Pediatric traumatic atlanto-occipital dislocation: five cases and a review

Traumatic atlanto-occipital dislocation (AOD) has been thought to be a rare and fatal injury. Recently, more survivors, especially children, have been reported. During a 10-year period, the authors have encountered five children with traumatic AOD. A retrospective review of traumatic AOD in children from 1985 to 1995 was performed. Clinical presentation, initial radiologic findings, and final outcome were emphasized. Distance from the dens to the basion and the ratio of Powers were measured from initial lateral cervical spine radiographs. The average distance from the dens to the basion was 9.8 mm. The average ratio of Powers was 1.38. There were three survivors, two having a concomitant spinal cord injury. All survivors underwent a posterior occipitovertebral fusion. Three cases initially went undiagnosed. The diagnosis of AOD by lateral cervical spine radiographs can be difficult. The authors recommend detailed measurements of the initial cervical spine radiographs in pediatric patients at risk for traumatic AOD.     

The relevance of various vulvar epithelial changes in the early detection of squamous cell carcinoma of the vulva

The objective of this study is to evaluate the possible relevance of vulvar epithelial changes as a risk factor for squamous cell carcinoma of the vulva. The data of 66 women surgically treated for squamous cell carcinoma of the vulva have been analyzed. More than 6500 slides from the resection specimens were revised with special emphasis on concurrent epithelial changes. Synchronous epithelial changes were seen in 63 patients. Thirty-nine patients had synchronous vulvar intra-epithelial neoplasia grade 1 (VIN I), 10 VIN II and 13 VIN III. Thirty-one patients had synchronous lichen sclerosus and 49 squamous cell hyperplasia. The difference between the percentage of patients with epithelial changes diagnosed preceding their carcinoma (30%) and the percentage of patients that had synchronous epithelial changes after reviewing the specimen (95%) was striking. It was concluded that more careful diagnosis, treatment and follow-up of these conditions might lead to an earlier recognition of squamous cell carcinoma of the vulva and therefore to a better prognosis.     

Good medical care at the borderline of mental incompetence

A 73-year-old woman with minor intellectual skills had complaints which suggested a vulvar carcinoma. Despite her refusal she was examined and admitted to hospital, on the basis of good professional care. The psychiatrist examined her and judged her incompetent. For the operation of the diagnosed vulvar carcinoma a court ordered representative was obtained. Two months later she underwent radiotherapy to prevent local complications and pain and a few weeks thereafter she died. Because medical decision-making in a doctor-patient relationship is not always possible decision-making power should be assigned to a third party. That forms the basis of proper medical care.     

Surgical treatment of early stage cervical carcinoma at Leids University Medical Center, 1984-1996: depth of invasion, number and bilaterality of metastatic lymph nodes prognostic for recurrence

OBJECTIVE: To analyse local tumour parameters of early cervical cancer that might be of prognostic significance for tumour relapse in the pelvis. DESIGN: Retrospective. METHOD: Data were collected from 308 patients who underwent radical hysterectomy and pelvic lymphadenectomy in the years 1984-1996 in the Leiden University Medical Centre, the Netherlands. Treatment policies and operating staff were the same during the study period. The existence of relapse was studied by physical, gynaecological, laboratory and, if indicated, radiological examination. RESULTS: Data on 294 patients were available for analysis. Their mean age was 45 years (range: 21-82). Postoperative radiation treatment was given to 119 patients (40%). Mean follow-up duration was 36 months (range: 1-136). Recurrences had developed in 46 patients (15.6%), 29 of whom had died. The calculated overall 5-year survival rate was 83%; 91% for those with negative and 53% for those with positive pelvic nodes. The calculated recurrence-free-5-year survival rate was 75% for the entire group, 83% for the patients without and 47% for those with lymph node metastases. When more than one lymph node region was affected, 5-year disease free survival was 19% and when lymph node metastasis occurred bilaterally, it was 22%. Multivariate analysis revealed that lymph node involvement (hazard ratio: 4.4), parametrial involvement (5.5), tumour size > 30 mm (4.6) and depth of invasion > 10 mm (5.1) were independent factors of prognostic significance for disease free survival. The current indications for adjuvant treatment might be extended with infiltration depth. The number and the bilaterality, if any, of affected lymph node stations might be indication for additional adjuvant therapy.     

Long-term follow-up of Lord's procedure for haemorrhoids

86 Patients treated for first or second degree haemorrhoids by Lord's manual dilatation of the anus were followed up for a mean period of 7.2 years. The outcome in the 76 patients traced was satisfactory or good in 76.3%. In only 14.5% was the result unsatisfactory. Lord's anal dilatation is a relatively simple procedure; the results of this study show that it gives good long-lasting results.     

Effect of MRI on therapeutic decisions in invasive cervical carcinoma. Direct comparison with the pelvic examination as a preperative test

OBJECTIVES: Our aim was to compare magnetic resonance imaging (MRI) with the current standard clinical practice (pelvic examination including general anesthesia in selected patients) with regard to treatment planning in invasive cervical carcinoma. It was of particular interest to compare the accuracy of both methods for allocating the patients to the appropriate treatment modality: surgery versus primary radiotherapy. METHODS: One hundred and three consecutive patients with primary invasive cervical carcinoma underwent both MRI at 1.5 T and pelvic examination. The gold standard for comparing treatment decisions was based on the surgico-pathologic data: tumor confined to the cervix (treatment decision for surgery) or extracervical tumor spread (treatment decision for primary radiotherapy). RESULTS: A gold standard was available in 91 patients. The pelvic examination made correct treatment decisions in 89% of patients. However, the sensitivity for extracervical spread was only 44% (8/18 patients). MRI was better at identifying extracervical tumor spread: 67 and 89% for observers 1 and 2, respectively. MRI, however, had more false positive results and correct treatment decisions were made in 69-84% of patients (observer 1, 76/91; observer 2, 63/91). CONCLUSION: Treatment decisions based on the pelvic examination were correct in 89%, with MRI not bringing improvement. MRI, however, is better in diagnosing extracervical spread, but at the cost of more false positives.     

Switch recombination breakpoints are strictly correlated with DNA recognition motifs for immunoglobulin S gamma 3 DNA-binding proteins

The deletion looping out model of switch (S) recombination predicts that the intervening DNA between switch regions will be excised as a circle. Circular excision products of immunoglobulin switch recombination have been recently isolated from lipopolysaccharide (LPS)-stimulated spleen cells. The recombination breakpoints in these large circles were found to fall within switch regions. Since switch recombination is clearly focused on switch regions, we hypothesized that some DNA-binding protein factor might be involved in specifically recognizing and facilitating the alignment of switch regions before recombination. Two DNA-binding proteins that specifically interact with two discrete regions of the S gamma 3 tandem repeat have been identified in crude and partially purified nuclear extracts derived from LPS- and dextran sulfate (DxS)-activated splenic B cells. The first factor has been found indistinguishable from NF-kappa B by mobility shift assays, methylation interference, competition binding studies, and supershift analysis using an antiserum specific for the p50 component. The second appears to be composed of two closely traveling mobilities that do not separate upon partial purification. This second complex is unique and specific for S gamma 3 by methylation interference assays and competition-binding analysis. The sites at which recombination occurs in the S gamma 3 switch region have been analyzed and found to strictly correlate with the binding sites of the S gamma 3 switch binding proteins.     

Detection of T helper responses, but not of human papillomavirus-specific cytotoxic T lymphocyte responses, after peptide vaccination of patients with cervical carcinoma

Human papillomavirus type 16 (HPV16)-encoded E7 oncoprotein is constitutively expressed in cervical carcinoma cells and is required for cellular transformation to be maintained. The E7 protein, therefore, forms an attractive target for T-cell-mediated immune intervention to prevent or treat HPV16+ tumors. The authors performed a peptide-based phase I/II vaccination trial to induce anti-tumor immune responses in patients with recurrent or residual cervical carcinoma. Fifteen HLA-A*0201+ patients with HPV16+ cervical carcinoma received vaccinations with synthetic peptides representing 2 HPV16 E7-encoded, HLA-A*0201-restricted cytotoxic T lymphocyte epitopes and a pan-HLA-DR-binding T-helper epitope, PADRE, in adjuvant. No signs of toxicity were observed. Two patients had stable disease for more than 1 year after vaccination, 3 patients died of the disease during or shortly after the vaccination period, and 10 patients maintained progressive cervical carcinoma. Specific immune responses directed against the vaccine components were analyzed in peripheral blood samples. No cytotoxic T lymphocyte responses against the HPV16 E7 peptides were detectable. After vaccination, strong PADRE helper peptide-specific proliferation was detected in 4 of 12 patients. In conclusion, peptide vaccination with 2 HPV16 E7 cytotoxic T lymphocyte epitopes and a universal T helper epitope is well tolerated by patients with advanced cervical carcinoma. Despite a reduction of in vitro cytolytic or proliferative recall responses to some, but not all, conventional antigens in this patient group, peptide-specific proliferative responses were induced in 4 patients. Based on the current study, it is now feasible to perform peptide vaccination in earlier stages of HPV16-induced cervical disease.     

Genetic variation of antigen processing machinery components and association with cervical carcinoma

The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of several APM components is associated with progression and clinical outcome in cervical carcinoma. Genetic variation in the genes encoding APM components is known to be associated with risk of occurrence of several malignancies. However, only limited evidence exists supporting the role of single nucleotide polymorphisms (SNPs) in APM components in cervical carcinoma. We have therefore investigated the occurrence of APM component SNP genotypes and haplotypes in cervical carcinoma. Thirteen coding SNPs in the LMP2, LMP7, TAP1, TAP2, and ERAP1 genes were genotyped in 127 cervical carcinoma patients and 124 controls. Individual genotype and allele distributions were assessed by single-marker analysis. Effects of various SNP combinations were estimated by haplotype construction and subsequent haplotype interaction analysis. Significant haplotypes were modeled on disease risk. Allele distributions at the LMP7-145, TAP2-651, ERAP1-127, and ERAP1-730 loci differed significantly between cases and controls with the major allele at the LMP7 and TAP2 loci and the minor allele at both ERAP1 loci associated with increased cervical carcinoma risk. A combination of the two haplotypes spanning these loci was associated with a three-fold increased risk (OR = 3.024; P < 0.001); approximately 12% of all cervical carcinoma occurrences were attributable to this combination. Our data indicate that combined genetic variation in the TAP2, LMP7, and ERAP1 genes is associated with increased cervical carcinoma risk.