"Wet Heparin" and "Wet Saline" EUS-Guided Liver Biopsy Techniques Both Provide High Rates of Specimen Adequacy for Benign Parenchymal Liver Disease.

BACKGROUND: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a viable mean to obtain core tissue, but the optimal tools and techniques are still an area of active investigation. AIMS: (1) To compare tissue adequacy using "wet saline" (WS) vs. "wet heparin" (WH) technique (2) To compare post-procedure pain between EUS-LB and percutaneous liver biopsy (PLB). METHODS: Retrospective review of consecutive patients who underwent EUS-LB and PLB for benign parenchymal liver disease between May 2017 to October 2019 at a single tertiary veterans affairs medical center. RESULTS: About 257 biopsies from 217 patients were included. Among the 102 EUS-LB specimens, 53 were obtained using WS technique and 49 were obtained using WH technique. Specimen adequacy was similar in both groups. Median Aggregate Specimen Length (ASL) and length of longest piece did not differ significantly between WS and WH groups. Clots were present more frequently in the WS group. Among patients who underwent EUS-LB of both right and left liver lobes, an adequate biopsy was obtained in 85% of patients in the WS group and 96% of patients in the WH group. The percentage of patients experiencing immediate post-procedure pain was higher with PLB compared to EUS-LB, but these results were not statistically significant. CONCLUSIONS: Both WS and WH EUS-LB techniques can offer high rates of specimen adequacy with low rates of pain and other post-procedure complications.

Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus.

INTRODUCTION: Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. METHODS: This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. RESULTS: One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. DISCUSSION: EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia. Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.

Freud's B'nai B'rith Dream: Having Lost His Way, His "Brethren Were Unkind and Scornful ".

On Tuesday, April 24, 1900, three days after Passover, Freud gave a talk at his B'nai B'rith lodge on Emile Zola's utopian novel penned in self-exile in London, Fécondité (1899). The next day Freud wrote Wilhelm Fliess that the night before the talk he had a dream in which "[t]he brethren … were unkind and scornful of me." In the dream his brethren's contempt signifies that Freud is making his impious move to destroy their Tree of Life: no Law, no Judaism, no Christianity, no miserable anti-Semitism. In Freud's utopia, an enlightened socially just world grounded in reason, which mirrors the brotherly atheistic utopia envisioned in Fécondité, the seed of Abraham at long last can move across frontiers freely, develop their talents, and satisfy their needs.

Deep learning systems detect dysplasia with human-like accuracy using histopathology and probe-based confocal laser endomicroscopy.

Probe-based confocal laser endomicroscopy (pCLE) allows for real-time diagnosis of dysplasia and cancer in Barrett's esophagus (BE) but is limited by low sensitivity. Even the gold standard of histopathology is hindered by poor agreement between pathologists. We deployed deep-learning-based image and video analysis in order to improve diagnostic accuracy of pCLE videos and biopsy images. Blinded experts categorized biopsies and pCLE videos as squamous, non-dysplastic BE, or dysplasia/cancer, and deep learning models were trained to classify the data into these three categories. Biopsy classification was conducted using two distinct approaches-a patch-level model and a whole-slide-image-level model. Gradient-weighted class activation maps (Grad-CAMs) were extracted from pCLE and biopsy models in order to determine tissue structures deemed relevant by the models. 1970 pCLE videos, 897,931 biopsy patches, and 387 whole-slide images were used to train, test, and validate the models. In pCLE analysis, models achieved a high sensitivity for dysplasia (71%) and an overall accuracy of 90% for all classes. For biopsies at the patch level, the model achieved a sensitivity of 72% for dysplasia and an overall accuracy of 90%. The whole-slide-image-level model achieved a sensitivity of 90% for dysplasia and 94% overall accuracy. Grad-CAMs for all models showed activation in medically relevant tissue regions. Our deep learning models achieved high diagnostic accuracy for both pCLE-based and histopathologic diagnosis of esophageal dysplasia and its precursors, similar to human accuracy in prior studies. These machine learning approaches may improve accuracy and efficiency of current screening protocols.

Semi-Supervised Classification of Noisy, Gigapixel Histology Images.

One of the greatest obstacles in the adoption of deep neural networks for new medical applications is that training these models typically require a large amount of manually labeled training samples. In this body of work, we investigate the semi-supervised scenario where one has access to large amounts of unlabeled data and only a few labeled samples. We study the performance of MixMatch and FixMatch-two popular semi-supervised learning methods-on a histology dataset. More specifically, we study these models' impact under a highly noisy and imbalanced setting. The findings here motivate the development of semi-supervised methods to ameliorate problems commonly encountered in medical data applications.

Neuroinflammation in Murine Cirrhosis Is Dependent on the Gut Microbiome and Is Attenuated by Fecal Transplant.

Cirrhosis and hepatic encephalopathy (HE) is associated with an altered gut-liver-brain axis. Fecal microbial transplant (FMT) after antibiotics improves outcomes in HE, but the impact on brain function is unclear. The aim of this study is to determine the effect of colonization using human donors in germ-free (GF) mice on the gut-liver-brain axis. GF and conventional mice were made cirrhotic using carbon tetrachloride and compared with controls in GF and conventional state. Additional GF mice were colonized with stool from controls (Ctrl-Hum) and patients with cirrhosis (Cirr-Hum). Stools from patients with HE cirrhosis after antibiotics were pooled (pre-FMT). Stools from the same patients 15 days after FMT from a healthy donor were also pooled (post-FMT). Sterile supernatants were created from pre-FMT and post-FMT samples. GF mice were colonized using stools/sterile supernatants. For all mice, frontal cortex, liver, and small/large intestines were collected. Cortical inflammation, synaptic plasticity and gamma-aminobutyric acid (GABA) signaling, and liver inflammation and intestinal 16s ribosomal RNA microbiota sequencing were performed. Conventional cirrhotic mice had higher degrees of neuroinflammation, microglial/glial activation, GABA signaling, and intestinal dysbiosis compared with other groups. Cirr-Hum mice had greater neuroinflammation, microglial/glial activation, and GABA signaling and lower synaptic plasticity compared with Ctrl-Hum mice. This was associated with greater dysbiosis but no change in liver histology. Pre-FMT material colonization was associated with neuroinflammation and microglial activation and dysbiosis, which was reduced significantly with post-FMT samples. Sterile pre-FMT and post-FMT supernatants did not affect brain parameters. Liver inflammation was unaffected. Conclusion: Fecal microbial colonization from patients with cirrhosis results in higher degrees of neuroinflammation and activation of GABAergic and neuronal activation in mice regardless of cirrhosis compared with those from healthy humans. Reduction in neuroinflammation by using samples from post-FMT patients to colonize GF mice shows a direct effect of fecal microbiota independent of active liver inflammation or injury.

Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett's esophagus.

BACKGROUND: For surveillance of Barrett's esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 - 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking. METHODS: Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer. RESULTS: In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia. CONCLUSIONS: pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.