Endoscopic ultrasonography and small‐bowel endoscopy: Present and future

Over the last decade, impressive technological advances have occurred in ultrasonography and small‐bowel endoscopy. Nowadays, endoscopic ultrasonography is an essential diagnostic tool and a therapeutic weapon for pancreatobiliary disorders. Capsule endoscopy and device‐assisted enteroscopy have quickly become the reference standard for the diagnosis of small‐bowel luminal diseases, thereby leading to radical changes in diagnostic and therapeutic pathways. We herein provide an up‐to‐date overview of the latest advances in endoscopic ultrasonography and small‐bowel endoscopy, focusing on the emerging paradigms and technological innovations that might improve clinical practice in the near future.     

Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA(iCCA),hilar CCA(hCCA) and distal CCA(dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy(RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant(OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.     

Effect of bacterial purified antigenic fractions on natural defence mechanisms

The in vitro ability of bacterial purified antigenic fractions to interfere with the immune system has been investigated on human mononuclear cells from peripheral blood. Exposure of purified monocytes to the drug at concentrations from 1 to 1000 micrograms/ml, for different periods from 0 to 18 h, significantly increased cell-mediated cytotoxicity against TU5 target cells. Moreover, monocytes exposed for 1 to 18 h to drug concentrations from 0.1 to 1000 micrograms/ml released significant amounts of tumor necrosis factor alpha in a dose-dependent manner in the culture supernatants. The drug was also tested on natural killer (NK) cell activity; mononuclear cells exposed to antigenic fractions for different periods showed a significant increase of NK cytotoxic activity against K562 target cells after 3 and 6, but not 0 and 18 h. Active concentrations were from 1 to 100 micrograms/ml, higher and lower doses being ineffective. Bacterial purified antigenic fractions thus have some ability to interfere in vitro with mechanisms of cytolysis mediated by cells and soluble factors.     

HCV RNA in serum of asymptomatic blood donors involved in post-transfusion hepatitis (PTH).

A group of blood donors involved in post-transfusion hepatitis was investigated for the presence of the anti-HCV antibody and of HCV RNA as a more direct infection marker. RNA was extracted from serum, reverse transcribed and amplified using primers which belonged to the non structural region. The amplified product of the PCR reaction was 582 base pairs. Seven (25.9%) of the 27 blood donors examined were found anti-HCV-positive by ELISA; five (71.4%) of these were HCV RNA positive. Among the 20 anti-HCV-negative blood donors, four (20.0%) were HCV RNA positive. ALT levels were below 45 UI/l in 18 donors, while the other nine had ALTs over the limit accepted for transfusion. The anti-HCV-negative HCV RNA-positive blood donors had normal ALTs. Our study offers a direct explanation for the substantial proportion of residual cases of anti-HCV-positive post-transfusion hepatitis and suggests the necessity of creating a register of blood donors who have at some time presented blood enzyme abnormalities and for whom second level investigations such as HCV RNA should be used.     

Mortality study of asbestos cement workers

The present study describes cause-specific mortality of asbestos cement workers in the Emilia Romagna region of Italy. The cohort included workers in ten factories, most of which started operating between 1955 and 1965. Asbestos, mainly chrysotile, constituted 10%–20% of the dry component of the mixture. Crocidolite range between 5% and 50% of total asbestos. Asbestos concentrations up to 44 ff/cc were reported prior to 1975, while in recent years they have usually been below 0–1 ff/cc. The cohort included 3341 workers who had at some time been employed in the ten factories under study. Their mortality experience was compared with that of the population resident in Emilia Romagna. Vital status was ascertained at 1989. Seventy-three subjects were lost to followup (2.2%). Mortality from all causes and from all types of cancer was increased in the cohort. Malignant neoplasms of the respiratory tract showed a significant increase (SMR: 134; 90% confidence interval: 101–175; 40 observed) due to lung cancer (SMR: 124; 90% confidence interval: 91–166; 33 observed) and neoplasms of the pleura, mediastinum, and other parts of the respiratory tract (SMR: 602; 90% confidence interval 237–1267; 5 observed). The discrepancy between observed and expected mortality mainly concerned subjects with at least 20 years of employment in the factories. Five more cases of histologically confirmed mesothelioma occurred after the end of follow-up.     

Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer

Summary Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from-65% to +85% for PAP, from-72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.Preliminary results of this study have been presented at the International Symposium on Hormonal Therapy of Prostatic Diseases —Basic and Clinical Aspects, April 6–8, 1987, Milan, Italy     

Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys

As originally demonstrated for the interleukin 1 (IL-1) type II receptor, some primary proinflammatory cytokines from the IL-1 and tumor necrosis factor families are regulated by decoy receptors that are structurally incapable of signaling. Here we report that concomitant exposure to proinflammatory signals and IL-10 generates functional decoy receptors in the chemokine system. Inflammatory signals, which cause dendritic cell (DC) maturation and migration to lymphoid organs, induce a chemokine receptor switch, with down-regulation of inflammatory receptors (such as CCR1, CCR2, CCR5) and induction of CCR7. Concomitant exposure to lipopolysaccharide (LPS) and IL-10 blocks the chemokine receptor switch associated with DC maturation. LPS + IL-10-treated DCs showed low expression of CCR7 and high expression of CCR1, CCR2 and CCR5. These receptors were unable to elicit migration. We provide evidence that uncoupled receptors, expressed on LPS + IL-10-treated cells, sequester and scavenge inflammatory chemokines. Similar results were obtained for monocytes exposed to activating signals and IL-10. Thus, in an inflammatory environment, IL-10 generates functional decoy receptors on DC and monocytes, which act as molecular sinks and scavengers for inflammatory chemokines.     

Serum complement pattern in essential mixed cryoglobulinaemia

In twenty-six patients affected by essential cryoglobulinaemia, 188 determinations of serum complement components (SCC) were made. A peculiar pattern was observed which was characterized by: (a) low levels of early components (Clq, Cls and C4), (b) normal levels of C3 and high concentrations of late components (C5, C9) and (c) CH50 values significantly lower than normal. No relationship could be observed between early SCC and C3 levels. Thirty-three crossed immunoelectrophoreses were performed in thirteen patient's blood samples. The C3c peaks were not different from normal. Follow-up data (156 serum samples from twenty-four patients) during a 6-40 month period showed a non-homogeneous SCC behaviour. However, no relationship was found between the complement concentrations and clinical score. These findings suggest that SCC abnormalities are related to a complement hyposynthesis, which could be caused by a reduced C2 production or by a negative feedback effect of active components or their fragments.