Urinary Polyamines in Patients with Advanced Cervical Cancer or Pelvic Cancer Recurrence During and After Radiotherapy

The urinary excretion of polyamines was evaluated before, during and after radiotherapy in 16 patients with advanced squamous cell carcinoma of the uterine cervix (stage IIb or IIIb) and in 7 cases with pelvic recurrence after surgery for various types of carcinoma. The concentration of spermidine was significantly higher in the patients with primary tumors than in those with recurrent tumors. After the first radiation fractions putrescine increased in the patients with primary tumors whereas it decreased in patients with recurrent tumors. The values tended to return to baseline levels with time following treatment initiation. Polyamine increased markedly during treatment in patients who remained disease-free for at least 5 years but not in the patients with progressive disease or relapse. The results suggest a different polyamine metabolism and a different response to radiotherapy of recurrent tumors compared to primary tumors. The increase of urinary polyamines, but not the baseline values, seemed to be correlated to the response after radiotherapy.     

Prevalence and localization of nodal metastases in squamous cell carcinoma of the oral cavity: role and extension of neck dissection

Lymph node (LN) metastases represent the most important negative prognostic factor in squamous cell carcinoma (SCC) of the oral cavity, even though controversies still exist regarding their management. The aim of this study was to retrospectively analyze our experience in surgical management of SCC of the oral cavity with particular focus on the prevalence and localization of lymph nodal metastases and recurrences. The clinical records of 89 consecutive patients treated from 1983 to 2002 by concomitant surgery on both the T and N sites, excluding those undergoing salvage surgery, were reviewed. A total of 119 neck dissections (ND) were performed. Survival outcomes were calculated by the Kaplan–Meier method, while univariate comparisons by the log-rank and non-parametric tests were performed between different groups of patients. Five-year overall and determinate survivals were 50 and 57%, respectively. LN metastases were observed in 52% (56% of these showing extracapsular spread) and their presence strongly correlated with determinate survival (p < 0.0001). The prevalence of clinical and occult nodal disease was not related to the pT status. Neck levels II (59%) and I (56%) were most frequently involved. Metastases to level IV accounted for 15% of positive LN, even though 28% of them turned out to be skip metastases. Five neck recurrences were observed, only one of which was salvaged by surgery. The high prevalence of clinical and occult LN metastases in this setting suggests that ND should be performed on a nearly routine basis, even for lesions with a low-T category and a cN0 neck. Moreover, ND should always encompass level IV due to the possibility of skip metastases, particularly in tumors involving the oral tongue. In patients with a cN+ neck, levels from I to V should be addressed, particularly in the presence of metastases at levels III and IV.     

Distribution of paresthesias in Carpal Tunnel Syndrome reflects the degree of nerve damage at wrist.

OBJECTIVE: To verify whether the distribution of paresthesias in patients with Carpal Tunnel Syndrome (CTS) is related to the degree of the neurophysiological involvement. METHODS: We performed a cross-sectional study and retrospectively evaluated 163 patients who referred to our electromyography lab and to which a clinical and electrophysiological diagnosis of CTS was made. We divided the patients into two groups: (1) patients complaining of paresthesias at the hand as a whole and (2) patients with paresthesias in the territory of the median nerve. We referred to the distribution of paresthesias at the hand as GLOVE and to the distribution in the territory of the median nerve as MEDIAN. We compared the neurophysiological impairment in GLOVE and MEDIAN distributions. Moreover, we performed multiple regression analysis to evaluate which clinical-neurophysiological variables determined GLOVE and MEDIAN distribution. RESULTS: In our sample, 70.4% of patients had GLOVE distribution and 29.6% of patients MEDIAN distribution. The risk of presenting MEDIAN distribution increases about twice (OR = 2.07; 95% IC: 1.51-2.83) for each unitary increment of neurophysiological class. CONCLUSIONS: The distribution of paresthesias reflects the degree of nerve damage at wrist; patients suffering of SEV/EXT CTS present MEDIAN distribution. SIGNIFICANCE: Our data have important clinical implications because they strongly suggest that we have to consider the possibility of a severe neurophysiological involvement of the median nerve at wrist in patients complaining of MEDIAN distribution.     

Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

Usefulness of osteoprotegerin in assessing responses to neridronate treatment in Paget's disease of bone

Osteoprotegerin (OPG) is a protein that inhibits of osteoclastogenesis. The aim this study was to evaluate the response of serum OPG levels to neridronate treatment in patients with Paget's disease of bone resistant to previous therapy. Nine patients (4 men) affected by active Paget’s disease of bone (6 polyostotic, 3 monostotic) not responsive to clodronate were studied. Serum OPG, osteocalcin, total and bone isoenzyme of alkaline phosphatase (AP and BAP, respectively), and urinary deoxypyridinoline (DPD) were measured before and 5 months after neridronate treatment (100 mg/day, i.v. for two days). A scintigraphic activity index (SAI) was also calculated before treatment. Mean baseline OPG levels were within normal values and were not significantly different 5 months after neridronate treatment. In contrast, there were significant reductions in AP (41.9%, p<0.02) and BAP (38.8%, p<0.04). Serum OPG levels correlated with DPD (r=0.925) and SAI (r=0.689). Although OPG is an important regulator of bone metabolism, in our series of already treated patients it was not a sensitive marker for diagnosing Paget's disease and for monitoring the response to pharmacological treatment, whereas AP and BAP confirmed their clinical usefulness. This preliminary study requires confirmation by a study with a larger population.     

Non invasive estimation of mean right atrial pressure utilizing the 2D-Echo transverse diameter of the left hepatic vein

Aim of our study was to assess if the 2D-Echo transverse diameter of the left hepatic vein (LHV) obtained from the subcostal approach is correlated with invasive mean right atrial pressure (RAP). Thirty-two consecutive patients with acute myocardial infarction were studied by simultaneous 2D-Echo and right heart catheterization. LHV could be adequately imaged in 90% of patients. Mean RAP values at catheterization ranged from 0 to 15mmHg (mean 6±3.5 mmHg). A correlation was found between mean RAP and LHV diameter calculated after inspiration (r=0.81, SEE=1.54 mm, slope=0.71,p< 0.001) as well as after expiration (r=0.82, SEE=1.32mm, slope=0.62,p< 0.001) or during post-expiratory apnoea (r=0.85, SEE=1.3 mm, slope=0.71,p< 0.001). Moreover, percent increments of LHV diameter correlated well with percent changes of mean RAP during rapid infusion of 250–500 cc of saline in 4 patients (r=0.98,p< 0.001). Thus, the 2D-Echo LHV diameter is a feasible measurement that seems to correlate well with invasive mean RAP over a wide range of mean RAP values in patients with myocardial infarction; the changes in LHV diameter correlate well with the percent increase in central venous pressure obtained with saline infusion. Underestimation of invasive RAP occurs when mean RAP value exceeds 12 mmHg and can be explained by limited venous compliance. However these preliminary results suggest that this method may represent a valid alternative to obtain a non invasive estimate of mean RAP with 2D-Echocardiography.