Is Long-Term Survival in Metastases from Neuroendocrine Neoplasms Improved by Liver Resection?

Background and Objectives: Although many of the neuroendocrine neoplasms (NEN) have a typically prolonged natural history compared with other gastrointestinal tract cancers, at least 40% of patients develop liver metastases. This study aims to identify whether liver resection improves the overall survival of patients with liver metastases from NEN. Materials and Methods: We conducted a retrospective study at “Fundeni” Clinical Institute over a time period of 15 years; we thereby identified a series of 93 patients treated for NEN with liver metastases, which we further divided into 2 groups as follows: A (45 patients) had been subjected to liver resection complemented by systemic therapies, and B (48 patients) underwent systemic therapy alone. To reduce the patient selection bias we performed at first a propensity score matching. This was followed by a bootstrapping selection with Jackknife error correction, with the purpose of getting a statistically illustrative sample. Results: The overall survival of the matched virtual cohort under study was 41 months (95% CI 37–45). Group A virtual matched patients showed a higher survival rate (52 mo., 95% CI: 45–59) than B (31 mo., 95% CI: 27–35), (p < 0.001, Log-Rank test). Upon multivariate analysis, seven independent factors were identified to have an influence on survival: location (midgut) and primary tumor grading (G3), absence of concomitant LM, number (2–4), location (unilobar), grading (G3) of LM, and 25–50% hepatic involvement at the time of the metastatic disease diagnosis. Conclusions: Hepatic resection is nowadays the main treatment providing potential cure and prolonged survival, for patients with NEN when integrated in a multimodal strategy based on systemic therapy.

Predictors of heart failure symptoms in hereditary hemorrhagic telangiectasia patients with hepatic arteriovenous malformations

Background Hepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms. Results 176 patients with HHT were evaluated with computed tomography angiography (CTA) between April 2004 and February 2019 at our HHT Center of Excellence. 63/176 (35.8%) patients were found to have hepatic AVMs on CTA. 18 of these patients were excluded because of the presence of another condition which could confound evaluation of heart failure symptoms. In the remaining 45 patients included in our cohort, 25/45 (55.6%) patients were classified as asymptomatic and 20/45 (44.4%) were classified as symptomatic, and these groups were compared. In symptomatic patients, mean common hepatic artery (CHA) diameter was significantly higher (11.1 versus 8.4 mm) and mean hemoglobin levels were significantly lower (10.7 vs 12.6 g/dL). A stepwise multiple logistic regression analysis demonstrated that both CHA diameter and hemoglobin level were independent predictors of heart failure symptoms with ORs of 2.554 (95% CI 1.372–4.754) and 0.489 (95% CI 0.299–0.799), respectively. The receiver operator characteristic (ROC) curve of our analysis demonstrated an AUC of 0.906 (95% CI 0.816–0.996), sensitivity 80.0% (95% CI 55.7–93.4%), and specificity 75.0% (95% CI 52.9–89.4%). Conclusions CTA is an effective and easily reproducible method to evaluate hepatic involvement of HHT. Utilizing CTA, clinical, and laboratory data we determined CHA diameter and hemoglobin level were independent predictors of heart failure symptoms.

Imaging of Biliary Involvement in Sarcoidosis: Computed Tomography, Magnetic Resonance Cholangiopancreatography, and Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid-Enhanced Magnetic Resonance Imaging Findings

Sarcoidosis is a multisystem disease usually affecting the chest, hilar lymph nodes, and lungs, but can potentially involve any organ; therefore, its clinical presentation may vary. Hepatobiliary involvement is rare, and typically asymptomatic; however, it can lead to cirrhosis, and may require liver transplantation. In this report, we present a rare case of a patient affected by sarcoidosis with hepatobiliary involvement. He presented to our hospital complaining of dyspnea triggered by moderate efforts and oppressive thoracic discomfort. Chest X-ray showed multiple bilateral nodular opacities and enlargement of both hilar regions, confirmed by a subsequent total-body computed tomography scan and positron emission tomography, which also revealed cardiac, splenic, and hepatic involvement. Liver function was studied via gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging, and magnetic resonance cholangiopancreatography (MRCP) was also performed. The diagnosis of sarcoidosis was finally achieved via liver biopsy, revealing non-necrotizing granulomas in the periportal space. The patient was treated with prednisone per os, with regression of all lesions at all levels. Although other cases of biliary sarcoidosis have been described, this report provides a complete image set of Gd-EOB-DTPA-enhanced magnetic resonance and MRCP images that is lacking in the English literature, and which may be useful for diagnosis.

Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis

Objectives Glycogen storage diseases (GSDs) are heterogeneous disorders caused by various enzyme deficiencies. GSD type IX α2, the most common subtype of GSD IX, is due to a deficiency of hepatic phosphorylase kinase. Herein we will report a novel mutation in this disease with an unusual presentation. Case presentation we describe a 3-year-old boy who suffered from hepatomegaly, fatty liver disease, and liver cirrhosis. The cause of cirrhosis at a young age was unknown based on the laboratory data and liver biopsy, so we performed a targeted-gene sequencing (TGS) covering 450 genes involved in inborn metabolic diseases consisting of glycogen storage disorders genes with hepatic involvement. He was found out to have a rare novel pathogenic variant in the PHKA2 gene. Conclusions This novel variant c.2226+2T > C expands the mutational spectrum of the PHKA2 gene. Also, severe liver damage (cirrhosis) in patients with GSD- IX α2 has rarely been reported, which needs further discussion. We hypothesize that unidentified PHKA2 variants may be a rare cause of childhood liver cirrhosis.

Clinical profile of post flood fever in a tertiary care hospital in Kerala

Background: Floods are an important source of infection epidemic worldwide. Analysis of different infections presenting during floods can lead us to have a unified approach during such periods.Methods: This study describes the clinical features of fever patients presented to a tertiary care hospital in Kerala after the 2018 flood. Clinical findings of the confirmed leptospirosis cases were also compared with non-leptospirosis cases.Results: A total of 48 patients with fever and myalgia were studied and majority of them were males (77%). 40 patients had contact with contaminated water. But only 10 of them had taken prophylactic doxycycline. Complications were seen less among those who took prophylactic doxycycline. The mean time from the first symptom to first medical care was 4.4 days. Leptospirosis was seen among 15 patients and 2 patients had dengue fever. Hepatic involvement and renal involvement were seen significantly higher among leptospirosis patients.Conclusions: This study emphasized the importance of prophylactic doxycycline and early initiation of antibiotics during flood outbreaks. Awareness among treating doctors and patients is required for the control of outbreaks and prevention of mortality during floods.

Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry

Background Telomere biology disorders (TBD) such as dyskeratosis congenita (DKC) lead to progressive multi-organ failure as impaired telomere maintenance disturbs cellular proliferative capacity. A wide range of hepatic manifestations from asymptomatic liver enzyme elevation to overt liver fibrosis/cirrhosis can be observed in TBD patients. However, the incidence of hepatic involvement remains unknown. Non-invasive transient elastography (TE) predicts early fibrosis by measuring liver stiffness and may uncover subclinical liver damage in TBD patients. Methods Liver screening procedures of nine TBD patients from the Aachen TBD Registry are being presented retrospectively. Following clinical suspicion, TBD was diagnosed using flow-FISH with telomere length (TL) below the 1% percentile and confirmed by next-generation sequencing (NGS) detecting pathogenic mutations in telomere maintenance genes TERC or TERT. Results In all patients, TBD was first diagnosed in adulthood. Patients showed normal to slightly elevated liver function test parameters. Hepatic ultrasound revealed inhomogeneous parenchyma in seven (77.7%) and increased liver echogenicity in four patients (44.4%). Median liver stiffness was 10.7 kilopascal (kPa) (interquartile range 8.4, 15.7 kPa). Using 7.1 kPa as cut-off, 88.8% of patients were classified as moderate fibrosis to cirrhosis. Conclusion Subclinical chronic liver involvement is frequent in patients with adult-onset TBD. TE could have a valuable role in the routine work-up of patients with telomere disorders including DKC for early detection of patients at risk for liver function impairment.

Spontaneous Bowel Perforation - A Rare and Fatal Complication in COVID-19 Patients: Case Report

Coronavirus 2019-nCoV (COVID-19) is a global pandemic and highly infectious disease, with most of the symptoms being related to the respiratory tract. However, more extrapulmonary symptoms and complications are evolving and directly associated with COVID- 19 pathogenesis. A recognized clinical manifestation of COVID-19 is gastrointestinal and hepatic involvement. We reported a middle-aged man admitted to the intensive care unit (ICU) with severe COVID-19 pneumonia; he developed spontaneous bowel perforation. He had not received tocilizumab as the latter was reported to be associated with bowel perforation. Key words: Coronavirus 2019-nCoV (COVID-19, bowel perforation.

Predictors of Heart Failure Symptoms in Hereditary Hemorrhagic Telangiectasia Patients With Hepatic Arteriovenous Malformations

BackgroundHepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms.Results176 patients with HHT were evaluated with computed tomography angiography (CTA) between April 2004 and February 2019 at our HHT Center of Excellence. 63/176 (35.8%) patients were found to have hepatic AVMs on CTA. 18 of these patients were excluded because of the presence of another condition which could confound evaluation of heart failure symptoms. In the remaining 45 patients included in our cohort, 25/45 (55.6%) patients were classified as asymptomatic and 20/45 (44.4%) were classified as symptomatic, and these groups were compared. In symptomatic patients, mean common hepatic artery (CHA) diameter was significantly higher (11.1 versus 8.4 mm) and mean hemoglobin levels were significantly lower (10.7 vs 12.6 g/dL). A stepwise multiple logistic regression analysis demonstrated that both CHA diameter and hemoglobin level were independent predictors of heart failure symptoms with ORs of 2.554 (95% CI 1.372-4.754) and 0.489 (95% CI 0.299-0.799), respectively. The receiver operator characteristic (ROC) curve of our analysis demonstrated an AUC of 0.906 (95% CI 0.816–0.996), sensitivity 80.0% (95% CI 55.7-93.4%), and specificity 75.0% (95% CI 52.9-89.4%).ConclusionsCTA is an effective and easily reproducible method to evaluate hepatic involvement of HHT. Utilizing CTA, clinical, and laboratory data we determined CHA diameter and hemoglobin level were independent predictors of heart failure symptoms.