Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. RESULTS: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. CONCLUSION: Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Progress of brown tumors in patients with chronic renal insufficiency undergoing dialysis.

In a group of 73 patients, affected by chronic renal insufficiency, whose skeleton was periodically checked, three cases of brown tumors were found. These cases demonstrated a variety of locations that were involved, especially the pelvis, ribs and mandible. During therapeutic treatment the brown tumors presented a different behavior; while some lesions tended toward complete sclerosis, others increased in size and in both instances new lesions appeared. Parathyroidectomy, carried out in two patients, determined a definitive sclerosis of these lesions. Brown tumors also correlate with high PTH levels and with lesions from osteitis fibrosa.

CT-guided transthoracic needle biopsy in the diagnosis of chest tumours.

Percutaneous Transthoracic Needle Biopsy (PTNB) is an accepted technique for the diagnosis of suspected intrathoracic malignancy and, although the appropriate indications have not been clearly defined yet, its use has rapidly expanded in the last years. The authors reviewed retrospectively their experience over one-year time biopsies and analyzed some controversies regarding this diagnostic procedure.

Computed tomography of renal metastases.

Since the advent of CT, secondary neoplastic lesions of the kidneys have been detected with increasing frequency. After reviewing a large series of cases of renal metastases, we have been able to classify the CT findings into seven major categories that are discussed and illustrated in this article. The differential diagnoses between metastatic disease of the kidneys and other lesions such as renal infarctions, renal lymphoma, and primary malignancies are also considered.

Cystic primary neoplasms of the liver of the adult. CT features.

Although rather rare, primary cystic neoplasms of the liver of the adult may represent a diagnostic challenge in everyday practice. We describe the features of such tumors visualized on computed tomography. This shows a wide range of morphological changes such as septa, papillary growths, solid/liquid ratio, wall characteristics, and vascularization. We conclude that although the differential diagnosis between these tumors and nontumoral cystic lesions may occasionally be reliable on computed tomography, proper management of hepatic cystic neoplasms still relies on the pathological findings.

CT of secondary neoplasms. Unusual structural features--a pictorial essay.

The newer anticancer therapies, the routine employment of cross-sectional imaging modalities for staging and follow-up, and the increased survival rate of patients with neoplastic lesions have markedly widened the range of pathological and imaging features of secondary neoplasms. Moreover, the changes occurring in morphological and structural aspects of metastases may be the direct effect of the improved therapeutic tools, and in turn may offer revealing clues to the clinician regarding the outcome of therapy itself. The scope of this essay is to show the atypical computed tomographic (CT) aspects of a series of metastatic lesions. We selected the lesions on the basis of their unusual structural features, such as calcification; hemorrhage; superinfection; pseudocystic, cystic, and lipoid appearance; and hypervascularity. A highly detailed assessment of such changes is nowadays possible and appears mandatory.

Adrenal carcinomas in AIDS. Report of three cases.

With the recent advances in treatment of AIDS, we have seen an increase in detection of malignant neoplasms in our patients. While some malignancies have an undoubted relationship with the HIV infection, others represent nothing more than sporadic reports and their relationship with the underlying immunological deficit is all but clear. We report the imaging findings in three patients with AIDS and an adrenal adenocarcinoma. We also discuss the peculiar imaging aspects of these pathological entities and report some pathogenetic theories on the relationship between AIDS and neoplasms.

US and CT findings of secondary neoplasms of the thyroid--a pictorial essay.

Although clinical series report a low (3%) incidence of metastases to the thyroid gland, autoptic studies have showed occurrences as high as 17%, probably because of the high vascularization of the thyroid. We selected 9 patients who had pathologically proven thyroid metastases at CT and US, during follow-up for a known primary neoplasm. The most common originating neoplastic primaries include mostly those that generally give rise to blood-borne metastases such as breast and lung cancers, mucoid adenocarcinoma of the stomach, colon cancer and renal cancer, as well as melanoma and leiomyosarcoma. Because of its diffusion, sensitivity, and noninvasiveness, ultrasonography can justifiably be introduced in the staging protocols of those neoplasm that more frequently give blood-borne metastases to the thyroid, but a US-guided biopsy is warranted for hypoechoic or otherwise suspicious nodules. This holds particularly true in disease-free patients or previously diagnosed with generally slow-growing malignancies (breast or kidney), since the secondary localization, often metachronous in our experience, may be effectively managed surgically. CT features, on the other hand, are extremely variable and are directly dependent on the histology of the primary lesion, as well as the size of the secondary lesions.

[Experimental microsurgical gastrocystoplasty] . / La gastrocistoplastica sperimentale microchirurgica.

BACKGROUND: Stomach tract used for bladder augmentation decreases urinary pH and produces the syndrome of dysuria and hematuria; gastric mucosa in contact with urine may develop prominent histopathological changes including proliferative lesions. The aim of this study was to investigate in an experimental model the possibility of detecting the factors involved in the mucosal damage. METHODS: Thirty-five Sprague Dawley rats randomly underwent microsurgical gastrocystoplasty or sham operation (5 controls). During operation elliptical gastric patch was isolated with its gastroepiploic vascular pedicle, bladder was opened with midline incision and anastomosis performed. Urine was aspirated from the bladder for culture, pH and electrolytes evaluation; venous blood was samples for electrolytes, BUN and creatinine. Mean follow-up time was 6 months. RESULTS: Of the 30 rats subjected to gastrocystoplasty 23 survived (77%). All of cultures were negative, the urinary pH decreased after operation and increased gradually two months later. Urinary sodium and potassium ions concentrations increased significantly in gastrocystoplasty (p < 0.05). There were no significant changes in serum electrolytes or renal function. CONCLUSIONS: This experimental model was useful to investigate the effects related to the presence of gastric mucosa in the urinary tract.

Mobility versus sedentariness in task arrangements for people with multiple disabilities: an assessment of preferences.

This study was an attempt to assess preferences between a task arrangement involving mobility and a task arrangement involving sedentariness with three adults with multiple disabilities. Periods in which participants were exposed to both task arrangements were followed by periods in which they were allowed to choose between them. One participant had a strong preference for the task arrangement involving mobility from the beginning of the assessment. The other two participants developed a strong preference for the same task arrangement and showed higher levels of on-task behavior and/or of positive mood expressions within that arrangement. Aspects of the assessment as well as the use of assessment in daily contexts were discussed.

Task variation versus task repetition for people with profound developmental disabilities: an assessment of preferences.

An assessment of preferences between task variation and task repetition with four adults with profound developmental disabilities was implemented. After participants were exposed to both task variation and task repetition conditions, they were allowed to choose between them. Results showed that all participants had strong preferences; three preferred task variation and one task repetition. Aspects of the assessment and use of assessment data for planning daily work conditions were discussed.

[Hypothyroidism in adults: a magnetic resonance study of cerebral and hypophyseal changes]. / Ipotiroidismo dell'adulto: studio con la risonanza magnetica delle alterazioni cerebrali e ipofisarie.

The case of a 55-year-old woman with postpartum (at age of 22) hypopituitarism is reported. The patient, with signs of myxedema, was admitted to a psychiatric hospital for hallucinations. In addition to routine tests and measurements of thyroid hormones level, magnetic resonance imaging (MRI) of the brain and pituitary region was performed. The results of MRI showed cerebral atrophy and a large "empty sella". On the basis of clinical, laboratory and instrumental data, a diagnosis of panhypopituitarism with prevalent hypothyroidism was achieved. Many hypotheses could be made regarding its pathogenesis. Initially we considered the diagnosis of Sheehan's syndrome in which the sella turcica usually presents normal or reduced dimensions. However the presence of a large "empty sella" with thin walls, excludes this diagnosis. The delay of menarche and the short stature suggest the hypothesis of a preexistent pathological condition. It is possible that the patient had liquefied pituitary adenoma as a consequence of the postpartum shock or that she was hypothyroid, a condition in which the "empty sella" is very common.

Supporting independent indoor travel of people with blindness and intellectual disability with reduced frequencies of auditory cues.

This study evaluated the feasibility of supporting independent indoor travel using reduced frequencies of auditory cues with two persons having total blindness and profound intellectual disability. For these persons, who had acquired satisfactory travel performance with cues occurring every 8 sec., the cue frequencies were reduced to one-half or one-third of the original level. Analysis showed that both participants could manage accurate travel under the new cue conditions, even though their travel time (efficiency) seemed negatively affected. Implications of the findings were discussed.

Effects of automatically delivered stimulation on persons with multiple disabilities during their use of a stationary bicycle.

We assessed the effects of automatically delivered favorite stimulation on engagement and indices of happiness of two adults with multiple disabilities during their use of a stationary bicycle. The participants typically received four 5-min. sessions per day over a period of about 3.5 mo. Analysis showed that one participant had a significant increase in both those measures while the other participant had a significant increase in engagement during the intervention phases of the study (when the stimulation was present) as opposed to the baseline periods (when the stimulation did not occur). Implications of the findings are discussed.

Extending the use of familiar microswitches to difficult daily situations: two case evaluations.

This study assessed the possibility of successfully extending the use of familiar microswitches by two adults with multiple disabilities to a difficult, standing-with-support situation. Analysis showed that the introduction of the familiar microswitches into this situation increased the participants' constructive engagement; they had repeated contacts with the microswitch systems and activated them fairly consistently. For one of the participants, improvement also occurred in terms of mood (smiling) and standing time.

Promoting functional activity engagement at appropriate times with people with multiple disabilities.

This study was aimed at teaching three persons with multiple disabilities to carry out functional activities at appropriate times independently. To this end, an electronic time system that produced vibratory alarms at preset times and a board with object-cues (instructions for the activities) were used. Data indicated that all three persons learned to perform the scheduled activities at the preset times independent of prompts from staff. Implications of the data and the combination of these activities with structured occupational periods were discussed.

[Nuclear magnetic resonance in oncologic radiotherapy]. / La risonanza magnetica nella radioterapia oncologica.

The possibilities of utilizing Nuclear Magnetic Resonance in Radiation Oncology are examined, on the basis of information provided by spectroscopy (MRS), studies on the tissues characterization of tumors, and preliminary practical application of imaging (MRI) to radiation therapy. MRS affords information on the bioenergetics of the tumor cells, and on the biochemical changes induced by ionizing radiation; further, some results of clinical importance were obtained in "monitoring" tumor response to radiation therapy and chemotherapy. Tissue characterization of normal tissues and of tumor is analyzed; technical factors, morphological elements, and structural elements are considered. Morphological elements include anatomical recognition, clinical and radiological evaluation, appraisal of the peritumoral tissues, and analysis of inhomogeneities. Among structural elements are considered some methods suitable to achieve a full evaluation of tissue characterization of tumors, on the basis of an appropriate employment of sequence parameters. Practical application of MRI on radiotherapy of tumors comprises staging procedures, contribution to the selection of differentiated radiation volumes for radiotherapy planning, and new data on the evaluation of biological effects of ionizing radiation on normal tissues of patients.

[Initial experiences in the study of the pelvis using nuclear magnetic resonance imaging with 6.36 MHz radiofrequency]. / Prime esperienze nello studio della pelvi mediante risonanza magnetica nucleare (RMN) ad immagini con radiofrequenze di 6,36 MHz.

Twenty-four patients with pelvic disease were examined using a resistive magnet operating at a field strength of 0.15 T. and a R.F. frequency of 6.36 MHz. Spin-echo, multiecho (TR = 0.5-2 s; TE = 50-100 ms) and Inversion Recovery techniques (TR = 1.4 s; TI = 0.4 s) were employed. The proliferative processes of the pelvic organs were subdivided into: prostate (adenoma 5 cases, carcinoma 5); bladder (carcinoma 3, lymphoma 1); uterus (fibroma 1, cervical carcinoma 6, endometrial carcinoma 3). All patients were evaluated with conventional methods and had histological diagnosis. The little respiratory motion of pelvic organs allowed to obtain good coronal, sagittal and axial images. The main aspects of normal anatomy and pathology are analized and described. The tissue characterization of normal structures provides good anatomic details; multiplanar images depict the extent of the lesions properly. N.M.R. is an interesting method in evaluating the extension of pelvic masses and staging pelvic tumors.

[Intracranial hemorrhage studied with a high-field (1.5T) NMR apparatus]. / Studio dell'emorragia intracranica con apparecchio di RMN ad alta intensità di campo (1.5T).

Fifty-two patients were studied with high-field magnetic resonance imaging (1.5T), with T1- and T2-weighted spin-echo pulse sequences. The study was aimed at assessing the efficacy of MR imaging in the evaluation of intracranial hematomas. Characteristic intensity patterns were observed in the evolution of the hematomas, due to the physicochemical changes in hemoglobin. No acute hematomas were observed. In 35 sub-acute hematomas, peripheral hyperintensity could be observed on T1- and T2-weighted pulse sequences. This hyperintensity eventually fills in the hematoma in the chronic stage. In 17 chronic hematomas, a peripheral hypointense ring due to hemosiderin deposits was seen on T1- and T2-weighted scans. The authors conclude that high-field MR imaging is a very sensible diagnostic method in the evaluation of sub-acute and chronic hematomas.