5.

Serrated lesions are the precursor lesions of a new model of colorectal carcinogenesis. From a molecular standpoint, the serrated pathway is thought to be responsible for up to 30% of all colorectal cancer cases. The three major processes of this molecular mechanism are alterations in the mitogen-activated protein kinase pathway, production of the CpG island methylation phenotype, and generation of microsatellite instability. Other contributing processes are activation of WNT, alterations in the regulation of tumor suppressor genes, and alterations in microRNAs or in MUC5AC hypomethylation. Although alterations in the serrated pathway also contribute, their precise roles remain obscure because of the various methodologies and definitions used by different research groups. This knowledge gap affects clinical assessment of precursor lesions for their carcinogenic risk. The present review describes the current literature reporting the molecular mechanisms underlying each type of serrated lesion and each phenotype of serrated pathway colorectal cancer, identifying those areas that merit additional research. We also propose a unified serrated carcinogenesis pathway combining molecular alterations and types of serrated lesions, which ends in different serrated pathway colorectal cancer phenotypes depending on the route followed. Finally, we describe some key issues that need to be addressed in order to incorporate the newest technologies in serrated pathway research and to improve overall knowledge for developing specific prevention strategies and new therapeutic targets.

Opioids have become the most widely prescribed analgesics in Western countries. Opioid-induced bowel dysfunction is a widely known adverse effect, with constipation the most common manifestation. Most of the opioid-related effects occur in the stomach, small intestine, and colon and have been widely studied. However, the effects related to esophageal motility are less known. Recently published retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction, reflecting symptoms similar to motility disorders, such as achalasia and functional esophagogastric junction outflow obstruction. The most common manometric findings, as reported in the literature, for patients with opioid-induced dysphagia undergoing long-term therapy with these drugs are impaired lower esophageal sphincter relaxation, high amplitude/velocity, and simultaneous esophageal waves, higher integrated relaxation pressure, lower distal latency, and the esophageal contractility can be normal, hypercontractile, or premature. Based on these studies, a new clinical entity known as opioid-induced esophageal dysfunction has been postulated. For these patients, the diagnostic method of choice is high-resolution manometry, although other causes should be ruled out through endoscopy or Computed Tomography (CT). The best therapeutic option for these patients is withdrawal of the opioid; however, this is not always possible, and other options need to be investigated, such as pneumatic dilation and botulinum toxin injection, considering the risks versus the benefits.

Background and study aims We aimed to describe the presence and combination of Hazewinkelʼs optical diagnosis (OD) criteria for sessile serrated lesions (SSL), determining which lesion characteristics increase the probability of a correct OD, with a focus on diminutive lesions. Patients and methods This was a prospective study describing the presence of Hazewinkelʼs OD criteria for SSL in lesions found in consecutive CRC screening colonoscopies. The presence of each OD criterion and their diagnostic combinations in SSL, related to the lesion’s NBI International Colorectal Endoscopic (NICE) classification category, size, and location, were described. The presence of two or more optical criteria was considered diagnostic of SSL. The OD was compared to pathology as the gold standard. Results Seventy-nine SSLs (5.6 %) were diagnosed. Cloud-like appearance was the most prevalent OD criterion (35, 44.3 %). OD criteria were more frequently identified in NICE type 1, ≥ 10 mm, and proximal lesions. Only 26 SLLs fulfilled the OD criteria (sensitivity 32.9 %, 95 % CI 29.1 %–36.7 %). The sensitivity for diminutive SSL was 14.7 %, (95 % CI 11.9 %–17.6 %). Eighty-five lesions were optically diagnosed as SSL. However, only in 26 SSL was this the definitive diagnosis (positive predictive value 30.6 %, 95 % CI 26.9 %–34.3 %). Size > 5 mm and proximal location increased the probability of a correct diagnosis. The overall accuracy of the optical criteria was 92.0 % (95 % CI, 89.8 %–94.2 %). Conclusions The Hazewinkelʼs optical criteria are not reliable for a positive diagnosis of SSL, particularly for diminutive lesions.

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