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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

Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic APC mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of BRAF or KRAS, microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.

Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn’s disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.

Docking protein-1 (DOK1) is a tumor suppressor frequently lost in malignant cells, however, it retains the ability to control activities of immune receptors in adjacent stroma cells of the tumor microenvironment. We therefore hypothesized that addressing DOK1 may be useful for cancer immunotherapy. DOK1 mRNA and DOK1 protein expression were downregulated in tumor cells of gastric cancer patients (n = 249). Conversely, its expression was up-regulated in cases positive for Epstein Barr Virus (EBV+) together with genes related to macrophage biology and targets of clinical immunotherapy such as programmed-cell-death-ligand-1 (PD-L1). Notably, high DOK1 positivity in stroma cells conferred poor prognosis in patients and correlated with high levels of inducible nitric oxide synthase in CD68+ tumor-associated macrophages. In macrophages derived from human monocytic leukemia cell lines, DOK1 (i) was inducible by agonists of the anti-diabetic transcription factor peroxisome proliferator-activated receptor-gamma (PPARγ), (ii) increased polarization towards an inflammatory phenotype, (iii) augmented nuclear factor-κB-dependent transcription of pro-inflammatory cytokines and (iv) reduced PD-L1 expression. These properties empowered DOK1+ macrophages to decrease the viability of human gastric cancer cells in contact-dependent co-cultures. DOK1 also reduced PD-L1 expression in human primary blood monocytes. Our data propose that the drugability of DOK1 may be exploited to reprogram myeloid cells and enforce the innate immune response against EBV+ human gastric cancer.

Background/study aims Laser lithotripsy can effectively fragment complicated biliary stones, but current cholangioscopes are limited by fragility, restricted mobility or moderate visual resolution. The efficacy and safety of a new digital single-operator peroral cholangioscope to guide laser lithotripsy were evaluated. Patients and methods In this prospective single-center series, consecutive patients with complicated biliary stones, defined as impacted stones > 1.5 cm in size and wider than the more distal common bile duct, or stones that failed extraction by basket mechanical lithotripsy, underwent ERCP and SpyGlass DS peroral cholangioscope (Boston Scientific, Marlborough, United States)-guided laser lithotripsy. Stone clearance rate and incidence of adverse events were determined. Results Seventeen patients (10 men, 7 women; median age 76 years) with a median biliary stone size of 2 cm underwent predominantly holmium:yttrium aluminum garnet laser lithotripsy, achieving a 94 % stone clearance rate over 1 median procedure. Lithotripsy was performed in 8 of 17 patients due to an impacted biliary stone. The remaining patients underwent lithotripsy due to prior failure of the basket mechanical lithotripter to capture or crush their stones. Post lithotripsy, 2 patients developed cholangitis and 1 patient with underlying COPD developed respiratory distress, all resolved with conservative management. There were no hemobilia, perforations, pancreatitis nor any deaths. Conclusion SpyGlass DS peroral cholangioscopy-guided laser lithotripsy is an efficient and safe modality for management of complicated biliary stones.

The existence of flat adenomas in the colon is well recognized. Whether they represent a distinct disease with a pathogenetic pathway different from that of the classical adenoma-carcinoma sequence in colorectal tumorigenesis and have higher malignant potential remains a matter of debate. To review the epidemiology, clinical features, detection and management of flat and depressed (non-polypoid) colonic neoplasm, we performed a thorough literature review on studies focusing on the prevalence, histological features, genetics, detection and treatment of flat and depressed (non-polypoid) colonic neoplasm. A high percentage of severe dysplasia in flat colonic adenomas has not been consistently demonstrated. Their malignant potential appears to be size-dependent. Flat adenomas are found to have a lower incidence of major genetic abnormalities involved in the classical adenoma-carcinoma sequence and that has raised suspicions that they may have a different pathogenesis. The depressed type of colorectal carcinoma is uncommon but shows more aggressive behavior. More advanced colonoscopic techniques, such as chromoendoscopy, may enhance the detection of small and inconspicuous colonic neoplastic lesions that lack a protruding configuration. It is essential for endoscopists to appreciate the existence and clinical significance of flat and depressed colonic lesions as an important variant of colonic neoplasms so that the goal of reducing colorectal carcinoma incidence by polypectomy can be better achieved. [ABSTRACT FROM AUTHOR]