Randomized controlled trial of effects of a familiarization video and patient-controlled Entonox inhalation on patient stress levels and clinical efficacy of flexible sigmoidoscopy without analgesia or sedation for investigation of fresh rectal bleeding.

BACKGROUND AND AIM: Flexible sigmoidoscopy (FS) without analgesia or sedation can be unpleasant for patients, resulting in unsatisfactory examinations. Prior familiarization videos (FVs) and intra-procedural Entonox inhalation have shown inconsistent effects. This study investigated their effects on undesirable participant factors (anxiety, stress, discomfort, pain, satisfaction, later unpleasant recall of procedure, and vasovagal reactions) and clinical effectiveness (extent of bowel seen, lesions detected, and procedural/recovery times). METHODS: This cluster-randomized single-center study evaluated 138 participants undergoing FS. There were 46 controls, 49 given access to FV, and 43 access to both FV and self-administered Entonox. Participant factors were measured by self-administered questionnaires, independent nurse assessments, and heart rate variability (HRV) metrics. RESULTS: Questionnaires showed that the FV group was slightly more tense and upset before FS, but knowledge of Entonox availability reduced anxiety. Nonlinear HRV metrics confirmed reduced intra-procedural stress response in the FV/Entonox group compared with controls and FV alone (P < 0.05). Entonox availability allowed more bowel to be examined (P < 0.001) but increased procedure time (P < 0.05), while FV alone had no effect. FV/Entonox participants reported 1 month after FS less discomfort during the procedure. Other comparisons showed no significant differences between treatment groups, although one HRV metric showed some potential to predict vasovagal reactions. CONCLUSIONS: Entonox availability significantly improved clinical effectiveness and caused a slight reduction in undesirable participant factors. The FV alone did not reduce undesirable participant factors or improve clinical effectiveness. Nonlinear HRV metrics recorded effects in agreement with stress reduction and may be useful for prediction of vasovagal events in future studies.

Development of high-quality artificial intelligence for computer-aided diagnosis in determining subtypes of colorectal cancer.

BACKGROUND AND AIM: There are no previous studies in which computer-aided diagnosis (CAD) diagnosed colorectal cancer (CRC) subtypes correctly. In this study, we developed an original CAD for the diagnosis of CRC subtypes. METHODS: Pretraining for the CAD based on ResNet was performed using ImageNet and five open histopathological pretraining image datasets (HiPreD) containing 3 million images. In addition, sparse attention was introduced to improve the CAD compared to other attention networks. One thousand and seventy-two histopathological images from 29 early CRC cases at Kyoto Prefectural University of Medicine from 2019 to 2022 were collected (857 images for training and validation, 215 images for test). All images were annotated by a qualified histopathologist for segmentation of normal mucosa, adenoma, pure well-differentiated adenocarcinoma (PWDA), and moderately/poorly differentiated adenocarcinoma (MPDA). Diagnostic ability including dice sufficient coefficient (DSC) and diagnostic accuracy were evaluated. RESULTS: Our original CAD, named Colon-seg, with the pretraining of both HiPreD and ImageNET showed a better DSC (88.4%) compared to CAD without both pretraining (76.8%). Regarding the attentional mechanism, Colon-seg with sparse attention showed a better DSC (88.4%) compared to other attentional mechanisms (dual: 79.7%, ECA: 80.7%, shuffle: 84.7%, SK: 86.9%). In addition, the DSC of Colon-seg (88.4%) was better than other types of CADs (TransUNet: 84.7%, MultiResUnet: 86.1%, Unet++: 86.7%). The diagnostic accuracy of Colon-seg for each histopathological type was 94.3% for adenoma, 91.8% for PWDA, and 92.8% for MPDA. CONCLUSION: A deep learning-based CAD for CRC subtype differentiation was developed with pretraining and fine-tuning of abundant histopathological images.

Toward a postbiotic era of microbiome science: Opportunities to advance immunotherapies for hepatocellular carcinoma.

The microbiome has revolutionized the field of cancer immunology and checkpoint therapeutics for gastrointestinal malignancies. Combating hepatocellular carcinoma (HCC) by immune checkpoint blockade (ICB) is a unique challenge due in part to chronic complications that arise from local and systemic metabolic dysfunctions. Gut microbial metabolites modulate key immunological processes that influence liver cancer susceptibility and resistance to ICB. This review discusses recent progresses in linking microbiota functions to HCC tumor immunity and highlights their therapeutic potential.

The safety of newly developed automatic temperature-controlled endobiliary radiofrequency ablation system for malignant biliary strictures: A prospective multicenter study.

BACKGROUND AND AIMS: Catheter-based endobiliary radiofrequency ablation (RFA) is an endoscopic local treatment for patients with malignant biliary stricture (MBS). However, excessive heating of the bile duct by the current RFA system can induce serious complications. Recently, a new RFA system with automatic temperature control was developed. In the present study, we examined the safety of the new RFA system in patients undergoing endobiliary RFA for extrahepatic MBS. METHODS: This prospective, multicenter study enrolled patients with unresectable or inoperable extrahepatic (> 2 cm from the hilum) MBS. Endobiliary RFA was performed using a newly developed RFA catheter (ELRA™, STARmed, Goyang, Korea) at a setting of 7 or 10 W for 120 s and with a target temperature of 80°C. A self-expandable metallic stent was inserted after endobiliary RFA. The rate of procedure-related adverse events was assessed. RESULTS: The 30 patients were enrolled in this study. Cholangiocarcinoma was diagnosed in 19 patients, pancreatic cancer was found in 9, and gallbladder cancers were recorded in 2. The mean stricture length was 22.1 ± 6.6 mm. Post-procedural adverse events occurred in three patients (10.0%; 2 mild pancreatitis and 1 cholangitis) without hemobilia and bile duct perforation. The pancreatitis and cholangitis resolved with conservative treatment. The cumulative duration of stent patency and survival were 236 and 383 days, respectively. CONCLUSIONS: Automatic temperature-controlled endobiliary RFA using a newly developed catheter was safely applied in patents with extrahepatic MBS. Further prospective studies are needed to confirm the efficacy of endobiliary RFA for MBS.

Doppler tissue perfusion parameters in recognizing pancreatic malignant tumors.

BACKGROUND: Histopathology, radiological imaging methods with the administration of contrast agents are efficient to differentiate focal lesions of the pancreas. Invasiveness, contrast toxicity, and limited accessibility ameliorate their application. Noninvasive and contrast-agent-free method could improve diagnostics and accelerate treatment. AIMS: The aim of the study is to evaluate the diagnostic properties of ultrasound parameters of organ perfusion in the detection of malignant tumors of the pancreas. METHODS: Thirty-six patients with a focal lesion of the pancreas underwent endosonography with color flow imaging and biopsy for histological evaluation. Five patients were excluded because of the absence of the Doppler signal in pancreatic lesion. In the dynamic tissue perfusion measurement (DTPM) means of flow velocity (FV), resistive index, pulsatility index, and perfusion relief intensity (PR) were estimated. RESULTS: In the group with malignant tumors FV was significantly lower compared with the group with inflammatory changes. In receiver operating characteristic (ROC) analysis FV below the optimal cut-off point of 2.382 cm/s identified patients with malignant lesions with a sensitivity of 92% and specificity of 90%. In the group with malignant tumors significantly lower values of PR in all considered percentiles were observed. Based on the ROC analysis in the group with solid tumors, it was found that PR25 ≤ 0.057 allowed to recognize malignancies with a sensitivity of 100% and specificity of 80%, and in the groups with solid and cystic tumors with a sensitivity of 100% and specificity of 79%. CONCLUSIONS: FV and PR intensity derived from DTPM are reliable markers in recognition of pancreatic malignant masses.

PNPLA3 in end-stage liver disease: alcohol consumption, hepatocellular carcinoma development, and transplantation-free survival.

BACKGROUND AND AIMS: The rs738409 variant (I148M) of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is associated with several liver malfunctions. Its impact on end-stage liver disease has not been addressed yet. METHODS: The I148M polymorphism was genotyped in a well-characterized cohort of 421 Caucasian patients and retrospectively analyzed from the time of enrollment at Eurotransplant. RESULTS: The G allele of the I148M variant was significantly overrepresented in patients with alcoholic liver disease (ALD, P < 0.001) and associated with hepatocellular carcinoma (HCC) development (odds ratio [OR] = 2.399; 95% confidence interval [CI]: 1.292-4.455; P = 0.008) while not affecting the other liver disease entities. Time until hydropic decompensation (P = 0.04) and hepatic encephalopathy (P = 0.043) was significantly impaired for ALD patients carrying either one or two mutated G alleles. Actuarial survival free of liver transplantation was further reduced for ALD carriers of the I148M variant (CC = 30.7 months ± 7.9, 95% CI: 15.1-46.2 vs CG/GG: 17.1 months ± 3.3, 95% CI: 3.3-10.6; P = 0.012) compared with wild-type patients. Cox multivariate analysis identified the PNPLA3 I148M genotype as an independent predictor actuarial survival free of liver transplantation (OR = 1.77; 95% CI: 1.27-2.47; P = 0.001). CONCLUSIONS: In end-stage liver disease patients, we identified ALD to be predominantly affected by the PNPLA3 I148M variant resulting in an increased risk of HCC and reduced transplantation free survival. Genetic testing of the I148M genotype in ALD patients awaiting liver transplantation might be beneficial for these patients.

Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN. AIM: We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN. METHODS: Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival. RESULTS: Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05). CONCLUSIONS: Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.

Hepatoid adenocarcinoma: A wolf in hepatocellular carcinoma's clothing.

Hepatoid adenocarcinoma (HAC) is a rare malignancy that may mimic hepatocellular carcinoma (HCC) given its hepatoid histologic appearance and production of alpha fetoprotein. Clinical management and prognosis of HAC varies considerably from HCC. We present two cases of metastatic HAC in a cirrhotic liver diagnosed after biopsy and histopathological evaluation. The cases underscore the importance of recognizing the limitations of diagnostic imaging and pursuing a biopsy where there is diagnostic uncertainty.