Clinical experience with spiramycin in bisphosphonate-associated osteonecrosis of the jaw.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) consists of an exposure of the jaw bone that persists for over 8 weeks in patients with positive history for bisphosphonates. Symptomatology is characterized by dull and ceaseless pain, and in advanced stages, the exposure of necrotic bone is evident, which is frequently associated with purulent secretions and faetor oris. Despite many different studies on BRONJ, there are no general guidelines to treat this disease. In this work, the authors present their experience in BRONJ conservative therapy with spiramycin by comparing the results achieved with amoxicillin and clavulanic acid. From January 1, 2008 to June 30, 2008, our department received 25 patients who were affected by osteonecrosis secondary to bisphosphonates. Thirteen had taken bisphosphonates for osteoporosis and 12 for malignancies. We divided the 25 patients into two groups: those who had not received any treatment and those who had received treatment. The first group of 13 patients had been treated only with spiramycin (S). The results from this group were only evaluated to test the efficacy of spiramycin and were not considered in the study. The second group of 12 patients had not undergone any previous treatment. This group was further divided in two groups of 6 patients each; one group was treated with spiramycin and the other with amoxicillin and clavulanic acid (ACA). The following criteria were used to evaluate the results of the study: pain, sensibility deficits, purulent secretion and bone exposure. All group results were evaluated according to the criteria chosen, and positive results were achieved in both groups S and ACA, such as reduction or disappearance of pain, sensibility deficits and purulent secretion and healing of bone exposition, although spiramycin showed itself to be more effective than the combination of amoxicillin and clavulanic acid. Spiramycin is a macrolide antibiotic with a wide spectrum of activity against Streptococci, Pneumococci, Diplococci, Gonococci and Staphylococci, which are typical in BRONJ. No resistance was indicated. Administration of the antibiotics can be intravenous, intramuscular, rectal or oral, which remains the most frequently used since spiramycin elimination also occurs with saliva and the antibiotic reaches high concentrations in the oral cavity where BRONJ is situated. Good compliance to the spiramycin regimen was observed in all three groups, with a general improvement in all of the parameters considered. In only two cases did patients have to undergo surgical curettage. The results showed that spiramycin can be a first choice drug in the treatment of BRONJ, and it should be strongly considered for patients where previous antibiotic therapy did not prove to be effective.

Assessment of left ventricular systolic dysfunction by tissue Doppler imaging to detect subclinical cardiomyopathy early after anthracycline therapy.

AIM: Anthracycline (ANT) chemotherapy for breast cancer, while associated with high response rates, is fraught by risks of irreversible cardiotoxicity. Unfortunately means to detect such cardiotoxicity early on and at a sublinical stage are lacking. We evaluated the role of systolic tissue Doppler imaging (TDI) in appraising postchemotherapy left ventricular (LV) remodelling. METHODS: Patients undergoing ANT-chemotherapy for breast cancer were enrolled, and underwent baseline and >6-months echocardiography (standard and TDI). According to the pattern of LV-TDI systolic remodelling from baseline to follow-up, patients were stratified in: group 1 (no LV-TDI worsening), group 2 (minor LV-TDI worsening), and group 3 (major LV-TDI worsening). Fifty-six patients were included (follow-up 9+/-6 months). RESULTS: At baseline, no patient had abnormal LV ejection fraction (LVEF), LV-TDI systolic dysfunction or New York Heart Association (NYHA) >1. Follow-up overall analysis showed significant deterioration in LVEF, end-diastolic diameter (EDD) end-systolic diameter (ESD), and TDI-systolic parameters (all P<0.05). Specifically, 29 (51.8%) patients showed no adverse LV-TDI systolic remodelling, while 17 (30.4%) were in group 2, and 10 (17.9%) in group 3. All groups shared similar conditions at baseline. Patients with adverse LV-TDI remodelling had significant increases in EDD and ESD, as well as a significantly decreased LVEF (all P<0.05). No patient in group 1 had abnormal LVEF at follow-up, while 1 patient in group 2 and 2 patients in group 3 had abnormal LVEF (P<0.05). CONCLUSION: Subclinical systolic dysfunction occurs in almost 50% of patients early after chemotherapy for breast cancer, with a more adverse by LV-TDI remodelling implying a more pronounced deterioration of standard echocardiographic parameters.

Correlation of MRI liver volume and doppler sonographic portal hemodynamics with histologic findings in patients with chronic hepatitis C.

PURPOSE: The purpose of this study was to correlate portal hemodynamics on sonography and liver volume on MRI with histologic findings in asymptomatic patients with chronic hepatitis C. METHODS: Portal blood flow in the left and right portal branches in 20 healthy volunteers and in 26 patients was measured using Doppler sonography during both fasting and postprandial states. Total liver and right-and left-lobe volumes were determined using MRI. The ratio between portal blood flow and liver volume determined the "portal flow index" of the right and left lobes. RESULTS: We observed a statistically significant difference (p < 0.01) between the volunteers and patients in the mean left-lobe volume (352 +/- 81 cm(3) versus 544 +/- 159 cm(3)) and in the mean left portal flow index (1.1 +/- 0.2 ml/minute/cm(3) versus 0.69 +/- 0.2 ml/minute/cm(3)) as measured before the subjects ate. After a meal, the portal blood-flow volume in the right lobe was similar in the 2 groups but in the left lobe was significantly lower in the patients (p = 0.0009). The left postprandial portal flow index was inversely correlated with the grade of liver fibrosis (r = 0.533). CONCLUSIONS: The left-lobe volume (positive predictive value, 83%; negative predictive value, 72%) and left postprandial portal flow index (positive predictive value, 86%; negative predictive value, 88%) are sensitive indicators of chronic hepatitis. The left postprandial portal flow index may be a useful test for differentiating patients with minimal or no fibrosis from patients with mild to severe fibrosis.

The impact of the new organization on the management of breast cancer.

The radical change in the health care service now going on for some years requires the commitment of medical specialists, as well as the acquisition of an adequate knowledge of the economic implications associated to the therapeutic choice. Among primary objectives of health care management in the field of breast cancer, the best cost-effective strategy and the rationalization and standardization of diagnostic and therapeutic approaches, should be identified. Problems related to breast cancer are examined for effective, efficient and economic optimization.

Doppler sonography of hemodynamic changes of the inferior mesenteric artery in inflammatory bowel disease: preliminary data.

OBJECTIVE: To our knowledge, Doppler data for the inferior mesenteric artery are currently restricted to healthy patients. The present study was conducted to evaluate changes in inferior mesenteric artery flow in patients with inflammatory bowel disease. SUBJECTS AND METHODS: Doppler sonography of the inferior mesenteric artery was prospectively performed in 24 patients with Crohn's disease (active, n = 15; inactive, n = 9), in 22 patients with ulcerative colitis (active, n = 14; inactive, n = 8), and in 40 healthy controls. Disease activity was determined with clinical and laboratory indicators (medical history, physical examination, laboratory data, and endoscopy with histology). Flow velocity, pulsatility index, and estimated flow volume were measured in all patients and compared with the corresponding values for control subjects. Hemodynamic parameters were then correlated with location of disease (small bowel and right and proximal transverse colon versus distal transverse and left colon) and disease activity or inactivity. RESULTS: Among patients with active disease, inferior mesenteric artery flow was significantly greater in those with left colon involvement (group 1, 20 patients) than in patients with involvement of the small bowel or right colon (group 2, nine patients) and in control subjects. Median flow values for group 1 were peak systolic velocity, 1.96+/-0.57 m/sec; mean velocity, 0.63+/-0.25 m/sec; minimum velocity, 0.17+/-0.20 m/sec; pulsatility index, 3.07+/-1.24; and estimated flow volume, 0.40+/-0.17 l/min. Median flow values for group 2 were peak systolic velocity, 1.27+/-0.56 m/sec; mean velocity, 0.29+/-0.14 m/sec; minimum velocity, 0.06+/-0.10 m/sec; pulsatility index, 4.71+/-0.98; and estimated flow volume, 0.14+/-0.11 l/min. Median flow values for control subjects were peak systolic velocity, 1.41+/-0.48 m/sec; mean velocity, 0.43+/-0.19 m/sec; minimum velocity, 0.10+/-0.16 m/sec; pulsatility index, 3.49+/-0.49; and estimated flow volume, 0.13+/-0.06 l/min. Compared with control subjects, patients with acute disease involving the left colon (group 1) presented increases in flow velocity (systolic velocity, p < .001; minimum velocity, p = .01; mean velocity, p < .001) and estimated flow volume (p < .001) and a decreased pulsatility index (p = .01). A significant increase in inferior mesenteric artery flow was also found when group 1 patients were compared with those of group 2 (active disease affecting the small bowel and right colon) and group 3 (13 patients with quiescent disease of the left colon). CONCLUSION: In this preliminary study, active inflammation of the left colon in patients with Crohn's disease or with ulcerative colitis was associated with a substantial increase in inferior mesenteric artery flow that could be seen on Doppler sonography.

Doppler sonographic assessment of functional response of the right and left portal venous branches to a meal.

PURPOSE: The aim of our study was to quantitate by Doppler sonography the blood flow in the right and left portal vein branches before and after a standard meal. We also assessed the functional response of the right and left lobes of the liver. METHODS: Portal blood flow was measured by Doppler sonography in the left and right portal vein branches and main portal trunk in 20 healthy volunteers in both fasting and postprandial states. The ratio between portal blood flow and liver volume (determined by MRI) was the portal flow index (PFI). RESULTS: Before the meal, a statistically significant difference in portal blood flow volume was observed between the right and left portal branches (p < 0.01). The right PFI (0.83 ml/minute/cm3) and left PFI (1.1 ml/minute/cm3) were also significantly different (p < 0.01). The increase in portal venous blood flow after a meal was found to be greater in the left portal branch (128%) than in the right portal branch (78%). The postprandial PFI also differed significantly (right, 1.54 ml/minute/cm3; left, 2.5 ml/minute/cm3). CONCLUSIONS: These findings suggest that the left lobe of the liver has a better postprandial compliance than the right lobe has.

Sonographic and Doppler assessment of the inferior mesenteric artery: normal morphologic and hemodynamic features.

BACKGROUND: We wanted to evaluate prospectively the feasibility of sonographic and Doppler assessment of the inferior mesenteric artery (IMA) and to provide data on its normal morphological and hemodynamic characteristics. METHODS: Sonography and Doppler study of the IMA were performed on 116 patients without splanchnic vessel pathology. Vessel diameter, systolic, diastolic, and time-averaged mean flow velocities, pulsatility index values, and flow volumes were correlated with patient age (< 50 years vs. > or = 50 years) using the Wilcoxon rank-sum test. Findings were verified by splanchnic angiography in 11 cases. RESULTS: Technically valid studies were obtained in 103/116 cases (88.8%). Flowmetric data showed high peripheral resistance (mean +/- SD: systolic flow velocity, 1.41 m/s +/- 0.48; minimal diastolic flow velocity, 0.10 m/s +/- 0.16; pulsatility index, 3.49 +/- 0.49). Mean flow volume calculated in 80 cases was 0.13 L/min +/- 0.06. Older subjects presented significantly higher time-averaged mean flow velocities and lower resistance than those younger than 50 years. CONCLUSIONS: The success rate for sonographic and Doppler study of the IMA is similar to that observed with larger splanchnic vessels. Knowledge of its normal characteristics is necessary for recognition of pathological conditions and for studies of its physiological behavior.

Two quality control procedures on radiotherapy beam calibration and treatment planning system implementation.

New challenging dosimetric approaches, such as narrow beams and 3D algorithms, are being used in radiotherapy. In this paper two quality control (QC) procedures are reported. The first one concerns the QC of the dosimetry of small x-ray beams, generally carried out by using silicon detectors. The comparison of dose values obtained by a silicon diode, a diamond detector, and radiochromic films shows that for x-ray beams of high energy, the silicon diode can give an overestimation of the output factors in phantom, up to 4%. This is due to the higher than unit density silicon diode and the surrounding envelope that restore the lateral electron equilibrium. About the 3D algorithms for breast treatment planning, a quality control test has been adopted to verify the accuracy of the computed dosimetry when "loss of scatter" occurs. The results show a sensible agreement (within 1.5%) between computed and experimental data.

Local control in breast cancer: impact on survival.

The role of radiotherapy in breast cancer is examined, based on a review of literature. Its impact on survival is discussed in the framework of a multidisciplinary treatment of the disease.

Preoperative radiotherapy in the conservative treatment for breast cancer.

Aim of this study was to evaluate the feasibility, therapeutic effectiveness and toxicity of a non conventional radiation therapy (180 cGy twice a day for a total dose of 36 Gy in 2 weeks in the treatment of breast cancer inoperable with conservative surgery as first choice. Ten patients were studied. Results were as follows: complete response: 20%, partial response: 70%; no change: 10%. Acute toxicity was negligible and late toxicity, after a mean 46-month follow-up, was practically absent; the cosmetic result was definitely good. The radiobiology and kinetic features of breast cancer indicate that the potential of accelerated treatment should be further explored, this fractionation being suitable for optimal combined modality treatment with preoperative chemotherapy.

Organ preservation with radiochemotherapy in locally advanced bladder cancer.

Bladder cancer is frequent in Western countries and predominantly affects males (ratio: 3:1). In 15-25% of cases there is muscular wall invasion. Treatment of > T1 tumors is radical cystectomy with or without preoperative radiotherapy. In T2 there is 60% survival at 5 years, 40% in T3. Exclusive radiotherapy used to prevent radical cystectomy has lower survival rates in T2 (30-40% at 5 years) as well as in T3 (20% at 5 years). Recently, concomitant radiotherapy and chemotherapy has been introduced again to prevent demolitive surgery. Results are similar or slightly superior than those of surgery alone. In our experience with radiotherapy 180 cGy daily for a total dose of 64 Gy in combination with fluorouracil in locally advanced tumors 40% bladder preservation was achieved.

[Comparison between measured and computed absorbed dose values in the tangential treatment of the breast]. / Confronto tra i valori misurati e calcolati della dose assorbita nel trattamento tangenziale della mammella.

The calculated absorbed dose values to the reference point of the breast tangential irradiation, obtained by 2-dimensional (2D) Treatment Planning Systems (TPS), were compared with the measured absorbed dose values obtained with a ionization chamber in an anthropomorphic phantom treated with two opposed photon beams of 60Co, 6 MV and 10 MV. This comparison was aimed at assessing the 2D algorithm dose overestimation due to the effect of missing tissue in the irradiated field. The ratio between the computed dose, Dc, and the measured dose, Dm, reached 1.08 for 60Co beams and 1.04 for X-ray beams of linacs. The Clarkson method gives an adequate correction factor for the calculated absorbed dose value in the reference point. The portal films of some patients were studied to estimate the correction factor for the treatment time or monitor units evaluated by TPS using tomographic breast central plane. The values of the correction factors reached 1.10 for 60Co photon beams and 1.04 for X-ray beams. The measurements were carried out with TLDs positioned in the central plane of the breast, covered by a special bolus, of a second anthropomorphic phantom. The dose homogeneity as well as the accuracy of the relative computed dose values in the breast phantom irradiated with 10 MV X-ray beams were assessed.

Coenzyme Q10 and colorectal neoplasms in aged patients.

Coenzyme Q10 (CoQ10), a quinone located in cellular membranes, is a compound with mitochondrial bioenergetic functions whose antioxidant activity has recently been defined. CoQ10 content in colorectal neoplasms is significantly higher than in normal colorectal mucosa. While older patients (aged over 70 years) have also a significantly higher CoQ10 content, not observed in younger patients (aged under 70 years), the normal mucosa, instead; shows constant CoQ10 levels in both groups. For the same local stage (T), an increase in lymph node involvement (N) was observed in older patients as compared to younger ones, but not in distant metastases (M) with the same 5-year survival. These results justify the same therapeutic approach for patients older or younger than 70 years.

Quality assurance in radiotherapy of head and neck tumors.

Radiation therapy represents an extensively experimented treatment modality for head and neck tumors. Recent studies have documented a close dependence of clinical results, especially in terms of local control and toxicity, on the radiation therapy quality. Thus the effort to improve the results of conventional radiotherapy has been achieved with the identification of new therapeutic modalities (non conventional fractionation, conformal therapy, fast neutron radiotherapy, concomitant or neoadiuvant chemotherapy) as well as with constant optimization of the accuracy of used procedures. Among them the following should be mentioned: 1) the systematic use of immobilization systems which enable a significant reduction in positioning errors; 2) checks before and during treatment by portal imaging which enable to identify and correct a relevant percentage of inaccuracies; 3) "in vivo" dosimetry which enables an overall assessment of treatment accuracy. The general evolution of the radiobiological knowledge occurred in recent years has introduced into radiotherapy of head and neck tumors new schemes of fractionation and new modalities of combination with other therapeutic procedures. Furthermore, while the widespread use of complex irradiation procedures calls for the urgent need of quality assurance of radiation treatments, this is by all means a mandatory requirement even in the most conventional clinical practice.

[Quantitative ultrasonography in the evaluation of postmenopausal osteoporosis. Comparison with dual energy x-ray absorptiometry]. / Ultrasonografia quantitativa nello studio dell'osteoporosi postmenopausale. Confronto con l'assorbimetria a raggi X a doppia energia.

In order to compare the capacities of quantitative ultrasonography and dual energy X-ray absorptiometry to measure bone mineral density (BMD) in postmenopausal women, 45 postmenopausal patients were studied. They were divided into two groups on the basis of the results of absorptiometry: Group A (20 patients) had BMD values within normal limits, and Group B (25 patients) had BMD values lower than 1 standard deviation (SD) of the average for an age and sex matched population. Ultrasonography of the non-dominant heel was carried out on both groups to determine broadband ultrasound attenuation (BUA), speed of sound (SOS) and bone velocity (BV). A negative correlation between age and BMD, BV, SOS, and BUA was observed in all subjects. A positive correlation between BMD and BV and between BMD and SOS was found. In Group A, age correlated negatively with BMD, BUA, SOS and BV, and BMD correlated positively with BV. In Group B, age correlated negatively with BMD, and BMD correlated positively with BV and SOS. BV values were significantly elevated in Group B. The study evidenced a relationship between ultrasonography and absorptiometry in determining bone density in postmenopausal women. As ultrasonography and absorptiometry provided comparable information on bone density, we point out that ultrasonography can be used as a simple and sensitive indicator for postmenopausal osteoporosis.

[Doppler ultrasonography assessment of the inferior mesenteric artery. Feasibility study and definition of morphologic and flowmetric characteristics]. / Valutazione eco-Doppler dell'arteria mesenterica inferiore. Studio di fattibilità e definizione dei caratteri morfologici e flussimetrici.

The conventional and Doppler US assessment of the inferior mesenteric artery has not been reported in the literature to date. In the present study, the feasibility of Doppler US of the inferior mesenteric artery was prospectively investigated in 112 consecutive nonselected patients; the corresponding morphological features (size and vessel course) and Doppler flowmetry (peak systolic, peak diastolic and mean velocities; pulsatility index) were defined. In 32 patients (29%) neither conventional nor color-Doppler nor duplex imaging was possible. Of the extant 80 patients, in 65 (81%) all the three methods allowed the correct assessment of the inferior mesenteric artery; in 15 patients (19%) the results were suboptimal (poor US visualization, or inadequate Doppler flowmetry). In 33/80 patients, arterial blood flow was quantitatively assessed in 1/min. As for the patients who underwent further diagnostic procedures--e.g., CT and angiography--a close correlation was demonstrated between the morphological and functional data obtained by Doppler US and the corresponding CT and angiographic features. The possibility of analyzing the inferior mesenteric artery with conventional and Doppler US, besides the celiac trunk and the superior mesenteric artery, should allow splanchnic circulation to be more completely assessed, thanks to information about normal hemodynamics (after a meal or in response to pharmacological treatments) as well as about the diseases known to affect intestinal perfusion--e.g., mesenteric ischemia.