Cytokine storm and severe hepatitis in pregnancy due to herpes simplex virus 2.

CASE PRESENTATION: A pregnant woman developed hepatitis due to a herpes simplex virus 2 primary infection with a severe systemic inflammatory response. Treatment with acyclovir and human immunoglobulin was given and both mother and baby survived. PURPOSE: We provide the first description of the inflammatory response associated with herpetic hepatitis in pregnancy.

Endoscopic Ultrasound-guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND AND AIMS: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. METHODS: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. RESULTS: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). CONCLUSIONS: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

Endomyocardial fibrosis of the right ventricle: A case report of successful surgery.

AIMS: The case we report, shows a successful treatment of right ventricle endomyocardial fibrosis. MATERIALS AND METHODS: Surgical therapy by endocardial decortication seems to be beneficial for many patients with advanced disease who are in functional-therapeutic class III or IV. The operative mortality rate is high, but successful surgery has a clear benefit on symptoms and seems to favourably affect survival as well.

The presence of rapid on-site evaluation did not increase the adequacy and diagnostic accuracy of endoscopic ultrasound-guided tissue acquisition of solid pancreatic lesions with core needle.

BACKGROUND: Rapid on-site evaluation (ROSE) improves the adequacy and accuracy of EUS-guided tissue acquisition, although it is not routinely widely available. Evidence suggested that core needles might overcome the absence of ROSE. The aim of this study was to evaluate the influence of ROSE on the adequacy and accuracy of EUS-guided tissue acquisition with core needles in patients with pancreatic solid lesions. METHODS: Patients who underwent EUS-guided tissue acquisition of pancreatic mass lesions were retrospectively identified at three tertiary referral centers and those performed with the core needle were included. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without ROSE was the primary outcome measure. The diagnostic accuracy and tissue core acquisition were the secondary outcome measures. RESULTS: A total of 333 patients with pancreatic solid mass lesions were included in the study; 140 cases sampled with ROSE and 193 cases without ROSE. The adequacy was 92.1 % in the group sampled with ROSE and 88.1 % in the group without ROSE (p = 0.227). In the ROSE group sensitivity, specificity, and accuracy were 90.7, 100 and 92.1 %, respectively. In the group without ROSE, sensitivity, specificity, and accuracy were 87.2, 100, and 88.1 %, respectively. No difference for all these figures was observed between the two groups. The tissue core was available in 61.4 and 53.4 % of cases with and without ROSE, respectively (p = 0.143). CONCLUSION: In the absence of ROSE, EUS-based tissue acquisition with Core needle should be considered since it achieves comparable tissue sampling adequacy and accuracy.

Incorporating the hepatobiliary phase of gadobenate dimeglumine-enhanced MRI in the diagnosis of hepatocellular carcinoma: increasing the sensitivity without compromising specificity.

BACKGROUND: Diagnosis of hepatocellular carcinoma (HCC) is centered on wash-in of contrast during the arterial phase followed by washout during the portal or delayed venous phase. Nodules showing hypointensity on the hepatobiliary phase are also likely to represent HCC, however, the role of this phase is not yet established. PURPOSE: To investigate the role of the hepatobiliary phase on Gadobenate dimeglumine (Gd-BOPTA) magnetic resonance imaging (MRI) in characterizing HCCs lacking the typical arterial enhancement and venous washout. MATERIAL AND METHODS: Ninety-seven cirrhotic patients (78 men, 19 women; mean age, 58.5 years) who underwent liver transplantation (2004-2012) and Gd-BOPTA enhanced MRI within 3 months of surgery were retrospectively reviewed. A nodule-by-nodule analysis was performed, followed by liver explant correlation. Statistical analysis was then performed by a biostatistician using commercially available software. RESULTS: A total of 193 HCCs were found in 97 liver explants, of which 24.9% (48/193) were not detectable on imaging. The 145 HCCs seen on imaging showed the typical wash-in/washout pattern (Pattern A) in 46.9% (68/145), arterial enhancement without washout (Pattern B) in 37.9% (55/145), and hypovascularity on arterial and venous sequences (Pattern C) in 15.2% (22/145). Pattern A was exclusive to HCC. Twenty-three of the 55 HCCs showing Pattern B were also hypointense on the hepatobiliary phase (Pattern B1). Combining Pattern B1 with Pattern A raises the sensitivity of HCC characterization from 46.9% to 62.8% (P = 0.007), with no significant compromise on specificity. CONCLUSION: When coupled with Pattern A, Pattern B1 augments sensitivity of HCC characterization with no significant compromise on the specificity.

Underwater colorectal EMR: remodeling endoscopic mucosal resection.

BACKGROUND: Underwater EMR (UEMR) has been reported as a new technique for the removal of large sessile colorectal polyps without need for submucosal injection. OBJECTIVE: To evaluate (1) outcomes of UEMR, (2) whether UEMR can be easily performed by an endoscopist skilled in traditional EMR without specific dedicated training in UEMR, and (3) whether EUS is required before UEMR. DESIGN: Prospective, observational study. SETTING: Single, tertiary-care referral center. INTERVENTION: Underwater EMR. MAIN OUTCOME MEASUREMENTS: Complete resection and adverse events. RESULTS: A total of 72 consecutive patients underwent UEMR of 81 sessile colorectal polyps. EUS was performed before UEMR in 9 cases (11.1%) with a suspicious mucosal/vascular pattern. The mean polyp size was 18.7 mm (range 10-50 mm); the mean UEMR time was 11.8 minutes. Fifty-five polyps (68%) were removed en bloc, and 26 (32%) were removed with a piecemeal technique. Histopathology consisted of tubular adenomas (25.9%), tubulovillous adenomas (5%), adenomas with high-grade dysplasia (42%), serrated polyps (4.9%), carcinoma in situ (13.6%), and hyperplastic polyps (8.6%). Surveillance colonoscopy was scheduled at 3 months. Complete resection was successful in all patients. No adverse events or recurrence was recorded in any of the patients. LIMITATIONS: Limited follow-up; single-center, uncontrolled study. CONCLUSION: Interventional endoscopists skilled in conventional EMR performed UEMR without specific dedicated training. EUS may not be required for lesions with no invasive features on high-definition narrow-band imaging. UEMR appears to be an effective and safe alternative to traditional EMR and could eventually improve the way in which we can effectively and safely treat colorectal lesions.

Endoscopic ultrasound-guided fine-needle biopsy of small solid pancreatic lesions using a 22-gauge needle with side fenestration.

BACKGROUND: Early detection of small pancreatic cancer is important because expected survival is markedly better for tumors ≤ 2 cm. A new endoscopic ultrasound-(EUS) guided biopsy needle with side fenestration has been recently developed to enable fine-needle biopsy (FNB) under EUS guidance. The aim of this study was to evaluate the outcome of EUS-FNB using a 22-gauge ProCore needle in solid pancreatic lesions ≤ 2 cm, in terms of diagnostic accuracy and yield. METHODS: From January 2011 to December 2012, all consecutive EUS-guided tissue sampling of small pancreatic lesions (≤ 2 cm) were performed using 22-gauge ProCore needles; the data of these patients were analyzed retrospectively. RESULTS: Sixty-eight patients with a mean age of 65.7 years were included. The mean lesion size was 16.5 mm (range 5-20). None of the patients developed complications. On pathological examination, the tissue retrieved was judged adequate in 58 out of 68 cases (85.3 %) and the presence of a tissue core was recorded in 36 out of 68 cases (52.9 %). The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80, 100, 100, 40, and 82 %, respectively. CONCLUSION: Our results suggested that EUS-FNB of small pancreatic lesions using a 22-gauge ProCore needle is effective and safe, and supports our hypothesis that EUS-FNB is highly useful in establishing the nature of small pancreatic lesions.

US-guided percutaneous liver biopsy in pediatric liver transplant recipients.

OBJECTIVES: The present study assesses the safety of ultrasound (US)-guided percutaneous liver biopsies (PLBs) within pediatric liver allograft recipients, describes the pathological results according to early (≤12 months) and late (>12 months) posttransplantation periods, and analyzes the value of liver function tests (LFTs) and Doppler US variables in determining these results. METHODS: A total of 219 US-guided PLBs in 85 pediatric patients with liver transplant (mean age 7 ±â€Š5 years, range: 6 months to 18 years) performed between March 2005 and May 2012 were retrospectively evaluated at a single institution. Doppler US and LFT evaluation (including total bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, alkaline phosphatase) occurred within 1 day of early (n = 92, 42%) and late term (n = 127, 58%) posttransplantation biopsies. RESULTS: The rate of major complications (hemorrhage requiring blood transfusion) was 0.91% (n = 2). The early versus late term biopsy results, respectively, included: cholestasis at 36% versus 18% (P = 0.003), minimal changes 16% versus 24% (not significant [NS]), acute rejection 13% versus 5% (P = 0.027), inflammatory diseases 15% versus 15% (NS), indeterminate acute rejection 11% versus 7% (NS), chronic rejection 4% versus 14% (P = 0.017), fibrotic diseases 4% versus 12% (NS), and other 0% versus 5% (NS). Neither LFT nor US variables were correlated with pathological outcomes. CONCLUSIONS: The rate of complications in pediatric patients after US-guided liver biopsy is low. A range of pathological results exists between early and late posttransplantation liver biopsies. LFT and Doppler US findings are not predictors of pathological results.

Telemedicine in Patients Affected by Chronic Liver Disease: A Scoping Review of Clinical Outcomes and the Devices Evaluated.

For patients with chronic liver disease (CLD), telemedicine is emerging as a useful tool to prevent liver decompensation or hospitalization, allowing access to and the decentralization of care, even for patients with limited resources. However, research and attendant evidence are still lacking; thus, this review aims to systematically explore the topic of telemonitoring for CLD to describe the currently used tools and clinical outcomes. The review was conducted by using key terms on PubMed/EMBASE and searching for observational studies or clinical trials (according to PRISMA recommendations) that were published between 6 April 2013 and 6 April 2023 to keep the technological framework limited to the last 10 years. The studies were described and grouped according to the aim of telemonitoring, the underlying disease, and the tools adopted to achieve remote monitoring. A total of 32 articles met the inclusion criteria. Of these, 11 articles report the successful use of a telehealth program to support and improve access to care in the management of HCV-related cirrhosis, eight articles examine the efficacy of telemedicine for remote monitoring interventions to prevent or decrease the risk of decompensation in high-risk patients, and five articles examine improvements in the physical performance and quality of life of cirrhotic patients through telehealth rehabilitation programs. Four studies were completed during the recent COVID-19 pandemic. Telehealth has the potential to provide and expand treatment access and reduce barriers to care for the most disadvantaged patients and might be able to reduce the need for hospital readmission for CLD, though most practice to test feasibility is still in the pilot stage.

Intraductal aspiration: a promising new tissue-sampling technique for the diagnosis of suspected malignant biliary strictures.

BACKGROUND: Brushing is the most commonly used technique for biliary sampling at ERCP, despite its limited sensitivity. OBJECTIVE: To evaluate intraductal aspiration (IDA) as a new combined endoscopic technique for cytodiagnosis, its cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. DESIGN: Prospective, observational study. SETTING: Single tertiary referral center. MAIN OUTCOME MEASUREMENTS: IDA cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. PATIENTS AND METHODS: From April 2009 to September 2010, 42 consecutive patients with suspected malignant biliary stricture underwent ERCP, with tissue sampling obtained with IDA. IDA included performance of standard brushing in all patients. After standard brushing, to perform IDA, we removed the brush from its catheter and used the tip of the catheter as a scraping device. The tip was scraped back and forth across the stricture at least 10 times. The catheter and a suction line were connected to a specimen trap to obtain intraductal aspiration of fluids and samplings. RESULTS: Our cytopathologists found adequate cellular yield in 39 of the 42 IDA samples (92.8%) versus 15 of the 42 brushing samples (35.7%) (P < .001). IDA showed a significantly higher sensitivity than brushing (89% vs 78% for adequate samples and 89% vs 37% for all samples) and provided significantly superior cellular adequacy (92.8% vs 35.7%). LIMITATIONS: Observational study, small number of patients. CONCLUSIONS: IDA significantly improves brushing cellular adequacy and has high sensitivity for cancer detection. It was also safe, simple, rapid, and applicable during routine diagnostic ERCP, with no additional costs.

Donor Preconditioning with Inhaled Sevoflurane Mitigates the Effects of Ischemia-Reperfusion Injury in a Swine Model of Lung Transplantation.

Primary graft dysfunction (PGD) and ischemia-reperfusion injury (IRI) occur in up to 30% of patients undergoing lung transplantation and may impact on the clinical outcome. Several strategies for the prevention and treatment of PGD have been proposed, but with limited use in clinical practice. In this study, we investigate the potential application of sevoflurane (SEV) preconditioning to mitigate IRI after lung transplantation. The study included two groups of swines (preconditioned and not preconditioned with SEV) undergoing left lung transplantation after 24-hour of cold ischemia. Recipients' data was collected for 6 hours after reperfusion. Outcome analysis included assessment of ventilatory, hemodynamic, and hemogasanalytic parameters, evaluation of cellularity and cytokines in BAL samples, and histological analysis of tissue samples. Hemogasanalytic, hemodynamic, and respiratory parameters were significantly favorable, and the histological score showed less inflammatory and fibrotic injury in animals receiving SEV treatment. BAL cellular and cytokine profiling showed an anti-inflammatory pattern in animals receiving SEV compared to controls. In a swine model of lung transplantation after prolonged cold ischemia, SEV showed to mitigate the adverse effects of ischemia/reperfusion and to improve animal survival. Given the low cost and easy applicability, the administration of SEV in lung donors may be more extensively explored in clinical practice.

Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling.

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA.

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

BACKGROUND: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. METHODS: 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators. RESULTS: Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07-13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12-2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03-1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13-0.93, p = 0.036). CONCLUSIONS: multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

A fatal case of a paint thinner ingestion: comparison between toxicological and histological findings.

Toluene and xylene are aromatic hydrocarbons commonly used as an industrial solvent for the manufacturing of pharmaceuticals, paints, and chemicals. The Occupational Safety and Health Administration has determined that toluene levels of 2000 parts per million (ppm) are considered dangerous to life and health. Several studies have examined the absorption of toluene and xylene following inhalation and oral ingestion in humans. Volatile organic compounds that are absorbed into the blood are distributed throughout the body; in particular, distribution of absorbed toluene and xylene in humans and rodents is characterized by preferential uptake in well-perfused and lipophil tissues such as the brain, liver, lungs, and body fat and also in central nervous system. The available studies indicate that xylenes are rapidly absorbed independently from the kind of exposition. We illustrate a fatal case of self-poisoning by ingestion of varnishes diluting solvents, reporting the identification and quantification of volatile organic compounds (toluene, o-m-p xylene) from human biologic liquids and viscera samples using the Solid-Phase Microextraction-Headspace-Gas Chromatography/Mass Spectrometry to toxicological analysis, and the histopathological findings evaluated in liver, kidney, and lungs.