Liver transplantation for hepatocellular carcinoma: Management after the transplant

Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post‐LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post‐LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.     

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.     

Prevalence of periodontitis in individuals with human leukocyte antigens (HLA) A9, B15, A2, and B5

Objective

Human leukocyte antigens (HLA) have been associated with periodontitis. Previous studies revealed HLA-A9 and HLA-B15 as potential susceptibility factors, while HLA-A2 and HLA-B5 might have protective effects. The aim of the study was to verify these associations in a group of HLA-typed blood donors with previously unknown periodontal status.

Materials and methods

In four German centers, 140 blood donors with known HLA class I status were enrolled and allocated to the following five groups: HLA-A9 (N = 24), HLA-B15 (N = 20), HLA-A2 (N = 30), HLA-B5 (N = 26), and controls (N = 40). Periodontal examination included the measurement of probing depths (PDs), clinical attachment level (CAL), bleeding on probing (BOP), and community periodontal index of treatment needs (CPITN).

Results

Carriers with HLA-A9 and HLA-B15 had higher values of mean PD (P < 0.0001), CAL (P < 0.0001), and BOP (P < 0.002) as well as sites with PD and CAL with ≥4 and ≥6 mm (P < 0.0003), respectively, than controls. Multiple regression analyses revealed HLA-A9, HLA-B15, and smoking as risk indicators for moderate to severe (CPITN 3–4; odds ratio (OR): 66.7, 15.3, and 5.1) and severe (CPITN 4; OR: 6.6, 7.4, and 3.8) periodontitis. HLA-A2 and HLA-B5 did not show any relevant associations.

Conclusion

The present data support a role of HLA-A9 and HLA-B15 as susceptibility factors for periodontitis, whereas HLA-A2 and HLA-B5 could not be confirmed as resistance factors.

Clinical relevance

Both HLA antigens A9 and B15 are potential candidates for periodontal risk assessment.

     

Platelet coagulation factor Va: the major secretory platelet phosphoprotein

Platelet-derived coagulation factor Va is the primary secreted substrate for a thrombin-stimulation-dependent platelet kinase. Human platelet factor Va, consisting of a molecular weight (M(r)) 105,000 heavy chain and an M(r) 74,000 light chain, incorporates phosphate in at least two sites on the light chain. Phosphorylated factor Va represents 50% of the secreted protein-associated phosphate. This modification occurs exclusively at serine residues and is inhibited by H-7 and staurosporine, which suggests a protein kinase C (PKC)-mediated event. Purified plasma factor V and Va are phosphorylated in the light chain region by rat brain PKC. The activity of platelet factor Va in prothrombinase on platelets is not altered when phosphorylation is inhibited by staurosporine. Plasma-derived factor Va in the presence of thrombin stimulated platelets is phosphorylated on both the heavy chain and the light chain. Plasma factor V and factor Va heavy chain phosphorylation occurs without light chain phosphorylation in the presence of added 32P gamma-ATP and non-stimulated or collagen- stimulated platelets or casein kinase II. This differential phosphorylation of factor Va heavy and light chain shows two independent platelet kinase activities that act on factor Va. The heavy chain factor V/Va kinase activity is similar to casein kinase II, which we have demonstrated previously to act on factor Va and accelerate activated protein C inactivation of the cofactor. Our data show platelet-dependent phosphorylation of platelet and plasma factor V and Va resulting in significant covalent modifications of the cofactor. These modifications may play a role in directing the extracellular distribution of factor V and factor Va.     

End diastolic flow velocity just beneath the aortic isthmus assessed by pulsed Doppler echocardiography: a new predictor of the aortic regurgitant fraction.

End diastolic flow velocity just beneath the aortic isthmus was measured within 72 hours of cardiac catheterisation by pulsed Doppler echocardiography in 30 controls and 61 patients with aortic regurgitation. The end diastolic flow velocity was determined at the peak R wave on a simultaneously recorded electrocardiogram. In all controls there was no reverse flow at the end diastole beneath the aortic isthmus. In patients with aortic regurgitation the end diastolic flow velocity correlated well with the angiographic grade of regurgitation (r = 0.81) and regurgitant fraction (r = 0.82). The mean (SD) values were 6.3 (5.2), 12.2 (4.3), 22.1 (5.7), and 34.3 (9.3) cm/s for patients with regurgitant fraction of less than 20%, between 20% and 40%, between 41% and 60%, and greater than 60%, respectively. An end diastolic flow velocity of greater than 18 cm/s predicted a regurgitant fraction of greater than or equal to 40% with a sensitivity of 88.5% and a specificity of 96%. The study suggests that the pulsed Doppler derived end diastolic flow velocity is a useful index in the routine non-invasive assessment of the severity of aortic regurgitation.     

Free-wall rupture during the acute phase of myocardial infarction. Apropos of 2 cases surgically treated with success

The authors report two cases of cardiac rupture during acute myocardial infarction successfully treated surgically. In the first case, rupture occurred 7 days after hospital admission for anteroseptal myocardial infarction. The patient developed sudden cardiogenic shock with signs of venous hypertension without left ventricular failure. The second patient was admitted for syncopal chest pain with transient hypotension which regressed after volume repletion and pressor amine therapy. On admission, the patient had signs of cardiac tamponade. The ECG showed recent inferolaterobasal myocardial infarction. In both cases the diagnosis was made by 2D echocardiography which showed voluminous circumferential pericardial effusions probably due to haemorrage, with an image very suggestive of a blood clot in the effusion of the second patient. The two patients underwent emergency cardiac surgery and both survived with a 4 and 1.5 month follow-up respectively. These two cases confirm the value of 2D echocardiography as an emergency bedside procedure for the diagnosis of cardiac rupture, especially when images of intrapericardial thrombosis are observed, as in our second patient. In addition, the first case raises once again the question of the role of late thrombolysis as a predisposing factor of cardiac rupture at a time when this technique is proposed up to 24 hours after the onset of symptoms.