MR cholangiography (MRC) in the evaluation of CBD stones before laparoscopic cholecystectomy

Background: The aim of our work was to evaluate the predictive value of MR cholangiography (MRC) in detecting CBD stones before laparoscopic surgical treatment. Methods: MRC was performed as a unique preoperative imaging modality in 45 selected patients (16 male; 29 female; age range: 28–72; mean age: 54.4) before laparoscopic cholecystectomy. MRC imaging was obtained with a 3D Turbo Spin-Echo sequence (TR = 3000 ms, TE = 700 ms, Echo Train Length—128) with an acquisition time of 5 min 48 s. Diagnostic confirmation was obtained in all the cases at i.o. cholangiography. When a stone was detected it was removed by transcystic or transcholedochal approach. Results: Eighteen of the 45 patients (40%) had CBD stones. MRC correctly evaluated 16 out of 18 stones, with a resulting sensitivity of 88.9%, specificity 100%, positive predictive value 100%, negative predictive value 90%, and accuracy 95.6%. Conclusions: Despite the good results of MRC, it cannot be proposed as a screening technique to be performed in all patients submitted to laparoscopic cholecystectomy due to high cost and the limited amount of MR equipment. In conclusion, only selected patients should be submitted to MRC before laparoscopic cholecystectomy.     

A Case of Pathological Complete Response and Resolution of Dermatomyositis Following Neoadjuvant Chemotherapy in HER2-Positive Early Breast Cancer

Introduction. Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) mainly characterized by subacute muscle weakness and skin rash sometimes associated with malignancy. Case Presentation. A 61-year-old female was admitted to our hospital because of progressive proximal muscular weakness, heliotropic rash and left breast rash. Muscle biopsy findings were consistent with dermatomyositis (DM). A full panel of myositis associated (MAA) and specific antibodies (MSA) revealed the presence of anti-nuclear antibodies (1:160, speckled), Anti-Ro52 and anti TIF1-γ antibodies. A whole body Computed Tomography Scan showed three left mammary nodules and homolateral axillary lymphadenopathy. The breast biopsy confirmed the diagnosis of ductal carcinoma. Patient was initiated to neoadjuvant chemotherapy followed by surgery for cancer, and corticosteroid and intravenous immunoglobulins for DM with a complete resolution of muscle weakness and pathological complete response of breast cancer. Discussion and conclusion. Similar cases in literature are commonly referred to a first-line surgery and the role of neoadjuvant chemotherapy is debatable.     

Cardiovascular aging and psychometric performances: correlations in a group of ultraseptagenarian elderly

Aging of the Italian population resulted in a net increase of the cardiovascular pathologies, and the correlated disabilities. In addition, the cardiovascular diseases represent actually in Italy the most frequent cause of death. With advancing age, both the heart and the blood vessels undergo numerous morphological and functional modifications, which are reducing the functional reserves of these organs. The present study looked for correlation between the cardiac functionality and the cognitive, as well as affective functions. Furthermore, we evaluated the functional variations of the autonomy and autosufficiency of the same patients. We had 171 enrolled subjects (108 women and 63 men), all above the age of 70 years. Based on the classification of the New York Heart Association (NYHA), 85 of these patients (35 men and 50 women) had a II class (Group A), and 86 of them (28 men and 58 women) a III NYHA class of heart function (Group B). We included only patients who did not have any cerebrovascular event yet, and were not bed-ridden. The psychometric performance has been evaluated by using the mini-mental state examination (MMSE), the geriatric depression scale (GDS), the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales. Cardiac functions have been measured by Doppler echocardiography, in M-mode. The Group A (of mean age 71 +/- 3 years) displayed ventricular ejection fraction (VEF) values in average of 43 +/- 4%, MMSE scores 27 +/- 2; GDS scores 14 +/- 3; IADL 6 +/- 1, and ADL = 6, i.e., maintained a complete autosufficiency. The Group B (mean age 74 +/- 4 years) displayed VEF values in average of 26 +/- 3%, MMSE scores 23 +/- 4; GDS scores 22 +/- 3; IADL 4 +/- 2, and ADL = 4 +/- 1, i.e., had a reduced autosufficiency. These results confirm that also the heart pays a toll for aging: the myocardial contractility becomes significantly altered, meaning the loss of cardiac functions itself. These morpho-functional heart alterations are accompanied by decreased psychometric performances during aging, with consequent reductions of cognitivity, affectivity, autosufficiency and autonomy, involving a complex decrease of the quality of life.     

Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis

The use of Alendronate for the treatment of senile diabetes with osteopenia or osteoporosis is a common practice today, although the reasons for the success of this treatment are not completely understood. We investigated 40 elderly female patients, over 70 years of age, divided in two Groups (A and B) 20 cases of each, with insulin-dependent senile diabetes and fair metabolic balance, with an average disease duration of 30 +/- 4 years. They all had osteoporosis shown by the mean T-score of bone mineral densitometry. The Groups were treated as follows, Group A with 10 mg/day of Alendronate per os, with morning fasting plus a supplementation of calcium and vitamin D3, while the Group B received only calcium and vitamin D3 per os. Bone mineral density (BMD) expressed in mg/cm2, and in terms of T-score and Z-score at the spine (L1-L4) was monitored over time after 12 and 24 months, using dexa technique with a Lunar DPX densitometer. Moreover, the variation of daily consumption of insulin (DCI) of all the study population was calculated 12 and 24 months after the start of treatments. The data of Group A showed an improvement of osteoporosis, as evidenced by the increase of BMD at both times of measurement, accompanied by a significant reduction in the DCI (-21.6% by the 12th month, and -36.2% by the end of the observation period). In the Group B only small, statistically insignificant changes were observed in both the BMD and DCI. The most plausible explanation of reduction of DCI in Group A seems to be that Alendronate has improved the clinical symptoms of osteoporosis (pain, rigidity, and reduction of movements) through its action on the bone mass recovery and slowing down the bone turnover and under these conditions the diabetic patients improved their own physical performance. The better and more extensive movements certainly produced a reduction in the DCI, since a correct and adequate physical activity does contribute to an improved glucose metabolism.     

Fasting cycles potentiate the efficacy of gemcitabine treatment in in vitro and in vivo pancreatic cancer models

Background/aims

Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. Short-term fasting cycles have been shown to potentiate the efficacy of chemotherapy against glioma. The aim of this study was to assess the effect of fasting cycles on the efficacy of gemcitabine, a standard treatment for PC patients, in vitro and in an in vivo pancreatic cancer mouse xenograft model.

Materials and Methods

BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in standard and fasting mimicking culturing condition to evaluate the effects of gemcitabine. Pancreatic cancer xenograft mice were subjected to 24h starvation prior to gemcitabine injection to assess the tumor volume and weight as compared to mice fed ad libitum.

Results

Fasted pancreatic cancer cells showed increased levels of equilibrative nucleoside transporter (hENT1), the transporter of gemcitabine across the cell membrane, and decreased ribonucleotide reductase M1 (RRM1) levels as compared to those cultured in standard medium. Gemcitabine was more effective in inducing cell death on fasted cells as compared to controls. Consistently, xenograft pancreatic cancer mice subjected to fasting cycles prior to gemcitabine injection displayed a decrease of more than 40% in tumor growth.

Conclusion

Fasting cycles enhance gemcitabine effect in vitro and in the in vivo PC xenograft mouse model. These results suggest that restrictive dietary interventions could enhance the efficacy of existing cancer treatments in pancreatic cancer patients.     

Assessment of cognitive and affective disorders in an elderly population undergoing hemodialysis

The purpose of this study was to assess the prevalence of cognitive and affective disorders in a group of elderly people suffering from chronic renal failure (CRF) and undergoing outpatient hemodialysis. Psychogeriatric assessment was performed on 39 individuals over 65 years of age suffering from CRF, and on a control group composed of 35 healthy elderly individuals. Assessment was made through Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activity Daily Living (ADL) and Instrumental Activity Daily Living (IADL) shortly before hemodialysis. A number of blood parameters were determined for both groups to evaluate the state of metabolic compensation. The elderly people undergoing hemodialysis did not seem to present a greater decline in cognitive capacity than their healthy peers, even if this is closely related to the level of anemia present in hemodialysis patients. On the other hand, affective disorders were widely observed, although in mild form, and seem to depend on factors other than age. There is certainly a reactive element deriving from the hemodialysis condition itself and the problems related to it, whereas an organic element linked to CRF cannot be excluded, and which seems to be related to anemia. Finally, the level of independence does not seem to be compromised in hemodialysis patients.     

Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients

Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.Methods A total of 11 cancer patients (4 male, 7 female, aged 50–68 years) were enrolled in this multicenter, randomized, open-label, two-period, crossover study. Patients received a single infusion of docetaxel monotherapy, 60–100 mg/m², on two occasions at least 3 weeks apart. During one of the cycles (treatment A), patients received docetaxel alone. During the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and 14.Results Ten patients completed the study. Concomitant administration of aprepitant did not cause any statistically or clinically significant changes in docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC_0–last was 3.26 vs 3.17 g h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC_0– 3.51 vs 3.39 g h/ml (P>0.25; ratio B/A 0.96); geometric mean C_max was 3.53 vs 3.37 g/ml (P>0.25; ratio B/A 0.95); and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m² (P>0.25; ratio B/A 1.04). The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles; the median absolute neutrophil count nadirs were 681/mm³ during treatment with docetaxel alone and 975/mm³ during aprepitant coadministration.Conclusions Aprepitant had no clinically significant effect on either the pharmacokinetics or toxicity of standard doses of docetaxel in cancer patients. Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4.     

T1-weighted dual-echo MRI for fat quantification in pediatric nonalcoholic fatty liver disease

AIM:To determine in obese children with nonalcoholic fatty liver disease (NAFLD) the accuracy of magnetic resonance imaging (MRI) in assessing liver fat concentration.METHODS:A case-control study was performed.Cases were 25 obese children with biopsy-proven NAFLD.Controls were 25 obese children matched for age and gender,without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin.Hepatic fat fraction (HFF) by MRI was obtained using a modification of the Dixon method.RESULTS:HFF ...