Effect of Sodium Hydroxide and Tripolyphosphate on Curcumin Release from Chitosan-Based Macroparticles.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP). The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied. All formulations showed excellent CUR trapping efficiency, exceeding 90%. In particular, the TPP-crosslinked macrobeads released 34 wt% of the charged CUR within minutes, while the remaining 66 wt% was released slowly. The results indicate that the correct choice of gelling agent and its concentration leads to spherical particles capable of encapsulating CUR and releasing it in a wide range of kinetics so that macrospheres can be used in different applications.

TACE with degradable starch microspheres (DSM-TACE) as second-line treatment in HCC patients dismissing or ineligible for sorafenib.

OBJECTIVES: To date, there is no approved second-line treatment for patients dismissing sorafenib or ineligible for this treatment, so it would be useful to find an effective alternative treatment option. The aim of our study was to evaluate safety, feasibility and effectiveness of transarterial chemoembolisation with degradable starch microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (sorafenib) due to unbearable side effects or clinical contraindications. METHODS: Forty consecutive BCLC stage B or C patients (31 male; age, 70.6 ± 13.6 years), with intermediate or locally advanced HCC dismissing or ineligible for sorafenib administration, who underwent DSM-TACE treatment cycle via lobar approach were prospectively enrolled. Tumour response was evaluated on multidetector computed tomography based on mRECIST criteria. Primary endpoints were safety, tolerance and overall disease control (ODC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At 1-year follow-up, ODC of 52.5% was registered. PFS was 6.4 months with a median OS of 11.3 months. CONCLUSIONS: DSM-TACE is safe and effective as a second-line treatment in HCC patients dismissing or ineligible for sorafenib. KEY POINTS: • DSM-TACE is safe and effective as second-line treatment in HCC patients dismissing or ineligible for sorafenib • DSM-TACE allows the temporary occlusion of the smaller arterial vessels, improving overall therapeutic effectiveness by reducing the immediate wash-out of the cytostatic agent • DSM-TACE also decreases the risk of systemic toxicity and post-embolic syndrome.

[Ultrasound parameter-based response to treatment with new drugs for secondary hyperparathyroidism: a retrospective analysis in a single dialysis center]. / Risposta terapeutica ai nuovi farmaci dell'iperparatiroidismo secondario in relazione al grado ecografico di iperplasia paratiroidea: analisi retrospettiva in un singolo centro dialisi.

In hemodialysis patients with secondary hyperparathyroidism (SHPT) ultrasonography of the parathyroid glands allows to assess the glandular growth and to define the limits of medical treatment. The present retrospective study evaluated the relationship between parathyroid gland hyperplasia and the effectiveness of new drugs. Fifty-three patients with SHPT (iPTH > 400 pg/mL) after treatment with oral calcitriol were included in the study. These patients underwent parathyroid ultrasonography and sequential therapy with intravenous calcitriol (first step), paracalcitol (second step), and paracalcitol + cinacalcet (third step). Patients with median PTH < 300 pg/mL during the period of therapy and follow-up were considered responders. The therapeutic response was correlated with ultrasound parameters (number of parathyroid glands, maximum longitudinal diameter, structural score, and vascular score). Four (10%) of 41 patients treated with IV calcitriol, 7 (27%) of 26 patients treated with paracalcitol, 7 (41%) of 17 patients treated with cinacalcet and paracalcitol, and 1 (20%) of 5 patients treated with cinacalcet alone were responders. ROC curve analysis showed that maximum longitudinal diameter (< 9 mm), number of parathyroid glands (< -1), structural score (< 2), and vascular score (< 2) predicted response to any treatment. New drugs (paracalcitol, cinacalcet) are more effective in SHPT than conventional ones. However, the traditional ultrasonographic cutoff for the efficacy of medical therapy remained unchanged. Thus parathyroid gland ultrasonography predicts the therapeutic response also to the new drugs.

Parathyroid gland ultrasound patterns and biochemical findings after one-year cinacalcet treatment for advanced secondary hyperparathyroidism.

Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium-phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 +/- 5.9 and 13.0 +/- 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 +/- 416.3 and 556.8 +/- 480.8 mm(3), respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns.

Usefulness of the combination of ultrasonography and 99mTc-sestamibi scintigraphy in the preoperative evaluation of uremic secondary hyperparathyroidism.

BACKGROUND: The usefulness of the combination of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) parathyroid scintigraphy and ultrasonography to detect parathyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) is still controversial. METHODS: In all, 21 patients with SHPT underwent parathyroidectomy. The sensitivity and specificity of ultrasonography and scintigraphy related to site, size, hyperplasia type of PTG, concomitant thyroid disease, and the frequency of intraoperative frozen sections were determined. RESULTS: The sensitivities of scintigraphy and ultrasonography were 62% and 55%, and the specificity was 95% for both procedures. The sensitivity of combined techniques was 73%. The scintigraphy detected 7/9 (78%) ectopic PTGs, whereas ultrasonography was always negative. A PTG maximum longitudinal diameter <8 mm, the presence of diffuse hyperplasia, the upper localization of glands, and the presence of concomitant thyroid disease reduced the sensitivity and specificity of imaging techniques. In cases of positive imaging, the rate of intraoperative frozen sections was significantly lower. CONCLUSIONS: The ultrasonography and sestamibi scintigraphy, which showed a higher sensitivity than that of either ultrasonography or scintigraphy alone, led to a reduction of intraoperative frozen sections and to preoperative diagnosis of ectopic (29%) or supernumerary PTGs (10%) and concomitant nodular thyroid disease (24%).

Congenital tumors of the retrorectal space in the adult: report of two cases and review of the literature.

AIMS AND BACKGROUND: To describe and discuss, on the basis of the authors' experience and a review of the literature, the main aspects regarding the etiology, diagnosis, treatment and prognosis of congenital tumors of the retrorectal space. METHODS: We present 2 cases of congenital retrorectal tumors, a sacrococcygeal teratoma and a dermoid cyst, which represent, from the pathogenetic point of view, the most frequent presentation of the rare tumors of the retrorectal space. RESULTS: The reported cases are typical. The teratoma presented as an encapsulated, mixed mass located in the pelvic cavity behind the rectum and the vaginal canal, without signs of sacral involvement. The dermoid cyst appeared as a unilocular lesion filled with sebum and hair, which extended laterally to the iliopubic branch, medially to the urethra and anal canal, and posteriorly to the adipose tissue of the right buttock. Pelvic MRI produced a precise picture of the extension of the lesion and of the relationship between the mass and the pelvic organs and surrounding bony structures. Both lesions were completely removed via the perineal approach without coccygectomy. No recurrences were observed at 2 years of follow-up. CONCLUSIONS: Congenital retrorectal tumors are rare. MRI is crucial for diagnosis and preoperative planning. Complete surgical removal is the treatment of choice. Resection of the coccyx is necessary only in case of its involvement by the neoplastic mass or suspected malignant transformation.

Ultrasound patterns of parathyroid glands in chronic hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: The role ofparathyroid glands (PTG) ultrasonography (US) in hemodialysis patients with secondary hyperparathyroidism (SHPT) is still controversial. The present study aimed at evaluating the relationship between US findings and SHPT degree as well as therapeutic outcome. METHODS: Twenty hemodialysis patients with moderate SHPT and 15 with severe SHPT underwent US to assess the PTG number, maximum longitudinal diameter (MLD), structural (1-hypoechoic, 2-slight heterogeneous, 3-high heterogeneous, 4-nodular) and vascular patterns (1-slight, 2-medium and 3-high). RESULTS: PTG number, MLD and US patterns were correlated with iPTH levels. MLD of patients with moderate or severe SHPT was 7.2 +/- 2.3 and 15 +/- 5.1 mm (p < 0.001). Most patients with moderate SHPT showed a single PTG with an MLD <9 mm associated with 1-2 structural and vascular pattern, whereas patients with severe SHPT exhibited more than one PTG with MLD >9 mm and 3-4 structural and vascular patterns. Thirteen patients were responders to treatment and 22 nonresponders. In nonresponders, a higher number of PTG was observed as well as higher echostructural and vascular patterns. In 14 patients who underwent parathyroidectomy, no differences were found between PTG US MLD and pathology diameter. All PTG with evidence of 3-4 structural and vascular score at ultrasound showed nodular hyperplasia at pathological examination. CONCLUSIONS: The adopted classification of US findings is correlated with SHPT degree and therapeutic outcome and might be an adjunctive predictive method useful to assess the SHPT severity and to plan the therapeutic strategy.