Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison

BackgroundManagement of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC.MethodsThis is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups.Results1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14–2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22–2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54–0.69; p<0.001).ConclusionCurative approaches may guarantee long-term survival in case of recurrence.     

Effects of fat mass reduction by dieting and by lipectomy on carbohydrate metabolism in obese patients

Summary The interrelation of enlarged body fat mass (BFM) with reduced carbohydrate tolerance and hyperinsulinemia was studied in obese subjects with chemical diabetes. These patients were subjected to lipectomy following weight loss induced by a low-calorie, low-carbohydrate diet. An improvement in glucose tolerance and in insulin sensitivity and a reduction in insulin release during OGTT was observed after a diet-induced BFM loss of 9.9 ± 1.2 kg. Subsequent surgical reduction of BFM by 6.0 ± 0.5 kg had no further effect upon carbohydrate tolerance, insulin release or insulin sensitivity though a marked decrease in basal plasma FFA values was observed. These findings suggest that fat mass enlargementper se has no effect on blood glucose homeostasis after oral or i.v. loading. The improvement in carbohydrate tolerance and in insulin resistance usually observed following diet-induced loss of BFM seems to be due to the reduction in calorie and carbohydrate intake rather than to decrease of BFM. Preliminary results of this study were presented at the 9th Congress of the International Diabetes Federation, held in New Delhi in 1976 (abstract ≠ 333).     

Increased intercellular adhesion molecule-1 serum concentration in cholestasis

Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes.Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasis were investigated. sICAM-1 levels and “classical” cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and “classical” cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves.Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251–2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257–2961 μg/l; median 760 μg/l) compared to healthy controls (n=12; 220–500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107–1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3–26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43–705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other “classical” cholestasis parameters. Increased sICAM-1 levels (range 257–2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin (r=0.8; p<0.01; range 0.3–19.7, median 1.6 mg/dl), γ-GTP (r=0.55; p=0.03; range 33–1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110–1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264–919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than “classical” cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.     

Prevalence of and risk factors for anal human papillomavirus infection in heterosexual men

In US men, the incidence of anal cancer, the primary cause of which is human papillomavirus (HPV) infection, has increased almost 3-fold in 3 decades; however, little is known about the epidemiology of anal HPV infection, especially in heterosexual men. In 2 US cities, behavioral data and anal biological specimens were collected from 253 men who acknowledged having engaged in sexual intercourse with a woman during the preceding year. On the basis of DNA analysis, overall prevalence of anal HPV infection was found to be 24.8% in 222 men who acknowledged having had no prior sexual intercourse with men. Of the men with anal HPV infection, 33.3% had an oncogenic HPV type. Risk factors independently associated with anal HPV were lifetime number of female sex partners and frequency of sex with females during the preceding month. These results suggest that anal HPV infection may be common in heterosexual men.     

Ceftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro

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Information and communication technology in chronic diseases: a patient’s opportunity

The increasing aging population, the prevalence of chronic diseases and rising costs have brought about some unique health care challenge to our global society. In response to the unmet health care needs, researchers are actively seeking for innovative solutions that target for (1) prevention of diseases and (2) personalized diagnosis and treatment. It is envisaged that by taking preventive measures for health monitoring, diagnosing and treating patients with a personalized approach at an early stage of disease development, health care will be more cost effective and sustainable. The authors provide an overview of the advancements in Information and Communication Technology (ICT), and explain how some innovative health solutions, through the use of Telemedicine, can now be an opportunity for patients and their family.     

Mast Cells Kill Candida albicans in the Extracellular Environment but Spare Ingested Fungi from Death

Mast cells (MCs) reside in tissues that are common targets of Candida spp. infections, and can exert bactericidal activity, but little is known about their fungicidal activity. MCs purified from rat peritoneum (RPMC) and a clinical isolate of C. albicans, were employed. Ingestion was evaluated by flow cytometry (FACS) and optical microscopy. The killing activity was assayed by FACS analysis and by colony forming unit method. RPMC degranulation was evaluated by β-hexosaminidase assay and phosphatidylserine externalization by FACS. Phagocytosing RPMC were also analyzed by transmission electron microscopy. Herein, we show that the killing of C. albicans by RPMC takes place in the extracellular environment, very likely through secreted granular components. Ultrastructural analysis of the ingestion process revealed an unusual RPMC–C. albicans interaction that could allow fungal survival. Our findings indicate that MCs have a positive role in the defense mechanism against Candida infections and should be included among the cell types involved in host-defense against this pathogen.     

A comparative in vivo ultrasonometric evaluation of normal and delayed fracture healing in sheep tibiae

OBJECTIVE:

To compare normal and delayed bone healing by measuring ultrasound conduction velocity across the bone callus.

METHODS:

A model of transverse linear and 5 mm resection osteotomies of sheep tibiae was used. Fourteen sheep were operated on and were divided into two groups of seven according to osteotomy type. The procedure was performed on the right tibiae and the intact left tibiae were used as controls. The transverse and axial ultrasound velocities were measured at 30-day intervals for 90 days, after which the animals were killed and both the right and left tibiae were resected for in vitro biomechanical analysis.

RESULTS:

Both the transverse and axial ultrasound velocities progressively increased, but the increase was smaller for the delayed union that resulted from the resection osteotomy. The mechanical resistance was higher for the normally healed tibiae that resulted from a linear osteotomy; this result closely correlated with the ultrasound velocity results. Significant differences were found for the comparisons between the intact and operated tibiae in both groups and between the groups for both the transverse and axial ultrasound velocities, but the differences were greater for the latter.

CONCLUSION:

We conclude that in vivo transverse and axial ultrasound velocities provide highly precise information about the healing state of both linear and resection diaphyseal osteotomies, but the axial ultrasound velocity most likely has greater discriminatory power. This method has the potential for clinical application in humans.