Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.     

Cytological analysis of benign breast disease.

The different histological lesions of benign breast disease (BBD) are the result of interactions and regional prevalence of epithelial, myoepithelial, apocrine, and "null" (undifferentiated) cell types. We conducted an immunocytochemical analysis on 14 cases of BBD. Specific markers were employed to identify the different cell types; proliferation in these cells was revealed either by bromo-deoxyuridine uptake or PCNA ("cyclin") localization. The results indicate that apocrine cells do not undergo proliferation, representing therefore a terminally differentiated cell. The question related to the preneoplastic potential of BBD and on which cell type might possibly represent the precursor of in situ cancerous lesions remains unanswered. However, our data tend to exclude that such a putative proliferating precursor might be represented by apocrine or myoepithelial cells or even by the epithelial cells featuring epitheliosis.     

Medullary carcinoma of the thyroid with atypical patterns.

A case of a highly invasive thyroid carcinoma, which occurred in a 68-year-old woman, was studied by light and electron microscopy, and histochemical and biochemical analysis. Light microscopical, histochemical, and biochemical features were consistent with a diagnosis of a calcitonin-producing, amyloid-rich medullary carcinoma; electron microscopical patterns, mainly the presence of lumina, microvilli, and extensively dilated cytoplasmic E.R., were reminiscent of the ultrastructural features of the follicular carcinoma. Electron-dense bodies interpreted as "secretory granules" were very scarce. This case appears very similar to the case recently presented by Valenta et al. and interpreted as a microfollicular carcinoma. The atypical features of our case of MCT seem to indicate that this tumor should be included in a group of atypical MCT; these should be kept separate from the typical (differentiated) ones on morphological, functional, and prognostic grounds.     

Detection of alkaline sphingomyelinase activity in human stool: proposed role as a new diagnostic and prognostic marker of colorectal cancer.

OBJECTIVES: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. MATERIALS AND METHODS: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. RESULTS: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. CONCLUSION: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms.     

Accidental ingestion of sodium molybdate at the workplace followed by short-term biomonitoring

Introduction:Most of the molybdenum (Mo) is used in metallurgical applications, the tetrathiomolybdate form is an experimental chelating agent for Wilson’s disease. Human data of acute Mo exposure are lacking and, no report of no-observed-adverse-effect level (NOAEL) has been described until now.Case study:We report a case of acute occupational exposure to molybdenum, with the related plasma and urine molybdenum concentrations, caused by an accidental ingestion of a sip of an anti-corrosion liquid for metal containing sodium molybdate. Our purpose was to evaluate potential systemic toxicity of molybdenum and to evaluate the dose-response/dose-effect relationship. We estimated the amount of ingested molybdenum to make a mg/kg relationship and performed repeated urine and plasma molybdenum determinations. The patient was hospitalized for three days to monitor possible development of acute symptoms/biochemical alterations.Discussion:We estimated the amount of the sip around 50 ml, with an estimation of a total of 5 gr of sodium molybdate that, for the patient bodyweight of 80 kg, would mean 62,5 mg/kg of ingested Mo. Blood and urine samples collected 2 hours after ingestion showed 50 mcg/L (reference range: 0.43 – 1.8 mcg/L) and 630 mcg/L (refence range: up to 116 mcg/L) of Mo respectively, confirming acute exposure. The patients remained asymptomatic confirming that an estimated oral dose of Mo of 62.5 mg/kg was not associated with adverse effects.Conclusions:Our value, being extrapolated by a single case, will require further confirmations from other studies to allow a full evaluation of a NOAEL. Nevertheless, it does not preclude its use in evaluating the probable absence of adverse effect in the context of acute Mo exposure.     

Ambulatory diastolic blood pressure: a marker of comorbidity in elderly fit hypertensive individuals?

BACKGROUNDMasked diastolic hypotension is a new blood pressure (BP) pattern detected by ambulatory blood pressure monitoring (ABPM) in elderly hypertensives. The aim of this study was to relate ABPM and comorbidity in a cohort of fit elderly subjects attending an outpatient hypertension clinic.METHODSComorbidity was assessed by Charlson comorbidity index (CCI) and CHA₂DS₂VASc score. All subjects evaluated with ABPM were aged ≥ 65 years. CCI and CHA₂DS₂VASc score were calculated. Diastolic hypotension was defined as mean ambulatory diastolic BP < 65 mmHg and logistic regression analysis was carried out in order to detect and independent relationship between comorbidity burden and night-time diastolic BP < 65 mmHg. RESULTSWe studied 174 hypertensive elderly patients aged 72.1 ± 5.2 years, men were 93 (53.4%). Mean CCI was 0.91 ± 1.14 and mean CHA₂DS₂VASc score of 2.68 ± 1.22. Subjects with night-time mean diastolic values < 65 mmHg were higher in females [54.7% vs. 45.3%, P = 0.048; odds ratio (OR) = 1.914, 95% CI: 1.047−3.500]. Logistic regression analysis showed that only CHA₂DS₂VASc score was independently associated with night-time mean diastolic values < 65 mmHg (OR = 1.518, 95% CI: 1.161−1.985; P = 0.002), but CCI was not. CONCLUSIONSABPM and comorbidity evaluation appear associated in elderly fit subjects with masked hypotension. Comorbid women appear to have higher risk for low ambulatory BP.

The global population is ageing, and the number of subjects with long-term disorders is increasing, with heavy consequences on medical commitment and health-care systems burden.^[1] Moreover, multimorbidity is associated with a higher mortality,^[2,3] and hypertension represents a frequent condition involving patients with multiple diseases.^[1] The relationship between multimorbidity and hypertension is bidirectional. Hypertension could cause organ damage and then development of comorbidity; on the other hand, comorbidity could worsen hypertension and its consequences. In elderly subjects, hypertension could cause brain damage that could be the cause of cognitive decline;^[4] moreover, systemic atheroembolic syndrome could worsen blood pressure (BP) variability leading to cardiovascular disease (CVD).^[5]Hypertension, both complicated or not complicated, is a variable taken into consideration in a series of risk scores applied to the general population to estimate the mortality risk, such as the Cumulative Illness Rating Scale,^[6] the Charlson comorbidity index (CCI),^[7] and the Elixhauser index.^[8] The CHA₂DS₂VASc score is widely used as predictor of the risk of stroke in patients with atrial fibrillation, it includes hypertension among the factors considered for score calculation and its importance is underlined by the same weight assigned to congestive heart failure (CHF), age > 75 years, and diabetes mellitus (1 point). ^[9] However, CHA₂DS₂VASc score has also been suggested to be able to stratify adverse clinical events in hypertensive patients.^[10]In patients with comorbidities, out-of-office monitoring of BP has been shown to be associated with reduced systolic BP (SBP) compared to usual care, representing a very useful tool in routine clinical practice.^[11] However, the discrepancy of measures between office and out-of-office BP measures, such as ambulatory blood pressure monitoring (ABPM), is known since two decades,^[12] and these two approaches have pros and cons depending also on type of patients. In untreated older patients with isolated systolic hypertension, for example, ambulatory SBP was a significant predictor of cardiovascular risk over and above conventional BP.^[13,14]It is widely accepted that ABPM is a crucial informative tool for the evaluation of BP behaviour in everyday clinical practice,^[15] and is recommended to identify white-coat hypertension and masked hypertension.^[15,16] However, its importance goes greatly beyond due to its capacity to provide information for clinical use.^[15] In fact, night-time evaluation of BP is crucial to detect abnormal patterns of night-time behaviour, such as non-dipping, inverse dipping, extreme dipping and the morning surge,^[17] and asleep SBP is a significant BP derived risk factor for CVD events.^[18,19]Recently, a novel BP pattern defined masked diastolic hypotension, frequently found in older patients under antihypertensive treatment, has raised attention.^[20] Knowledge related to clinical use of ABPM in elderly subjects is still a matter of debate, and information about BP components and circadian profiles in subjects with high comorbidity burden is scarce.^[21]The aim of this study was investigate the possible relationship between the BP components (recorded by ABPM) and the comorbidity burden (assessed by means of CCI and CHA₂DS₂VASc score) in a cohort of fit elderly subjects attending an outpatient hypertension clinic.     

Role of Bowel Ultrasound in the Diagnosis and Follow-up of Patients with Crohn's Disease

Crohn's disease (CD) is an inflammatory chronic bowel disorder; it can involve the whole gastrointestinal tract, but its localization in the ileum or colon is most common. The reference standard for the diagnosis of CD is ileocolonoscopy with histologic assessment. The reference standard for the detection of any complications is surgery. However, imaging techniques have an important role both in the detection/localization of CD and in the follow-up of CD patients. In the last few years, the technical development of ultrasound equipment, the advent of new technologies such as elastography and mostly the increased expertise of sonographers have boosted the role of bowel ultrasound in assessment of the gastrointestinal tract. In fact, bowel ultrasound is particularly attractive thanks to its widespread availability, non-invasiveness, low cost and good reproducibility, as it can be easily repeated during follow-up. The aim of this article is to provide an extensive overview of the actual role of bowel ultrasound in the detection and follow-up of patients with CD.