UNASSIGNED: Loss of bone morphogenetic protein (BMP) signaling in the stomach, achieved by transgenic expression of the BMP inhibitor noggin (H + /K + -Nog mice), causes parietal cell (PC) loss, spasmolytic polypeptide-expressing metaplasia, a marker of preneoplasia, and activation of cell proliferation. We examined if specific inhibition of BMP signaling in PCs leads to aberrations in epithelial homeostasis.
UNASSIGNED: Mice with floxed alleles of BMP receptor 1a (Bmpr1a flox/flox mice) were crossed to H + /K + -Cre mice to generate H + /K + -Cre;Bmpr1a flox/flox mice. Morphology of the mucosa was analyzed by hematoxylin and eosin staining. Distribution of H+/K+-ATPase-, IF-, and Ki-67-positive cells was analyzed by immunostaining. Expression of pit and neck cell mucins was determined by staining with the lectins Ulex Europaeus Agglutinin 1 and Griffonia (Bandeiraea) simplicifolia lectin II, respectively. Isolation of PCs from control and Nog-expressing mice was achieved by crossing H + /K + -Nog mice to Rosa26-tdTomato (Tom) mice to generate H + /K + -Nog;Rosa26-tdTom mice. H + /K + -Cre mice were then crossed to H + /K + -Nog;Rosa26-tdTom mice to generate H + /K + -Cre;H + /K + -Nog;Rosa26-tdTom mice. Tom-labeled PCs were purified by flow cytometry. Changes in PC transcripts were measured by RNA-Seq.
UNASSIGNED: Six-month-old H + /K + -Cre;Bmpr1a flox/flox mice exhibited increased epithelial cell proliferation, presence of transitional cells showing colocalization of IF with both Griffonia (Bandeiraea) simplicifolia lectin II-binding mucins and the H+/K+-ATPase, and expansion of Ulex Europaeus Agglutinin 1-positive cells. PC transcripts from Nog-expressing mice demonstrated induction of markers of Spasmolytic Polypeptide-Expressing Metaplasia.
UNASSIGNED: PC-specific loss of BMP signaling alters the homeostasis of the gastric epithelium leading to the development of metaplasia.

UNASSIGNED: Management of intraductal papillary mucinous neoplasms (IPMNs) relies on clinical and imaging features to select patients for either pancreatectomy or periodic image-based surveillance. We aimed to compare outcomes in patients with IPMNs who underwent surgery at diagnosis with those who underwent surgery after a period of surveillance and identify preoperative clinical and imaging features associated with advanced neoplasia.
UNASSIGNED: Patients with surgically resected IPMN (n = 450) were divided into 2 groups: \"immediate surgery\": resection within 6 months of IPMN detection, and \"surveillance surgery\": resection after surveillance >6 months. Survival was analyzed with Kaplan-Meier estimates and Cox proportional hazard models.
UNASSIGNED: Pancreatic cancers in the surveillance surgery group (n = 135) was more frequently stage I compared with the immediate surgery group (9/13, 69.2% vs 41/110, 37.3%; P = .027). Among Fukuoka \"worrisome features,\" only main pancreatic duct dilation 5-9 mm (odds ratio [OR] = 3.12, 95% confidence interval [CI]: 1.72-5.68; P < .001) and serum CA 19-9≥ 35 U/mL (OR = 2.82, 95% CI: 1.31-6.06; P = .008) were significantly associated with advanced neoplasia. In addition, smoking history was associated with increased risk of advanced neoplasia (OR = 2.05, 95% CI: 1.23-3.43). Occurrence of future cancer was 16-fold higher in IPMN with high-grade dysplasia when compared with low-grade dysplasia (hazard ratio: 16.5; 95% CI: 4.19-64.7).
UNASSIGNED: Surveillance-detected pancreatic cancers in patients with IPMNs are more frequently stage I, and IPMN-HGD on surgical pathology is associated with significant risk of future pancreatic cancer. In addition to known \"high-risk\" features, main pancreatic duct dilation 5-9 mm, CA 19-9 elevation, and smoking history are significantly associated with advanced neoplasia.

OBJECTIVE: We aimed to compare the clinical and endoscopic characteristics of sessile serrated lesions (SSLs) with dysplasia/carcinoma (SSLD/Cs) and SSLs without dysplasia in this systematic review and meta-analysis.
METHODS: MEDLINE, EMBASE, and Cochrane Library databases and Clinicaltrials.gov were searched for relevant studies published up to August 28, 2023. The primary outcome was lesion size in SSLD/Cs and SSLs without dysplasia. The secondary outcomes included risk of dysplasia/carcinoma, morphology (classified based on the Paris classification), and lesion features such as mucus cap and nodules/protrusions in the two groups.
RESULTS: Thirteen studies with 14 381 patients were included. The proportion of SSLD/Cs ≥10 mm was significantly higher than that of SSLs without dysplasia (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.21-12.02, p = 0.02). There was no significant difference in the risk of dysplasia/carcinoma between the proximal (OR 0.80, 95% CI 0.57-1.14) and distal colon (OR 1.25, 95% CI 0.88-1.77, p = 0.21). The 0-Ip (OR 2.47, 95% CI 1.50-4.09) and 0-IIa + Is (OR 10.38, 95% CI 3.08-34.98) morphologies were more prevalent among SSLD/Cs, whereas the 0-IIa morphology (OR 0.38, 95% CI 0.22-0.65) was more prevalent among SSLs without dysplasia (all p < 0.001). Furthermore, mucus cap (OR 0.61, 95% CI 0.42-0.89, p = 0.01) was more common among SSLs without dysplasia, whereas nodules/protrusions (OR 7.80, 95% CI 3.07-19.85, p < 0.001) were more common in SSLD/Cs.
CONCLUSIONS: SSLs >10 mm, 0-Ip or 0-IIa + Is morphologies, and those with nodules/protrusions are significantly associated with dysplasia/carcinoma.

OBJECTIVE: We investigated the relationship between bile amylase (AMY) levels and biliary epithelial changes in pancreaticobiliary maljunction (PBM), a congenital anomaly characterized by pancreaticobiliary reflux due to duct fusion outside the duodenal wall.
METHODS: We enrolled 43 children with congenital biliary dilatation (CBD) of Todani types Ia, Ic, and IVa who underwent surgery at the Hokkaido Medical Center for Child Health and Rehabilitation between November 2007 and June 2023. We defined total AMY exposure in bile as bile AMY levels multiplied by the patient\'s age (months), representing amount of estimated AMY exposure until surgery. We retrospectively investigated the relationships between bile AMY levels and clinicopathological findings.
RESULTS: All patients exhibited hyperplasia in the gallbladder and bile duct epithelium, with dysplasia observed in 13 cases, but no carcinoma. Exposure to bile AMY ≥ 662,400 IU/L × months was an independent risk factor for dysplasia.
CONCLUSIONS: The amount of estimated AMY exposure in bile rather than AMY levels in the bile is an independent risk factor for dysplasia in the biliary mucosa.

BACKGROUND: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) marked by rectal and colon inflammation, leading to relapsing symptoms. Its prevalence is increasing, particularly in developed nations, impacting patients\' health. While its exact cause remains unclear, genetic and environmental factors are implicated, elevating the risk of colorectal cancer (CRC). Colectomy, though declining, is still performed in select UC cases, necessitating further study.
METHODS: We analyzed data from the Iranian Registry of Crohn\'s and Colitis (IRCC) to examine UC patients undergoing colectomy. We collected demographic and clinical data from 91 patients, focusing on dysplasia. Statistical analyses assessed dysplasia risk factors.
RESULTS: Patients with dysplasia were older at diagnosis and surgery compared to those without dysplasia. Age emerged as a significant risk factor for dysplasia in UC patients undergoing colectomy. No significant associations were found between dysplasia and other factors.
CONCLUSIONS: Age plays a crucial role in dysplasia risk among UC patients undergoing colectomy. Older age at diagnosis and surgery may indicate a higher risk of dysplasia and CRC. Clinicians should consider age when managing UC patients and implementing screening protocols. Further research with larger samples is needed to confirm these findings.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates reaching 60%, mainly due to its excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules exhibiting expressional dysregulation in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting seed-matching and the reverse interplay between miRNA levels and their target genes\' expression. Incorporating gene-expression data from our group\'s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia, and early invasion, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is under-expressed in dysplasia and early invasion. The malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p, and miR-34a-5p. The identification of stage-specific miRNAs may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Despite advancements in treatment, the squamous cell carcinoma (OSCC) patient survival rate remains stagnant. Conventional therapies have limited effectiveness, necessitating novel agents. Our study aims to synthesize and characterize amorphous calcium phosphate nanoparticles (nACPs), assess their potential cytotoxic effects on premalignant and malignant OSCC cells, and investigate possible mechanisms of action. The morphological features of nACP were investigated by field emission scanning coupled with energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), and particle size distribution (PSD). Then, we examined the effect of nACPs on nanoparticle uptake, cell adhesion, viability, invasion ability, cell cycle, and gene expression. nACP uptake was dose-dependent, induced limited selectivity in cytotoxicity between healthy and malignant cells, and affected cellular adhesion and invasion. Early apoptosis was the predominant type of cell death. The nACP effect on viability was verified by alterations in the genes associated with apoptosis and proliferation. A high concentration of nACP was shown to arrest the cell cycle progression in the G0/G1 phase of both malignant and premalignant cells. This type of nACP justifies the development of a strategy for its potential use as an anti-cancer agent and/or anti-cancer active carrier for various drugs in oral cancer treatments.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colitis-associated neoplasia (CAN), including colorectal cancer (CRC), through the inflammation-dysplasia-neoplasia pathway. Dysplasia is the most reliable, early and actionable marker for CAN in these patients. While such lesions are frequently encountered, adequate management depends on an accurate assessment, complete resection and close surveillance. With recent advances in endoscopic technologies and research in the field of CAN, the management of dysplastic lesions has significantly improved. The American Gastroenterology Association and Surveillance for Colorectal Endoscopic Neoplasia Detection (SCENIC) provide a guideline framework for approaching dysplastic lesions in patients with IBD. However, there are significant gaps in these recommendations and real-world clinical practice. Accurate lesion assessment remains pivotal for adequate management of CAN. Artificial intelligence-guided modalities are now increasingly being used to aid the detection of these lesions further. As the lesion detection technologies are improving, our armamentarium of resection techniques is also expanding and includes hot or cold polypectomy, endoscopic mucosal resection, endoscopic sub-mucosal dissection and full-thickness resection. With the broadened scope of endoscopic resection, the recommendations regarding surveillance after resection has also changed. Certain patient populations such as those with invisible dysplasia or with prior colectomy and ileal pouch anal anastomosis need special consideration. In the present review, we aim to provide a state-of-the-art summary of the current practice of endoscopic detection, resection and surveillance of dysplasia in patients with IBD and provide some perspective on the future directions based on the latest research.

Juvenile polyposis syndrome lies within the family of hamartomatous polyposis syndromes characterized by polyps that appear benign but harbor an increased risk of colorectal and gastric cancer. This 27-year-old man with severe ulcerative colitis was discovered to have concomitant juvenile polyposis syndrome during diagnostic workup for gastrointestinal bleeding. The implications of this rare association complicate both diagnostic and treatment modalities since both diseases confer an increased risk of cancer.

UNASSIGNED: The causes of pedicle cleft include congenital dysplasia and stress fractures, both of which are rare conditions. Secondary lumbar spondylolisthesis with combined unilateral pedicle cleft and contralateral spondylolysis is extremely rare and can be easily misdiagnosed. We report two cases with these conditions from different causes and discuss the diagnostic and therapeutic features in the context of the literature review.
UNASSIGNED: Case 1 was a 58-year-old female with a stress fracture change at the left L5 pedicle. Case 2 was a 47-year-old female with a pedicle cleft due to hypoplasia of the left L5 pedicle. Both patients had a combined contralateral spondylolysis and Meyerding grade one lumbar spondylolisthesis, while neither had a clear history of lumbar trauma. After initial conservative treatments failed, both patients underwent a single-segment posterior lumbar interbody fusion with bilateral pedicle screw fixation. Both patients were followed up for more than 1 year postoperatively with clinical symptom relief and bony fusion at the pedicle cleft suggested by a CT scan.
UNASSIGNED: Lumbar spondylolisthesis with unilateral pedicle cleft and contralateral spondylolysis is rarely reported and can be clinically misdiagnosed as simple spondylolisthesis with bilateral spondylolysis. There is no widely accepted surgical option for patients for whom conservative treatment has failed. Our experience suggests that good clinical results may be achieved by single-segment posterior interbody fusion and bilateral pedicle screw fixation. Precise screw placement into the deficient pedicle and sufficient exiting nerve decompression are prerequisites for the success of this surgical option.