Treatment of Non-Anastomotic Biliary Strictures after Liver Transplantation: How Effective Is Our Current Treatment Strategy?

BACKGROUND: Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. METHODS: All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes. RESULTS: A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare. CONCLUSIONS: EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis.

Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

MELD-Lactate Predicts Poor Outcome in Variceal Bleeding in Cirrhosis.

BACKGROUND: Predictors of poor outcome associated with variceal bleeding remain suboptimal. In patients with cirrhosis, serum lactate combined with Model for End-Stage Liver Disease (MELD-LA) improved prediction across heterogeneous populations. However, prognostic properties have not yet been assessed in the context of variceal bleeding. AIMS: We aimed to evaluate the predictive performance of MELD-LA compared to MELD, lactate, and nadir hemoglobin in cirrhosis patients with variceal bleeding. METHODS: In this multicenter study, we identified 472 patients with variceal bleeding from a German primary cohort (University Hospitals Hamburg/Frankfurt/Cologne), and two independent external validation cohorts [Veterans Affairs (VA), Baylor University]. Discrimination for 30-day mortality was analyzed and scores were compared. MELD-LA was evaluated separately in validation cohorts to ensure consistency of findings. RESULTS: In contrast to nadir hemoglobin, MELD and peak-lactate at time of bleeding were significantly higher in 30-day non-survivors in the primary cohort (p = 0.708; p < 0.001). MELD-LA had excellent discrimination for 30-day mortality (AUROC 0.82, 95% CI 0.76-0.88), better than MELD and peak-lactate (AUROC 0.78, 95% CI 0.71-0.84; AUROC 0.73, 95% CI 0.66-0.81). MELD-LA predicted 30-day mortality independently of age, sex, severity of liver disease and vasopressor support (HR 1.29 per 1-point-increase of MELD-LA; 95% CI 1.19-1.41; p < 0.001). Similarly, MELD-LA demonstrated excellent discrimination for 30-day mortality in the VA (AUROC = 0.86, 95% CI 0.79-0.93) and Baylor cohort (AUROC = 0.85, 95% CI 0.74-0.95). CONCLUSIONS: MELD-LA significantly improves discrimination of short-term mortality associated with variceal bleeding, compared to MELD, peak-lactate and nadir hemoglobin. Thus, MELD-LA might represent a useful and objective marker for risk assessment and therapeutic intervention in patients with variceal bleeding.

Cutaneous Basal Cell Carcinoma: Does Noninvasive Ventilation Accelerate Tumor Progression?

A 56-year-old woman presented to the emergency to be department with diarrhea, asthenia, cough, and dysgeusia. The patient had chronic obstructive pulmonary disease (COPD) and was found infected with coronavirus disease 2019 (COVID-19). On physical examination, a small basal cell carcinoma (BCC) lesion was identified on her scalp; however, following the administration of noninvasive ventilation, the appearance of both macroscopic and microscopic BCC worsened dramatically. Our findings point to positive pressure noninvasive ventilation used to treat COVID-19 associated with COPD as a possible causative agent for the progression of cutaneous BCC. (SKINmed. 2022;20:463-465).

A faecal microbiota signature with high specificity for pancreatic cancer.

BACKGROUND: Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) aetiology and progression. OBJECTIVE: To explore the faecal and salivary microbiota as potential diagnostic biomarkers. METHODS: We applied shotgun metagenomic and 16S rRNA amplicon sequencing to samples from a Spanish case-control study (n=136), including 57 cases, 50 controls, and 29 patients with chronic pancreatitis in the discovery phase, and from a German case-control study (n=76), in the validation phase. RESULTS: Faecal metagenomic classifiers performed much better than saliva-based classifiers and identified patients with PDAC with an accuracy of up to 0.84 area under the receiver operating characteristic curve (AUROC) based on a set of 27 microbial species, with consistent accuracy across early and late disease stages. Performance further improved to up to 0.94 AUROC when we combined our microbiome-based predictions with serum levels of carbohydrate antigen (CA) 19-9, the only current non-invasive, Food and Drug Administration approved, low specificity PDAC diagnostic biomarker. Furthermore, a microbiota-based classification model confined to PDAC-enriched species was highly disease-specific when validated against 25 publicly available metagenomic study populations for various health conditions (n=5792). Both microbiome-based models had a high prediction accuracy on a German validation population (n=76). Several faecal PDAC marker species were detectable in pancreatic tumour and non-tumour tissue using 16S rRNA sequencing and fluorescence in situ hybridisation. CONCLUSION: Taken together, our results indicate that non-invasive, robust and specific faecal microbiota-based screening for the early detection of PDAC is feasible.

Trends and the course of liver cirrhosis and its complications in Germany: Nationwide population-based study (2005 to 2018).

BACKGROUND: Cirrhosis is known to have a high prevalence and mortality worldwide. However, in Europe, the epidemiology of cirrhosis is possibly undergoing demographic changes, and etiologies may have changed due to improvements in standard of care. The aim of this population-based study was to analyze the trends and the course of liver cirrhosis and its complications in recent years in Germany. METHODS: We analyzed the data of all hospital admissions in Germany within diagnosis-related groups from 2005 to 2018. The diagnostic records of cirrhosis and other categories of diseases were based on ICD-10-GM codes. The primary outcome measurement was in-hospital mortality. Trends were analyzed through Poisson regression of annual number of admissions. The impact of cirrhosis on overall in-hospital mortality were assessed through the multivariate multilevel logistic regression model adjusted for age, sex, and comorbidities. FINDINGS: Of the 248,085,936 admissions recorded between 2005 and 2018, a total of 2,302,171(0•94%) were admitted with the diagnosis of cirrhosis, mainly as a comorbidity. Compared with other chronic diseases, patients admitted with cirrhosis were younger, mainly male and had the highest in-hospital mortality rate. Diagnosis of cirrhosis was an independent risk factor of in-hospital mortality with the highest odds ratio (OR:6•2[95%CI:6.1-6•3]) among all diagnoses. The prevalence of non-alcoholic fatty liver disease has increased four times from 2005 to 2018, while alcoholic cirrhosis is 20 times than other etiologies. Bleeding was found to be decreasing over time, but ascites remained the most common complication and was increasing. INTERPRETATION: This nationwide study demonstrates that cirrhosis represents a considerable healthcare burden, as shown by the increasing in-hospital mortality, also in combination with other chronic diseases. Alcohol-related cirrhosis and complications are on the rise. More resources and better management strategies are warranted. FUNDING: The funders had no influence on this study.

Variceal bleeding has increased mortality compared to nonvariceal bleeding only in males.

BACKGROUND: Gastrointestinal bleedings (GIBs) are frequent in cirrhotic patients and lead to high morbidity and mortality. Lately, there have been conflicting reports on the role of and bleeding type [variceal bleeding and nonvariceal bleeding (NVB)]. This study investigated the predictors of mortality in patients with variceal bleeding and NVB with relationship to sex differences. MATERIALS AND METHODS: A total of 271 patients with suspected upper GIB who underwent endoscopy were included. Patients were followed up at 1 week, 6 months and 1 year after admission. Univariate and multivariate logistic or Cox regression analyses investigated correlations of predictive factors and clinical outcomes. Propensity score matching was performed to control for severity of disease and compare groups for sex and bleeding type. RESULTS: A total of 42 patients were excluded (cirrhosis or bleeding not confirmed). The remaining patients were classified by bleeding type into patients with variceal bleeding (n = 115) or NVB (n = 156). Males (n = 155) had higher mortality in variceal bleeding than in NVB, while in females (n = 116) mortality was similar in the two bleeding types. This was confirmed after matching in males (n = 116) and females (n = 82). Further independent predictors of mortality in males were model for end-stage liver disease (MELD) at baseline, blood urea nitrogen, alanine aminotransferase, while in females age, leukocytes, MELD, history of ascites and hepatic encephalopathy. CONCLUSION: This study shows that variceal bleeding has higher mortality in males compared to NVB, while in females the type of GIB does not impact the outcome. This highlights that sex-specific clinical management should be based on bleeding type after endoscopy.

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.

High-Intensity Focused Ultrasound for Pain Management in Patients with Cancer.

Cancer-related pain affects up to 80% of patients with malignancies. Pain is an important distressing symptom that diminishes the quality of life and negatively affects the survival of patients. Opioid analgesics are generally the primary therapy for cancer-related pain, with surgery, radiation therapy, chemotherapy, and other interventions used in cases of treatment-resistant pain. These treatments, which can be associated with substantial side effects and systemic toxicity, may not be effective. High-intensity focused ultrasound is an entirely noninvasive technique that is approved for treatment of uterine fibroids, bone metastases, and essential tremors. With magnetic resonance imaging or ultrasonographic guidance, high-intensity ultrasound waves are focused on a small well-demarcated region to result in precise localized ablation. This treatment may represent a multimodality approach to treating patients with malignant diseases-facilitating pain palliation, enhanced local drug delivery and radiation therapy effects, and stimulation of anticancer specific immune responses, and potentially facilitating local tumor control. Focused ultrasound can be used to achieve pain palliation by producing several effects, including tissue denervation, tumor mass reduction, and neuromodulation, that can influence different pathways at the origin of the pain. This technology has several key advantages compared with other analgesic therapies: It is completely noninvasive, might be used to achieve rapid pain control, can be safely repeated, and can be used in combination with chemotherapy and radiation therapy to enhance their effects. Online supplemental material is available for this article. ©RSNA, 2018.