Adoption of multimodality treatment approach for rectal cancer has resulted in significant improvements in oncologic outcomes. The roles of chemotherapy, radiation, and surgery in rectal cancer ...treatment are continuously evolving with the goal of achieving the best possible oncologic and functional outcome while minimizing treatment toxicity. The aim of this review is to summarize the most recent trials focusing on organ‐sparing treatment strategies and the optimal selection of patients for neoadjuvant radiation therapy.
There is an alarming trend of increased colorectal cancer in the young. Why this is happening needs to be evaluated, and the unique characteristics that define this population and potential ...differences in comparison with older age rectal cancers should be explored.
See referenced original article on pages 3510‐19, this issue.
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a ...disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
OBJECTIVE:To evaluate the independent prognostic ability of the American Joint Committee on Cancer (AJCC) tumor regression scores within pathologic stage II and III rectal cancers.
...BACKGROUND:Response to neoadjuvant chemoradiation (nCRT) has been debated as a biologic surrogate for tumor biology and prognosis in rectal cancer. AJCC regression scores have been shown to correlate with prognosis.
METHODS:Patient demographics, tumor characteristics, and AJCC scores (0 = complete response; 1 = isolated tumor cells remaining; 2 = residual cancer outgrown by fibrosis; 3 = extensive residual cancer) were assessed from 545 rectal cancer patients treated by nCRT followed by surgery at a single institution. Patients were classified as responders (score 0–2) or nonresponders (score 3). Survival analyses were performed using Cox proportional hazards models.
RESULTS:Of 545 cases, 123 and 182 were pathologic stage II and III, respectively. Median follow-up was 4.9 years. AJCC regression scores were not independently prognostic within stage II cancers. However, AJCC scores were strongly associated with prognosis within stage III cancers (nonresponse 5-year overall survival OS 27% vs 67%, P < 0.001). Stage III responders (N = 139, 76.4%) had similar outcomes to stage II (5-year OS 67% vs 74%, P = 0.89). Conversely, stage III nonresponders (N = 43, 23.6%) approached stage IV outcomes (5-year OS 27% vs 18%, P = 0.09). On multivariable analysis, nonresponse (hazard ratio 3.2, 95% confidence interval 1.7–6.2), along with positive margin, abdominoperineal resection, and no adjuvant chemotherapy administration were independently associated with worse OS.
CONCLUSIONS:AJCC response score after nCRT is a novel prognostic factor in pathologic stage III rectal cancer and may guide surveillance and adjuvant therapy decisions.
Cancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, even though distal regulatory elements play a central role in controlling ...transcription patterns. We used the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome-wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a specific transcriptional program to promote colon carcinogenesis.
BACKGROUND:The American Joint Committee on Cancer and the College of American Pathologists provide guidelines for reporting pathologic response to neoadjuvant treatment of rectal cancer. The clinical ...relevance of these tumor regression grading guidelines is undefined.
OBJECTIVE:This study evaluates the prognostic significance of the American Joint Committee on Cancer/College of American Pathologists regression grading.
DESIGN:This is a retrospective cohort study based on data from a prospectively maintained colorectal cancer database. The cohorts were defined by American Joint Committee on Cancer/College of American Pathologists tumor regression grade.
SETTING:This study was performed at a single tertiary referral center.
PATIENTS:Five hundred thirty-eight patients with primary rectal adenocarcinoma who underwent neoadjuvant therapy between 1992 and 2012 were identified.
MAIN OUTCOME MEASURES:The primary outcome measures were overall and disease-free survival, cancer-specific mortality, and cumulative recurrence rate.
RESULTS:Five hundred thirty-eight patients were included, 105 of whom (19.5%) were American Joint Committee on Cancer/College of American Pathologists grade 0, 153 patients (28.4%) were grade 1, 181 patients (33.6%) were grade 2, and 99 (18.4%) were grade 3. Kaplan-Meier analysis revealed that American Joint Committee on Cancer/College of American Pathologists grade was associated with significant differences in overall survival (p < 0.001), disease-free survival (p < 0.001), and cumulative recurrence (p < 0.001). No local recurrences were observed in American Joint Committee on Cancer/College of American Pathologists grade 0 patients. Five-year overall survival rates were 89%, 74%, 63%, and 40% (p < 0.001); 5-year disease-free survival rates were 85%, 64%, 54%, and 33% (p < 0.001); and 5-year recurrence rates were 7%, 18%, 25%, and 33% (p <0.001) for American Joint Committee on Cancer/College of American Pathologists grades 0, 1, 2, and 3. After adjusting for significant covariates, including pathologic stage, American Joint Committee on Cancer/College of American Pathologists grade remained an independent predictor of overall survival (p < 0.001), disease-free survival (p < 0.001), and cumulative recurrence (p < 0.001) in Cox regression analyses.
LIMITATIONS:This was a retrospective study. There was a low local recurrence rate in our population, limiting the sensitivity of recurrence analyses.
CONCLUSIONS:This is the first study to delineate American Joint Committee on Cancer/College of American Pathologists regression grade as an independent oncologic prognostic factor. This information can be used in discussions with patients who have rectal cancer.
BACKGROUND:Disease-free survival estimated from the time of surgery does not account for the changing likelihood of survival based on time already accrued. Conditional disease-free survival is ...defined as the probability of remaining disease free after reaching a specific time point without recurrence.
OBJECTIVE:The purpose of this study was to evaluate conditional disease-free survival for patients with rectal cancer who were treated by proctectomy after neoadjuvant chemoradiation.
DESIGN:Demographics, tumor characteristics, and tumor regression scores were assessed. Three-year conditional disease-free survival was estimated at x year after surgery based on the formula cDFS3 = DFS(x+3)/DFS(x), where DFS is disease-free survival and cDFS is conditional disease-free survival. Analyses were performed using Cox proportional hazards models.
SETTING:The study was conducted at a single tertiary referral center.
PATIENTS:A total of 545 patients with rectal cancer who were treated by neoadjuvant chemoradiation and curative intent surgery between 1992 and 2012 were included.
MAIN OUTCOME MEASURES:Disease-free survival and conditional disease-free survival were measured.
RESULTS:The median patient age was 57.5 years, and 28.4% were women. Median follow-up was 5.9 years. Disease-free survival at 1, 3, and 5 years was 89%, 71%, and 63%. The probability of remaining disease free for an additional 3 years for patients disease free at 1, 3, and 5 years was 75%, 83%, and 82%. Tumor regression, pathologic stage, margin status, differentiation, and procedure (low anterior versus abdominoperineal resection) were associated with disease-free survival on multivariable analysis (p < 0.05), but their relevance varied over time. R1 resection and differentiation were initially significant but not at 5 years. In contrast, tumor regression after neoadjuvant chemoradiation had a long-lasting impact on survival (at 5 y, conditional disease-free survival for an additional 3 y91%, 85%, 76%, and 71% for regression scores 0, 1, 2, and 3; p = 0.002).
LIMITATIONS:This was a retrospective study over 20 years, with evolution in adjuvant therapies during this time.
CONCLUSIONS:Conditional disease-free survival estimates improved over time, confirming that most patients will see a recurrence within the first few years. The impact of specific prognostic factors evolves variably over time. This information is useful to patients and providers and can help guide counseling and surveillance. See Video Abstract at http://links.lww.com/DCR/A771.
Hereditary Colorectal Cancer Hampel, Heather; Kalady, Matthew F; Pearlman, Rachel ...
Hematology/oncology clinics of North America
36, Številka:
3
Journal Article
Recenzirano
Around 10% to 16% of colorectal cancer patients have a pathogenic variant in a cancer susceptibility gene. Some of these variants are in cancer genes that are associated with colorectal cancer while ...others are not. The hereditary colorectal cancer syndromes can be divided into two major categories, the nonpolyposis and the polyposis conditions. The nonpolyposis conditions can be divided into those that lead to colorectal tumors with defective mismatch repair and those that do not. The polyposis conditions are further divided by predominant histology into the adenomatous, hamartomatous, serrated, and mixed polyposis conditions. All of these conditions are described in detail herein.
Nonspecific acute pouchitis is common in patients with ulcerative colitis who undergo IPAA, but there is disagreement about the rate at which this occurs in patients with familial adenomatous ...polyposis.
This study aimed to define the rate at which nonspecific acute pouchitis occurs in patients with familial adenomatous polyposis.
This study was conducted at a hereditary colorectal cancer center in a large academic medical center.
This is a retrospective cohort study using prospectively gathered data.
Patients with familial adenomatous polyposis who have had IPAA were included.
Symptoms, pouchoscopy and pouch radiography, and pouch biopsy were evaluated.
The primary outcomes measured were the presence of nonspecific acute pouchitis and the alternative diagnosis of pouch dysfunction.
There were 250 patients with familial adenomatous polyposis who had undergone IPAA; 38 (15.2%) had been labeled as having "pouchitis": 23 men and 15 women. Median age was 55 years (range, 18-90 years). No patient had nonspecific, acute pouchitis as defined by our criteria. In 9 cases, the diagnosis was derived from benign ulcers common in ileal pouches. Stool frequency was the most common symptom associated with the "pouchitis" label, but actual causes for the frequency included poor pouch emptying, poor eating habits, poor bowel habits, and afferent limb syndrome. Median stool frequency was 9, ranging from 4 to 15 per day. Every patient had at least 1 pouch endoscopy, and the median number was 19 per patient (range, 1-21). Nine patients had pouch biopsies to rule out inflammation; all showed chronic active enteritis, a normal finding in ileal pouches.
This study was limited by its retrospective nature.
We could not confirm any case of nonspecific acute pouchitis in patients with familial adenomatous polyposis. Those caring for patients with familial adenomatous polyposis who have a pouch should seek causes for pouch-related symptoms other than "pouchitis." See Video Abstract at http://links.lww.com/DCR/B666.POUCHITIS AGUDA INESPECÍFICA EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: MENOS COMÚN DE LO QUE PENSAMOSANTECEDENTES:La pouchitis aguda e inespecífica es común en pacientes con colitis ulcerativa, sometidos a anastomosis de bolsa ileoanal, pero no hay acuerdo sobre la frecuencia en que se presenta en pacientes con poliposis adenomatosa familiar (PAF).OBJETIVO:Definir la frecuencia en la que se presenta pouchitis aguda inespecífica en pacientes con poliposis adenomatosa familiar.ENTORNO CLINICO:Centro de cáncer colorrectal hereditario en un gran centro médico académico.DISEÑO:Estudio de cohorte retrospectivo utilizando datos recopilados prospectivamente.PACIENTES:Pacientes con poliposis adenomatosa familiar sometidos a bolsa con anastomosis ileoanal.INTERVENCIONES:Síntomas, proctoscopia, radiografía y biopsia de bolsa ileoanal.PRINCIPALES MEDIDAS DE VALORACION:Presencia de pouchitis aguda inespecífica; diagnósticos alternos de disfunción de la bolsa ileal.RESULTADOS:De 250 pacientes con poliposis adenomatosa familiar sometidos a una anastomosis anal de la bolsa ileal; 38 (15,2%), habían sido etiquetados como "pouchitis", 23 hombres y 15 mujeres. La mediana de edad fue de 55 años (rango de 18 a 90 años). Ningún paciente tuvo pouchitis aguda inespecífica según lo definido por nuestros criterios. En 9 casos el diagnóstico se derivó de úlceras benignas frecuentes en bolsas ileales. La frecuencia de las evacuaciones fue el síntoma más común asociado con la etiqueta "pouchitis", pero las causas reales de la frecuencia, incluyeron un mal vaciado de la bolsa, malos hábitos alimenticios, malos hábitos intestinales y síndrome de asa aferente. La frecuencia media de las evacuaciones fue de 9, con un rango de 4 a 15 por día. A cada paciente se le realizó al menos una endoscopia de la bolsa: la mediana fue de 19 por paciente (rango de 1 a 21). A 9 pacientes se les realizó biopsia de bolsa para descartar inflamación: todos mostraron enteritis activa crónica, un hallazgo normal en las bolsas ileales.LIMITACIONES:Naturaleza retrospectiva del estudio.CONCLUSIONES:No pudimos confirmar ningún caso de pouchitis aguda e inespecífica en pacientes con PAF. Aquellos que atienden a pacientes con PAF con bolsa ileal, deben buscar otras causas para los síntomas relacionados con la bolsa que no sean "pouchitis". Consulte Video Resumen en http://links.lww.com/DCR/B666. (Traducción-Dr. Fidel Ruiz Healy).
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