Assessment of disease-free survival in patients with laryngeal squamous cell carcinoma treated with radiotherapy associated or not with chemotherapy

In early stage (I and II) laryngeal squamous cell carcinoma, both surgery and radiotherapy results in significant local and regional control. In advanced tumors (III and IV), radiotherapy alone has local-regional control rates of 32-43%. Aim: To assess disease-free survival in SCC laryngeal carcinoma patients submitted to radiotherapy alone and/or associated with chemotherapy. Materials and Methods: Retrospective study involving 84 cases of laryngeal SCC treated with radiotherapy or chemotherapy together with radiotherapy. Fifty-three cases were treated with intension to cure and 31 because of impossibility to resect the disease. As to clinical stage (CS), 12 were CS I, 15 II, 21 III and 5 IV. In the second group, 11 cases were EC III and 20 IV. Results: Mean age was 60 years, 84.5% were men. Fifty-eight (69.1%) cases had complete response and 26 (30.9%) had persistent or residual disease. Five-year disease-free survival was of 42.5%; 62.5% of the patients with organ preservation indication and 9.75 in the group of irressecable disease. Conclusion: disease-free survival of those patients submitted to radiotherapy because of laryngeal SCC was of 62.5%

MET Is Highly Expressed in Advanced Stages of Colorectal Cancer and Indicates Worse Prognosis and Mortality

The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients submitted to surgical resection due to primary colorectal adenocarcinoma. Patients and Methods: A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware of patient clinical and histopathological data. Results: The tumor marker expression was positive in 236 (79%) out of a total of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and recurrence (p=0.89) or disease-free interval (p=0.91) was observed. Conclusion: MET has shown significant expression at advanced stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker for poor prognosis in colorectal cancer patients.

Iliac-hepatic arterial bypass for compromised collateral flow during modified Appleby operation for advanced pancreatic cancer

Involvement of the celiac trunk and common hepatic artery are two of the most common forms of vascular invasion by tumours of the distal pancreas, and until recently this finding was considered a contra-indication to resection. We described a modified Appleby operation for locally advanced distal pancreatic cancer with compromised hepatic collateral flow that needed hepatic arterial revascularization, successfully accomplished by left external iliac-hepatic arterial bypass with Dacron prosthesis. Patient recovery was uneventful and he was discharged on the 10th postoperative day. Postoperative angio-CT disclosed a patent arterial bypass. Patient is well and asymptomatic 13 months after operation. At the time of this writing, postoperative CT scan showed no evidence of disease and CA 19-9 level is normal. There is a well established rationale to perform extended resection of pancreatic carcinomas that compromise vascular structures. Modified Appleby procedure can safely be performed, has oncological advantages to palliative procedures and provides relief of pain but is reserved for selected patients. Preservation of hepatic arterial flow has utmost importance to avoid hepatobiliary complications as liver necrosis, liver abscess, gallbladder necrosis or cholecystitis. In this case, hepatic revascularization was particularly challenging, but was successfully accomplished by left external iliac-hepatic arterial bypass. To our knowledge this type of arterial bypass has never been described so far in the English literature and its description may be important for surgeons dealing with advanced pancreatic cancer. (C) 2009 Elsevier Ltd. All rights reserved.

Conservative Versus Surgical Treatment for Repair of the Medial Patellofemoral Ligament in Acute Dislocations of the Patella

Purpose: The objective of this study was to analyze and compare the results obtained after 2 types of treatment, surgical and conservative, for acute patellar dislocations. Methods: We divided 33 patients with acute patellar dislocations into 2 groups. One group with 16 patients underwent conservative treatment (immobilization and subsequent physiotherapy), and the other group with 17 patients underwent surgical treatment. A radiographic examination was performed in the evaluation of the patients to verify predisposing factors for patellofemoral instability, and the Kujala questionnaire was applied with the intention of analyzing the improvement of pain and quality of life. The chi(2) test, t test, and Fisher test were used in the statistical evaluation. A significance level of P<.05 was adopted. Results: The groups were considered parametric in relation to age and sex. The conservative treatment group exhibited a higher number of recurrent dislocations (8 patients) than the surgical treatment group, which did not have any relapses. In addition, the surgical treatment group obtained a better mean score on the Kujala test (92) than the conservative treatment group (69). Conclusions: We conclude that surgical treatment afforded better results. There were no recurrences in the surgical treatment group, but there were 8 recurrences in the conservative treatment group. The mean Kujala score was 92 in the surgical treatment group and 69 in the conservative treatment group.

Twenty seven-year experience with sternal cleft repair

Congenital sternal cleft is a rare disease, and primary repair in the neonatal period is its best management. In 1998 we presented three surgical techniques for sternal cleft correction, but since 1999 we have elected one of them as our procedure of choice. Our latest results are now presented. It is a review of 15 patients operated from October 1979 to December 2007. Surgical repair consisted of 3 sliding chondrotomies, 10 reconstructions basec on a `posterior sternal wall`, 1 reconstruction combined to Ravitch operation for pectus excavatum and 1 associated with total repair of Cantrell`s pentalogy. Data concerning epidemiological features, surgical reconstruction, aesthetic results, postoperative major complications, mortality and hospital stay, were collected from hospital charts. Follow-up ranged from 4 months to 27 years. All patients submitted to surgical, correction had a good aesthetic and functional result. Neither postoperative mortality nor major complication was observed. Two patients had subcutaneous fluid collection that prolonged the drainage duration. The mean hospital stay was 6 days. In conclusion, reconstructing sterna. cleft with a `posterior periosteal flap from sternal bars and chondral graft` is an effective option with good aesthetic and long-term functional results. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

THERAPEUTIC ULTRASOUND DID NOT INCREASE THE MECHANICAL PROPERTIES OF FLEXOR TENDONS AFTER THEIR REPAIR

Objective: Experimental study idealized to investigate the mechanical properties of deep flexor tendons of rabbits that underwent the tenotomy followed by tenorrhaphy and early application of therapeutic ultrasound with different intensities, in comparison to tendons submitted to tenorrhaphy only. Material and Method: Forty-four rabbits were divided into four experimental groups according to the ultrasound application. They were all submitted to a section of deep flexor tendon in zone 2 and immobilized with an orthosis maintained throughout the experiment. Group A received ultrasonic treatment with an intensity of 1.4 W/cm(2), group B with 0.6 W/cm(2), both in continuous mode, group C with 0.6 W/cm(2) SATA, in pulsated mode at 50% and group D did not receive any ultrasonic treatment. The ultrasonic frequency employed was 1 MHz. After euthanasia, the tendons were dissected and submitted to the mechanical test of traction and qualitative histological analysis. The evaluated mechanical properties were: maximum force, deformation in maximum force and stiffness. Results: There were no statistically significant differences among the experimental groups. Conclusion: Therapeutic ultrasound did not improve the mechanical properties of the flexor tendons after repair.

Ultrasonographic Evaluation of Achilles Tendon Repair After Percutaneous Sectioning for the Correction of Congenital Clubfoot Residual Equinus

Background: Most cases of congenital clubfoot treated with the Ponseti technique require percutaneous Achilles tenotomy to correct the residual equinus. Clinical evidence suggests that complete healing occurs between the cut tendon stumps, but there have not yet been any detailed studies investigating this reparative process. This study was performed to assess Achilles tendon repair after percutaneous section to correct the residual equinus of clubfoot treated with the Ponseti method. Method: A prospective study analyzed 37 tenotomies in 26 patients with congenital clubfoot treated with the Ponseti technique, with a minimum follow-up of 1 year after the section. The tenotomy was performed percutaneously with a large-bore needle bevel with patient sedation and local anesthesia. Ultrasonographic scanning was performed after section to ascertain that the tenotomy had been completed and to measure the stump separation. In the follow-up period, the reparative process was followed ultrasonographically and assessed at 3 weeks, 6 months, and 1 year posttenotomy. Results: The ultrasonography performed immediately after the procedure showed that in some cases, residual strands between the tendon ends persisted, and these were completely sectioned under ultrasound control. A mean retraction of 5.65 mm +/- 2.26 mm (range, 2.3 to 11.0 mm) between tendon stumps after section was observed. Unusual bleeding occurred in one case and was controlled by digital pressure, with no interference with the final treatment. After 3 weeks, ultrasonography showed tendon repair with the tendon gap filled with irregular hypoechoic tissue, and also with transmission of muscle motion to the heel. Six months after tenotomy, there was structural filling with a fibrillar aspect, mild or moderate hypoechogenicity, and tendon scar thickening when compared with a normal tendon. One year after tenotomy, ultrasound showed a fibrillar structure and echogenicity at the repair site that was similar to a normal tendon, but with persistent tendon scarring thickness. Conclusions: There is a fast reparative process after Achilles tendon percutaneous section that reestablishes continuity between stumps. The reparative tissue evolved to tendon tissue with a normal ultrasonographic appearance except for mild thickening, suggesting a predominantly intrinsic repair mechanism.

Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146(+) perivascular cells and fibroblasts

Objective. The relationship of multipotent mesenchymal stromal cells (MSC) with pericytes and fibroblasts has not been established thus far, although they share many markers of primitive marrow stromal cells and the osteogenic, adipogenic, and chondrogenic differentiation potentials. Materials and Methods. We compared MSCs from adult or fetal tissues, MSC differentiated in vitro, fibroblasts and cultures of retinal pericytes obtained either by separation with anti-CD146 or adhesion. The characterizations included morphological, immunophenotypic, gene-expression profile, and differentiation potential. Results. Osteogenic, adipocytic, and chondrocytic differentiation was demonstrated for MSC, retinal perivascular cells, and fibroblasts. Cell morphology and the phenotypes defined by 22 markers were very similar. Analysis of the global gene expression obtained by serial analysis of gene expression for 17 libraries and by reverse transcription polymerase chain reaction of 39 selected genes from 31 different cell cultures, revealed similarities among MSC, retinal perivascular cells, and hepatic stellate cells. Despite this overall similarity, there was a heterogeneous expression of genes related to angiogenesis, in MSC derived from veins, artery, perivascular cells, and fibroblasts. Evaluation of typical pericyte and MSC transcripts, such as NG2, CD146, CD271, and CD140B on CD146 selected perivascular cells and MSC by real-time polymerase chain reaction confirm the relationship between these two cell types. Furthermore, the inverse correlation between fibroblast-specific protein-1 and CD146 transcripts observed on pericytes, MSC, and fibroblasts highlight their potential use as markers of this differentiation pathway. Conclusion. Our results indicate that human MSC and pericytes are similar cells located in the wall of the vasculature, where they function as cell sources for repair and tissue maintenance, whereas fibroblasts are more differentiated cells with more restricted differentiation potential. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Efficiency of the DNA repair and polymorphisms of the XRCC1, XRCC3 and XRCC4 DNA repair genes in systemic lupus erythematosus

Impaired DNA repair efficiency in systematic lupus erythematosus (SLE) patients has been reported ill some studies, mainly regarding the repair of oxidative damage, but little is known about repair kinetics towards primarily single-stranded DNA breaks. In the present study, we aimed to investigate: (a) the efficiency of SLE peripheral blood leucocytes in repairing DNA damage induced by ionizing radiation and (b) the association of DNA repair gene (XRCC1 Arg399Gln, XRCC3 Thr241Met and XRCC4 Ile401Thr) polymorphisms in SLE patients, considering the whole group, or stratified sub-groups according to clinical and laboratory features. A total of 163 SLE patients and 125 healthy control were studied. The kinetics of DNA strand break repair was evaluated by the comet assay, and genotyping for DNA repair genes was performed by PCR-RFLP. Compared with controls. SLE leucocytes exhibited decreased efficiency of DNA repair evaluated at 30 min following irradiation. A significant association with DNA repair gene polymorphisms was not observed for the whole group of SLE patients; however, the XRCC1Arg399Gln polymorphism was associated with the presence of anti-dsDNA antibody. The concomitance of two DNA repair polymorphic sites was associated with the presence of neuropsychiatric manifestations and antiphospholipid antibody syndrome. Taken together, these results indicated that SLE leucocytes repair less efficiently the radiation-induced DNA damage, and DNA repair polymorphic sites may predispose to the development of particular clinical and laboratory features. Lupus (2008) 17, 988-995.

DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric, cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2:? methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.

Impact of Surgical Staging in Locally Advanced Cervical Cancer and Subsequent Chemotherapy

Background: Surgical staging (SS) is the gold standard for determination of the true extent of a patient`s disease and is an important prognostic factor in cervical cancer. We investigated whether lymph node dissection (LND) prior to chemotherapy (CT) followed by radical surgery (RS) could modified overall (OS) and disease-free survival (DFS). Methods: We performed a cohort analysis of 98 patients with cervical carcinoma. The experimental group consisted of 36 patients who underwent SS followed by neoadjuvant chemotherapy, and then by RS (objective response) or chemo-radiation therapy (with or without subsequent surgery when not possible). The control group consisted of 62 similarly treated patients without pretreatment SS. The value of this procedure as a diagnostic tool in defining the extent of disease was evaluated. Furthermore, LND/CT-associated treatment complications and the impacts on OS and DFS were also evaluated. Results: Fourteen (38.9%) patients had pelvic LN metastases and three (8.3%) patients had pelvic and para-aortic LN metastases. The 39-month OS and DFS rates for the current study were 90.6% for the staged group and 52% for non-staged treatment (P < 0.001). Conclusion: SS in cervical cancer is a feasible and safe pretreatment procedure, and when associated with CT, it improves OS and DFS. J. Surg. Oncol. 2009;100:505-510. (C) 2009 Wiley-Liss, Inc.

Clinical Criteria as Predictive Factors of Response to Primary Hormone Therapy in Locally Advanced Breast Cancer

This study investigates the efficacy of clinical criteria in selecting patients for primary tamoxifen therapy. A total of 60 breast cancer patients with large primary tumors and unknown hormonal receptor status were subjected to primary hormone therapy. Inclusion criteria were age over 60 years old or menopausal status for at least 10 years and no clinical evidence of inflammatory disease and fast tumor growth. The objective response rate was 55%. There was a positive correlation between the lack of clinical response and axillary lymph node metastasis (p = 0.009). Patients with objective response had significantly improved disease-free (p = 0.045) and overall (p = 0.0002) survival over those who did not have response to hormonal therapy. In multivariate analysis, the clinical response to therapy was the most powerful prognostic factor. This analysis demonstrates that clinical criteria were very effective predictor of response to neo-adjuvant hormone therapy in large breast tumors for postmenopausal women. Response to therapy is the major prognostic factor in primary tamoxifen-treated breast cancer.