65 research outputs found
Surgical Treatment Strategies and Prognosis of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC is the fifth most common cause of mortality worldwide and
the third cancer related cause and is responsible for about 1 million deaths yearly [1]. The ageadjusted
worldwide incidence is 5.5-14.9 per 100.000 population. In some areas of the world,
such as sub-Saharan Africa and Southeast Asia, HCC represents the first cause of cancer death
with an incidence of 52 per 100.000. Furthermore, in Europe and USA, HCC incidence has
progressively raised in the past decade representing a burden problem.
HCC is one of the few cancers for which a number of risk factors are known in great detail [2,
3]. HCC is almost always (80%) associated with cirrhosis, at least in developed countries, and
chronic hepatitis C and B infection, alcoholic cirrhosis and haemocromatosis are some of the
established risk factors [4]. The metabolic syndrome related to hypertension, central obesity,
diabetes and obesity has been identified as a new risk factor. As a result, screening programs
have developed, with the use of ultrasound and \u3b1-fetoprotein (AFP), with a hope to increase
the chances of diagnosing small HCC and unltimately increase the rate of curability.
Definitive diagnosis relies on the demonstration of a typical vascular pattern per liver imaging
techniques (triple-phase CT-scan or MRI) of tumors larger than 2 cm with arterial hypervascularity
and venous wash- out. Nodules, smaller than 2 cm, should be rechecked every six months
or, if highly suspect, subjected to needle biopsy. It\u2019s likely that the study of tumor-specific tissue
markers with prognostic value could introduce a systematic use of needle biopsy.
Over the past 20 years, surgical treatment of hepatocellular carcinoma has seen an immense
boost and improvement, with good survival outcomes and reduced morbidity and mortality.Liver resection (LR) and orthotopic liver transplantation (OLT) and ablative therapies are now
considered the only potentially curative treatments for this cancer. LR has achieved improvement
in survival within the past decade as a result of advances in diagnosis, surgical management
of HCC and perioperative care. However, the long-term prognosis remains poor, and
the 5-year overall survival rate ranges between 33% and 44%, with a 5-year cumulative
recurrence rate of 80% to 100%.
OLT could be viewed as the optimal treatment for HCC that is accompanied by advanced
cirrhosis because of the widest possible resection margins for tumour and for a definitive cure
of cirrhosis and its related complications. OLT for HCC performed within well-defined
oncologic criteria (Milan criteria \u201creference\u201d) has shown long-term results comparable with
those of transplantation for non-HCC patients. However, the critical shortage of available
donated organs, together with the increasing number of patients awaiting transplantation,
makes this therapeutic option available to only a small percentage of patients. Owing to the
limited organ supply, many liver transplant centers usually make a selection to resect patients
with compensated liver cirrhosis, defined as Child\u2013Pugh A chronic liver disease and resectable
tumor and to reserve transplantation for those with impaired liver function (Child-Pugh class
B-C) and small oligonodular HCC considered within the currently accepted criteria for
transplantation.
Radiofrequency and microwave ablation are relatively new percutaneous techniques in
clinical use for HCC, that can produce tumour necrosis. Complete response rates are high in
large series if tumour is less that 3 cm in diameter.
This chapter will consider the main surgical techniques for the treatment of HCC in the light
of the major guidelines currently available and of personal experience.
Also, we will review HCC prognostic factors, and the particular situation of \u201clarge\u201d HCC and
the strategy for liver tumours located at the hepato-caval confluence
Biomarkers in Breast Cancer
Breast cancer is the most common cancer in women and its incidence experienced an important increase, thanks to the introduction of a systematic screening. The increased incidence of early breast cancer has led to debates on its over-treatment, which may cause unnecessary harm to patients with favorable prognosis. Therefore, modern research is in the quest of finding the perfect prognostic marker to avoid overtreatment in patients with a favorable prognosis. In this perspective, many molecular markers have been studied in the last decades in order to provide both a useful prognostic tool, able to determine whether the cancer is likely to be indolent or aggressive, and a possible therapeutic target. In this chapter, we review the current knowledge about the principal biomarkers, which are usually immunohistochemically tested on breast surgical specimens, including ER and PR, Mib1/Ki-67 and HER2/neu expression. Furthermore, we will analyze other possible prognostic markers which may have in the future a key role in breast cancer management, such as several multigene panels (OncotypeDX, Mammaprint, NanoString Prosigma). Finally, we will discuss the role of genetic tests for some know genetic mutations associated with higher breast cancer susceptibility (BRCA1 and 2 genes)
Breast and Axilla Treatment in Ductal Carcinoma In Situ
Ductal carcinoma in situ (DCIS) represents a challenge for the breast unit team, beginning from its difficult radiological detection and continuing with its controversial multimodal treatment and management. With the introduction of the mammographic screening, DCIS has become a common diagnosis. In fact, today DCIS is mostly identified by mammography or magnetic resonance imaging (MRI). The increased prevalence of DCIS diagnosis, in the past, raised the problem of the therapeutic management. In this chapter, the breast and axillary surgery in case of DCIS and the most controversial aspects regarding DCIS management are reviewed based on international guidelines and on the current literature
Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study
Abstract To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2\u2032-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of
8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases
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