IL-6 Promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy.

Major hepatic resection in cirrhotic patients is associated with impaired liver regeneration and failure, leading to high peri-operative mortality. In this work, the causes of defective regeneration in cirrhotic liver and the utility of IL-6 treatment were investigated in an experimental model combining cirrhosis and partial hepatectomy in the rat. Relative to normal controls, decompensated cirrhotic animals showed decreased survival, while compensated cirrhotic animals showed similar survival but reduced hepatic DNA synthesis and newly regenerated liver mass amount. Defective liver regeneration was associated with a decrease in STAT3 and NF-kB activation, consistent with an increased accumulation of their respective inhibitors PIAS3 and IkBalpha, and with a decreased induction of Bcl-xL. Treatment with recombinant IL-6 enhanced survival of decompensated cirrhotic animals, while it did not affect survival of compensated cirrhotic animals but sustained liver regeneration, by restoring STAT3 and NF-kB activation and Bcl-xL induction to the levels found in normal controls. The pro-growth effects exerted by IL-6 treatment in cirrhotic liver were attained also at low, pharmacologically acceptable doses. In conclusion, our results suggest that IL-6 treatment may be therapeutic in major resection of cirrhotic liver.

Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an unusual tumour. METHODS: The clinicopathological data of 67 patients with ICC and combined hepatocellular-cholangiocarcinoma (HCC-ICC) are presented. RESULTS: HCV-HBV infection was present in 37.3% and chronic liver disease in 38.7% of cases, a rate higher than in the normal population; in these patients the cancer was small, often asymptomatic and of combined type. Liver resection was performed in 51 patients; at 1, 3 and 5 years, overall survival was 87.9%, 59.0%, and disease-free survival was 47.7% and 78.8%, 51.4%, and 46.7%, respectively. The better results were in the group of cirrhotic patients in whom ICC was diagnosed by a screening program for HCC (5-year survival 76.6%). Nodal metastasis showed negative prognostic value for both overall and disease-free survival; in N+ patients mean survival was 14.7 months after liver resection and lymph node dissection. CONCLUSION: Viral infection and cirrhosis may be considered risk conditions for ICC and combined HCC-ICC; in resected patients survival was good. Nodal metastases must not be considered a contraindication for liver resection.

Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat liver.

Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury.

[Deferred elective colonic resection in complicated acute diverticulitis]. / Resezione colica differita in elezione nelle diverticoliti acute complicate.

Twenty-three patients with acute diverticulitis complicated by pericolic or paracolic abscesses (Hinchey stage I-II) after a first phase of medical treatment were treated with deferred elective resection of the descending colon and sigmoid plus colorectal anastomosis performed on average 30 days after the onset of the acute episode. The pathologist's investigation of the surgical specimens demonstrated persistence of severe inflammatory lesions despite the apparently satisfactory clinical outcome. These data explain the frequent recurrences and indicate surgical treatment as being the only therapy capable of definitively resolving the condition. As compared with the emergency surgery performed by others, deferred elective resection makes it possible to operate on patients who, once the acute phase has been overcome, can have their hydroelectrolytic balance perfectly restored and be adequately monitored with treatment of associated diseases and perfect colon preparation. This strategy has allowed us to eliminate operative mortality and reduce the postoperative morbidity, both of which are significantly present in emergency surgical operations. Also the overall hospital stay in the two admissions, the interval between which can be reduced in ideal cases, does not significantly differ from that reported for emergency operations.

Telomerase gene expression in intraductal papillary-mucinous tumors (IPMT): preliminary findings.

BACKGROUND AND AIM: The surgical management of IPMT is based upon a preoperative suspicion of malignancy, that is difficult to obtain from the available diagnostic tools. METHODS: Telomerase gene expression was investigated by means of hTERT/RT-PCR on total RNA from peripheral blood, tumour and non-tumour pancreatic samples of 2 patients with IPMT. RESULTS: Histological diagnosis was mild-grade dysplasia in the first case and invasive carcinoma in the second. Telomerase expression was undetectable in all the samples derived from the first case. Blood and tumour samples from the second patient were positive for telomerase mRNA expression, while the pancreatic non-tumour specimen was not. CONCLUSIONS: The following suggestions are made: 1) the telomerase gene expression seems to be implicated in the malignant evolution of IMPT; 2) the malignant transformation may be limited to a single area of the gland; 3) the presence of invasive carcinoma may be preoperatively suspected by peripheral venous blood sample collection. A possible clinical employment of telomerase gene expression determination in the management of IPMT is thus hypothesized.