Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer.

BACKGROUND: Little is known about mechanisms of resistance to poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy in patients with metastatic breast cancer and BRCA1/2 mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure. PATIENTS AND METHODS: We obtained tumor biopsies from metastatic breast cancer patients with BRCA1/2 deficiency before and after acquired resistance to PARPi or platinum chemotherapy. Whole exome sequencing was carried out on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was carried out for functional assessment of intact homologous recombination (HR). RESULTS: Pre- and post-resistance tumor samples were sequenced from eight patients (four with BRCA1 and four with BRCA2 mutation; four treated with PARPi and four with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germline BRCA1 deficiency acquired genomic alterations anticipated to restore HR through increased DNA end resection: loss of TP53BP1 in one patient and amplification of MRE11A in another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of HR. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy. CONCLUSIONS: Genomic reversion in BRCA1/2 was the most commonly observed mechanism of resistance, occurring in four of eight patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.

A systematic review of outcome reporting in laser treatments for dermatological diseases.

The standardization of outcome reporting is crucial for interpretation and comparison of studies related to laser treatment of skin disorders. In collaboration with the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN), a procedure has been proposed to find consensus on the most important generic outcome domains (what to measure) for implementation in the international Laser TrEAtment in Dermatology (LEAD) registry. As the first step in the development of a generic outcome set for the LEAD registry, we undertook a systematic review to identify outcomes, outcome measurement instruments, methods and definitions reported in recently published literature of laser treatments for skin disorders. A systematic search was conducted and generated a total of 707 papers. We assessed 150 studies including all types of studies involving laser treatments for the skin. Two researchers independently extracted the type, definition and frequency of all outcomes and used outcome measurement instruments. We identified 105 verbatim outcomes that were categorized into eight domains recommended by the COMET framework: appearance, long-term effects, physician and patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning and adverse events. Heterogeneity in outcome reporting (e.g. categories and outcome measurement instruments) was high, and definitions were insufficiently reported. There was a clear under representation of life impact domains, including satisfaction (23%) quality of life (3%) and psychological functioning (1%). Outcome reporting concerning laser treatments for the skin is heterogeneous. Standardized outcomes are needed for improving evidence synthesis. Results of this review will be used in the next step to reach consensus between stakeholders on the outcome domains to be implemented in the LEAD registry.

Bile acid changes after metabolic surgery are linked to improvement in insulin sensitivity.

BACKGROUND: Metabolic surgery is associated with a prompt improvement in insulin resistance, although the mechanism of action remains unknown. The literature on bile acid changes after metabolic surgery is conflicting, and insulin sensitivity is generally assessed by indirect methods. The aim of this study was to investigate the relationship between improvement in insulin sensitivity and concentration of circulating bile acids after biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). METHODS: This was a prospective observational study of nine patients who underwent BPD and six who had RYGB. Inclusion criteria for participation were a BMI in excess of 40 kg/m2 , no previous diagnosis of type 2 diabetes and willingness to participate. Exclusion criteria were major endocrine diseases, malignancies and liver cirrhosis. Follow-up visits were carried out after a mean(s.d.) of 185·3(72·9) days. Fasting plasma bile acids were assessed by ultra-high-performance liquid chromatography coupled with a triple quadrupole mass spectrometer, and insulin sensitivity was measured by means of a hyperinsulinaemic-euglycaemic clamp. RESULTS: A significant increase in all bile acids, as well as an amelioration of insulin sensitivity, was observed after metabolic surgery. An increase in conjugated secondary bile acids was significantly associated with an increase in insulin sensitivity. Only the increase in glycodeoxycholic acid was significantly associated with an increase in insulin sensitivity in analysis of individual conjugated secondary bile acids. CONCLUSION: Glycodeoxycholic acid might drive the improved insulin sensitivity after metabolic surgery.

Early wound healing outcomes after regenerative periodontal surgery with enamel matrix derivatives or guided tissue regeneration: a systematic review.

BACKGROUND: Proper wound healing after regenerative surgical procedures is an essential issue for clinical success. Guided tissue regeneration (GTR) and application of enamel matrix derivatives (EMD) are common means to regenerate periodontal tissues. Both methods bear considerable advantages due to their special characteristics, but also go along with certain disadvantages. Today, there is no consensus in the literature whether GTR or EMD show better results regarding early wound healing, which is considered a crucial stage in periodontal regeneration. Therefore, the aim of the present systematic review was to compare the early wound healing after regenerative periodontal surgery with either EMD or GTR treatment. METHODS: An electronic literature search in PubMed was performed to identify randomized clinical trials (RCTs) or clinical trials (CTs) comparing regenerative surgery employing EMD and/or GTR in patients with chronic periodontitis. Among the finally included studies, a qualitative and quantitative data extraction regarding early wound healing parameters was performed. Primary outcome parameters were early wound healing index (EWH), flap dehiscence, membrane exposure, suppuration and abscess formation during the first 6 weeks. As secondary parameters, swelling and allergic reactions were assessed. RESULTS: Seven studies reporting 220 intrabony periodontal defects in 199 patients were analysed. Flap dehiscence was observed in two studies in 12% of the GTR treated sites and in 10.3% of those treated with EMD. Membrane exposure was evaluated in five studies and was registered in the 28.8% of the defects, while no dehiscence was reported on the EMD group. Swelling was reported only in one study in 8/16 GTR sites and 7/16 EMD sites. Due to considerable heterogeneity of parameters no meta-analysis was possible. CONCLUSIONS: Due to considerable heterogeneity of the published studies a clear beneficial effect of the EMD on the early wound healing outcomes after surgical treatment of periodontal intrabony defects cannot be confirmed. Standardized RCT studies are needed in order to allow for proper comparison of early wound healing after both types of surgical approaches.

Laser treatment of hyperpigmented lesions: position statement of the European Society of Laser in Dermatology.

BACKGROUND: Lasers and intense pulsed light sources (IPLS) are proposed for the treatment of many pigmentary disorders. They are sometimes considered as magic tools able to remove any type of lesions. Although being the best option for several hyperpigmented lesions, they can also worsen some conditions and have potential side-effects. OBJECTIVE: The aim of this review was to give evidence-based recommendations for the use of lasers and IPLS in the treatment of hyperpigmented lesions. METHODS: These recommendations were produced for the European Society of Laser Dermatology by a consensus panel made up of experts in the field of pigment laser surgery. Recommendations on the use of lasers and light treatments were made based on the quality of evidence for efficacy, safety, tolerability, cosmetic outcome, patient satisfaction/preference and, where appropriate, on the experts' opinion. RESULTS: Lasers and IPLS are very effective for treating many hyperpigmented lesions such as lentigos, dermal hypermelanocytosis or heavy metal depositions. In the other hand, they have to be considered with great caution for other disorders, such as café au lait macules, melasma or postinflammatory hyperpigmentation. After making the correct diagnosis, if lasers or IPLS are indicated, the optimal wavelengths and parameters will be chosen taking into account the skin phototype, origin and depth of the target pigments. CONCLUSION: Although potentially very effective, lasers and IPLS cannot be proposed for all types of hyperpigmented lesions. In all cases, precise recognition of the disorder is mandatory for choosing between these devices and other therapeutic approaches.

Risk factors including the presence of inflammation at the resection margins for colorectal anastomotic stenosis following surgery for diverticular disease.

AIM: The aim of this study was to investigate risk factors for anastomotic stenosis in patients operated on for diverticular disease. Histological inflammation and diverticula at the resection margins were also considered. METHOD: Patients' characteristics, the surgical technique and postoperative complications were collected from the medical records. Anastomotic stenoses were evaluated prospectively by rigid sigmoidoscopy during follow-up examination. Histological specimens were examined by a single pathologist who investigated inflammation and diverticula at the resection margins. Twenty patients with anastomotic colorectal stenosis from a single tertiary centre were compared with 24 consecutive patients without stenosis. They were all operated on for diverticular disease over a specified time period. RESULTS: Histological inflammation and diverticula were found in 25% and 30% of the resection margins respectively. Univariate analysis showed that age > 71 years (P = 0.0002), female gender (P = 0.0069) and anastomoses located below 12 cm from the anal verge (P = 0.020) were risk factors for stenosis. No correlation was found between anastomotic stenosis and the presence of histological inflammation or diverticula at the resection margins. By multivariate analysis, only age > 71 years was found to be a statistically significant risk factor for stenosis (P = 0.0003, OR = 60.8, 95% CI: 6.4-575.5). CONCLUSION: Anastomotic stenosis is a frequent, long-term complication following surgery for diverticular disease. An analysis demonstrated that age is a risk factor for colorectal stenosis and that histological inflammation and the presence of diverticula near/at the resection margins have no effect on the incidence of stenosis.

Bipolar versus monopolar transurethral resection of the prostate: a prospective randomized trial focusing on bleeding complications.

PURPOSE: We compare monopolar vs bipolar transurethral resection of the prostate in patients with benign prostatic hyperplasia, focusing on functional outcomes as well as rates of bleeding complications and the transurethral resection syndrome. MATERIALS AND METHODS: A total of 137 patients with benign prostatic hyperplasia (mean age 67 years, range 47 to 91) were prospectively randomly assigned to undergo monopolar (67) or bipolar (70) transurethral resection of the prostate. Patient characteristics of the 2 groups were similar. Hemoglobin (as a marker of blood loss) was measured preoperatively and perioperatively. I-PSS, I-PSS-QoL score, maximal flow rate and post-void residual urine volume were assessed preoperatively and 3 and 12 months postoperatively. Duration of surgery, indwelling catheter use and hospitalization were also documented, as were postoperative clot retention requiring removal by catheterization or surgery, and rates of bladder neck and/or urethral strictures. RESULTS: No significant perioperative differences were found in duration of surgery, catheterization or hospitalization, or in blood loss or rates of blood transfusion and transurethral resection syndrome. Postoperatively there were no significant differences in I-PSS or I-PSS-QoL scores, or rates of rehospitalization, clot retention, blood transfusions, reoperation or urethral strictures. However, bladder neck stricture occurred significantly more often in the bipolar group (8.5% vs 0%, p = 0.02). The 3 and 12-month followup showed significant and equal improvement in micturition in the 2 groups. CONCLUSIONS: Bipolar and monopolar transurethral resection of the prostate are effective and safe techniques for the surgical treatment of benign prostatic hyperplasia. The only significant difference between them was a significantly higher rate of bladder neck strictures with bipolar resection of the prostate.

Best practice options for hair removal in patients with unwanted facial hair using combination therapy with laser: guidelines drawn up by an expert working group.

Hirsutism is a common disorder affecting between 5 and 15% of the population. One of the most devastating consequences of hirsutism is the presence of unwanted facial hair. Treatment of hirsutism involves a two-pronged approach: treating the underlying cause and reduction of visible hair. Laser hair removal is one of the most effective options for reducing visible hair, however, it may not be wholly effective in all patients and combination therapy may need to be considered. Pharmacological therapy is often used in combination with mechanical hair removal due to the time needed for the drug treatment to demonstrate visible results. Clinical data investigating the use of laser treatment in combination with other treatments has focused on laser with topical eflornithine. The expert working group reviews existing data and provides guidance on the use of eflornithine in combination with laser for resistant hirsutism.

A randomized phase II trial evaluating standard (50 mg/min) versus low (10 mg/min) infusion duration of gemcitabine as first-line treatment in advanced non-small-cell lung cancer patients who are not eligible for platinum-based chemotherapy.

PURPOSE: Gemcitabine is one of the most active drugs against non-small-cell lung cancer (NSCLC). Preclinical data suggested that gemcitabine efficacy could be improved by increasing the dose or by increasing the infusion duration. This study has been designed in order to explore two different approaches of gemcitabine dose intensification in patients with advanced NSCLC. PATIENTS AND METHODS: A total of 121 chemonaive patients with locally advanced or metastatic NSCLC not suitable for a platinum-based chemotherapy were randomly allocated to chemotherapy with gemcitabine 1500 mg/m2 on days 1 and 8 every 3 weeks by standard 30 min intravenous infusion (arm A), or gemcitabine 10 mg/m2/min for 150 min on days 1 and 8 every 3 weeks by intravenous infusion at fixed dose rate (arm B). RESULTS: One hundred and seventeen patients were fully analyzed. No difference in response rate (16.1% versus 9.9%, p=0.28), median time to disease progression (4 months versus 4.5 months, p=0.34) median survival (9.8 months in both arms), and 1-year survival (42.6% versus 39.0% p=0.98) was detected in arms A and B, respectively. No treatment-related deaths occurred. Main hematological toxicities were grade 3-4 neutropenia observed in 17.9% of patients in group A and in 49.2% of individuals in group B (p=0.0002). The incidence of febrile neutropenia was 3.3% in arm A and 0% in arm B (p=0.17). Grade 3-4 thrombocytopenia was more frequently observed in arm B patients (9.9% versus 1.8%, p=0.057). Non-hematological toxicity was similar in both arms, and consisted in grade 1-2 gastrointestinal toxicity observed in 48.2% of patients in arm A and 41.0% in arm B. CONCLUSION: Intensification of standard doses or prolonged infusion schedule did not result in efficacy improvement. Gemcitabine infusion duration does not warrant further investigation in patients with advanced NSCLC.

A multicenter phase II study of the cryptophycin analog LY355703 in patients with platinum-resistant ovarian cancer.

LY355703 is a synthetic product structurally related to the cryptophycin family isolated from the blue-green algae, which exerts a potent destabilization of microtubules during mitosis. This study was performed to determine the activity of LY355703 in patients with platinum-resistant advanced ovarian cancer and to characterize its toxicity profile. Twenty-six patients were enrolled in this study. Resistant disease was defined as a platinum-free interval of <6 months from primary treatment or rechallenge. LY355703 (1.5 mg/m(2)) was administered intravenously on days 1 and 8, every 3 weeks, infused over 2 h. From 24 patients evaluable for response, three partial responses (12.5%) and seven disease stabilizations were registered (29.2%), for an overall clinical benefit of 41.7%. Fourteen patients (58.3%) experienced a progression of the disease during treatment. Among the 25 patients evaluable for toxicity, two episodes of grade 3 anemia (8%); one, grade 3 thrombocytopenia (4%); one, grade 4 elevation of creatinine (4%); and one, grade 3 hyperbilirubinemia (4%) were reported. LY355703 has a modest activity in patients with platinum-resistant advanced ovarian cancer. Nevertheless, the considerable rate of disease stabilization in the absence of serious adverse events in this poor-prognosis study population suggests that this novel cryptophycin may deserve further investigation in this setting.

Gemcitabine in epithelial ovarian cancer treatment: current role and future perspectives.

Newer agents and combinations are needed in order to improve current results in ovarian cancer treatment. Gemcitabine is a novel agent that has shown consistent activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile. Because of its clinical and preclinical synergism with platinum analogs, gemcitabine has been combined with carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients. Further combination of gemcitabine and other agents, including paclitaxel, is also feasible and has been actively studied in order to establish the role of gemcitabine in the management of treated and untreated ovarian cancer patients.

Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to bacillus Calmette-Guérin therapy.

INTRODUCTION: Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS). MATERIAL AND METHODS: Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months. RESULTS: Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2-4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed. CONCLUSION: Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.

A closed system for the clinical banking of umbilical cord blood.

Umbilical cord blood (UCB) is a source of hematopoietic progenitor cells and is used as an alternative to the bone marrow or peripheral blood for treatment of several onco-hematological diseases. Because of the limited number of CD34+ hematopoietic stem cells present in UCB units and of the elevated costs of cryopreservation, it is of paramount importance to select the UCB units that are clinically useful before storage and optimize banking efficiency by designing reliable procedures to process and freeze the selected units. Among the different parameters characterizing UCB, nucleated cell (NC) and CD34+ cell content provides useful criteria to select UCB units since clinical data documented that the infused cell load (both NC and CD34+ cells) plays an important role in the successful outcome of transplants. By evaluating volume, CD34+ cell content, NC total amount, and NC density of 117 UCB units, we found a significant association between CD34+ cell content and NC density and total amount, indicating these parameters as useful to decide UCB clinical utility. Furthermore, we set up a fast procedure to process UCB units for storage. A system for NC separation and volume reduction of UCB samples in a dedicated, germ-free, closed circuit was developed, where plasma and red blood cells (RBC) depletion was obtained by sedimentation in the presence of a 3.5% Polygeline solution. By this separation system, both RBC depletion and high NC and CD34+ cell recoveries were achieved in 60 min, and the yield was comparable to the one obtained by other separation methods. Since Polygeline has been clinically used as a plasma expander and no toxic effects on patients were reported, the protocol can be applied in the large-scale banking of UCB.

Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study.

This trial was conducted to assess the activity and tolerability of the gemcitabine, epirubicin, taxol triplet combination in patients with operable breast cancer. After core biopsy, 43 women with stage II-IIIA breast cancer were treated with gemcitabine 1000 mg m(-2) over 30 min on days 1 and 4, epirubicin 90 mg m(-2) as an intravenous bolus on day 1, and taxol 175 mg m(-2) as a 3-h infusion on day 1, every 21 days for four cycles. The primary end point was the percentage of pathological complete responses (pCR) in the breast; secondary end points were tolerability, clinical response rates, overall and progression-free survival, tumour biomarkers before and after primary chemotherapy (PCT). All patients were included in safety and survival analyses; 41 eligible patients were evaluated for response. The overall clinical response rate was 87.8% (95% CI 77.8-97.8), with 26.8% complete responses (95% CI 13.3-40.3). A pCR in the breast was observed in six patients (14.6%; 95% CI 3.8-25.4); 15 patients (36.6%; 95% CI 21.9-51.3) had negative axillary lymph nodes. Grade 4 neutropenia was observed in 67.4% of the patients; febrile neutropenia occurred in 1.9% of cycles (granulocyte colony-stimulating factor was used in 3.2% of the cycles to shorten the duration of neutropenia). A statistically significant difference between Mib-1 at baseline (> or =20% in 71.4% of the patients) and at definitive surgery (28.6%, P < 0.05) was observed. The gemcitabine, epirubicin, taxol regimen is active and well tolerated as PCT for operable breast cancer. This combination allows the administration of full doses of active agents with a low incidence of febrile neutropenia.

Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer.

This phase II study evaluated the response rate and tolerability of gemcitabine-oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients. Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m(-2) on days 1 and 8, followed by oxaliplatin 130 mg m(-2) on day 1. Cycles were repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60 patients were enrolled into the study in seven Italian institutions. We observed one complete response (1.7%) and 14 partial responses (23.3%), for an overall response rate of 25.0% (95% confidence interval, 14.7-37.9%). The median duration of response was 5.9 months (range 1.5-17.1 months). With a median follow-up of 6.7 months, median time to progressive disease and overall survival were 2.7 (range 1.9-3.4 months) and 7.3 months (range 7.2-8.6 months), respectively. The main grade 3-4 haematological toxicities were transient neutropenia in 11.7% and thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3-4 nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%) patients developed grade 3 neurotoxicity. Our results show that gemcitabine-oxaliplatin chemotherapy is active and well tolerated in patients with advanced NSCLC, deserving further study, especially for patients not eligible to receive cisplatin.

[Bowel preparation for colonoscopy with sodium picosulphate and magnesium citrate in children and adolescents]. / Preparo intestinal para colonoscopia com picossulfato sódico e citrato de magnésio em crianças e adolescentes.

BACKGROUND: The efficacy of colonoscopic examination depends directly on bowel cleansing preparation. There are few studies in the medical literature about bowel preparation in children. AIM: To determinate the efficacy of picosulphate sodium with magnesium citrate as a bowel preparation in children and adolescents. PATIENTS AND METHODS: In an open prospective and consecutive trial, we included all children above 1 year of age submitted to colonoscopy for different indications. All patients received the drug the day before the procedure and was allowed no solid food but a liberal intake of clear fluids. The adequacy of the preparation was graded as follows: gI--excellent, gII--good, gIII--fair and gIV--poor. RESULTS: Forty-six patients were included. The age ranged from 12 months to 16.1 years (median = 6.6y), 54.3% were males. Bowel preparation was made according to instructions in 37/46 (80.4%) of patients, 9 patients did not adhere to diet of clear liquids and 22/46 (47.8%) had side effects. The adequacy of the bowel preparation was: gI in 41.3%, gII in 52.2%, gIII in 6.5% and none in gIV. CONCLUSION: Bowel preparation with picosulphate sodium and clear fluids provides an effective, practical method of preparing the bowel for colonoscopy in children and adolescents and could be recommended.

Preparo intestinal para colonoscopia com picossulfato sódico e citrato de magnésio em crianças e adolescentes / Bowel preparation for colonoscopy with sodium picosulphate and magnesium citrate in children and adolescents

RACIONAL: A eficácia do exame colonoscópico depende diretamente da limpeza colônica. Ao contrário do paciente adulto, há poucos relatos na literatura sobre preparo colônico em crianças. OBJETIVO: Avaliar a eficácia do preparo colônico à base de picossulfato sódico e citrato de magnésio em crianças e adolescentes. PACIENTES E MÉTODOS: Realizou-se estudo aberto, prospectivo e consecutivo em crianças maiores de 1 ano, de ambos os sexos, que realizaram colonoscopia por diferentes indicações. Os pacientes receberam a medicação associada à dieta líquida e pastosa sem resíduos no dia anterior ao exame. A eficácia do preparo foi classificada em: Grau I: ótimo; Grau II: bom; Grau III: regular; Grau IV: ruim. RESULTADOS: A idade variou de 12 meses a 16 anos e 1 mês (mediana: 6 anos e 6 meses), sendo 54,3 por cento do sexo masculino. O preparo foi feito conforme a orientação em 37/46 (80,4 por cento) dos pacientes, sendo que 9 não fizeram a dieta adequadamente e 22/46 (47,8 por cento) referiram efeitos colaterais. A eficácia do preparo foi: GI em 41,3 por cento, GII em 52,2 por cento, GIII em 6,5 por cento e GIV em 0 por cento. CONCLUSAO: Preparo intestinal com picossulfato sódico e citrato de magnésio é eficiente e prático, podendo ser recomendado de rotina nos exames de colonoscopia em crianças e adolescentes.

Rationale for the use of gemcitabine in breast cancer (Review).

Many active cytotoxic drugs and several regimens exist for breast cancer therapy. However, these conventional treatments have not changed the outcome of patients with locally advanced and metastatic disease. As a consequence, the dynamic balance between chemotherapy-induced side effects and benefits attributable to relief of cancer-related symptoms must be carefully considered in this setting. Gemcitabine is a pyrimidine nucleoside antimetabolite that has shown activity in a variety of solid tumors, a good toxicity profile, and non-overlapping toxicity with other chemotherapeutic drugs. As a single agent, gemcitabine yields response rates ranging from 14 to 37% as first-line treatment for advanced breast cancer and 12-30% as salvage therapy for patients previously treated with anthracycline and/or taxane treatment. Combined with vinorelbine, platinum, anthracyclines, and taxanes as doublets or triplets, response rates of 50 to 80% have been reported in phase II clinical studies. Gemcitabine in combination with anthracyclines and taxanes has been evaluated in the neoadjuvant setting in patients with early-stage breast cancer with interesting clinical and pathological response rates. Preliminary results of gemcitabine in combination with the biologic agent, trastuzumab, are encouraging. Phase III trials of gemcitabine combinations compared to standard regimens are ongoing with the aim to assess the independent contribution of gemcitabine.