Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.     

233例结直肠腺瘤摘除术后随访和内镜监测的临床分析

目的 了解结直肠腺瘤(CRA)摘除后复发情况和结肠镜监测现状,探讨CRA复发的相关危险因素.方法 收集2005年6月至2009年12月安徽医科大学第一附属医院符合研究标准283例CRA摘除住院患者临床资料并进行随访.统计分析CRA摘除后复发率,结肠镜监测间期和CRA复发的关系及CRA复发的相关危险因素;分析肠镜监测组监测间期、频次,及未行监测的原因.结果 共随访CRA摘除后患者235例,随访率83.0％(235/283),其中生存患者233例,随访时间最短者12个月,最长66个月,随访时间中位数为(35.1±14.2)个月.结肠镜监测组患者115例,监测率为49.4％(115/233),复发率45.0％(50/111),未监测组118例;年龄≥60岁、体重指数≥25kg/m2、多发腺瘤(≥2个)与CRA复发明显相关,差异有统计学意义(x2值分别=4.299、5.291和8.883,P值分别=0.038、0.021和0.027);未监测组患者对CRA需要定期监测的知晓率明显低于监测组,差异有统计学意义(x2=37.819,P＜0.01).结论 CRA摘除术后复发率较高;高龄、高体重指数、多发腺瘤是预测CRA复发的独立危险因素;我院CRA摘除后结肠镜监测率低,主要原因在于患者对CRA摘除后定期监测重要性的认识不足.     

Aspirin-exacerbated respiratory disease: characteristics and management strategies

Aspirin-exacerbated respiratory disease is a clinical entity comprising chronic rhinosinusitis with nasal polyposis, asthma and intolerance to COX-1 inhibiting drugs. The pathogenesis is not completely understood at this point, but abnormal arachidonic acid metabolism is a key feature in this syndrome. The diagnosis is confirmed only by direct drug challenge. Aspirin desensitization followed by daily aspirin therapy is a useful treatment option in these patients. In this review article are discussed the important characteristics and treatment of aspirin-exacerbated respiratory disease.     

Hypermethylation of adenomatous polyposis coli gene promoter is associated with novel Wnt signaling pathway in gastric adenomas

Background and Aim: Gastric adenomas (GAs) are considered as premalignant lesions of gastric adenocarcinoma. The role of Wnt signaling pathway in GAs is rarely identified. In the present study, we aimed to determine whether Wnt signaling plays a role in the pathogenesis of GAs, and to clarify the mechanism of Wnt signaling in GAs. Methods: The study investigated the relationship between clinicopathological characteristics, Helicobacter pylori (Hp) infection, adenomatous polyposis coli (APC) promoter methylation, APC and β‐catenin immunohistochemistry expression and mutation status, compared with 38 gastric adenoma and periadenomatous tissues (PTs). Results: The abnormal expression of β‐catenin in PTs, low‐grade adenomas (LGAs) and high‐grade adenomas (HGAs) was 0%, 9.09% and 81.25%. For APC, immunoreactive score (IRS) was 5.50 ± 0.5 in PTs, 3.59 ± 1.4 in LGAs and 1.8 ± 2.0 in HGAs. The scores in LGAs and HGAs were significantly lower than those in PTs (P = 0.000). IRS reflected significantly reduced expression of APC in HGAs (P = 0.002). The absent expression of APC had a correlation with the expression of β‐catenin (P = 0.000). Four LGAs (18.18%) and nine HGAs (56.25%) had methylation of APC. APC promoter methylation correlated with the grade (P = 0.014) and the expression of β‐catenin and APC (P = 0.000). Genes mutation was detected in only two adenomas (5.3%). The presence of Hp in HGAs (43.8%) was significantly higher than in LGAs (13.6%) (P = 0.038). But there was no statistical correlation to growth pattern, size, APC hypermethylation and gene mutation. Conclusion: Hypermethylation of APC promoter, instead of mutations involving APC and β‐catenin, may play a role in the development and progression of GAs contributing to moderate activation of Wnt signaling. Helicobacter pylori may accelerate the progress of gastric adenoma, but the pathogenesis needs further research.     

Role of ileostomy in restorative proctocolectomy

Restorative proctocolectomy (RP) is the treatment of choice in patients affected with refractory ulcerative colitis or familial adenomatous polyposis. Surgery in elective settings is often performed in 2 stages, fashioning an ileostomy which is closed 2-3-mo later. It is still debated whether omitting ileostomy could offer advantages in the management of patients undergoing RP.     

Primary and secondary restorative proctocolectomy for familial adenomatous polyposis: complications and long‐term bowel function

Aim The aim of the study was to evaluate intra‐operative difficulties, complications and long‐term bowel function in polyposis patients undergoing conversion of an ileorectal anastomosis to an ileoanal pouch, compared with patients with a primary ileoanal pouch operation. Method A national register‐based retrospective study was performed with clinical follow‐up and a questionnaire on long‐term bowel function. Results There were 84 patients in the study: 59 (70%) had a primary pouch operation and in 25 (30%) a secondary pouch procedure was attempted. This was abandoned, in one case, leaving 24 patients who had a successful secondary restorative proctocolectomy. The median (range) follow‐up was 123 (0–359) months. There were no intra‐operative difficulties in the 59 primary operations, but intra‐operative difficulties were reported in nine of 25 secondary operations (P < 0.001). Complications within 1 month of surgery occurred in six of 59 primary operations and in none of 24 secondary operations (P < 0.001); and late surgical complications occurred in eight of 55 primary operations and in eight of 24 secondary operations (P = 0.13). The only difference in bowel function was a lower frequency of nocturnal defaecation after secondary pouch formation (P = 0.02). Conclusion Reoperation with proctectomy after a previous ileorectal anastomosis and conversion to restorative proctocolectomy is feasible in polyposis patients, with morbidity and functional results similar to those seen after a primary pouch operation.     

Direct contact in inviting high-risk members of hereditary colon cancer families to genetic counselling and DNA testing

Background

Identification of hereditary predisposition to cancer has limited significance if not followed by efficient cancer prevention in the family. Probands are traditionally left to inform their relatives about the increased risk, but distant relatives may remain uninformed. An approach to contacting directly at‐risk persons assumed to be unaware of their increased cancer risk was taken. With cancer prevention as the ultimate goal, the study was aimed at investigating attitudes towards and psychosocial consequences of this novel strategy.

Methods

In families with hereditary non‐polyposis colorectal cancer (Lynch syndrome), 286 healthy adult relatives with a 50% risk of a predisposing mutation were contacted by letter. Of these, 112 participated in counselling and predictive testing. Baseline information and information obtained 1 month after the test for 73 respondents were compared with 299 corresponding subjects, approached via the proband (family‐mediated approach in our previous study) in these families.

Results

After the contact letter, 51% consented to the study. Of these, 92% approved of the direct contact and 33% had tried to seek information. In 34% of the mutation carriers, neoplasia was identified in the first post‐test colonoscopy. Although post‐test fear of cancer increased among the mutation carriers and decreased among noncarriers, almost all participants were satisfied with their decision to participate, independently of their test results, parallel to the family‐mediated approach.

Conclusion

In this large‐scale study, relatives in cancer families were actively contacted to inform them of the condition and genetic counselling. Their attitudes were encouraging, and the psychosocial consequences were similar to the family‐mediated approach. Our results suggest the appropriateness of direct contact as an alternative method of contact in cases of life‐threatening treatable disease.     

Analysis of APC/beta-catenin genes mutations and Wnt signalling pathway in desmoid-type fibromatosis

OBJECTIVE: The abnormalities of the Wnt signalling pathway in desmoid-type fibromatosis were analysed, with the purpose of exploring the mechanism of tumorigenesis and progression. METHODS: The clinical and histopathological features of 96 cases were analysed. Beta-catenin, cyclin-D1, c-myc, and Ki-67 proteins were detected in 69 cases using formalin-fixed, paraffin-embedded tissues. Using the same materials, apoptosis of the tumour cells was investigated by terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) testing. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) assay, and sequencing were performed to detect abnormalities of the adenomatous polyposis coli (APC) and beta-catenin genes. RESULTS: APC gene mutations were found in 18 cases (26.1%, 18/69). Somatic mutations of codon 41 in exon 3 of beta-catenin were detected in 13 cases (18.8%, 13/69). No correlation of beta-catenin abnormal expression with the mutations of APC gene or beta-catenin gene was identified (p>0.05). The cases with abnormal beta-catenin expression showed a higher level of c-myc protein expression (69.7%, 23/33) than those without (22.2%, 8/36, p = 0.001). The apoptotic indices (AIs) were significantly lower in cyclin-D1 positive cases and c-myc positive cases (p = 0.015, p = 0.007). CONCLUSIONS: There are somatic mutations of the APC and beta-catenin gene in desmoid-type fibromatosis, and there are abnormalities in the Wnt signalling pathway. These abnormalities may result in aberrant cell proliferation and apoptosis, which are likely to be important factors in tumorigenesis and progression.