G. Orlando, L. Tariciotti, T.M. Manzia, G. Gravante, R. Sorge, M. Manuelli, F. Pisani, P. Di Cocco, C. Scelzo, G.M. Burke, S. Soker, L. Baiocchi, J. Lerut, M. Angelico, G. Tisone. Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk for Pneumocystis jirovecii pneumonia. Transpl Infect Dis 2009. All rights reserved Abstract: At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

BACKGROUND: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. OBJECTIVE: To survey the clinical approach to the subset of patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. METHODS: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D>/=2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. RESULTS: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018) of the gastric primary and by the therapeutic approach to the metastases (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p<0.001). CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible.

BACKGROUND: We report the update of the Tor Vergata immunosuppression (IS) weaning protocol in stable hepatitis C virus (HCV) liver transplant (LT) recipients. METHODS: The weaning off IS was attempted in 34 patients who had received a LT 63.5+/-20.1months earlier, for HCV-related end stage liver disease. Patients were observed over a period of 6.5years. During this time, yearly protocol liver biopsies were performed. Primary endpoints were determined as the feasibility of weaning off IS and its impact on the long term disease progression. Secondary endpoints were defined as the impact on patient morbidity and quality of life. RESULTS: Of the 8 originally tolerant patients, 7 remain alive and in good condition, while 1 died of severe HCV recurrence 10years post-LT and 6years after complete removal of IS. Four out of 26 intolerant individuals died of HCV recurrence (2x), lung carcinoma (1x) and acute myocardial infarction (1x), after a mean follow up period from LT of 115 (range 100-124). The 10-year survival from LT was comparable (89% vs. 87.5%). Liver graft pathology showed no significant differences between the two groups in terms of staging, fibrosis progression rate, and grading. Quantitative HCV RNA assay showed a significant non-logarithmic difference between the two groups (p = 0.03). The two groups were comparable in terms of liver function tests and lipid profile, whereas they differed with regards to glycaemia. While all tolerant individuals were euglicemic, 11 intolerant individuals developed new onset diabetes that required specific treatment (p = 0.03). Finally, significantly more intolerant patients are suffering from either cardiovascular (14/22 vs. 0/7, p = 0.01) or infectious diseases (13/22 vs. 0/7, p = 0.01). CONCLUSIONS: After a 6.5-year follow up, the complete withdrawal of IS in HCV LT recipient remains safe and beneficial to patients, because it reduces the IS-related morbidity and increases the quality of life. The impact on HCV disease recurrence is less marked than after 3.5years.

Background Malignancies arising from the biliopancreatic tree are often diagnostic challenges for the gastroenterologist and the pathologist, especially when strictures without masses are present. Aim To evaluate the diagnostic yield of p53 immunocytology for the detection of malignancies in material obtained by biliopancreatic tree brushing by means of an increased cell-yield procedure. Patients and Methods Cytologic specimens obtained from biliary and pancreatic tree brushing in 24 patients with biliary strictures suspected for malignancy were assessed by conventional Papanicolau staining and p53 immunocytochemistry. Results Papanicolau staining detected 67% and p53 87% of the malignancies in the study group. p53 immunocytology displayed excellent sensitivity, specificity, and diagnostic accuracy. Conclusions p53 immunocytology may represent a useful diagnostic tool in the detection of malignancies from biliary and pancreatic tree brushing, especially when using an increasing cell-yield procedure.

Cholestasis, induced by liver ischemia-reperfusion injury (IRI), is characterized by dilatation of bile canaliculi and loss of microvilli. Tauroursodeoxycholic acid (TUDCA) is an anti-cholestatic agent, modulating protein kinase C (PKC) alpha pathway. PKC reduces ischemic damage in several organs, its isoform alpha modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCalpha-ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzer + 10 mm TUDCA (4 degrees C for 6 h) were reperfused (37 degrees C with O(2)) with Krebs-Ringer bicarbonate + 2.5 mumol/min of Taurocholate or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCalpha and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCalpha inhibitor Go-6976. TUDCA-treated livers showed increased bile flow (0.25 +/- 0.17 vs. 0.042 +/- 0.02 mul/min/g liver, P < 0.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCalpha and ezrin expression (P = 0.03 and P = 0.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCalpha inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCalpha-ezrin pathway.

A 64-year-old man with HBV-related cirrhosis presented with a liver nodule measuring 2.8 cm revealed by a routine ultrasound and concomitant increased alpha-fetoprotein (AFP) up to 400 UI/l. Contrast-enhanced CT was suggestive of hepatocellular carcinoma (HCC) and the patient underwent laser ablation procedure. Five months later, because of raised AFP up to 1600 UI/l, ultrasonography and abdominal CT were repeated, showing an increased diameter of liver nodule, measuring 3.8 cm. The patient underwent down-staged trans-arterial chemoembolization (TACE) and then was entered into the active liver transplant (LT) list. Lamivudine was already started and the patient underwent LT showing HBV-DNA serum levels <10(3) log/copies at the time of surgery. Pathological analysis performed on the explanted liver showed, instead of the suspected HCC, hepatic yolk sac tumor with the presence of typical 'Schiller-Duval bodies'. The first 12 months of postoperative follow-up were excellent, with no evidence of tumor recurrence.

Hepatitis C virus (HCV) re-infection after liver transplantation (LT) is characterized by an accelerated disease progression in recent years with unclear mechanisms. We evaluate the relationship between progression of liver fibrosis and histological necro-inflammation in HCV recipients, according to age of transplant. Fifty-five patients transplanted (1993-2002) for HCV liver disease, were included in the study. Recipients were retrospectively stratified in three different age of transplant, of 40 months each: group 1) from January 1993 to May 1996; group 2) from June 1996 to august 1999; group 3) from September 1999 to December 2002. Grading (necro-inflammation) and staging (fibrosis) scores were evaluated in liver biopsies at 1, 2 and 3 years from LT (Ishak classification). For all age of transplant the main factor associated with fibrosis progression, was grading score (p < 0.05). However mean staging score for each point of grading increased from 0.3 +/- 0.2 in older LT to 0.7 +/- 0.5 in newer ones (p = 0.01). In conclusion in HCV-LT patients (1) liver fibrosis is strictly associated to histological necro-inflammation;(2) the proportion of this relationship has been changing in recent years since newer LT patients, show an increased amount of fibrosis in comparison with the older ones, for similar grading score.

A 55-year-old woman with hereditary haemorrhagic telangiectasia (HHT) underwent a left lateral liver bisegmentectomy (removal of segments 2 and 3) for hepatic-based arteriovenous malformations. This lesion determined a progressive fatigue and invalidating effort dyspnoea. The postoperative course was uneventful and the patient is currently doing well at 4 years after surgery. To our knowledge, this is the first case of hepatic-based HHT treated with liver resection. This anecdotal report should promote the evaluation of this approach in order to define its role in the treatment of liver involvement in this rare disease.