Study of the parameters related to anticancer effect of somatostatin on hepatomas

Somatostatin (sst) is a hormone - regulatory peptide with multiple and diverse role in the central nervous system, the gastrointestinal tract and other peripheral tissues. SST has inhibitory actions on various secretory and growth processes. Its actions are implemented via G-protein bound receptor family. The receptors (sstr1-5) bound with high afinity with natural sst, whereas synthetic analogues (created to overcome the limitation of short half-life of the natural sst) bound mainly to sstr 2, 3, and 5. Somatostatin receptors’ expression in human tumours in vivo & in vitro, in non-tumoural tissues and in vessels, provided the ground for intense research and important applications in the diagnosis and treatment, most characteristically in neuroendocrine tumours. The identification of somatostatin receptors in the liver experimentally (sinusoidal cells, Kupffer cells), in chronic liver diseases and in hepatocellular carcinoma – HCC) together with the clear value of sst in the treatment of portal hypertension, gave the evidence for the use of sst in the treatment of HCC. HCC is an important neoplasm as it represents the third cause of death from cancer. Its incidence rises worldwide. The radical therapeutic options (liver transplantation, resection or radiofrequency ablation in small HCC) are possible for a minority of HCC patients as screening is far from ideal. Palliative treatments (radiofrequency ablation, transarterial chemoembolisation) can prolong life in selected patients. Nevertheless many people are not candidates for any of the abovementioned treatments. The experience from the experimental models, the identification of sstr in liver strctures and the success of somatostatin analogues in neuroendocrine tumours gave the evidence to treat inoperable HCC with these regimens and study the factors related to the response and the outcome. After the original randomised study of octreotide in HCC, we conducted an open prospective study of long acting somatostatin analogues (octreotide, lanreotide) in 32 patients with inoperable HCC. The study showed better survival in the study group versus historic controls (median 15 months vs. 8, p<0.01) with relative risk for death in untreated patients 2.7. There has been a stabilisaton or reduction of the tumour in 40% of patients, almost all with good or improving quality of life (Karnofsky Performance Scale). The percentage of patients that responded was remarkably analogous with the percentage of HCCs that express sstr. Additionally, the positive effect of the treatment regimen was identified after 6 months treatment. The majority of HCC patients of the previous clinical study, together with a group of 30 cirrhotics and 48 healthy controls were studied regarding a significant clinical parameter, the thrombotic complications. We studied the role of acquired and genetic risk factors. In serum of patients with cirrhosis and HCC, low levels of protein C, S, antithrombin and lipoprotein (a) has been found. HCC patients had statistically higher homocystein levels compared to the other two groups. On the contrary the prevalence of APC resistance, factor V Leiden, G20210GA mutation in prothrombin gene and C677T polymorphism of methylentrahydrofolate reuctase had no statistical significant differences. We further studied comparativelly all the clinical reports of somatostatin analogues’ treatment for HCC, either randomised trials, case control studies, or case reports. Various problems and significant heterogeneity in the design of such trials was identified. Major clinical trials included moribund patients, frequently receiving 1 month treatment at most, thus failing to subject the patients into the critical 6 months therapeutic period, as shown in our studies. Thus, despite the good tolerance of the regimen and the excellent quality of life, the results vary significantly from impressive to poor. The “rule” of 40% of patients who benefit from such treatment is again confirmed, implying the relation with sstr. On the other hand this might reveals the insufficient targeting of implicated sstr from the available sst analogues. We analyze the potential mechanisms of action and resistance of HCC in this drug. Furthermore, the poor results of somatostatin analogues on HCC in studies including big numbers of alcoholics were confirmed in an analysis of the patients in our clinical study. Thus, patients with non alcoholic aetiology had mean survival 12 months vs. 5 months of patients with alcoholic aetiology. Trying to explore further this phenomenon, we studied experimentally in HepG2 cell line the effect of ethanol and its metabolite (acetaldehyde) in the expression of sstr2 and sstr5. SSTR induction was identified from octreotide, ethanol and acetaldehyde separately. When octreotide and ethanol were incubated together, as well as acetaldehyde and octreotide, we found suppression of the expression of sstr. We propose that this mechanism has important role in the clinical result of alcoholic patients treated with long acting somatostatin analogues

Percutaneous rheolytic mechanical thrombectomy in thrombosed direct intrahepatic portosystemic shunt: Report of two cases

We report two patients with Budd–Chiari syndrome, who underwent direct intrahepatic portosystemic shunt complicated by shunt thrombosis. Percutaneous AngioJet mechanical thrombectomy in combination with manual catheter aspiration and balloon disruption of the residual clot was successful, restoring patency of the thrombosed shunt

Transcatheter arterial chemoembolization combined with radiofrequency or microwave ablation for hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) is the sixth most common type of malignancy. Several therapies are available for HCC and are determined by stage of presentation, patient clinical status and liver function. Local–regional treatment options, including transcatheter arterial chemoembolization, radiofrequency ablation or microwave ablation, are safe and effective for HCC but are accompanied by limitations. The synergistic effects of combined transcatheter arterial chemoembolization and radiofrequency ablation/microwave ablation may overcome these limitations and improve the therapeutic outcome. The purpose of this article is to review the current literature on these combined therapies and examine their efficacy, safety and influence on the overall and recurrence-free survival in patients with HCC

Immunosuppression and HCV recurrence after liver transplantation

SummaryHCV related liver disease is the most common indication for liver transplantation. Recurrence of HCV infection is universal and has a substantial impact on patient and graft survival. Immunosuppression is a major factor responsible for the accelerated recurrence and compressed natural history of recurrent HCV infection. Accumulating experience has provided data to support certain strategies for immunosuppressive regimens.From the available evidence, more severe recurrence results from repeated bolus corticosteroid therapy and anti-lymphocyte antibodies used to treat rejection. Low dose and slow tapering of steroids are better than high dose maintenance and/or rapid tapering. Recent meta-analyses favour steroid-free regimens but these are complicated to interpret as the absence of steroids may simply represent less immunopotency.There is no difference in HCV recurrence between tacrolimus and cyclosporine regimens, but tacrolimus increases graft and patient survival in HCV transplanted patients. There may be a beneficial effect of maintenance azathioprine given for 6months or longer. There is no conclusive evidence for benefit of mycophenolate and interleukin-2 receptor blockers. Few data are available for mTOR inhibitors. Better evidence is needed to establish the optimal immunosuppressive regimen for HCV recipients and more randomized trials should be performed

Acute TIPS occlusion due to iatrogenic arteriovenous shunt in a cirrhotic patient with total portal vein thrombosis

A 69-year-old man with portal hypertension was admitted with decompensated alcoholic cirrhosis and diuretic resistant ascites. Ultrasound revealed partial portal thrombosis. Due to diuretic intolerance, transjugular intrahepatic portosystemic shunt (TIPS) was decided during which a hepatic arterial branch was inadvertently catheterized. Finally, TIPS was created, but the patient continued gaining weight. Color-Doppler ultrasonography (CDUS) showed upper stent part patency with absence of flow in lower stent portion. Twenty-five days later, the patient presented melena. Endoscopy revealed blood emerging from the Vater papilla. Hepatic angiography revealed arteriovenous shunt between a hepatic arterial branch and the proximal part of the TIPS shunt. Covered stent placement restored sufficient TIPS flow. The patient deteriorated and died 1 month later. We found out that our major technical drawback was that we did not inject a small amount of contrast after puncturing the supposed portal vein, in order to confirm correct position of the needle

Sedation/Analgesia Administration Practice Varies according to Endoscopy Facility (Hospital- or Office-Based) Setting: Results from a Nationwide Survey in Greece

Objectives. To examine the impact of endoscopy setting (hospital-based vs. office-based) on sedation/analgesia administration and to provide nationwide data on monitoring practices among Greek gastroenterologists in real-world settings. Material and Methods. A web-based survey regarding sedation/analgesia rates and monitoring practices during endoscopy either in a hospital-based or in an office-based setting was disseminated to the members of the Hellenic Society of Gastroenterology and Professional Association of Gastroenterologists. Participants were asked to complete a questionnaire, which consisted of 35 items, stratified into 4 sections: demographics, preprocedure (informed consent, initial patient evaluation), intraprocedure (monitoring practices, sedative agents’ administration rate), and postprocedure practices (recovery). Results. 211 individuals responded (response rate: 40.3%). Propofol use was significantly higher in the private hospital compared to the public hospital and the office-based setting for esophagogastroduodenoscopy (EGD) (85.8% vs. 19.5% vs. 10.5%, p&lt;0.0001) and colonoscopy (88.2% vs. 20.1% vs. 9.4%, p&lt;0.0001). This effect was not detected for midazolam, pethidine, and fentanyl use. Endoscopists themselves administered the medications in most cases. However, a significant contribution of anesthesiology sedation/analgesia provision was detected in private hospitals (14.7% vs. 2.8% vs. 2.4%, p&lt;0.001) compared to the other settings. Only 35.2% of the private offices have a separate recovery room, compared to 80.4% and 58.7% of the private hospital- and public hospital-based facilities, respectively, while the nursing personnel monitored patients’ recovery in most of the cases. Participants were familiar with airway management techniques (83.9% with bag valve mask and 23.2% with endotracheal intubation), while 49.7% and 21.8% had received Basic Life Support (BLS) and Advanced Life Support (ALS) training, respectively. Conclusion. The private hospital-based setting is associated with higher propofol sedation administration both for EGD and for colonoscopy. Greek endoscopists are adequately trained in airway management techniques.</jats:p