Ten-year Retrospective Study of Treatment of Malignant Colonic Obstructions with Self-expandable Stents

Purpose: To describe the use of self-expandable metallic stents to manage malignant colorectal obstructions and to compare the radiation dose between fluoroscopic guidance of stent placement and combined endoscopic and fluoroscopic guidance. Materials and Methods: From January 1998 to December 2007, 467 oncology patients undergoing colorectal stent placement in a single center were included in the study. Informed consent was obtained in all cases. All procedures were performed with fluoroscopic or combined fluoroscopic and endoscopic guidance. Inclusion criteria were total or partial colorectal obstruction of neoplastic origin. Exclusion criteria were life expectancy shorter than I month, suspicion of perforation, and/or severe colonic neoplastic bleeding. Procedure time and radiation dose were recorded, and technical and clinical success were evaluated. Follow-up was performed by clinical examination and simple abdominal radiographs at 1 day and at I, 3, 6, and 12 months. Results: Of 467 procedures, technical success was achieved in 432 (92.5%). Thirty-five treatments (7.5%) were technical failures, and the patients were advised to undergo surgery. Significant differences in radiation dose and clinical success were found between the fluoroscopy and combined-technique groups (P < .001). Total decompression was achieved in 372 cases, 29 patients showed remarkable improvement, 11 showed slight improvement, and 20 showed clinical failure. Complications were recorded in 89 patients (19%), the most significant were perforation (2.3%) and stent migration (6.9%). Mean interventional time and radiation dose were 67 minutes and 3,378 dGy.cm(2), respectively. Conclusions: Treatment of colonic obstruction with stents requires a long time in the interventional room and considerable radiation dose. Nevertheless, the clinical benefits and improvement in quality of life justify the radiation risk.

UPGRADING THE GLEASON SCORE IN EXTENDED PROSTATE BIOPSY: IMPLICATIONS FOR TREATMENT CHOICE

Purpose: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. Methods and Materials: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. Results: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. In 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. Conclusion: In the extended biopsy era and after the International Society of Urological Pathology consensus on G, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects. (c) 2009 Elsevier Inc.

Use of cholesterol-rich nanoparticles that bind to lipoprotein receptors as a vehicle to paclitaxel in the treatment of breast cancer: pharmacokinetics, tumor uptake and a pilot clinical study

Purpose In animal experiments paclitaxel oleate associated with a cholesterol-rich nanoemulsion concentrated in the neoplastic tissues and showed reduced toxicity and increased antitumor activity compared with paclitaxel-Cremophor EL. Here, a clinical study was performed in breast cancer patients to evaluate the tumoral uptake, pharmacokinetics and toxicity of paclitaxel associated to nanoemulsions. Methods Twenty-four hours before mastectomy [(3)H]paclitaxel oleate associated with [(14)C]-cholesteryl oleatenanoemulsion or [(3)H]- paclitaxel in Cremophor EL were injected into five patients for collection of blood samples and fragments of tumor and normal breast tissue. A pilot clinical study of paclitaxel-nanoemulsion administered at 3-week intervals was performed in four breast cancer patients with refractory advanced disease at 175 and 220 mg/m(2) dose levels. Results T(1/2) of paclitaxel oleate associated to the nanoemulsion was greater than that of paclitaxel (t(1/2) = 15.4 +/- 4.7 and 3.5 +/- 0.80 h). Uptake of the [(14)C]-cholesteryl ester nanoemulsion and [(3)H]- paclitaxel oleate by breast malignant tissue was threefold greater than the normal breast tissue and toxicity was minimal at the two dose levels. Conclusions Our results suggest that the paclitaxel-nanoemulsion preparation can be advantageous for use in the treatment of breast cancer because the pharmacokinetic parameters are improved, the drug is concentrated in the neoplastic tissue and the toxicity of paclitaxel is reduced.

USE OF ANTIBIOTIC SPACERS FOR KNEE ENDOPROSTHESIS INFECTIONS TREATMENT

Objective: The aim of this study is to evaluate the use of cement spacers impregnated with antibiotics for the treatment of infections in the nonconventional endoprostheses of the knee. Methodology: We have treated seven patients since 2004 (of which six were submitted to surgery in our service and one patient had been submitted to a primary tumor surgery in another removal service) with deep infection in knee tumor prosthesis. All patients were submitted to endoprosthesis removal and reconstructed with antibiotic cement spacer All patients were monitored both clinically and by lab tests as for monitoring the evolution, being considered able for reviews after 6 (six) months without infections signs. Results: We have noted a small predominance of infectious processes on the prosthesis inserted on proximal tibia as compared with distal femur (57.1% x 42.9%). The mean follow-up time of patients was 68.2 months. During the follow up, one patient died as a result of the root disease. Six patients out of seven were regarded as cured and one persisted with infection signs and symptoms. Conclusion: The results obtained up to date have motivated us to continue using this method of treatment.

Clinical Treatment of Ocular Demodex folliculorum by Systemic Ivermectin

PURPOSE: To report clinical outcomes of the treatment of ocular Demodex folliculorum with oral ivermectin. DESIGN: Noncomparative, interventional case series. METHODS: Setting. Institutional. Study Population. Twenty-four eyes of 12 patients (3 male and 9 female; mean age +/- standard deviation, 50.4 +/- 21.0 years) with refractory posterior blepharitis with the presence of D. folliculorum in lash samples were enrolled in this study. Intervention. Patients were instructed to take 1 dose of oral ivermectin (200 mu g/kg). All patients were instructed to repeat the treatment after 7 days. Main outcome measures. Tear meniscus height, Schirmer I test results, noninvasive tear film break-up time (BUT), quantification of the absolute number of D. folliculorum found in the lashes, and corneal fluorescein and rose bengal staining scores were obtained from all patients 1 day before and 28 days after treatment. RESULTS: Statistical improvement was observed in the absolute number of D. folliculorum found in the lashes after the treatment with oral ivermectin. Average values of Schirmer I test results and tear film break-up time improved statistically after the treatment of oral ivermectin. No statistical improvement was observed in average lacrimal meniscus height or value of corneal fluorescein and rose bengal staining after treatment with oral ivermectin. CONCLUSIONS: Ivermectin successfully reduced the number of D. folliculorum found in the lashes of patients with refractory blepharitis. Oral ivermectin may be very useful as a complement in the treatment of D. folliculorum infestation with ocular manifestation, especially in cases of unsuccessful treatment related to patient compliance. (Am J Ophthalmol 2011;151:1030-1034. (C) 2011 by Elsevier Inc. All rights reserved.)

Intraorbital polyacrylamide gel injection for the treatment of anophthalmic enophthalmos

Purpose: To evaluate the use of orbital polyacrylamide gel injection for the correction of anophthalmic enophthalmos. Methods: Noncontrolled clinical trial of 21 patients (14 with ocular implants, 5 with phthisis bulbi, and 2 with dermis-fat graft). Orbital CT was performed to estimate the volume of polyacrylamide gel needed to restore orbital volume. Polyacrylamide gel was injected using a 22-gauge (30 x 0.7 min) needle transcutaneously inserted in the lateral third of the lower eyelid, directed to the orbital muscle cone. A second injection was administered 15 days later. if necessary. CT was repeated 30 days after the last procedure. Exophthalmometry was performed before Bind 90 days after file procedure. Results: The mean total volume injected per orbit was 2.4 +/- 0.7 ml (range 1-3.5 ml). The volume of the enophthalmic orbit increased front 26.9 +/- 5.0 ml to 29.3 +/- 4.9 ml (p < 0.001). The mean difference in exophthalmometry readings was 3.3 +/- 1.6 mm (range, 1.5-8.0 mm) before the procedure and 1.0 +/- 0.9 mm (range, 0.0-3.0 mm) after 3 months (p < 0.001). Adjustment of the ocular prosthesis or fabrication of a new one was necessary in 11 patients (52.4%), and the mean volume of the ocular prosthesis was reduced front 2.0 +/- 0.6 ml to 1.6 +/- 0.6 ml (p = 0.003). All patients were satisfied with the aesthetic results. No serious adverse events were observed. The initial results were maintained 1 year after the procedure. Conclusions: Polyacrylamide gel injection in the orbital space effectively reduces enophthalmos in ocular prosthesis wearers.

Effectiveness of Endoclips for the Treatment of Stigmata of Recent Hemorrhage in the Colon of Patients with Acute Lower Gastrointestinal Tract Bleeding

Coaptive thermo coagulation (CTC) for the treatment of stigmata of recent hemorrhage (SRH) in the colon is risky. We evaluated the safety and effectiveness of endoclips in 13 patients with acute lower gastrointestinal bleeding (GIB). Thirty-day re-bleeding and complication rates were comparable to a historical cohort of 41 patients (group 2) who underwent CTC/IE (injection epinephrine) for the management of acute lower GIB. There was no difference in the 30-day re-bleeding rates in the two groups. In group I, immediate hemostasis was successful in all patients. Three of 13 patients (23.1%) developed re-bleeding. In group II, 41 patients from six prior studies underwent CTC and/or IE for the treatment of HRS where 12 (29.3%) developed re-bleeding. There were no immediate complications. Endoclip deployment is as effective as CTC and/or IE for treatment of SRH in the colon.

A phase II study of UFT with leucovorin administered as a twice daily schedule in the treatment of patients with metastatic colorectal cancer

Prolonged infusions have been shown to be safer and potentially more effective than bolus regimens of 5-fluorouracil (5-FU) as treatment for metastatic colorectal cancer (mCRC). However, infusional 5-FU requires central venous access and costly infusion pumps. Oral fluoropyrimidines enable longer exposures to 5-FU with increased convenience. Tegafur - uracil (UFT) with leucovorin (LV) given thrice daily has improved safety plus comparable survival and response rates to bolus 5-FU/LV. We conducted a phase II clinical study in 98 patients with mCRC to evaluate if UFT with LV given twice daily provided comparable time to progression ( TTP), efficacy and tolerability to that reported for thrice daily in two phase III clinical studies. Secondary objectives included overall response rate ( ORR) and overall survival ( OS). Median TTP was 3.8 months, when compared with 3.5 months for thrice daily. The ORR ( 11%) and median OS ( 12.8 months) with twice daily administration were similar to that of thrice daily administration ( 12% and 12.4 months). The incidence of grade 3/4 treatment-related diarrhoea was 30% on the twice daily and 21% on the thrice daily schedule. These results suggest that twice daily administration has similar efficacy and tolerability to thrice daily administration and is an acceptable alternative for patients who would benefit from UFT with LV therapy.

Resolution of sexual dysfunction during acute treatment of major depression with milnacipran

Objective The sexual function and enjoyment questionnaire (SFEQ) was developed to assess and detect changes in sexual function in men and women. The aim of the present study was to use the SFEQ to evaluate the effects of the serotonin-noradrenaline reuptake inhibitor, milnacipran, in the treatment of depression in two culturally different populations. Methods The SFEQ was employed in two studies investigating milnacipran in the treatment of major depression: a 12-week open study in Brazil and a 6-week randomised controlled study in Europe. Results At endpoint, 61.3% (Brazil) and 78.4% (Europe) of patients had >= 50% reduction of baseline Hamilton Depression Rating (HAMD) score. All SFEQ items showed improvements in sexual function in both Studies at endpoint, 60% (Brazil) and 56% (Europe) of patients stating that their Sexual desire was as great as or greater than it had been before their depressive episode. Conclusions Milnacipran appears to improve sexual function in parallel with improvement in other symptoms of depression. The SFEQ is a sensitive instrument for measuring changes in sexual function and appears to be unaffected by Cultural differences as shown by similar findings in Brazil and Europe. Copyright (C) 2008 John Wiley & Sons, Ltd.

High prevalence of pituitary magnetic resonance abnormalities and gene mutations in a cohort of Brazilian children with growth hormone deficiency and response to treatment

Data were retrospectively collected from 69 Brazilian patients (45 boys) with growth hormone deficiency (GHD) who received exogenous growth hormone (GH) for a median duration of 4 years (range 1-13 years). Forty-two patients had multiple pituitary hormone deficiencies and 27 had isolated GHD. Peak GH was <7 ng/ml (IRMA) or <3.2 ng/ml (IFMA) after two stimulation tests.. Therapy was started at median age of 10.0 years (range 2.2-21.6 years), bone age of 5.8 years (0.5-13.5 years) and height standard deviation score -4.4 (range -9.3 to -1.6). MRI revealed pituitary abnormalities in 87% of patients. Homozygous mutations in PROP-1, GHRH-R, GH-1 or HESX-1 genes were found in 12 patients. Mean height velocities were 3.3 pretreatment and 10.3, 7.8, 7.4 and 6.4 cm/yr, respectively, during 1-4 years of treatment with GH. In conclusion, the high prevalence (96%) of genetic and/or pituitary abnormalities probably reflects the stringent diagnostic criteria used, and GH replacement resulted in significant catch-up growth.

Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study

Objective To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder (BD) patients during depressive or mixed phases. Methods We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication. Subjects were randomized to receive 6 weeks of double-blind placebo or celecoxib (400 mg/day) treatment. Current mood stabilizer or antipsychotic medication remained at the same doses during the trial. Results Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale (HamD) scores after 1 week of treatment compared to the patients receiving placebo, but this difference was not statistically significant (p=0.09). The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial (p=0.03). The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial. Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash. Conclusions Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes. Copyright (C) 2008 John Wiley & Sons, Ltd.

A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group-`DLPFC`); anodal tDCS of the occipital cortex (active control group-`occipital`) and sham tDCS (placebo control group-`sham`). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4 % (+/-25.8%)] compared to occipital [HDRS reduction of 21.3 % ( +/-12.9%)] and sham tDCS [HDRS reduction of 10.4 % (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.

Long-term outcomes of acute gastric variceal bleeding in 48 patients following treatment with cyanoacrylate

Objectives (1) Study the effectiveness of intravariceal injection of n-butyl-2-cyanoacrylate to treat acute gastric variceal (GV) bleeding and (2) study the impact of the type of GV and hepatic function on endoscopic hemostasis and mortality outcomes. Methods Fourty-eight patients with acute GV bleeding underwent intravariceal injection of n-butyl-2-cyanoacrylate and were followed until death or study conclusion (12-52 months). Results Primary hemostasis (no re-bleeding within 48 h) was accomplished in 42 patients (87.5%). Appearance of the bleeding site at the time of initial endoscopy, grade of cirrhosis and location of GV were not significant predictors of immediate hemostasis. Early re-bleeding (48 h to 6 weeks) occurred in 20.5% of patients and late re-bleeding (beyond 6 weeks) in 20.5% of patients. While the Child-Pugh score was predictive of re-bleeding and mortality, the type of GV and stigmata at initial endoscopy were not significant predictors of re-bleeding and mortality. Over a mean follow-up of 18 months, mortality rates were 43.9% and bleeding was the commonest cause of death. Conclusion Endoscopic injection of n-butyl-2-cyanoacrylate is effective and safe for treating bleeding GV. Patients with poor hepatic function are at higher risk of re-bleeding and death after acute gastric variceal bleed.

Post-craniotomy headache: characteristics, behaviour and effect on quality of life in patients operated for treatment of supratentorial intracranial aneurysms

We prospectively studied headache characteristics during 6 months after craniotomy performed for treatment of cerebral aneurysms in 79 patients. Semistructured interviews, headache diaries, the Hospital Anxiety and Depression Scale and the Epworth Sleepiness Scales, the Short Form-36 Health Survey (SF-36) and McGill Pain Questionnaire were used. Seventy-two patients had headaches, half before the fifth day after surgery. Changes were observed in headache diagnosis, side and site in the postoperative period. Headache frequency increased immediately after surgery and then decreased over time. Headache frequency was associated with depressive and anxiety symptoms. Pain intensity was higher in women and in patients with more anxiety symptoms. An incidence of post-craniotomy headache of 40% was observed according to International Headache Society classification criteria, 10.7% of the acute and 29.3% of the chronic type. The bodily pain domain of the SF-36 was worse in patients with more anxiety symptoms. Greater frequencies of headache were associated with lower scores on bodily pain and social functioning.