Renza Cristofani

Relationship Between Time Interval From Primary Surgery to the Start of Taxane- Plus Platinum-Based Chemotherapy and Clinical Outcome of Patients With Advanced Epithelial Ovarian Cancer: Results of a Multicenter Retrospective Italian Study

PURPOSE To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. PATIENTS AND METHODS The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). RESULTS The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (< or = 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. CONCLUSION The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.

Assessment of Swallowing by Oropharyngoesophageal Scintigraphy in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disease in adults, and dysphagia is one of its most frequent and disabling symptoms. Oropharyngoesophageal scintigraphy (OPES) permits a functional and semiquantitative study of the various stages of swallowing. We studied 28 ALS patients (12 females and 16 males; mean age = 63.57 ± 10.39 yr SD), who were clinically rated against the ALSFRS scale (Amyotrophic Lateral Sclerosis Functioning Rating Scale) and underwent OPES with 99mTc-nanocolloid using either a liquid or a semisolid bolus. The semiquantitative parameters we analyzed were Oral Transit Time (OTT), Pharyngeal Transit Time (PTT), Esophageal Transit Time (ETT), Retention Index (RI), and Esophageal Emptying Rate (EER10s). Hence, the OPES performed with a semisolid bolus produced a higher proportion of pathologic values for the swallowing variables than when liquid bolus was used. Analyzed by grouping the patients into classes according to their bulbar ALSFRS scores, we found a significant increase in the OTT (p < 0.005), PTT (p < 0.02), and Oropharyngeal Retention Index (OPRI) (p < 0.0004) variables in ALS patients with more severe bulbar involvement. OPES has turned out to be a very important examination for detecting tracheal-bronchial inhalation and it also offers the possibility of acquiring a semiquantitative evaluation of the amount of food inhaled. In our experience, OPES in patients with ALS has been easy to use, economic, well tolerated, and capable of supplying precise indications with regard to the extent of the swallowing disorder, which permits a better clinical definition of the ALS patient.

Acupuncture treatment for balance disorders following whiplash injury.

In this study, by means of computerized static posturography, we evaluated the postural changes after acupuncture treatment in a group of 15 patients with balance disorders caused by cervical torsion due to Whiplash Injury (WI). The acupuncture treatment consisted of 3 sessions (one weekly session for 3 weeks) during which the acupuncture points Bladder 10 (Bl.10) and Gall Bladder 20 (G.B.20). VB were stimulated by means of piercing with needles, and manipulating the needles for 20 seconds. Each patient underwent posturographic evaluations before and just after each session of acupuncture. The posturographic tests were performed with open eyes (OE), closed eyes (CE) and closed eyes with retroflexed head (CER). As a control group, we used 17 patients complaining of the same symptoms as the study group due to WI, but treated with drugs (FANS and myorelaxing) and physiotherapy only. The patients of the control group also underwent posturographic tests once a week for three weeks. We observed a significant difference between the two groups regarding the reduction of the CER Length of the statokinesigram just before each session of acupuncture and reduction of the frequency oscillations (FFT) of the patients on the sagittal plane in the study group, in CER, whereas in the control group we observed a progressive increase in these values. The high percentage of positive results in our WI patients leads us to advocate the therapeutic efficacy of acupuncture for balance disorders due to cervical pathology, where it can be associated with or be a valid alternative to pharmacological treatment.

Circulating Lipid Levels and Severity of Diabetic Retinopathy in Type I Diabetes mellitus

Plasma lipid levels have been proposed as probable risk factors of diabetic retinopathy. To clarify this question, we evaluated the apolipoprotein levels in 68 type I diabetic patients (39 +/- SD 14 years; duration of diabetes 13 +/- SD 8.4 years). By the analysis of fluorescein angiography we have classified diabetic retinopathy as follows: absent retinopathy (AR, n = 23), minimal retinopathy (MR, n = 16), exudative retinopathy (ER, n = 15), proliferative retinopathy (PR, n = 14). For all patients we measured: total, LDL- and HDL-cholesterol (T-CH, LDL-CH, HDL-CH), apolipoproteins A and B (Apo A and B), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1). The mean age of the patients with ER (47 +/- SD 14 years) was greater than those with MR (36 +/- SD 15 years) or AR (33 +/- SD 13 years) (p less than 0.05). Significant differences within groups were not found for relative body weight, daily insulin dose, FPG, HbA1% (analysis of variance, ANOVA). The groups differed between each other with regard to T-CH, LDL-CH and HDL-CH/LDL-CH ratio (T-cholesterol: AR 186 +/- SD 34, MR 191 +/- SD 32, ER 212 +/- SD 52, PR 215 +/- SD 41 mg/dl; LDL-cholesterol: AR 124 +/- SD 28, MR 122 +/- SD 18, ER 148 +/- SD 38, PR 145 +/- SD 33 mg/dl; HDL/LDL-cholesterol ratio: AR 0.38 +/- SD 0.1, MR 0.35 +/- SD 0.1, ER 0.30 +/- SD 0.1, PR 0.29 +/- SD 0.1). The total-CH levels increased and HDL-CH/LDL-CH ratio decreased along with the severity of the retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids

BACKGROUND Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization. OBJECTIVES To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids. METHODS Nineteen patients were treated with thalidomide for 24 months starting with 200 mg/d for first 2 weeks, followed by 100 mg/d for 11 weeks and a maintenance dose of 100mg on alternate days for 35 weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28). RESULTS Skin score significantly decreased (P<0.001). Lower skin scores occurred after 3 and 6 months (P<0.05). s-ACE levels decreased over time at the third month (P<0.001). CXR assessed by radiological stage significantly improved during the first 6 months (P<0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment. CONCLUSIONS Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids.

Immunohistochemical study of 49 cutaneous melanomas: p53, PCNA, Bcl-2 expression and multidrug resistance

Aims and Background Thickness and level of invasion are the main morphological elements for an approximate but not sufficiently sensitive prognostic evaluation of cutaneous melanomas. By using immunohistochemical methods it is possible to detect biological markers related to prognosis. We have studied p53, PCNA, Bcl-2 and P-gp expression in 49 primary cutaneous melanomas. Materials We used the immunophosphatase APAAP immunohistochemical method. The percentage of labeled cells (according to four classes of positivity: <5%; 5-25%; 25-50%; >50%) and the localization of immunoreactivity were expressed for each marker. Statistical analysis was performed to determine the correlations between markers and level or thickness of melanomas. Results We found a good correlation between p53 expression and melanoma thickness (P <0.005), PCNA and P-gp expression. No relationship was observed between Bcl-2 expression and the different variables considered or other markers. Conclusions Our data seem to indicate an unfavorable prognostic role of higher nuclear p53 expression. However, we believe that our results need to be integrated with patients’ clinical follow-up and with the study of the expression of these markers in benign melanocytic lesions to gain more accurate information about their prognostic significance.

A 4-year evaluation of toxoplasmosis seroprevalence in the general population and in women of reproductive age in central Italy

This study aimed to estimate possible changes in seroprevalence of anti-Toxoplasma gondii IgG and IgM antibodies in people living in the area of Massa and Carrara (central Italy), in recent years. Serum samples from over 13 000 individuals were tested for both IgG and IgM anti- Toxoplasma antibodies using an immunoenzymatic method (Access® Toxo IgG, and Access® Toxo IgM II, Beckman Coulter Inc., USA). Our survey showed a decreasing trend of overall seroprevalence of 24.4% [95% confidence interval (CI) 22.62–25.71] in 2010 compared to 31.0% (95% CI 29.29–32.72) in 2007. A positive trend according to age was found, with low positivity observed in younger age groups. For women of reproductive age the prevalence of IgG antibodies was 30.2% (95% CI 28.44–31.96) in 2007 and 23.6% (95% CI 22.05–25.20) in 2010. IgM seroprevalence in women of this age group also progressively decreased from 1.6% to 0.97% during the study period. Our study confirms a decline of toxoplasmosis in Western countries.

The clinical outcome of epithelial ovarian cancer patients with apparently isolated lymph node recurrence: A multicenter retrospective Italian study

OBJECTIVES To assess the clinical outcome of epithelial ovarian cancer patients who developed an apparently isolated lymph node recurrence after primary therapy. METHODS The authors retrospectively assessed 69 patients with epithelial ovarian cancer who were clinically or pathologically free of disease after primary therapy and who subsequently developed an apparently isolated lymph node recurrence. The median follow-up of survivors was 74.5 months. RESULTS Median age was 58 years, FIGO stage was III-IV in 52 (75%) patients, residual disease after primary surgery was >1 cm in 36 (52%), first-line chemotherapy consisted of paclitaxel-/platinum-based chemotherapy in 44 (64%), time to recurrence was >12 months in 43 (62%), recurrence was pelvic and/or para-aortic in 41 (59%), and treatment at recurrence consisted of chemotherapy alone in 44 (64%), surgery plus chemotherapy in 22 (32%), surgery alone in one patient, surgery plus irradiation in one, and irradiation alone in one patient. Survival after recurrence was significantly related to the type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 20.8 months versus not reached, p=0.0002), and patient age (>58 versus <58 years, median: 26.8 versus 44.0 months, p=0.02). Overall survival was significantly related to the type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 45.4 months versus not reached, p=0.0001), patient age (>58 versus <58 years, median: 45.4 versus 62.9 months, p=0.03) and time to recurrence (<12 months versus >12 months, median: 45.4 versus 66.9 months, p=0.01). Cox model showed that treatment at recurrence was the strongest independent prognostic variable for both survival after recurrence (hazard ratio [HR]=0.277, p=0.0003) and overall survival (HR=0.249, p=0.0002). CONCLUSION Patients who underwent surgery plus chemotherapy had a 72% reduction in the risk of death after recurrence and a 75% reduction in the risk of death after initial diagnosis when compared with those treated with chemotherapy alone. Secondary cytoreductive surgery appears to be able to prolong survival in epithelial ovarian cancer patients with apparently isolated lymph node recurrence.

Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients

SummaryIn this study we evaluated the relationships between plasma metformin levels, measured by reversed-phase high-performance liquid chromatography, and serum lipid levels in 20 metformintreated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 ± 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r=−0.574, p<0.01), HDL-cholesterol (r=0.583, p<0.01) and HDL2-cholesterol (r=0.670, p<0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL3-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metforminc concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.

Hemostatic Alterations in Patients with Acute, Unilateral Vestibular Paresis:

OBJECTIVES: The etiopathogenesis of acute unilateral peripheral vestibulopathy (APV) still remains a matter of debate; ischemic changes in the circulation of the labyrinth may play a role. We consequently looked for possible hemostasis alterations in a group of patients with APV of an unknown nature. METHODS: We evaluated blood parameters known to be involved in circulation disorders, including total and HDL cholesterol, tryglycerides, apolipoprotein A and B, lipoprotein(a), homocysteine, folate, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III, protein C, protein S, activated protein C resistance, and anticardiolipin IgG and IgM antibodies. A series of 23 patients affected with APV were consecutively referred to our department, in the acute phase, before treatment, and in the follow-up phase after 4 to 6 weeks of pharmacologic washout. The aforementioned blood parameters were also measured in a series of 15 patients with Menières disease. RESULTS: The patients with APV in the acute phase compared with the patients with Menières disease in the acute phase exhibited increased plasma levels of fibrinogen (mean, 338.3 ± 135.9 SD vs 271.3 ± 69.8 SD mg/dL, P = 0.05), increased plasma levels of D-dimer (mean, 320 ± 207.8 SD vs 226.7 ± 138.7 SD NG/mL), enhanced plasma levels of lipoprotein(a) (41.4 ± 38.6 SD vs 16 ± 18.2 SD mg/dL, F = 5.67, P = 0.02), high leukocyte count (9.1 ± 2.7 SD vs 6.5 ± 1.3 SD x 10 3 /μL; F = 8.42, P < 0.006), and low serum folate concentration (5.3 ± 1.8 SD vs 7.1 ± 2.7 NG/mg; F = 4.34, P = 0.04). During follow-up the prothrombin time was prolonged (F = 4.34, P = 0.04) and leukocyte count decreased (F = 7.39, P < 0.019) in the APV patients, whereas fibrinogen, D-dimer, lipoprotein(a), and folate were unchanged. CONCLUSION: Our results provide evidence suggesting an involvement of the hemostatic system in APV.