Advanced age as risk factor in liver resection surgery

To evaluate the influence of age on the outcome of liver resections, 105 consecutive patients undergoing hepatic resection were divided into two groups: age > or = 65 years [Old Group (O-Group)] and age < 65 years [Young Group (Y-Group)]. O-Group and Y-Group patients were analyzed comparatively in terms of primary diagnosis, concomitant diseases, previous surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The end points of the study were postoperative mortality, morbidity, transfusions, and length of post-operative hospitalization. The Y-Group included 61 resections in 60 patients, with a mean age of 52 +/- 10 years (mean +/- SD), range 23-64 years, and the O-Group 44 resections in 43 patients, with a mean age of 71 +/- 4 years, range 65-82 years. The O-Group included more cases of hepatoma (45.4% vs 18%, p = 0.002) and cirrhosis (40.9% vs 18.7%, p = 0.017). Median length of operation was slightly higher in the Y-Group (330 vs 270 minutes, p = 0.003). The O- and Y-Groups were comparable (p = n.s.) when evaluated for all other variables listed. As regards the end points of the study, length of post-operative hospitalization was identical in both groups (median 9 days, range 5-60 days) and neither PRBC transfusions (O-Group vs Y-Group: 16% vs 25%) nor FFP transfusions (O-Group vs Y-Group: 13.6% vs 6.5%) showed any statistically significant difference. Postoperative mortality consisted in 1 death among the younger patients while no deaths were recorded among the older patients. Postoperative morbidity was higher in the Y-Group than in the O-Group (31.1% vs 20.5%, p = 0.59). Advanced age does not negatively affect the outcome of liver resections.     

Role of hepatic resection in the treatment of hepatolithiasis.

BACKGROUND: The aim of the present study was to evaluate the safety and the efficacy of hepatic resection in the treatment of hepatolithiasis with intrahepatic biliary strictures. METHODS: Experimental design: retrospective study. Setting: University hospital, Italy. Patients: 6 consecutive patients with single lobe hepatolithiasis operated on during the 4-year period 1994-98 inclusive. Interventions: major hepatic resections (3 left hepatectomies, 2 left lobectomies, 1 right hepatectomy). Main outcome measures: type and duration of the surgical procedure, intra/postoperative blood losses, intra/postoperative course and complications, pathology, and hepatolithiasis recurrence. RESULTS: Mean operative time was 3.34+/-0.02 hrs (range 3.0-4.3 hrs). Mean blood loss was 233+/-150 ml (range 100-500 ml). No patient required intra/postoperative blood transfusions. No intraoperative complication was recorded. Mean postoperative hospitalization was 17+/-7 days (range 6-28 days). Postoperative course was uneventful in 4 (66%) cases. No postoperative mortality was recorded. One pancreatitis and 1 biliary fistula occurred, for an overall postoperative morbidity of 33%. Pathology showed cholangiocarcinoma in 2 cases (33%). During the follow-up period (range 3-48 months, mean 19.1+/-16.4 months), 1 patient had recurrent cholangitis due to right lobe lithiasis and 1 patient died for cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis and unreversible biliary strictures or possible presence of cholangiocarcinoma. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.     

The De Ritis ratio as prognostic biomarker of in‐hospital mortality in COVID‐19 patients

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID‐19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in‐hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID‐19) admitted to three COVID‐19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91‐1.64 vs 1.67; IQR: 1.38‐1.97, P = .002) whilst there were no significant between‐group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603‐0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan‐Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05‐5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in‐hospital mortality in COVID‐19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.     

Preoperative methylprednisolone administration maintains coagulation homeostasis in patients undergoing liver resection: importance of inflammatory cytokine modulation

Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. Seventy-three patients undergoing liver resection were randomized to a steroid group or to a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of coagulation parameters (prothrombin time, platelets, fibrinogen, plasma fibrin degradation products [D-dimer], antithrombin III) and inflammatory mediators (IL-6 and TNF-alpha) were measured before and immediately after the operation and on postoperative days 1, 2, and 5. Multivariate analysis was performed to identify factors related to the characteristics of the patients and surgery affecting coagulation parameters between the two groups. Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.     

Amoxicillin-associated interference in an HPLC–EC assay for urinary fractionated metanephrines: Potential pitfall in pheochromocytoma biochemical diagnosis

Objective

Measurement of urinary fractionated metanephrines represents a first-line test for the biochemical diagnosis of pheochromocytoma. The high performance liquid chromatography coupled to electrochemical detection (HPLC–EC) assays used in the routine clinical laboratory can be subjected to analytical interferences by the presence of drugs or their metabolites. In this paper we describe the interference on urinary normetanephrine (uNMN) caused by amoxicillin.

Design and methods

Two pediatric patients suspected of pheochromocytoma had very high uNMN levels (2543 and 4227 μg/g Cr respectively; upper reference value: 339 μg/g Cr). Amoxicillin interference was assessed by comparison for co-elution with uNMN and by LC–MS/MS analysis.

Results

After amoxicillin interference was suspected and the therapy was stopped uNMN levels returned to normal (149 and 214 μg/g Cr respectively). Chromatograms obtained by HPLC–EC clearly showed that amoxicillin co-elutes with uNMN. Patients' uNMN levels measured by LC–MS/MS were in the normal range.

Conclusion

Amoxicillin is responsible for analytical interference on HPLC–EC assay for uNMN. This finding can be of help in distinguishing true-positive from false-positive results in the course of a biochemical diagnosis for pheochromocytoma.     

Genetic analysis of the 2q33 region containing CD28-CTLA4-ICOS genes: association with non-Hodgkin's lymphoma

There is strong evidence that altered immunological function entails an increased risk of lymphoma, although the current knowledge of aetiological factors for lymphomas is limited. The CTLA4 gene encodes a receptor that provides a negative signal to the T-cell once an immune response is initiated and completed. We analysed the 2q33 chromosomal region harbouring CD28, CTLA4 and ICOS genes, which are closely linked and have related functions in immune regulation, for association in 100 non-Hodgkin's lymphoma (NHL) patients and in 128 healthy controls; both groups originated from Sardinia. There was a strong association of the CTLA4 49A and the 3'-untranslated region (AT)(82) alleles with NHL [odds ratio (OR) = 2, 95% confidence interval (CI) = 1.2-3.2, and OR = 1.6, 95% CI = 1.1-2.4 respectively]. CTLA4-318C:49A:(AT)(82) was the most represented haplotype in the studied population and was associated with NHL (P = 0.0029, OR = 1.76, 95% CI = 1.2-2.5). Strong linkage disequilibrium was detected between CD28, CTLA4 and ICOS and a 'common' haplotype was found very frequently among NHLs. However, no independent association between CD28, ICOS, D2S72 markers and NHL was observed. Our findings enable CTLA4 from adjacent functionally related genes as the true causative risk gene for NHL susceptibility at least in Sardinian patients.