Ischemic preconditioning attenuates portal venous plasma concentrations of purines following warm liver ischemia in man

Background/Aims: Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning (IPC). Thus, we questioned in patients undergoing partial hepatectomy whether (i) IPC will increase plasma purine catabolites and whether (ii) formation of purines in response to vascular clamping (Pringle maneuver) can be attenuated by prior IPC. Methods: 75 patients were randomly assigned to three groups: group I underwent hepatectomy without vascular clamping; group II was subjected to the Pringle maneuver during resection, and group III was preconditioned (10 min ischemia and 10 min reperfusion) prior to the Pringle maneuver for resection. Central, portal venous and arterial plasma concentrations of adenosine, inosine, hypoxanthine and xanthine were determined by high-performance liquid chromatography. Results: Duration of the Pringle maneuver did not differ between patients with or without IPC. Surgery without vascular clamping had only a minor effect on plasma purine transiently increased. After the Pringle maneuver alone, purine plasma concentrations were most increased. This strong rise in plasma purines caused by the Pringle maneuver, however, was significantly attenuated by IPC. When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine, the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning. Conclusion: These data demonstrate that (i) IPC increases formation of adenosine, and that (ii) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC. Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences, IPC might possibly decrease disturbances in the energy metabolism in the intestine as well. Copyright (C) 2005 S. Karger AG, Basel

Prognostic role of chromosome 9P deletion in patients with clear cell renal cell carcinoma

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Surgically Returning to Randomized lib(c)

To strengthen systems against code injection attacks, the write or execute only policy (W + X) and address space layout randomization (ASLR) are typically used in combination. The former separates data and code, while the latter randomizes the layout of a process. In this paper we present a new attack to bypass W + X and ASLR. The state-of-the-art attack against this combination of protections is based on brute-force, while ours is based on the leakage of sensitive information about the memory layout of the process. Using our attack an attacker can exploit the majority of programs vulnerable to stack-based buffer overflows surgically, i.e., in a single attempt. We have estimated that our attack is feasible on 95.6% and 61.8% executables (of medium size) for Intel x86 and x86-64 architectures, respectively. We also analyze the effectiveness of other existing protections at preventing our attack. We conclude that position independent executables (PIE) are essential to complement ASLR and to prevent our attack. However, PIE requires recompilation, it is often not adopted even when supported, and it is not available on all ASLR-capable operating systems. To overcome these limitations, we propose a new protection that is as effective as PIE, does not require recompilation, and introduces only a minimal overhead

Malignant PEComa: a case report with emphasis on clinical and morphological criteria

<p>Abstract</p> <p>Background</p> <p>Malignant perivascular epitheliod cell tumor (PEComa) is a very rare entity composed of distinctive perivascular epitheliod cells with variable immunoreactivity for melanocytic and muscle markers. At present this neoplasm does not have a known normal cellular counterpart and the natural history is often unpredictable. Up to now, few cases of PEComa have been described and treatment modalities are still controversial, particularly in advanced conditions.</p> <p>Case presentation</p> <p>We handled the case of a 42-year-old man with unresectable PEComa of the abdomen. A 7 cm hepatic hypodense lesion between segment V and VIII of the liver and diffuse intraperitoneal nodules of 0,3-3,5 cm along the right subcapsular hepatic region, were documented by a CT scan. Radiological images showed abnormal lymph nodes of the right internal mammary chain and anterior mediastinum. The patient underwent an explorative laparotomy for uncontrolled intrabdominal hemorrhage without a well-defined preoperative tumor diagnosis. At surgery, multiple lobulated nodules containing hemorrhagic fluid on the liver surface, peritoneum and omentum were confirmed. The procedure had a palliative intent and consisted of hemostasis, hematomas evacuation and omentectomy. The diagnosis of PEComa was made after surgery on the basis of morphological and immunohystochemical criteria. Radiological and intra operative findings suggest that the mass has an hepatic origin with diffuse involvement of hepatic capsule and suspensory ligaments. The patient received medical support care with blood and plasma transfusions. In our experience, PEComa was clinically malignant, leading to a fatal outcome 25 days after hospital admission of patient.</p> <p>Conclusions</p> <p>Here we report and discuss the peculiar clinical, radiological and morphological presentation of unresectable PEComa. Although in the majority of the reported series, PEComas show a more better prognosis, our case presents with a particular aggressive biological behaviour. The importance of a correct preoperative diagnosis, the need for more effective targeted therapies based on tumor molecular knowledge and evidence-based clinical studies are emphasized together with a revision of the concerning scientific literature.</p

PD-1 blockade therapy in renal cell carcinoma: current studies and future promises

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway

Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder: case report

BACKGROUND: The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. CASE PRESENTATION: The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. CONCLUSION: This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms

Seventh tumor-node-metastasis staging of gastric cancer : five-year follow-up

Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world

Abstraction-based Malware Analysis Using Rewriting and Model Checking

International audienceWe propose a formal approach for the detection of high-level malware behaviors. Our technique uses a rewriting-based abstraction mechanism, producing abstracted forms of program traces, independent of the program implementation. It then allows us to handle similar be- haviors in a generic way and thus to be robust with respect to variants. These behaviors, defined as combinations of patterns given in a signa- ture, are detected by model-checking on the high-level representation of the program. We work on unbounded sets of traces, which makes our technique useful not only for dynamic analysis, considering one trace at a time, but also for static analysis, considering a set of traces inferred from a control flow graph. Abstracting traces with rewriting systems on first order terms with variables allows us in particular to model dataflow and to detect information leak