Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares / Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: our preliminary results

INTRODUCCIÓN: Nuestro objetivo fue evaluar los cambios metabólicos corticales y el resultado clínico en los pacientes afectados por la hidrocefalia idiopática de presión normal (iNPH) después de la colocación de una derivación ventriculoperitoneal (VP). MATERIALES Y MÉTODOS: Diez pacientes afectados por la sospecha de iNPH se sometieron a una evaluación de la hidrodinámica del LCR basada en una prueba de infusión lumbar. El principal criterio de selección para la cirugía se basó en la elasticidad intracraneal (EI)>0,30. Todos los sujetos con una EI> 0,30 se sometieron a una exploración PET con 18 fluorodesoxiglucosa (18F-FDG) en la línea de base (PET1) y un mes después de la cirugía (PET2). Además, los mismos pacientes fueron sometidos a una evaluación clínica antes y un mes después de la cirugía mediante pruebas neuropsicológicas y análisis de la marcha. RESULTADOS: Se realizó un número total de 20 exploraciones de PET 18F-FDG en todos los pacientes reclutados. En comparación con la PET1, la PET2 mostró un aumento en el consumo de glucosa en el lóbulo frontal izquierdo y el lóbulo parietal izquierdo en la PET2 en comparación con la PET1 (p < 0,001). Todos los pacientes reclutados presentaron un aumento significativo en las puntuaciones neuropsicológicas (i.e. Batería de evaluación frontal y Evaluación cognitiva de Montreal) y han mejorado clínicamente en el análisis de la marcha. Se encontró una correlación significativa entre el aumento del consumo de glucosa cortical en el área parietal izquierda y la mejoría cognitiva detectable por la evaluación neuropsicológica. CONCLUSIONES: La mejora en 18F-FDG PET del metabolismo de la glucosa podría considerarse un marcador de imagen útil para la evaluación de la respuesta de la iNPH a la derivación ventriculoperitoneal

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting

Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: Our preliminary results. / Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares.

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting.

Anesthesia and analgesia in breast surgery: the benefits of peripheral nerve block.

Breast surgery is frequently associated with postoperative pain, nausea and vomiting, that result in increased patient's suffering, prolongation of hospital stays and related costs. Thoracic paravertebral nerve block (TPVB) is a viable option to the classic multimodal analgesia in breast surgery as it enhances surgical anesthesia and postoperative analgesia. In this review, we report the results of a number of studies on the role of TPVB in breast surgery. This technique is associated with a superior control of the pain, a reduction in opioids consumption after surgery, a decrease in postoperative nausea and vomiting, and an overall decrease in length of hospital stay. In particular, TPVB seems to provide the most benefits in patients undergoing an unilateral or bilateral mastectomy followed by immediate reconstruction. Some studies also suggest that the use of regional anesthesia-analgesia could attenuate perioperative immunosuppression and minimize metastases in breast cancer patients. TPVB can be also coupled with other regional anesthetic techniques such as pectoral nerve block (PNB), thus increasing the reduction in postsurgical pain, opioids consumption and length of hospital stays.

Stage IV Kienböck's disease: Proximal row carpectomy and application of RCPI implant.

Kienböck disease is an aseptic osteonecrosis of the lunate, which gradually leads to total carpal collapse. Lichtman's classification relates radiographic evidence of wrist damage to four different stages and supports surgical decision-making. This study pertains to six patients (2 males and 4 females) affected by stage IV Kienböck's disease who underwent proximal row carpectomy and received an RCPI implant. The clinical outcomes consisted of wrist range of motion (ROM), pain on a VAS scale (0-10), the DASH score and the patient's level of satisfaction. The mean follow-up was 27.6 months (16-36). Pain relief and improvements in wrist flexion - extension ROM, radial - ulnar deviation and strength were achieved in every patient. There were no cases of implant failure or dislocation. Considering the good results obtained, we believe that proximal row carpectomy associated with the use of a pyrocarbon RCPI implant is a valid surgical technique for the treatment of stage IV Kienböck's disease. It is a good alternative to carpal fusion, which leads to wrist immobility, and to total wrist joint replacement, which has a high incidence of dislocation and fracture.

Comparative study of oncoplastic versus non-oncoplastic breast conserving surgery in a group of 211 breast cancer patients.

OBJECTIVE: Breast conserving surgery (BCS) followed by radiotherapy is the standard of care for most patients with early breast cancers; however, the aesthetic outcomes of this procedure is not always desirable. Oncoplastic breast surgery is an innovative approach that aims at the safe and effective treatment of the cancerous lesion while achieving the best possible aesthetic outcome. The aim of this study was to evaluate and compare oncoplastic and non-oncoplastic procedures. PATIENTS AND METHODS: A retrospective observational study was conducted on a group of patients who underwent oncoplastic or non-oncoplastic breast surgery at the Breast Unit of the University of Rome Tor Vergata. RESULTS: Out of 211 patients, 154 (73%) underwent non-oncoplastic surgery, while 61 (27%) underwent an oncoplastic procedure. The percentage of patients requiring re-excision was twice greater for women in the non-oncoplastic group: 12.9% vs. 6.5% in the oncoplastic group. The rate of complications was higher in the oncoplastic group compared to the non-oncoplastic one (4.9% vs. 1.3%). The size of the tumor, the number of the patients receiving post-operative radiation, the interval between surgery and radiotherapy and follow-up were similar between the two groups. CONCLUSIONS: Oncoplastic surgery represents a valid alternative to breast conserving surgery for patients with breast cancer, with only minimal differences in long-term complications and similar results in terms of local recurrence and number of metastasis.

An arthroscopic-assisted minimal invasive method for the reconstruction of the scapho-lunate ligament using a bone-ligament-bone graft.

UNLABELLED: We report the outcomes of an arthroscopic-assisted minimally invasive technique to reconstruct the scapho-lunate ligament using a bone-ligament-bone graft in 11 patients (11 wrists). The mean follow-up time was 29 months (range 20 to 38). The preoperative mean wrist flexion, extension, grip strength and patient-rated wrist evaluation score values were 61°, 54°, 115 N and 54, respectively. The postoperative mean values were 64°, 58°, 142 N and 15, respectively. There were no statistical differences between the pre- and postoperative wrist flexion and extension, whereas changes in grip strength and patient-rated wrist evaluation score were significant. Scapho-lunate angles decreased significantly from 69° to 60°. Based on our clinical outcomes, this method provides a reliable alterative for the reconstruction of the scapho-lunate ligament in patients with persistent Geissler type 3 and 4 lesions in the short-term. LEVEL OF EVIDENCE: IV.

Study of proteolysis in river buffalo mozzarella cheese using a proteomics approach.

The guarantee of the origin and quality of raw material is essential for the protection and valorization of Campana buffalo mozzarella cheese. The risk of utilization of semifinished products and stored milk in substitution for fresh milk is increasing, due to the continuous desire to reduce production costs. A proteomics approach and electrophoresis survey of retail mozzarella cheeses indicated different rates of proteolysis in the production of dairy industries. The use of fresh milk and correct cheesemaking protocol yielded only γ-caseins, which are derived from ß-casein by plasmin, and para-κ-casein, which is derived from κ-casein by chymosin. The detection of abnormal hydrolysis resulting in ß- and αS1-casein fragments, identified by mass spectrometry, indicates the use of stored milk or stored and pressed curd, or the reuse of unsold mozzarella cheese, to produce mozzarella. The formation of γ-caseins and other fragments during a long storage of raw materials at room or refrigeration temperature was ascribed to plasmin (endogenous milk enzyme), whereas formation of αS1-casein fragments, mainly αS1-I(6P)- and αS1-I(7P)-casein during the storage of curd was ascribed to the action of chymosin (exogenous enzyme) from rennet. Sodium dodecyl sulfate-PAGE and alkaline urea-PAGE permitted us to evaluate the freshness of the raw materials used in the manufacturing of buffalo mozzarella cheese and to reveal possible inappropriate preservation.

Investigational Paradigms in Downscoring and Upscoring DCIS: Surgical Management Review.

Counseling patients with DCIS in a rational manner can be extremely difficult when the range of treatment criteria results in diverse and confusing clinical recommendations. Surgeons need tools that quantify measurable prognostic factors to be used in conjunction with clinical experience for the complex decision-making process. Combination of statistically significant tumor recurrence predictors and lesion parameters obtained after initial excision suggests that patients with DCIS can be stratified into specific subsets allowing a scientifically based discussion. The goal is to choose the treatment regimen that will significantly benefit each patient group without subjecting the patients to unnecessary risks. Exploring the effectiveness of complete excision may offer a starting place in a new way of reasoning and conceiving surgical modalities in terms of "downscoring" or "upscoring" patient risk, perhaps changing clinical approach. Reexcison may lower the specific subsets' score and improve local recurrence-free survival also by revealing a larger tumor size, a higher nuclear grade, or an involved margin and so suggesting the best management. It seems, that the key could be identifying significant relapse predictive factors, according to validated risk investigation models, whose value is modifiable by the surgical approach which avails of different diagnostic and therapeutic potentials to be optimal. Certainly DCIS clinical question cannot have a single curative mode due to heterogeneity of pathological lesions and histologic classification.

Physico-chemical features of the environment affect the protein conformation and the immunoglobulin E reactivity of kiwellin (Act d 5).

BACKGROUND: Allergy diagnostic systems sometimes give false positive or negative results. In this respect, the influence of protein conformational changes on the allergen-IgE interaction sites is worthy to be investigated. OBJECTIVE: To investigate the influence of different experimental conditions on the structural properties and IgE reactivity of kiwellin (Act d 5) as a model system. METHODS: Act d 5 was purified from the natural source. To study its conformational features, experiments of circular dichroism (CD) in different media were performed. The IgE reactivity was investigated by skin testing, immunoblotting and ISAC microarray system, in a population of kiwifruit allergic subjects. RESULTS: CD experiments indicated that Act d 5 has a mainly helical structure and the conformation is strongly affected by the experimental conditions. The protein is more structured in low polarity media and at acidic pH values, similar to those of the natural source. Eleven subjects of 29 (38%) allergic to kiwifruit were positive to purified natural Act d 5 by skin test. Among them, three patients (10%) showed a reaction only to Act d 5 at pH 4.5, and three (10%) showed a reaction only to the allergen in standard neutral conditions. No one of the 11 subjects with positive skin test recognized Act d 5 immobilized on the ISAC system. Eight of nine subjects detected Act d 5 by IgE immunoblotting. One subject did not recognize the sequence epitopes of Act d 5 in IgE immunoblotting experiments and reacted to the skin test only when the allergen was in acidic conditions. CONCLUSIONS AND CLINICAL RELEVANCE: The conformation and IgE reactivity of Act d 5 are affected by the physico-chemical characteristics of the solvent. These findings suggest that the assay conditions influence the results of the diagnostic systems by modulating the pattern of exposed antigenic epitopes.

First-line stereotactic treatment of thalamic abscesses: report of three cases and review of the literature.

Solitary pyogenic thalamic and basal ganglia abscesses are relatively uncommon. Even if widespread antibiotic therapy and modern imaging technologies combined with minimally invasive techniques have improved the outcome in patients with brain abscesses, this is counterbalanced by an increasing population of immunocompromised patients. Basal ganglia, thalamic, brainstem or multiple abscesses are usually of hematogenous origin with an underlying source of infection which can include congenital heart disease, thoracic sepsis or, less frequently, an odontogenic or otogenic source. However, no evident foci of sepsis or predisposing factors may be found. Only a few studies are reported in the literature, because midline abscesses are usually included in studies dealing on the treatment of abscesses in general. Different treatment options and the timing of treatment are described. We report our experience in 3 consecutive cases of thalamic abscess, treated by stereotactic puncture as the first step, followed by histological analysis, external drainage and targeted intrathecal and systemic antibiotic therapy. Deep-seated abscesses seem to behave differently as they are associated with an increased risk of intraventricular rupture and antibiotic resistance, a fact which justifies a more aggressive and immediate surgical treatment. We review the literature on this topic in the last 20 years.

In vivo assessment of hydrocephalus shunt.

OBJECTIVES: Over a 3-year period, we have performed 312 tests in 197 shunted patients. The data have been analyzed retrospectively to: (1) investigate the parameters describing CSF dynamics that correlate with shunt under-drainage and (2) estimate accuracy of this method. METHODS: Constant rate infusion tests into shunt prechamber were performed. RESULTS: In 161 of the 312 infusion tests, results indicated under-draining shunts. Patients in the under-draining group had higher baseline and plateau CSF pressures, higher resistance to CSF outflow and higher levels of baseline pulse amplitude waveform. During the test, a significantly greater vasogenic waves and lower compensatory reserve was noticed in patients with blocked shunts. In 21 patients with suggestion of shunt blockage and who subsequently underwent operative revision of the shunt, reports of intraoperative shunt patency were available. Shunt blockage was confirmed intra-operatively during surgery in 19 cases. CONCLUSIONS: In vivo shunt testing is easy, safe and clinically useful, aiding decision in difficult clinical situations, where shunt malfunction is suspected but not certain. It also has satisfactory positive predictive power.

Pathological classification of DCIS and planning of therapeutic management.

BACKGROUND: Ductal intraepitelial neoplasia (DIN) represents a spectrum of disease that may progress from usual hyperplasia to ductal carcinoma in situ (DCIS) grade 3. The aim of the study was to asses the correlation between the DIN classification and the surgical treatment including sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: In this retrospective study, 229 patients with DIN had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. RESULTS: Breast conservative surgery was the definitive treatment in 80% of the cases. The H&E evaluation of excised sentinel nodes was negative for metastatic disease; nevertheless the immunohistochemical (IHC) evaluation revealed the presence of metastatic cells in 6 patients (3.7%). CONCLUSION: In cases of DIN lesions SLNB is not indicated. The only reason SLNB should be considered is when there is an evidence of invasive foci at definitive histology or when radical mastectomy is proposed.

Cerebral blood flow autoregulation during intracranial hypertension: a simple, purely hydraulic mechanism?

OBJECTIVE: In this paper, we re-propose the role of a hydraulic mechanism, acting where the bridging veins enter the dural sinuses in cerebral blood flow (CBF) autoregulation. MATERIALS AND METHODS: We carried out an intraventricular infusion in ten albino rabbits and increased intracranial pressure (ICP) up to arterial blood pressure (ABP) levels. We measured CBF velocity by an ultrasound probe applied to a by-pass inserted in a carotid artery and recorded ICP by an intraventricular needle. Diastolic and pulsatile ICP and ABP values were analyzed from basal conditions up to brain tamponade and vice versa. CONCLUSIONS: A biphasic pattern of pulsatile intracranial pressure (pICP) was observed in all trials. Initially, until the CBF velocity remained constant, pICP increased (from 1.2 to 5.4 mmHg) following a rise in diastolic intracranial pressure (dICP); thereafter, in spite of a further rise in dICP, pICP decreased (2.87 mmHg) following CBF velocity reduction until intracranial circulation arrest (pICP=1.2 mmHg). A specular pattern was observed when the intraventricular infusion was stopped and CBF velocity returned to basal levels. These findings can be interpreted as indicating a hydraulic mechanism. Initially, when CBF is still constant, pICP rise is due to an increase in venous outflow resistance; subsequently, when CBF decreases following a further increase in venous outflow resistance, the vascular engorgement produces an arteriolar vasodilation. This vasodilation determines an increase in vascular wall stiffness, thus reducing pulse transmission to surrounding subarachnoid spaces.

How does CSF dynamics change after shunting?

OBJECTIVE: Hydrocephalus is much more complex than a simple disorder of cerebrospinal fluid (CSF) circulation. Shunting primarily corrects disturbed fluid flow which may have an impact on cerebral blood flow and metabolism. We studied hydrocephalic patients before and after shunting to characterize changes in their CSF compensatory parameters. MATERIAL AND METHODS: We selected 25 patients and studied them retrospectively. All patients had ventriculomegaly and clinical symptoms of normal pressure hydrocephalus. After shunting, they were still presenting with some adverse symptoms, mainly headaches, slow improvement or no improvement of ventriculomegaly. Therefore, they underwent further infusion studies to assess shunt function. In all cases, the shunts were confirmed to be draining CSF adequately. Parameters of CSF dynamics: baseline intracranial pressure (ICP), resistance to CSF outflow, cerebrospinal elasticity, content of vasogenic pressure waves (pulse, respiratory and B waves) and compensatory reserve assessed as moving correlation coefficient between mean CSF pressure and pulse amplitude (RAP), were compared before and after shunting. RESULTS: Mean ICP and resistance to CSF outflow decreased (P < 0.003) after shunting. All vasogenic pressure waves decreased (P < 0.005). Compensatory reserve (RAP) significantly improved (P < 0.005). CONCLUSION: A functioning shunt has an important impact on CSF circulation and pressure-volume compensation. Infusion studies can demonstrate the return of disturbed CSF dynamics to normal values even if clinical or radiological changes are not dramatic.

Insulin aspart improves meal time glycaemic control in patients with Type 2 diabetes: a randomized, stratified, double-blind and cross-over trial.

AIMS: This randomized, multi-centre, double-blind, stratified, two period, cross-over trial was undertaken to assess the pharmacokinetics and pharmacodynamics of insulin aspart injected immediately before compared with regular human insulin injected 30 min before a Mediterranean-style meal in 37 (23 M, 14 F) patients with Type 2 diabetes. METHODS: Insulin aspart or regular human insulin was given subcutaneously (0.15 U/kg) in random sequence, using a double-dummy technique (at one visit: human regular insulin at t=-30 min and placebo at t=0; at the other visit: placebo at t=-30 min and aspart insulin at t=0). Serum glucose and insulin concentrations (15 points) were measured after each meal for 240 min. RESULTS: Post-prandial glycaemic excursions were 20% lower with insulin aspart (IAsp) compared with regular human insulin (HI) treatment [ratio (Iasp/HI)=0.80, CI=(0.66-0.98), P=0.034]. The maximum serum glucose (SG) concentration was similar for the two treatments (P=NS). The (median) time to maximum SG was 25 min shorter for IAsp compared with HI (P=0.048). Maximum serum insulin concentration was higher after IAsp compared with HI (P=0.023) as well as the area under the 4-h serum insulin curve (P=0.006). Furthermore, the time to maximum serum insulin concentration was 27 min shorter after IAsp (P=0.039), even though IAsp was injected 30 min after HI. No adverse events occurred during the trial. CONCLUSIONS: In patients with Type 2 diabetes a more favourable insulin profile and a better glycaemic control were found with IAsp injected immediately before compared with HI injected 30 min before a Mediterranean-style meal.

A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer.

The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.

Stop-flow technique for loco-regional delivery of high dose chemotherapy in the treatment of advanced pelvic cancers.

AIM: To verify the rationale of a pelvic stop-flow technique for the perfusion of high-doses of mitomycin C and anthacyclines in patients with inoperable, recurrent pelvic cancer. METHODS: The stop-flow technique was realized by using percutaneous double-balloon arterial-venous catheters that selectively isolate the pelvic vascular section and a perfusion provided by an extracorporeal pump for 20 min. Ten patients (pts) with unresectable pelvic recurrence from colon-rectal cancer were treated with a combination of Mitomycin C (MMC, 20 mg/sqm) plus doxorubicin (DOXO, 75 mg/sqm; 8pts) or epirubicin (EPI, 75 mg/sqm; 2pts) infused into the isolated pelvic compartment. Blood samples were collected from the extracorporeal vascular flow and from peripheral plasma, and analysed for drug quantitation. RESULTS: During the procedure, there were no technical or hemodynamic complications, and no deaths occurred during surgery or in the postoperative period. MMC and DOXO peak levels measured in the extracorporeal system which irrotates the tumor area, were on average 21.6 (range: 4.3-44.3, MMC) and 17.2 (range: 1.8-48.4, DOXO) times higher than those observed in the peripheral blood. Similarly; the area under concentration (AUC) versus time curves measured in the pelvic compartment during stop-flow perfusion were 19.9 (range: 3.8-45.0, MMC) and 13.4 (range: 1.2-26.6, DOXO) times higher than the corresponding value in peripheral circulation. The drug percentage eliminated in the ultra filtrate was only 7.7% (MMC) and 0.9% (DOXO), and the plasmatic AUC(0-24) were similar to those observed with iv bolus of equivalent drug doses. Minimal systemic and local toxicities were observed. One complete pathological and 2 partial responses were observed; pain remission in 8/10 patients. median survival was 12 months (8-31). CONCLUSION: The endo-arterial administration into the local vasculature produces high pelvic-systemic concentration gradients during the stop-flow perfusion with limited local and systemic toxicity. The encouraging clinical results suggest further evaluation.