important for determining the outcome and success of surveillance. It has long been assumed that colon carcinogenesis in IBD follows a sequential progression from inflammation to dysplasia (low grade then high grade) and, finally, invasive cancer. Although this model is conceptually useful and serves as a reasonable paradigm, it is by no means absolute. There are instances in which patients who have undergone regular colonoscopic surveillance developed CRC without any prior history of dysplasia.73 Also, at the time of colectomy for CRC, concurrent dysplasia may be absent in up to 25% of cases.108–110 Similarly, not all cases of LGD progress through a stage of detectable HGD before developing cancer.66,71,111 This disconcerting fact may be explained, at least in part, by the recent recognition of a type of colitis-associated CRC, termed low-grade tubuloglandular adenocarcinoma. This type of invasive cancer seems to arise directly from LGD and is characterized by the presence of deceptively benign-appearing glands that lack a desmoplastic stromal reaction in the invasive component. This tumor may account for up to 10% of all CRC cases in IBD.106 These examples highlight the limitations in predicting the natural history of dysplasia in UC.
• Interpretación correcta de la displasia• Displasia prevalente vs incidente• Displasia recurrente
Historia natural
• Displasia recurrente• Focalidad de la displasia
Riesgo de progresión de la displasia
Riesgo de desarrollar CCR en pacientes con displasia de bajo grado
OR 9 (IC 95% 4.0,20.5)
Thomas T. Alimentary Pharmacol Therapeutic 2007;25:657-68
Riesgo de progresión de la displasia
NNC 8 CCRNNC 6 DAG
5,2 años
Riesgo de desarrollar DAG ó CCR en pacientes con displasia de bajo grado
Thomas T. Alimentary Pharmacol Therapeutic 2007;25:657-68
OR 11.9 (IC 95% 5.2,27)
BACKGROUND: The cancer risk of low-grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious. AIM: To determine the risk of cancer or any advanced lesion once LGD is diagnosed. METHODS: A MEDLINE, EMBASE and Pub Med search was conducted using the key words 'surveillance', 'colorectal cancer', 'low-grade dysplasia' and 'ulcerative colitis'. A random effects model of meta-analysis was used. RESULTS: Twenty surveillance studies had 508 flat LGD or LGD with dysplasia-associated lesion or mass. An average of 4.3 colonoscopies was performed/patient post-LGD diagnosis (range: 3-7.6). An average of 18 biopsies taken per colonoscopy (range: 9-24) detected 73 advanced lesions (cancer or high-grade dysplasia) pre-operatively. The cancer incidence was 14 of 1000 (95% CI: 5.0-34) person years duration (pyd) and the incidence of any advanced lesion was 30 of 1000 pyd (95% CI: 12-76). When LGD is detected on surveillance there is a ninefold risk of developing cancer (OR: 9.0, 95% CI: 4.0-20.5) and 12-fold risk of developing any advanced lesion (OR: 11.9, 95% CI: 5.2-27). CONCLUSIONS: The risk of developing cancer in patients with LGD is high. These estimates are valuable for decision-making when LGD is encountered on surveillance.
• St Mark’s Hospital (Connell. Gastroenterology 1994)
– N=249 LGD– N=52 no displasiaRevisión “a ciegas” :
Historia natural: Interpretación correcta
Revisión “a ciegas” :249 LGD: 16% evolucionan a HGD o CCRLGD “verdaderas”: 54% evolucionan a HGD o CCR
Needless to say, correct pathologic interpretation of dysplasia influences the subsequent “natural history” of neoplasia in any given patient. The importance of accurate histologic interpretation with respect to subsequent clinical outcome is highlighted by the long-term prospective surveillance study from St Mark’s Hospital, which began enrolling patients in 1971.108 In that study, all available biopsy specimens showing dysplasia (n 249) and a sample of biopsy specimens showing no dysplasia (n 52) were blindly reviewed using the 1983 IBD Morphology Study Group criteria, and outcomes of patients were analyzed according to both the original and the revised histologic diagnosis. Among patients in whom LGD was diagnosed in flat mucosa during any examination using the original diagnostic scheme, the cumulative 5-year rate of progression to HGD or CRC was 16%. By excluding cases that were deemed nondysplastic, the revised cumulative 5-year rate of progression to HGD or CRC increased to 54%. Importantly, of the 73 biopsy specimens originally interpreted as LGD before 1983, only 5 were considered to be definitely dysplastic on later review; of the 34 biopsy specimens interpreted as LGD, only 17 (50%) were considered truly dysplastic upon re-review. Indefinite dysplasia is a histologic diagnosis with its
• En colonoscopia inicial, progresión a CCR: 13-18% (Rutter. Gastroenterology 2006)
• En colonoscopias de seguimiento, progresión a CCR: 28% (Bernstein. Lancet 1994)
Historia natural: Displasia indeterminada
• DD entre epitelio “reactivo” y LGD: – Aumento del tamaño de núcleos– Estratificación nuclear– Nucleolos prominentes– Hipercromatismo– Mitosis
Indefinite dysplasia is a histologic diagnosis with its own natural history. When indefinite for dysplasia is detected on initial colonoscopy, progression to advanced neoplasia occurs in approximately 13% to 18%.6,64 When indefinite for dysplasia was found at some time during surveillance, the progression rate was 28%.64 In a study from Mount Sinai Hospital in New York, the 5-year rate of progression to either HGD or CRC was 1.1%, 9%, and 45% in patients who initially had no dysplasia, indefinite for dysplasia, and LGD, respectively.112 Overall, determination of the grade of dysplasia is performed on the basis of a combination of microscopic features, including architectural alterations of the crypts and cytologic abnormalities of the dysplastic cells. Reactive (regenerating) epithelium, located in areas of inactive or active colitis, is categorized as negative for dysplasia. Regenerative features are often prominent in the presence of fresh erosions or ulcerations. Unfortunately, regenerating epithelium may acquire some cytologic features that mimic dysplasia and may, on occasion, cause difficulty in pathologic differentiation from true dysplasia. In this circumstance, the category of indefinite for dysplasia is used, which implies that definite distinction between markedly reactive epithelium and truly dysplastic epithelium cannot be established with complete certainty on the basis of the tissue available for analysis. For instance, regenerating epithelial cell nuclei are often enlarged and more variable in size, show nuclear stratification, vesicular nuclei, prominent nucleoli, increased hyperchromatism, and more abundant mitoses, features that overlap with true LGD. Although surface maturation, which corresponds to the progressive acquisition of cytoplasmic mucin in cells located close to, and on, the luminal surface, is a feature commonly assumed to represent evidence in favor of regeneration, true dysplasia may also, rarely, show evidence of surface maturation as well.76 Cases are best considered indefinite for dysplasia when the cytologic and architectural features approach that ofLGD but, due to the presence of active inflammation or ulceration in the area, the observer is uncertain as to the neoplastic status of the tissue. Other potential reasons why pathologists may use the category of indefinite for dysplasia include instances in which epithelium shows unusual growth patterns or has processing or sectioning artifact that makes interpretation difficult. In the original standardized classification for dysplasia proposed in 1983, the indefinite for dysplasia category was further subdivided into “probably negative” or “probably positive.” 75 This subdivision has not been used among expert gastrointestinal pathologists in recent years. True dysplasia is categorized as low or high
• Prevalente: progresión a HGD (29%) o CCR (13%)• Incidente: progresión a HGD (16%) o CCR (8%)(Bernstein. Lancet 1994)
• Recurrente: (Woolrich. Gastroenterology 1992)
– N=22
Historia natural: Displasia prevalente vs incidente. Displasia recurrente. Focalidad
– N=22– A los 2 años:
• 7 (31%) con displasia (4 LGD, 2 HGD, 1 CCR)• 15 (69%) sin displasia. A los 7 años: 6 desarrollaron
HGD o CCR• Focalidad: Unifocal/Multifocal. Hª natural desconocida
Prevalent versus incident dysplasia. There may be an important difference in natural history depending on whether dysplasia is prevalent or incident. Patients who demonstrate prevalent dysplasia (that which is found on the initial, screening colonoscopy) have shown a higher rate of progression to CRC compared to patients whose dysplasia is detected during the course of surveillance colonoscopy (incident dysplasia). A review of 10 prospective studies reported that when LGD was found at initial surveillance colonoscopy (prevalent LGD), HGD or CRC developed in 16 of 55 patients (29%) at some time during further follow-up, with CRC developing in 7 (13%).64 However, if LGD was found during surveillance (incident LGD), only 33 of 204 patients (16%) progressed to either HGD or CRC, with 17 (8%) progressing to CRC. For comparison, when no dysplasia is found on initial colonoscopy, the rate of subsequent progression to CRC ranges from 1.1% to 3.1%.64,108,111,113 Recurrent dysplasia. Many clinicians are reluctant to recommend colectomy for LGD unless it is detected on at least one other subsequent surveillance colonoscopy. This raises the question as to whether colitis- associated dysplasia can spontaneously regress. Certainly, the finding of recurrent LGD raises concern that the colon is at increased risk for HGD/CRC, and although some studies have used this as an indication for colectomy,108 others have not.114 Given the limitations of detecting LGD, it is conceivable that even with careful surveillance, recurrent LGD may be missed. Thus, after detection of LGD on one examination, does not finding LGD on subsequent examinations offer any reassurance that the colon is truly at a lower risk for neoplasia? Few studies have addressed this issue. Woolrich et al retrospectively reviewed their series of patients who underwent surveillance colonoscopy for UC.73 Among 22 patients who had LGD on initial colonoscopy after 7 years of UC, 7 (31%) continued to have dysplasia (4 LGD, 2 HGD, 1 CRC) on their second surveillance colonoscopy within 2 years, but 15 (69%) had no dysplasia on their second colonoscopy. Of the latter group, 6 (40%) still went on to develop subsequent dysplasia (3 recurrent LGD, 3 CRC at 5–10 years without intervening HGD). Ullman also reported several patients with flat LGD who had a second surveillance examination negative for dysplasia, yet HGD or CRC subsequently developed upon follow-up.71 In contrast, a Swedish prospective surveillance study, in which progression rates from LGD to HGD or cancer were extremely low, reported that 16 of 60 patients (27%) with LGD had no further LGD despite a mean of 6 follow-up colonoscopies.114 Focality of dysplasia. It is sometimes casually assumed that a colon manifesting only one area of dysplasia (unifocal dysplasia) would be at a lower risk for developing CRC than if more than one dysplastic focus (multifocal dysplasia) is detected. Unifocal dysplasia is more common than multifocal dysplasia.60,115 Few studies have reported the outcome of patients based on the focality of dysplasia. In general, if multifocal dysplasia is detected, even on one colonoscopic examination, (and especially if any biopsy site manifests HGD), colectomy is often recommended. However, the natural history of multifocal LGD is not known. A recent study specifically addressed focality of LGD, and found that the overall 53% 5-year progression rate of flat LGD to either HGD or CRC was nearly identical among the 39 patients with unifocal LGD and the 7 patients with multifocal LGD.116 Until more data are acquired on this issue, unifocal flat LGD should not be discounted.
Displasia y CCR en EII
Frecuencia
Factores de riesgo
FisiopatologíaFisiopatología
Clasificación e historia natural
Tratamiento profiláctico
Tratamiento de la displasia
Imposibilidad de estudios 5-ASA vs
placebo
Imposibilidad de estudios 5-ASA vs
placebo
Eficacia para mantener remisión
Eficacia para mantener remisión
5260 pacientes durante 10 años para
demostrar eficacia
5260 pacientes durante 10 años para
demostrar eficacia
Tratamiento profiláctico. Quimioprevención: 5-ASA
Estudios epidemiológicos
Estudios epidemiológicos
Estudios experimentales
Estudios experimentales Estudios clínicosEstudios clínicos
36000 pacientes/brazo para comparar 2.4 vs 4.8
36000 pacientes/brazo para comparar 2.4 vs 4.8
Quimioprevención: 5-ASA
Velayos. AJG 2005
FIGURE 2. Odds ratios for the effect of 5-aminosalicylic acid on the development of (A) colorectal cancer/dysplasia or (B) colorectal cancer alone.** Reproduced with permission from Blackwell Publishing (2005).31 *All cancer patients in the study by Rutter et al had taken 5-ASA for at least 3 months and therefore there was no reference group; †only unadjusted odds ratio reported; ‡number of cancer cases/number of dysplasia cases; OR, odds ratio; CI, confidence interval. Multiple studies have assessed the utility of 5-ASA in preventing dysplasia and cancer in patients with UC, whereas fewer studies have assessed this endpoint in patients with CD. Looking across the UC studies, a recent meta-analysis of 9 observational studies involving a total of 1932 patients reported a protective association between 5-ASA use and CRC (OR 0.51; 95% CI: 0.37– 0.69) or a combined endpoint of CRC and dysplasia (OR 0.51; 95% CI: 0.38–0.69; Fig. 2),10,13,27,31–37 which equates to a 49% reduction in the risk of CRC or CRC/dysplasia with regular 5-ASA use. The derivative studies generally reported similar findings, even though they were subject to their own unique limitations and strengths in how they were performed. Even with these supporting data, several questions still Inflamm Bowel Dis ? Volume 14, Number 2, February 2008 Colorectal Cancer in IBD 269 need to be addressed. First, should all UC patients be taking 5-ASA to reduce the risk of cancer? At present, less information is available regarding chemopreventive action of other IBD therapies compared with that of 5-ASA, and it is currently unclear whether a patient receiving another treatment (e.g., azathioprine) would benefit from additional 5-ASA in terms of chemoprevention. Second, is one 5-ASA therapy better than another? As already stated, some studies have shown a difference between sulfasalazine and mesalamine in CRC risk reduction.13,15,38 It is possible, however, that sociodemographic factors may have had a bearing on this effect. For example, sulfasalazine is cheaper than most mesalamine formulations. Hence, cost may influence prescribing decisions. Also, sulfasalazine has been available for more than 60 years, whereas the newer mesalamine formulations were only introduced in the early 1990s. Sulfasalazine users may therefore be older than mesalamine users and have other factors that may make them at higher risk of developing CRC. Because sulfasalazine inhibits the absorption of folate39 and folate deficiency may be associated with a higher risk of sporadic colon cancer,40 it is also possible that the lack of a chemopreventive effect with sulfasalazine may be a result of reduced folate. Third, what is the optimal 5-ASA dose for chemoprevention? Two studies have found a dose–response in which the odds of CRC or dysplasia/CRC decreased as the total dose of 5-ASA increased.15,35 In both studies, 5-ASA doses equivalent to mesalamine of at least 1.2 g/day provided the greatest risk reduction (72%–81%). However, these studies assessed dose–response in different ways, making it difficult to interpret the data as whole. Finally, how important is prevention of dysplasia relative to prevention of cancer? Some studies have assessed both parameters as a combined endpoint,31 which makes it difficult to determine the relative importance of preventing dysplasia compared with CRC. Nevertheless, the vast majority of IBD patients who develop CRC will first develop dysplasia, and because dysplasia can be monitored and a colectomy can be performed prior to CRC development, dysplasia may be the more relevant endpoint. Approximately 10 studies between 1996 and 2006 have looked at the association between 5-ASA use and a potentially protective effect against colorectal cancer. These studies have yielded conflicting results and as a result a consensus on their therapeutic potential are lacking. All studies of 5-ASA have inherent flaws due to the ethical constraints a randomized control trial would pose by withholding a potentially beneficial treatment. Conclusions from observational studies have been mixed. All 10 studies had relatively small sample sizes and hence lacked statistical power, limiting the ability to perform meaningful subgroup analyses. Given the criticisms of the various studies noted above, a meta-analysis was performed in 2005 by Velayos et al12 This had the benefit of providing a pooled estimate (and hence increased statistical power) as well as allowing for the measurement of other clinically important treatment variables such as duration of treatment, compliance with treatment, and 5-ASA dosage. The authors performed a comprehensive literature search between the years of 1996 and 2004. They found 9 studies that met the criteria of evaluating and clearly defining exposure to 5-ASA in UC patients. They reported CRC or dysplasia outcomes and RRs or ORs in their calculations. The 9 studies included 3 cohort and 6 case-control studies, contained 334 cases of CRC, 140 cases of dysplasia, and a total of 1932 subjects who satisfied all inclusion criteria. Use of 5-ASA was clearly associated with a lower risk of CRC (OR 0.51, 95% CI 0.37– 0.69) and CRC and dysplasia combined (OR 0.51, CI 0.38–0.69). Interestingly, the study showed no benefit of 5-ASA on the endpoint of dysplasia Levine and Burakoff Inflamm Bowel Dis ? Volume 13, Number 10, October 2007 1294 alone (OR 1.18, CI 0.41–3.43). The authors ascribed this inconsistency to the smaller number of available studies looking at an endpoint of just dysplasia.12
Quimioprevención: 5-ASA
Velayos. AJG 2005
FIGURE 2. Odds ratios for the effect of 5-aminosalicylic acid on the development of (A) colorectal cancer/dysplasia or (B) colorectal cancer alone.** Reproduced with permission from Blackwell Publishing (2005).31 *All cancer patients in the study by Rutter et al had taken 5-ASA for at least 3 months and therefore there was no reference group; †only unadjusted odds ratio reported; ‡number of cancer cases/number of dysplasia cases; OR, odds ratio; CI, confidence interval. Multiple studies have assessed the utility of 5-ASA in preventing dysplasia and cancer in patients with UC, whereas fewer studies have assessed this endpoint in patients with CD. Looking across the UC studies, a recent meta-analysis of 9 observational studies involving a total of 1932 patients reported a protective association between 5-ASA use and CRC (OR 0.51; 95% CI: 0.37– 0.69) or a combined endpoint of CRC and dysplasia (OR 0.51; 95% CI: 0.38–0.69; Fig. 2),10,13,27,31–37 which equates to a 49% reduction in the risk of CRC or CRC/dysplasia with regular 5-ASA use. The derivative studies generally reported similar findings, even though they were subject to their own unique limitations and strengths in how they were performed. Even with these supporting data, several questions still Inflamm Bowel Dis ? Volume 14, Number 2, February 2008 Colorectal Cancer in IBD 269 need to be addressed. First, should all UC patients be taking 5-ASA to reduce the risk of cancer? At present, less information is available regarding chemopreventive action of other IBD therapies compared with that of 5-ASA, and it is currently unclear whether a patient receiving another treatment (e.g., azathioprine) would benefit from additional 5-ASA in terms of chemoprevention. Second, is one 5-ASA therapy better than another? As already stated, some studies have shown a difference between sulfasalazine and mesalamine in CRC risk reduction.13,15,38 It is possible, however, that sociodemographic factors may have had a bearing on this effect. For example, sulfasalazine is cheaper than most mesalamine formulations. Hence, cost may influence prescribing decisions. Also, sulfasalazine has been available for more than 60 years, whereas the newer mesalamine formulations were only introduced in the early 1990s. Sulfasalazine users may therefore be older than mesalamine users and have other factors that may make them at higher risk of developing CRC. Because sulfasalazine inhibits the absorption of folate39 and folate deficiency may be associated with a higher risk of sporadic colon cancer,40 it is also possible that the lack of a chemopreventive effect with sulfasalazine may be a result of reduced folate. Third, what is the optimal 5-ASA dose for chemoprevention? Two studies have found a dose–response in which the odds of CRC or dysplasia/CRC decreased as the total dose of 5-ASA increased.15,35 In both studies, 5-ASA doses equivalent to mesalamine of at least 1.2 g/day provided the greatest risk reduction (72%–81%). However, these studies assessed dose–response in different ways, making it difficult to interpret the data as whole. Finally, how important is prevention of dysplasia relative to prevention of cancer? Some studies have assessed both parameters as a combined endpoint,31 which makes it difficult to determine the relative importance of preventing dysplasia compared with CRC. Nevertheless, the vast majority of IBD patients who develop CRC will first develop dysplasia, and because dysplasia can be monitored and a colectomy can be performed prior to CRC development, dysplasia may be the more relevant endpoint. Approximately 10 studies between 1996 and 2006 have looked at the association between 5-ASA use and a potentially protective effect against colorectal cancer. These studies have yielded conflicting results and as a result a consensus on their therapeutic potential are lacking. All studies of 5-ASA have inherent flaws due to the ethical constraints a randomized control trial would pose by withholding a potentially beneficial treatment. Conclusions from observational studies have been mixed. All 10 studies had relatively small sample sizes and hence lacked statistical power, limiting the ability to perform meaningful subgroup analyses. Given the criticisms of the various studies noted above, a meta-analysis was performed in 2005 by Velayos et al12 This had the benefit of providing a pooled estimate (and hence increased statistical power) as well as allowing for the measurement of other clinically important treatment variables such as duration of treatment, compliance with treatment, and 5-ASA dosage. The authors performed a comprehensive literature search between the years of 1996 and 2004. They found 9 studies that met the criteria of evaluating and clearly defining exposure to 5-ASA in UC patients. They reported CRC or dysplasia outcomes and RRs or ORs in their calculations. The 9 studies included 3 cohort and 6 case-control studies, contained 334 cases of CRC, 140 cases of dysplasia, and a total of 1932 subjects who satisfied all inclusion criteria. Use of 5-ASA was clearly associated with a lower risk of CRC (OR 0.51, 95% CI 0.37– 0.69) and CRC and dysplasia combined (OR 0.51, CI 0.38–0.69). Interestingly, the study showed no benefit of 5-ASA on the endpoint of dysplasia Levine and Burakoff Inflamm Bowel Dis ? Volume 13, Number 10, October 2007 1294 alone (OR 1.18, CI 0.41–3.43). The authors ascribed this inconsistency to the smaller number of available studies looking at an endpoint of just dysplasia.12
RR de displasia o cáncer ursodesoxicólicovsplacebo: 0.26 (95%CI: 0.06-0.92) p=0.034
Ursodeoxycholic acid, a synthetic bile acid that has been shown to positively influence the progress of liver disease in primary sclerosing cholangitis (PSC) patients, has been recently studied as a chemoprophylactic agent for patients with UC and concomitant primary sclerosing cholangitis. Its chemoprotective effect is exerted in several ways. First, ursodiol reduces the colonic concentration of deoxycholic acid, which is a procarcinogenic secondary bile acid to the colonic epithelia.25 Second, ursodiol has been shown to block 2 separate neoplastic pathways that are perturbed in UC: modulating protein kinase C and phospholipase A2 expression.26 Both of these pathways have been associated with CRC formation in both rat and human models. Lastly, ursodiol is an established antioxidant, which stabilizes the mitochondrial membrane and prevents oxidative injury to DNA.27 Tung et al23 performed a cross-sectional survey on 59 patients with both UC and PSC who were undergoing colonoscopic surveillance. In their study, the use of ursodiol was associated with a significantly lower prevalence of having colonic dysplasia (OR 0.18) compared with those not taking the drug. The reduced prevalence was found even when data were adjusted for the use of sulfasalazine or 5-ASA. Pardi et al24 took a subset of patients from a study they were performing on PSC patients in an attempt to show the influence of ursodiol on liver disease. The original study used a dose of ursodiol of 13–15 mg/kg.28 From this cohort, 85 patients were randomized to receive either ursodiol or placebo. Patients were treated with ursodiol for a median of 42 months and with placebo for 40 months. Colonoscopic surveillance was well matched in the 2 groups in terms of frequency, biopsy/colonoscopy, and the median time between surveillance. Neoplasia developed in 3 patients (10%) assigned to the treatment group and in 8 patients initially assigned to the placebo arm (35%). The relative risk for dysplasia or cancer for patients in the ursodiol arm compared to placebo was 0.26 (95% CI 0.06–0.92, P 0.034), showing a significant protective effect with ursodiol. The findings matched well with the results from Tung et al. While the protective effects in combined UC and PSC patients are increasingly accepted, a trial with UC patients without PSC has yet to be conducted. Pardi: Background & Aims: Ursodeoxycholic acid (UDCA) has shown effectiveness as a colon cancer chemopreventive agent in preclinical studies. In addition, a recent report suggests that it also may decrease the risk for developing colorectal dysplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We sought to evaluate the effect of UDCA on colorectal neoplasia in a group of patients with UC and PSC enrolled in a randomized, placebo-controlled trial. Methods: From a prior, randomized, placebo-controlled trial of UDCA therapy in PSC at our center, we followed-up patients with concomitant UC to assess the effect of UDCA on the development of colorectal dysplasia and cancer as compared with placebo. Results: Fifty-two subjects were followed-up for a total of 355 person-years. Those originally assigned to receive UDCA had a relative risk of 0.26 for developing colorectal dysplasia or cancer (95% confidence interval, 0.06-0.92; P = 0.034). Many of the patients originally assigned to the placebo group eventually received open-label UDCA. Assigning these patients to the UDCA group from the time they began active therapy did not change the magnitude of the protective effect (relative risk, 0.26; 95% confidence interval, 0.07-0.99; P = 0.049). Conclusions: UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC.
Quimioprevención: Ácido fólico
• Papel central en la metilación y síntesis de nucleótidos.• Implicación en la carcinogénesis de diversos tumores,
especialmente el CCR.• Deficiencia crónica relacionada con incremento del riesgo de
CCR. Ingesta elevada relacionada con disminución del riesgo CCR. Ingesta elevada relacionada con disminución del riesgo de adenomas y CCR. (Giovannucci. J Nutr 2002)
• En ausencia de estado carencial, puede promover la progresión de lesiones paraneoplásicas o neoplásicas (Kim. Cancer Epidemiol Biomarkers Prev. 2008)
Nutritional folate supplementation has been studied in both animal models and humans as a potential prophylactic agent. Folate has a central role in biological methylation and nucleotide synthesis and it is felt that low levels increase cancer risk by alteration of the normal DNA methylation process, causing an imbalance of the steady-state levels of DNA precursors as well as changes in chromatin. DNA methylation status is also involved with cell cycle control and has been shown to be a factor in prohibiting unchecked cell turnover.29 Dietary intake and blood levels of folate have been shown to be inversely associated with the risk of developing sporadic colorectal cancer or adenoma.29,30 These studies suggest an 40% reduction in the risk of CRC in individuals with the highest dietary intake of folate compared with those with the lowest intake. Folate supplementation in UC may be particularly indicated for 2 reasons. First, sulphapyridin, a moiety of sulfaslazine, is a competitive inhibitor of folate absorption, thus causing an imbalance between the antiinflammatory effect and the procarcinogenic effect of folate deficiency.31 Rutter et al4 performed a subanalysis on data they had obtained examining various potential risk factors for neoplasia. Their results showed a nonsignificant trend toward an increased risk of colorectal neoplasia among sulfasalazine users (whereas users of other types of mesalamine did not show this trend). Second, symptomatic UC may be a direct cause of folate deficiency by causing inadequate nutritional intake in patients (secondary to anorexia) and increased malabsorption of many nutrients, including folate, in patients with active disease.25 Lashner et al performed the first studies specifically looking at the effects on carcinogenesis in UC patients. A cohort study from 1989 by Lashner et al32 showed a nonstatistically significant association with folate use and reduced dysplasia risk. Interpretation was limited by insufficient information regarding duration of surveillance, duration of folate supplementation, and actual measurements of red blood cell folate levels. Also, there was no demonstration of a dose–response effect, raising the question of whether a threshold level existed. In 1997 Lashner et al33 performed a retrospective cohort study evaluating 98 patients with longterm UC (defined as greater than 6 years). Documented folic acid supplementation was also an inclusion criterion and analyzed as a dichotomous variable with use for at least 6 months compared to less than 6 months or no use. Of the cohort, the total adjusted relative risk of patients taking folate was 0.72 (P 0.042, 95% CI 0.28 –1.23). More important, there was a dose–response relationship, with a dose of 0.4 Levine and Burakoff Inflamm Bowel Dis ? Volume 13, Number 10, October 2007 1296 mg/day having a relative risk of 0.76 and a dose of 1 mg/day having a relative risk of 0.4.
Quimioprevención: Ácido fólico
• Estudio retrospectivo de cohortes• N=98 pacientes con CU de larga evolución• Tratamiento con ác. fólico al menos 6 meses• Disminución no significativa del riesgo de displasia o CCR del
28% (RR ajustado=0.72; 95%CI:0.28-1.23)28% (RR ajustado=0.72; 95%CI:0.28-1.23)• Efecto dosis-respuesta. Efecto máximo con 1g/d vs 0.4g/d
(RR=0.4; 95%CI: 0.20-1.48) vs (RR=0.76;95%CI:0.36-1.61)
Lashner. Gastroenterology 1997
Nutritional folate supplementation has been studied in both animal models and humans as a potential prophylactic agent. Folate has a central role in biological methylation and nucleotide synthesis and it is felt that low levels increase cancer risk by alteration of the normal DNA methylation process, causing an imbalance of the steady-state levels of DNA precursors as well as changes in chromatin. DNA methylation status is also involved with cell cycle control and has been shown to be a factor in prohibiting unchecked cell turnover.29 Dietary intake and blood levels of folate have been shown to be inversely associated with the risk of developing sporadic colorectal cancer or adenoma.29,30 These studies suggest an 40% reduction in the risk of CRC in individuals with the highest dietary intake of folate compared with those with the lowest intake. Folate supplementation in UC may be particularly indicated for 2 reasons. First, sulphapyridin, a moiety of sulfaslazine, is a competitive inhibitor of folate absorption, thus causing an imbalance between the antiinflammatory effect and the procarcinogenic effect of folate deficiency.31 Rutter et al4 performed a subanalysis on data they had obtained examining various potential risk factors for neoplasia. Their results showed a nonsignificant trend toward an increased risk of colorectal neoplasia among sulfasalazine users (whereas users of other types of mesalamine did not show this trend). Second, symptomatic UC may be a direct cause of folate deficiency by causing inadequate nutritional intake in patients (secondary to anorexia) and increased malabsorption of many nutrients, including folate, in patients with active disease.25 Lashner et al performed the first studies specifically looking at the effects on carcinogenesis in UC patients. A cohort study from 1989 by Lashner et al32 showed a nonstatistically significant association with folate use and reduced dysplasia risk. Interpretation was limited by insufficient information regarding duration of surveillance, duration of folate supplementation, and actual measurements of red blood cell folate levels. Also, there was no demonstration of a dose–response effect, raising the question of whether a threshold level existed. In 1997 Lashner et al33 performed a retrospective cohort study evaluating 98 patients with longterm UC (defined as greater than 6 years). Documented folic acid supplementation was also an inclusion criterion and analyzed as a dichotomous variable with use for at least 6 months compared to less than 6 months or no use. Of the cohort, the total adjusted relative risk of patients taking folate was 0.72 (P 0.042, 95% CI 0.28 –1.23). More important, there was a dose–response relationship, with a dose of 0.4 Levine and Burakoff Inflamm Bowel Dis ? Volume 13, Number 10, October 2007 1296 mg/day having a relative risk of 0.76 and a dose of 1 mg/day having a relative risk of 0.4.
Quimioprevención: Inmunomoduladores
• Cohorte retrospectiva de 315 pacientes con CU• 96 pacientes (30.5%) fueron tratados con 6MP o AZA a dosis
completas durante una media de 7.4 años• No hubo diferencias entre los tratados y no tratados respecto
a la progresión de cualquier grado de neoplasia a la progresión de cualquier grado de neoplasia (RR=1.06;95%CI:0.59-1.93) o neoplasia avanzada (RR=1.30;95%CI:0.45-3.75)
Matula. Clin Gastroenterol Hepatol 2005
Since the chemoprotective effects of 5-ASA are felt to be based in part on its antiinflammatory activity, 6-mercaptopurine (6MP) and azathioprine (AZA) have drawn interest as candidate chemoprophylactic agents. Their specific modes of action continue to be investigated but they both ultimately reduce colonic inflammation and are accepted as treatment to maintain remission in UC. Studies already cited by Lashner et al,33 Tung et al,23 and Rutter et al4 looked at chemoprevention by 6MP and AZA as chemoprophylaxis; however, these drugs were not the primary endpoint in any of their studies. Lashner et al reported that the use of AZA for at least 6 months had no protective effect (RR 1.12, 95% CI, 0.26– 4.17). Tung et al found the use of AZA had no significant protection in UC patients. In both of these studies, medication dose and duration of use were not specified. Rutter et al showed a nonsignificant trend toward a protective effect of AZA use for 1–5 years, or greater than 5 years, with ORs of 0.34 (95% CI 0.09 –1.25) and 0.73 (95% CI 0.30 –1.78), respectively. A recent study from Matula et al35 addressed this issue by performing a retrospective cohort study, which took into account the dose and duration of 6MP and AZA use. From a cohort of 315 patients, 96 (30.5%) were exposed to 6MP or AZA. Of these patients the average duration of use was 7.4 years and the average dose while on the medication was 60.6 19.5 mg/day of 6MP equivalents. There was no statistically significant difference in the development of any grade of dysplasia between the users and nonusers. The authors performed a subanalysis calculating the average use of 6MP and AZA over time. They calculated a threshold dose of 25 mg/day as a cutoff between users and nonusers. This subanalysis also showed no significant protection or harm. Of interest, there has been concern that immunomodulating drugs might enhance the development of cancer in IBD (particularly lymphoma), but the study by Matula et al., found that the use of these agents did not appear to promote carcinogenesis of colonic epithelium. 6MP and AZA appear to exert their antiinflammatory effect by inducing the apoptosis of activated T cells. The lack of a chemopreventive property led the authors to theorize that mesalamine-based medications may work by a unique mechanism such as inducing apoptosis in dysplastic cells, the accumulation of cells in specific stages of mitosis, or improved DNA replication fidelity.
En CU, 5-ASA se asocia a una disminución del riesgo de CCR, y del riesgo de displasia y CCR (variable conjunta)
La prevención de CCR con 5-ASA debería considerarse en pacientes con CU
Estudios experimentales sugieren efectos anticarcinogénicos dosis-dependiente
El efecto se asocia a su uso regular a una dosis mínima de 1.2g/d
Tratamiento profiláctico. Quimioprevención
El ácido ursodesoxicólico (13-15mg/d) debería considerarse en pacientes con EII y CEP
Los folatos podrían se útiles en la prevención de CCR en pacientes con CU
Los inmunomoduladores no han demostrado tener un efecto preventivo beneficioso
No existen datos sobre fármacos biológicos
Displasia y CCR en EII
Frecuencia
Factores de riesgo
FisiopatologíaFisiopatología
Clasificación e historia natural
Tratamiento profiláctico
Tratamiento de la displasia
Tratamiento DALM
resecable
No resecableColon tubular, pseudopólipos…
Lesión elevada y resecada Intervalo inicial Control posterior en ausencia de lesiones
ECCO (2008) 3m 6m
AEG (2009) 3-6m 6m
OMC (2009) 3m 6m
AGA (2010) 6m 6m
Seguimiento DALM
AGA (2010) 6m 6m
S. Británica (2010) No definido No definido
GETECCU 3m 6m (12m si dos consecutivas negativas)
La inicial de 3 m. sería para confirmar la resección completa con nuevas biopsias en la base de resección. Nos mojamos en períodos más reales tras dos negativas asumiendo cromo.
Tratamiento de la displasia plana
Displasia indefinidaDBG
Colonoscopia a los 6 meses
Intentar resección Colonoscopia a los 6
meses
DAG
Colectomía
DAG o DBG Negativo
Colonoscopia a los 6 meses
DBG Negativo
Colonoscopia/1-3 años según
riesgo
INDEFINIDA LGD PLANA UNIFOCAL(colonoscopia inicial)
LGD PLANA UNIFOCAL
(colonoscopias siguientes)
ECCO (2008) 3-6m 3-6m ? (3-6m)
AEG (2009) 3-6m 3-6m 6m
Seguimiento Displasia
AEG (2009) 3-6m 3-6m 6m
OMC (2009) 6m 3-6m 6m
AGA (2010) 3-6m si probable +
6-12m si probable -
3-6m No definido
S.Británica (2010) 3m 12m 12m
GETECCU 6m 3-6m 6m (12m si dos consecutivas neg.)
Criterios para decidir vigilancia
1. El diagnóstico precoz comporta mejor pronóstico (supervivencia, función, QoL)
2. El sistema permite la realización del programa y la provisión de tratamiento para resultados positivos
3. Los pacientes con diagnóstico precoz positivo seguirán las 3. Los pacientes con diagnóstico precoz positivo seguirán las recomendaciones terapéuticas
4. Los componentes del programa de detección han probado su eficacia
5. Las características de la enfermedad justifican la acción6. El coste, precisión y aceptabilidad del programa de
vigilancia son adecuados para el propósito
Sackett, Clinical Epidemiology 1991
CONCLUSIONES
Los pacientes con EII del colon de larga evolución tienen mayor riesgo de desarrollar un CCR
El riesgo es mayor en colitis extensa e intermedio en colitis distal. No hay riesgo en pacientes con proctitis
El comienzo precoz de la enfermedad y la asociación con una CEP pueden tener un riesgo incrementado
La inflamación mantenida de forma crónica y la historia familiar de CCR también contribuyen al riesgo
CONCLUSIONES
Las colonoscopias de despistaje permiten una detección másprecoz de CCR y un mejor pronóstico
No existen evidencias claras que el programa de despistajeaumente la supervivencia en pacientes con CUaumente la supervivencia en pacientes con CU
El programa de despistaje debe iniciarse a los 8-10 años del diagnóstico para reevaluar la extensión. Si la colitis es extensadeben realizarse endoscopias periódicamente (1-2 años)
Si existe una CEP, el programa debe iniciarse desde el diagnóstico
CONCLUSIONES
La DAG y el adenocarcinoma sobre mucosa plana son indicaciones de colectomía
Un paciente con DBG sobre mucosa plana debe escoger entre colectomía o repetición de la endoscopia en un plazo de 3-6 mesesmeses
Una lesión elevada debe ser completamente extirpada. En ausencia de displasia en la mucosa adyacente, debe realizarseun seguimiento endoscópico frecuente y meticuloso
Si la resección endoscópica no es posible o existe displasia en la mucosa adyacente debe recomendarse la colectomía
CONCLUSIONES
La quimioprevención con 5-ASA podría reducir la incidencia de CCR
En pacientes con CEP se recomienda el uso de ácido ursodesoxicólico para prevenir el CCR
Informar al paciente de la evidencia actual sobre el beneficio de programas de vigilancia adecuados y que intervenga en la toma de decisiones.
Y, si lo incluimos, hacerlo bien:
- Colonoscopia inicial- Intervalos entre exploraciones- Procedimiento (biopsias, cromoendoscopia…)- Plan de actuación según hallazgos (colectomía, acortar intervalos)
