Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples.

AIM: This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. METHODS: We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. RESULTS: HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. CONCLUSIONS: HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts.

Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance.

BACKGROUND AND AIMS: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. MATERIALS AND METHODS: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. RESULTS: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity (FVC) (r(s) = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s (FEV(1))/FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. CONCLUSION: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival.

Structural biology of membrane-acting peptides: conformational plasticity of anticoccidial peptide PW2 probed by solution NMR.

The bottleneck for the complete understanding of the structure-function relationship of flexible membrane-acting peptides is its dynamics. At the same time, not only the structure but also the dynamics are the key points for their mechanism of action. Our model is PW2, a TRP-rich, cationic peptide selected from phage display libraries that shows anticoccidial activity against Eimeria acervulina. In this manuscript we used a combination of several NMR techniques to tackle these difficulties. The structural features of the membrane-acting peptide PW2 was studied in several membrane mimetic environments: we compared the structural features of PW2 in SDS and DPC micelles, that were reported earlier, with the structure properties in different lipid vesicles and the peptide free in water. We were able to unify the structural information obtained in each of these systems. The structural constraints of the peptide free in water were fundamental for the understanding of plasticity necessary for the membrane interaction. Our data suggested that the WWR sequence is the region responsible for anchoring the peptide to the interfaces, and that this same region displays some degree of conformational order in solution. For PW2, we found that affinity is related to the aromatic region, by anchoring the peptide to the membrane, and specificity is related to the N- and C-termini, which are able to accommodate in the membrane due to its plasticity.

Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system.

PURPOSE: To critically review the accuracy of the current American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma and propose a more useful staging system. METHODS: Retrospective evaluation of the published data as well as a reanalysis of the University of Alabama and Sydney Melanoma Unit (UAB/SMU) data bases (n = 4,568) for patients with primary melanoma was performed to examine specifically the impact of level of invasion and ulceration on the prognostic value of tumor thickness. In addition, an overlay graphic technique was used to compare the Kaplan-Meier survival curves of patients with local recurrences, satellites, in-transit metastases, and nodal metastases reported in the literature. RESULTS: Tumor thickness and ulceration remained the most powerful prognostic indicators in patients with stage I and II disease. Level of invasion provided statistically significant prognostic information only in the subgroup of patients with tumor thickness < or = 1 mm, but the absolute 10-year survival differences were small and inconsistent (level II, 95%; level III, 85%; level IV, 89%). The best statistical fit for tumor thickness cutoffs was at 1 versus 2 versus 4 mm. The overlay graphic technique showed that patients who developed satellite lesions or local recurrence had prognoses similar to those of patients with stage III disease. The most important prognostic factor for patients with nodal metastases was number of involved nodes rather than size. CONCLUSION: Our analysis showed that the current AJCC staging system has many inaccuracies that should be modified to conform to published data. On the basis of our analysis and review of the literature, we propose a new and more accurate staging system.

Prognostic value of size of lymph node metastases in patients with cutaneous melanoma.

PURPOSE: To determine the prognostic significance of the size of the lymph node mass as measured by physical examination (PE) and of the size of the largest node measured by pathologic analysis (path) in patients with cutaneous melanoma and nodal metastases. PATIENTS AND METHODS: The medical records of all patients with nodal metastases seen at The University of Texas M.D. Anderson Cancer Center from January 1, 1973 to December 31, 1989 were reviewed. Patient eligibility criteria included the following: (1) availability of data describing the nodal size either by PE or by path and the number of positive nodes; (2) no history of preoperative chemotherapy or radiotherapy; and (3) no history or presence of in-transit, satellite, local, or distant metastases. Eleven variables, including largest diameter of the nodal mass by PE and diameter of the largest node by path, were examined as potential prognostic factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Of 800 patients evaluated, 442 met the eligibility criteria and are the subjects of this study. In the univariate analysis, size of the nodal mass by PE was marginally significant for survival as a continuous variable (P = .045), but not as a categorical variable using a cutoff size of < or = 3 or more than 3 cm as indicated by the American Joint Committee on Cancer (AJCC) staging system (P = .61). Size of the largest node by path was not significant for survival. In the multivariate analysis, only the number of positive nodes (P < .001), age (P < .001), and tumor thickness (P < .001) were significant for survival. CONCLUSION: Size of the nodal mass by PE and size of the largest node by path are not useful prognostic factors for survival and should be eliminated from the current staging system. More powerful and well-established prognostic factors, such as the number of positive nodes, should be considered for inclusion in staging.

Role of computed tomography in the staging of patients with local-regional metastases of melanoma.

PURPOSE: To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level. PATIENTS AND METHODS: The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient. RESULTS: Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules. CONCLUSION: TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.

Pharyngostomy with double tube and anastomosis in the posterior wall of the stomach as a method of avoiding leakage after esophagectomy.

The cervical esophagogastrostomy is a surgical method that has frequent fistula-like complications and it increases the morbidity and mortality rate in surgical treatment for carcinoma of the esophagus. One-hundred and thirty-eight instances of carcinoma of the esophagus were treated surgically from 15 October 1968 to 30 April 1986. In the last 15 instances (10.8 per cent), esophageal anastomosis with the posterior wall of the stomach was done. The decompression of anastomosis and enteral nutrition are done by a Kher drain and Levine catheter, respectively, that are exteriorized by a pharyngostomy. With this method, no fistulas occurred after cervical esophagogastrostomy.

Tratamento cirurgico do carcinoma de esofago. / Surgical treatment of carcinoma of the esophagus

O carcinoma de esofago e uma neoplasia de dificil abordagem e de terrivel prognostico. O cirurgiao que recebe um paciente com carcinoma esofagiano ja o recebe em estado avancado, nada podendo fazer para cura-lo a unica conduta que pode ter e para a paliacao, pois quando sintomaticos, esses se apresentam com cerca de 2/3 da circunferencia do orgao comprometidos. Em nosso Servico, tivemos cerca de 89 pacientes, num periodo de 1968-1981, que foram submetidos a tratamento cirurgico do carcinoma esofagiano. Destes, cerca de 23 pacientes tiveram um procedimento menos cruento, sendo submetidos a ostomia - 17 gastrostomias e 6 gastrostomias associadas a esofagostomias. Os restantes 66 pacientes tiveram uma cirurgia paliativa por by-pass com ou sem resseccao do tumor. Dos 66, cerca de 34 pacientes foram submetidos somente ao by-pass e os outros 32 pacientes tiveram o by-pass e resseccao tumoral, pois estavam dentro dos criterios de ressecabilidade que usamos no Servico. A taxa de mortalidade hospitalar (13,5%) e morbidade sao comparaveis a de outros autores

Abdomen aberto: nova opcao para o tratamento da peritonite grave generalizada multi-septada. / Open abdomen: new option for the treatment of severe generalized peritonitis with multiple abscess in the cavity

Os autores trazem a experiencia de 26 meses com o uso do abdomen aberto, para o tratamento da peritonite aguda grave multi-septada. A cavidade peritoneal e deixada aberta e tratada como se fosse um grande abscesso e assim drenar todos os multiplos abscessos intracavitarios. Protegem as alcas com uma tela de polipropileno que e mantida por fios de nylon O, que transfixam aponeurose e peritonio parietal.Apos um intervalo de quatro a oito dias, a cavidade peritoneal e fechada sob anestesia geral, ficando pele e tecido celular subcutaneo para fechamento por segunda intensao. A tela de polipropileno e abandonada na cavidade peritoneal nao tendo prejuizo para o paciente ja que a tela e de um material inerte. Durante esse periodo de 26 meses foram deixadas abertas as cavidades de 17 pacientes, todos com peritonite grave multi-septada. Ocorreram quatro obitos: tres deles sem relacao com a causa da peritonite e um correlacionado. Esse metodo, em relacao a outros, que usam o fechamento da cavidade, tem concorrido com menor taxa de mortalidade e morbidade pos-operatoria

Hernia incisional: correcao com tela de polipropleno. / Incisional hernia - reparation with polypropylene mesh

Apresentamos a casuistica do nosso servico em 132 hernias incisionais operadas em sete anos Fechamos todas as camadas da pareda abdominal com fio polipropileno, material identico ao da tela que usamos para correcao dessas hernias, a qual e suturada sobre a aponeurose sa da parede abdominal com fio de polipropileno.As complicacoes devidas ao uso desse material protetico foram poucas; em decorrencia dos bons resultados obtidos, esse material tem sido o de escolha para correcao das hernias incisionais, quando seu uso se faz necessario ou seja, quando houver certeza de qualquer tensao na parede abdominal

[Recurrent hematuria of glomerular origin]. / Hematuria recurrente de origen glomerular

Nine hundred and forty children with hematuria were admitted to the nephrology service from 1958 to 1973. Percutaneous renal biopsies were performed in all of them. Thirty cases out of this group had recurrent hematuria and constitute the clinical material of this study. The clinical picture was: acute nephrotic syndrome in 19; monosymptomatic hematuria in 8, anaphylactoid purpura nephritis in 2, and hematuria associated with nephrotic syndrome in one patient. All patients with nephritic syndrome showed in their biopsies various types of glomerular lesions; most of the patients with monosymptomatic hematuria had normal glomeruli; at the light microscopy, the immunofluorescence was positive in some of them. Both patients with anaphylactoid nephritis showed diffuse endocapillary and focal extracapillary proliferation and in the only one with nephrotic syndrome, the hematuria was familial and the biopsy showed features of Alport's syndrome. Twenty-four patients who were followed for over two years showed no relationship between the age of onset, sex, initial significant proteinuria, hypertension, frequency of bouts of hematuria and the clinical evolution. At the end of the study, 7 patients had prolonged remission: the light microscopy showed normal glomeruli, endocapillary proliferation and endo and extracapillary proliferation with less than 30% of the glomeruli affected by "crescents". The remaining cases were still active and one of them with endo and extracapillary glomerulonephritis with more than 30% of the glomeruli affected by "crescents", developed chronic renal insufficiency. In conclusion, the prognosis of recurrent hematuria of glomerular origen is related with the type of glomerular lesions and constitutes an indication for renal biopsy. Renal specimens must be studied under light microscopy and immunofluorescence techniques; electromicroscopy is required when hematuria is present in more than one member of the family.