Two common gastrointestinal cancers, namely, gastric and colorectal cancers, cause high mortality and morbidity. The development of gastrointestinal cancers usually follows stepwise processes with recognizable pre-neoplastic changes. A class of noncoding RNA known as microRNA (miRNA) is increasingly recognized to play pleiotropic functions in the multistep development of gastrointestinal cancers. Abnormal patterns of miRNA expression in gastric and colorectal cancers have been widely reported. These dysregulated miRNAs function as novel proto-oncogenes and tumor-suppressor genes by controlling cellular malignant phenotypes, including unchecked cell proliferation, resistance to apoptosis, enhanced invasiveness and metastasis, and angiogenesis. Moreover, certain polymorphisms in miRNA genes or miRNA-binding sites are associated with disease risks whereas detection of circulating or fecal miRNAs may facilitate early diagnosis. The prognostic functions of a number of dysregulated miRNAs in gastrointestinal cancers have also been established. Delineating the pathophysiological basis of miRNA dysregulation will further our understanding of the pathogenesis of these two potentially fatal diseases. Such efforts will also result in the development of miRNA-based biomarkers and therapeutics for the risk stratification, diagnosis, prognostication, and treatment of gastrointestinal cancers.
Apoptosis ; Biomarkers ; Cell Proliferation ; Colorectal Neoplasms ; Early Diagnosis ; Gastrointestinal Neoplasms ; MicroRNAs ; Neoplasm Metastasis ; Phenotype ; Prognosis ; Proto-Oncogenes ; RNA, Untranslated ; Stomach Neoplasms

BACKGROUND/AIMS: While it is well established that acupuncture relieves somatic pain, its therapeutic effect on visceral pain such as irritable bowel syndrome (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral hyperalgesia in an animal model. METHODS: Sprague-Dawley rats (n = 8 per group) with prior neonatal maternal separation stress were randomly allocated to receive 3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint ST-36. Another group of rats without prior maternal separation was included as non-handled controls. Colorectal distension was performed on the day after acupuncture treatment. The 3 groups were compared for pain threshold as determined by abdominal withdrawal reflex and visceromotor response as measured by electromyogram. Colon, spinal cord, and brainstem were sampled for topographic distribution and quantitative assessment of serotonin and Fos expression by immunohistochemistry. RESULTS: Rats in EA group had significantly higher pain threshold compared to those in sham acpuncture group (25.0 +/- 5.7 mmHg vs 18.7 +/- 5.2 mmHg, p = 0.01) and it was comparable with that of non-handled treatment naive controls (29.4 +/- 9.3 mmHg, p = 0.28). They also had lower visceromotor response as measured by electromyogram compared to those received sham acupuncture at all colorectal distension pressures. EA significantly suppressed Fos expression in doral raphe nuclei of brainstem, superficial dorsal horn of spinal cord and colonic epithelium but suppressed 5-HT expression only in brainstem and spinal cord. CONCLUSIONS: Electro acupuncture attenuates visceral hyperlagesia through down-regulation of central serotonergic activities in the brain-gut axis.
Acupuncture ; Acupuncture Points ; Animals ; Axis, Cervical Vertebra ; Benzodiazepines ; Brain Stem ; Colon ; Down-Regulation ; Electroacupuncture ; Epithelium ; Horns ; Hyperalgesia ; Immunohistochemistry ; Irritable Bowel Syndrome ; Models, Animal ; Nociceptive Pain ; Pain Threshold ; Raphe Nuclei ; Rats ; Rats, Sprague-Dawley ; Reflex ; Salicylamides ; Serotonin ; Spinal Cord ; Visceral Pain

Artificial intelligence (AI) is coming to medicine in a big wave. From making diagnosis in various medical conditions, following the latest advancements in scientific literature, suggesting appropriate therapies, to predicting prognosis and outcome of diseases and conditions, AI is offering unprecedented possibilities to improve care for patients. Gastroenterology is a field that AI can make a significant impact. This is partly because the diagnosis of gastrointestinal conditions relies a lot on image-based investigations and procedures (endoscopy and radiology). AI-assisted image analysis can make accurate assessment and provide more information than conventional analysis. AI integration of genomic, epigenetic, and metagenomic data may offer new classifications of gastrointestinal cancers and suggest optimal personalized treatments. In managing relapsing and remitting diseases such as inflammatory bowel disease, irritable bowel syndrome, and peptic ulcer bleeding, convoluted neural network may formulate models to predict disease outcome, enhancing treatment efficacy. AI and surgical robots can also assist surgeons in conducting gastrointestinal operations. While the advancement and new opportunities are exciting, the responsibility and liability issues of AI-assisted diagnosis and management need much deliberations.

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.
Humans ; Male ; Early Detection of Cancer/methods* ; East Asian People ; Image-Guided Biopsy/methods* ; Magnetic Resonance Imaging/methods* ; Prostate/pathology* ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology* ; Retrospective Studies ; Middle Aged ; Aged