Proposal for reclassification of the TNM staging system in patients with locally advanced (pT3-4) renal cell carcinoma according to the cancer-related outcome

OBJECTIVES: The optimal stratification of locally advanced renal cell carcinoma (RCC) is controversial, with the prognostic relevance of ipsilateral adrenal gland invasion and cranial extension of vena cava thrombosis being the most debatable issues. We evaluated the prognosis of patients with locally advanced RCC and identified a new model to stratify their outcome. MATERIALS AND METHODS: We analyzed the data of 227 patients who had undergone partial or radical nephrectomy for pT3-4 RCC at two academic centers between 1986 and 2002. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analysis, respectively. RESULTS: At a median follow-up of 29 mo, we censored 108 (47.6%) cancer-related deaths. On univariate analysis, the 2002 T stage was not statistically significant. According to cancer-related outcome, we identified three subgroups of patients with different prognoses: pT3a(n): tumors with perirenal fat invasion or renal vein thrombosis or thrombosis within the vena cava below the diaphragm; pT3b(n): tumors with renal vein thrombosis or thrombosis within the vena cava below the diaphragm and concomitant perirenal fat invasion; pT4(n): adrenal gland or Gerota fascia invasion or thrombosis within the vena cava above the diaphragm. The three subgroups had significantly different prognoses. The new reclassification was an independent predictive variable on multivariate analysis, as well as the pathologic lymph node stage. CONCLUSIONS: The 2002 version of TNM of locally advanced RCC did not stratify patient outcome. The present study suggests the possibility of reclassifying pT3-4 RCC into three categories capable of predicting cancer-specific survival, regardless of all other prognostic factors.     

Genomic analysis of the 8p11-12 amplicon in familial breast cancer

Amplification of 8p11-12 has been recurrently reported in sporadic breast cancer. These studies define a complex molecular structure with a set of minimal amplified regions, and different putative oncogenes that show a strong correlation between amplification and over-expression such as ZNF703/FLJ14299, SPFH2/C8orf2, BRF2 and RAB11FIP. However, none of these studies were carried out on familial breast malignancies. We have studied the incidence, molecular features and clinical value of this amplification in familial breast tumors associated with BRCA1, BRCA2 and non-BRCA1/2 gene mutations. We detected 9 out of 80 familial tumors with this amplicon by chromosomal comparative genomic hybridization. Next, we used a high-resolution comparative genomic hybridization array covering the 8p11-12 region to characterize this chromosomal region. This approach allowed us to define 2 cores of common amplification that largely overlap with those reported in sporadic tumors. Our findings confirm the molecular complexity of this chromosomal region and indicate that this genomic event is a common alteration in breast cancer, present not only in sporadic but also in familial tumors. Finally, we found correlation between the 8p11-12 amplification and proliferation (Ki-67) and cyclin E expression, which further proves in familial tumors the poor prognosis association previously reported in sporadic breast cancer.     

CD105 is a marker of tumour vasculature and a potential target for the treatment of head and neck squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 361–367 Background: The importance of angiogenesis in solid tumour growth is well recognised. Tumour angiogenesis is considered the result of an imbalance between pro‐ and anti‐angiogenic factors produced by both the malignancy and normal cells. Endoglin (CD105) is a proliferation‐associated, hypoxia‐inducible glycoprotein that seems to be clinically superior to other pan‐endothelial markers in the selective evaluation of tumour angiogenesis. Several studies have revealed CD105 up‐regulation in a wide range of tumour endothelia. Since 2002, endothelial CD105 expression has also been retrospectively investigated in patients with head and neck squamous cell carcinoma (HNSCC). Methods: An exhaustive literature review was performed to investigate available evidence on CD105 expression and its biological role and therapeutic potential in HNSCC. Results: The available evidence supports the hypothesis that CD105 expression in HNSCC may be a valuable parameter for pinpointing patients at greater risk of recurrent malignancy and with a worse prognosis. A high CD105 expression in HNSCC was associated with metastatic lymph nodes in most of the studies. Conclusions: Prospective studies are mandatory to confirm that CD105 expression is a significant prognostic hallmark in HNSCC. The results of prospective studies could be relevant for the adoption of stricter follow‐up protocols and/or alternative therapeutic regimens for patients with a high CD105 expression in HNSCC. Great interest is currently being focused on vascular targeting for therapeutic purposes. Preclinical studies on appropriate animal models resembling HNSCC to investigate the effects of inhibiting CD105 may show the efficacy of combined treatment strategies associating angiogenic‐targeted with conventional therapies for HNSCC.     

Advancing the Neurophysiological Understanding of Delirium

Delirium is a common problem associated with substantial morbidity and increased mortality. However, the brain dysfunction that leads some individuals to develop delirium in response to stressors is unclear. In this article, we briefly review the neurophysiologic literature characterizing the changes in brain function that occur in delirium, and in other cognitive disorders such as Alzheimer's disease. Based on this literature, we propose a conceptual model for delirium. We propose that delirium results from a breakdown of brain function in individuals with impairments in brain connectivity and brain plasticity exposed to a stressor. The validity of this conceptual model can be tested using Transcranial Magnetic Stimulation in combination with Electroencephalography, and, if accurate, could lead to the development of biomarkers for delirium risk in individual patients. This model could also be used to guide interventions to decrease the risk of cerebral dysfunction in patients preoperatively, and facilitate recovery in patients during or after an episode of delirium.     

Characteristics and outcome of therapy‐related myeloid neoplasms: Report from the Italian network on secondary leukemias

Therapy‐related myeloid neoplasms (t‐MN) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. We report data on 277 t‐MN patients, recruited between 1999 and 2013 by the Italian Network on Secondary Leukemias (104 retrospectively and 173 prospectively registered). Median age at t‐MN diagnosis was 64 years (range, 21–87). Most frequent primary malignancies (PMs) were lymphoproliferative diseases and breast cancer. One hundred and thirty‐three patients had received chemotherapy (CHT), 43 patients radiotherapy (RT), and 101 patients combined CHT/RT for PM. Median time between cytotoxic treatment and t‐MN was 5.7 years, with t‐MN following RT alone associated with significantly longer latency, compared to CHT or combined CHT/RT (mean, 11.2 vs. 7.1 years, P = 0.0005). The addition of topoisomerase‐II inhibitors to alkylating agents was associated with shorter latency compared to alkylating agents alone (median, 6 vs. 8.4 years, P = 0.02). Median survival was 14.6 months from t‐MN diagnosis, and was significantly longer in patients treated with allogeneic stem cell transplantation. Significant factors for survival at the multivariable analysis included age, adverse karyotype, and degree of anemia. Our data underline the prognostic importance of karyotype and age in t‐MN, similar to de novo acute myeloid leukemia. Treatment approaches should not preclude the use of conventional treatments for younger t‐MN patients, including allogeneic stem cell transplantation as potentially curative approach. Am. J. Hematol. 90:E80–E85, 2015. © 2015 Wiley Periodicals, Inc.     

Thrombosis of abdominal aorta in congenital afibrinogenemia: case report and review of literature

Thrombotic events in congenital hypo‐afibrinogenemia have been rarely reported, either in association or not with replacement therapy or thrombotic risk factors. We describe clinical findings and management of thrombosis of abdominal aorta with peripheral embolism in a patient with congenital afibrinogenemia. A review of arterial thrombosis in inherited hypo‐afibrinogenemia was also performed. The patient with a severe bleeding history requiring prophylaxis with fibrinogen concentrates (FC) was admitted for ischaemia of the 4th right toe. An angio‐CT of abdominal aorta showed a thrombosis from the origin of renal arteries to the carrefour with a distal floating part. No thrombotic risk factors were found; a previous traumatic lesion of aortic wall might have triggered the thrombus formation, whereas the role of FC prophylaxis remains uncertain. The patient was successfully treated with FC, enoxaparin followed by fondaparinux, and low‐dose aspirin without bleeding or thrombosis recurrence. After 2 years, aortic thrombus was almost completely recovered. Sixteen hypo/afibrinogenemia patients with arterial thrombosis were found in Literature, showing that thrombosis often occurs at a young age, involves large vessels, its recurrence is not unusual, and therapeutic strategy is not defined yet. Our therapeutic approach was effective and also safe, but further studies are needed to improve the knowledge of pathogenesis and the anti‐thrombotic management in this peculiar setting.     

The attracting power of the gaze of politicians is modulated by the personality and ideological attitude of their voters: a functional magnetic resonance imaging study

Observing someone rapidly moving their eyes induces reflexive shifts of overt and covert attention in the onlooker. Previous studies have shown that this process can be modulated by the onlooker's personality, as well as by the social features of the person depicted in the cued face. Here, we investigated whether an individual's preference for social dominance orientation, in‐group perceived similarity (PS), and political affiliation of the cued‐face modulated neural activity within specific nodes of the social attention network. During functional magnetic resonance imaging, participants were requested to perform a gaze‐following task to investigate whether the directional gaze of various Italian political personages might influence the oculomotor behaviour of in‐group or out‐group voters. After scanning, we acquired measures of PS in personality traits with each political personage and preference for social dominance orientation. Behavioural data showed that higher gaze interference for in‐group than out‐group political personages was predicted by a higher preference for social hierarchy. Higher blood oxygenation level‐dependent activity in incongruent vs. congruent conditions was found in areas associated with orienting to socially salient events and monitoring response conflict, namely the left frontal eye field, right supramarginal gyrus, mid‐cingulate cortex and left anterior insula. Interestingly, higher ratings of PS with the in‐group and less preference for social hierarchy predicted increased activity in the left frontal eye field during distracting gaze movements of in‐group as compared with out‐group political personages. Our results suggest that neural activity in the social orienting circuit is modulated by higher‐order social dimensions, such as in‐group PS and individual differences in ideological attitudes.