Considerações sobre o câncer localmente avançado de mama (CLAM) acrescidas de identificação dos receptores de estrogênios usando anticorpos monoclonais.

The effects of therapy in locally advanced breast cancer submitted to combined conventional telecobalt therapy plus chemotherapy with cyclophosphamide and 5-fluorouracil were studied in 49 patients. Associated to radical mastectomy in operable cases. Local tumor control was achieved in 86.7%. There were no local recurrences in those submitted to surgery but they reached 21.7% in inoperable patients who received only radiation therapy and chemotherapy. The median follow-up time for dead patients was 29.5 months and for living patients 79.3 months. The index of complete responses was 24.5% and the median disease free interval was 22.9 months. The overall survival rate, between three and five years, was 32.7%. Estrogen receptors were identified by using immunohistochemical assay ER-ICA and monoclonal antibody H222-SP gamma, Abbott. There were no differences in the complete response index, disease free interval and survival rates, among ER-positive and ER-negative patients, explained by the far advanced stage of the disease. ER-positivity was significantly correlated with histological features of the tumors: cell differentiation, presence of elastosis, absence of lymphocytic infiltration and absence of tumor necrosis.

Systemic use of metronidazole in the treatment of chronic periodontitis: a pilot study using clinical, microbiological, and enzymatic evaluation

The aim of the present parallel, double-blind investigation was to evaluate the effect of using systemic metronidazole alone or associated to scaling and root planing on adult chronic periodontal disease, monitored at baseline, 30, 60 and 90 days. Twelve subjects were divided into three groups: the first group (Group I - 22 sites) was submitted to scaling and root planing (SRP) alone; the second group (Group II - 30 sites) received SRP and 250 mg of metronidazole (3 times a day for 10 days), and the third group (Group III - 31 sites) was treated with metronidazole alone. The clinical parameters evaluated were probing depth (PD), clinical attachment level (CAL), plaque index (PlI), gingival index (GI) and bleeding upon probing (BP). Microbiological (BANA test) and enzymatic (Pocket Watch) tests were also performed. All three proposed treatments produced significant improvements in clinical conditions of subjects, from baseline, 30, 60 and 90-day period, except for clinical attachment level. The results obtained by microbiological and enzymatic tests did not show statistical differences among the groups for the 90-day period (r = 0.7924 and r = 0.7757, respectively). In relation to clinical parameters, statistical differences among groups were observed only for the gingival index (p = 0.0261) between Groups I and II, and probing depth (p = 0.0124) between Group I and the others. We conclude that the use of systemic metronidazole did not produce additional effects on the microbiological conditions of these patients with chronic periodontal disease.

BMP implant associated with platelet-rich plasma in orbit fracture repair

Purpose: To evaluate a bone morphogenetic protein (BMP) implant with and without platelet-rich plasma (PRP), which is supposed to accelerate fracture consolidation in the orbit fracture treatment. Methods: Thirty-six white rabbits were subjected to orbital fracture and treated in three groups: BMP implant fracture repair (G1), BMP plus PRP implant fracture repair (G2), and fracture and spontaneous repair (G3). The animals were sacrificed at 7, 30, 90, and 180 days after surgery. A radiology evaluation was carried out on the 7th day after the fracture and at the sacrifice moments. After the animals' death, the orbital content material was removed and prepared for morphological and morphometric analysis. Results: Radiology suggested intramembranous and progressive cavitation and ossification without a reduction in implant size and with signs of calcium deposition; these events were confirmed by histological analysis, which showed a lymphomononuclear inflammatory reaction in G1 and G2, more intense 7 days after surgery and reducing after 30 days. Associating PRP with BMP did not accelerate bone induction. Conclusion: BMP implant promotes bone induction, integration at fracture site, scarce inflammatory reaction, and may be a good alternative in orbit fracture reconstruction. The addition of PRP to the BMP plate did not accelerate the resolution, and its use is not necessary. Copyright © Informa Healthcare USA, Inc.

Lip cavernous hemangioma in a young child

Hemangiomas are benign tumors of infancy and childhood, characterized by a phase of fast growth with endothelial cell proliferation, occurring in 10-12% of children at 1 year of age. It is known that hemangiomas of infancy are most commonly located on the head and neck region (around 60% of cases) and occur more frequently in the lips, tongue, and palate. Approximately 50% of hemangiomas have complete resolution, and 90% of them are resolved up to the age of 9. Complications occur in only 20% of the cases, the most common problem being ulceration with or without infection. The treatment depends on lesion location, size and evolution stage, and the patient's age. Surgery is usually indicated when there is no response to systemic treatments, or even for esthetic reasons, being performed as a simple excision in combination or not with plastic surgery. This paper reports a case of lip cavernous hemangioma in a 4-year-old child, who was submitted to 3 sessions of vascular sclerosis due to the size of the lesion, before undergoing simple excision of the hemangioma. Two years of postoperative clinical follow-up shows treatment success with no recurrence of the lesion.

Recidiva Neural em hanseníase multibacilar após 6 anos de tratamento

This article presents a case of relapse, with isolated neural manifestation, in a multibacillary patient previously treated with multidrug therapy for multibacillary leprosy (24 doses). The patient returned to the service six years after the end of treatment, with pain in hands and legs. He was investigated, and the serological monitoring showed an important increase in anti-phenolic glycolipid serum levels. A neural recurrence was suspected, since the patient had no new skin lesions. A new biopsy in the right ulnar nerve showed a bacilloscopy of 2 +, compatible with relapse. This is a literature review of the etiological, clinical, propedeutical and diagnostic aspects of this situation so poorly understood. © 2012 by Anais Brasileiros de Dermatologia.

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.

Maxillo-mandibular counter-clockwise rotation and mandibular advancement with TMJ Concepts (R) total joint prostheses Part I - Skeletal and dental stability

The purpose of this study was to evaluate skeletal and dental stability in patients who had temporomandibular joint (TMJ) reconstruction and mandibular counterclockwise advancement using TMJ Concepts total join, prostheses (TMJ Concepts Inc. Ventura, CA) with maxillary osteotomies being performed at the same operation. All patients were operated at Baylor University Medical Center, Dallas TX, USA, by one surgeon (Wolford). Forty-seven females were studied; the average post-surgical follow-up was 40.6 months. Lateral cephalograms were analyzed to estimate surgical and post-surgical changes. During surgery, the occlusal plane angle decreased 14.9 +/- 8.0 degrees. The maxilla moved forward and upward. The posterior nasal spine moved downward and forward. The mandible advanced 7.9 +/- 3.5 mm at the lower incisor tips, 12.4 +/- 5.4 mm at Point B, 17.3 +/- 7.0 mm at menton, 18.4 +/- 8.5 mm at pogonion, and 11.0 +/- 5.3 mm at gonion. Vertically, the lower incisors moved upward -2.9 +/- 4.0 mm. At the longest follow-up post surgery, the maxilla showed minor horizontal changes while all mandibular measurements remained stable. TMJ reconstruction and mandibular advancement with TMJ Concepts total joint prosthesis in conjunction with maxillary osteotomies for counter-clockwise rotation of the rnaxillo-mandibular complex was a stable procedure for these patients at the longest follow-up.

Chin augmentation with conchal cartilage

Profile enhancement most frequently involves mentoplasty. For this purpose, the author performs conchal grafts to the chin. A total of 28 women aged 15 to 76 years (mean age, 38.11 ± 15.11 years) requested mentoplasty by itself or combined with rhinoplasty, rhytidoplasty, or submental lipoplasty. The conchal cartilage was harvested subperichondrally through a posterior 3-cm incision. The specimen measured 3 x 1 cm, which was sufficient to project the chin 2 to 3 mm. For 4 to 5 mm of projection, both cartilages were used. The graft was positioned under the periosteum and held with two 5-0 nylon sutures. In these cases, the conchal cartilage graft was a suitable option for chin augmentations up to 5 mm.

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.

Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma.

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy. METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed. RESULTS: Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival. CONCLUSIONS: Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy.

Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. Patients and methods: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). Conclusion: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.

Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).

PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. RESULTS: One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

Gene scanning of VDJH-amplified segments is a clinically relevant technique to detect contaminating tumor cells in the apheresis products of multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation.

Contaminating tumour cells in apheresis products have proved to influence the outcome of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (APBSCT). The gene scanning of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) is a reproducible and easy to perform technique that can be optimised for clinical laboratories. We used it to analyse the aphereses of 27 MM patients undergoing APBSCT with clonally detectable VDJH segments, and 14 of them yielded monoclonal peaks in at least one apheresis product. The presence of positive results was not related to any pre-transplant characteristics, except the age at diagnosis (lower in patients with negative products, P = 0.04). Moreover, a better pre-transplant response trended to associate with a negative result (P = 0.069). Patients with clonally free products were more likely to obtain a better response to transplant (complete remission, 54% vs 28%; >90% reduction in the M-component, 93% vs 43% P = 0.028). In addition, patients transplanted with polyclonal products had longer progression-free survival, (39 vs 19 months, P = 0.037) and overall survival (81% vs 28% at 5 years, P = 0.045) than those transplanted with monoclonal apheresis. In summary, the gene scanning of apheresis products is a useful and clinically relevant technique in MM transplanted patients.

Does prenatal diagnosis modify neonatal treatment and early outcome of children with esophageal atresia?

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