The impact of HPV cervical screening on negative large loop excision of the transformation zone (LLETZ): A comparative cohort study.

OBJECTIVE: To determine the incidence and predictors of negative large loop excision of the transformation zone (LLETZ) following the introduction of Human Papillomavirus (HPV) cervical screening. METHOD: A retrospective cohort study. Two independent cohorts, who attended for a LLETZ procedure, before and after the introduction of HPV cervical screening were compared. For each cohort, 401 individuals were randomly selected from a colposcopy database. Clinical and colposcopic variables were extracted. The incidence of negative LLETZ was estimated in each cohort. Regression analysis was used to adjust for potential confounders and explore predictors of negative LLETZ. RESULTS: Eighty women (19.9%) from the pre-HPV testing cohort and 54 women (13.4%) from the post-HPV cohort were negative for cervical intraepithelial neoplasia (RR 0.75, CI: 0.55 to 0.93). In the post-HPV testing cohort, independent predictors of negative LLETZ were low grade cytology (RR 3.60, CI: 2.18-5.97) and a type 3 transformation zone (TZ) (RR 2.88, CI: 1.76-4.72). Women with both low grade cytology and a TZ type 3 were 10.4 times more likely to have a negative LLETZ (absolute risk 40%, 95% CI: 27-54%). CONCLUSIONS: Despite a 25% reduction in negative LLETZ following the introduction of HPV cervical screening, the incidence is still high. These results highlight the importance of continuing to improve the specificity of cervical intraepithelial neoplasia screening; this should include the use of biomarkers that detect HPV-transforming infections and techniques that sample an entirely endocervical transformation zone.

Muscle Fibre Typology as a Novel Risk Factor for Hamstring Strain Injuries in Professional Football (Soccer): A Prospective Cohort Study.

BACKGROUND: Hamstring strain injuries (HSI) are prevalent in team sports and occur frequently in the later phase of matches. In the search for interindividual factors that determine muscle fatigue and possibly injury risk, muscle fibre typology is a likely candidate. OBJECTIVE: The aim of the study was to determine whether muscle fibre typology is a risk factor for HSI. METHODS: A prospective cohort study was conducted over three seasons in professional football players competing in the Belgian Jupiler Pro League (n = 118) and in the English Premier League (n = 47). A total of 27 HSI were sustained during this period. Muscle fibre typology was non-invasively estimated using proton magnetic resonance spectroscopy and was characterized as a fast, slow, or intermediate typology based on the carnosine concentration in the soleus. A multivariate Cox model was used to identify risk factors for HSI. RESULTS: Football players exhibited a wide variety of muscle typologies (slow 44.9%, intermediate 39.8%, fast 15.3%). In the combined cohort, players with a fast typology displayed a 5.3-fold (95% confidence interval [CI] 1.92-14.8; P = 0.001) higher risk of sustaining an index HSI than slow typology players. This was also independently observed in both leagues separately as, respectively, a 6.7-fold (95% CI 1.3-34.1; P = 0.023) and a 5.1-fold (95% CI 1.2-20.4; P = 0.023) higher chance was found in fast typology players than in slow typology players of the Jupiler Pro League and the Premier League cohort. CONCLUSION: We identified muscle fibre typology as a novel and potent risk factor for HSI in team sports.

CORP: quantification of human skeletal muscle carnosine concentration by proton magnetic resonance spectroscopy.

Noninvasive techniques to quantify metabolites in skeletal muscle provide unique insight into human physiology and enable the translation of research into practice. Proton magnetic resonance spectroscopy (1H-MRS) permits the assessment of several abundant muscle metabolites in vivo, including carnosine, a dipeptide composed of the amino acids histidine and beta-alanine. Muscle carnosine loading, accomplished by chronic oral beta-alanine supplementation, improves muscle function and exercise capacity and has pathophysiological relevance in multiple diseases. Moreover, the marked difference in carnosine content between fast-twitch and slow-twitch muscle fibers has rendered carnosine an attractive candidate to estimate human muscle fiber type composition. However, the quantification of carnosine with 1H-MRS requires technical expertise to obtain accurate and reproducible data. In this review, we describe the technical and physiological factors that impact the detection, analysis, and quantification of carnosine in muscle with 1H-MRS. We discuss potential sources of error during the acquisition and preprocessing of the 1H-MRS spectra and present best practices to enable the accurate, reliable, and reproducible application of this technique.

The Wallace technique of ureteroileal anastomosis and its use in gynecologic oncology: a study of 81 cases.

OBJECTIVE: To report the indications for surgery, morbidity, and results of treatment using the Wallace ileal conduit for supravesical urinary diversion. METHODS: Over a 15-year period (1977-1991), 81 patients, all with an underlying gynecologic malignancy requiring urinary diversion, had ileal conduit surgery performed at the Regional Department of Gynecological Oncology, Gateshead, England using the Wallace technique. Patient details stored in a computerized data base were reviewed retrospectively. RESULTS: Thirty-nine patients (48%) had received radiotherapy before conduit surgery. In 70% of cases, urinary diversion was performed as part of an exenterative procedure. Early postoperative complications occurred in 56% of cases and were mainly related to infection. Long-term complications included fistula (three), stoma retraction (three), loss of renal function (three), tumor metastases (two), and stoma herniation (one). There was one postoperative death secondary to septicemia. By 1991, 42 patients (52%) had died of their primary disease. CONCLUSION: We believe that for urinary diversion in the gynecologic oncology patient, the ileal conduit, in particular the Wallace technique, is the procedure of choice.

MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In the search for a diagnostic test for amyotrophic lateral sclerosis (ALS), especially upper motor neuron (UMN) involvement, MR imaging and proton spectroscopy techniques have each received attention, but their findings have not been correlated. The purpose of this study was to identify relationships among the results of current techniques, taking into account the severity of clinical UMN disease, so that objective measures of the pathogenesis of ALS may be established. METHODS: Eighteen subjects with clinically diagnosed ALS and 12 healthy volunteers underwent MR imaging of the brain and localized proton MR spectroscopy. Water-suppressed spectra from the left precentral gyrus and from the left cuneus gyrus were analyzed with the LCModel method, yielding concentrations for N-acetyl (NA), total creatine (Cr), choline (Cho), glutamate (Glu), glutamine (Gin), and myo-inositol (Ins) metabolic substrates. Signal intensities of the precentral gyrus on T2-weighted images were assessed qualitatively in a blinded fashion. RESULTS: For the precentral gyrus, mean Cho (1.3 mM) and Ins (3.25 mM) for the ALS group were significantly increased. After adjustment for Cr covariance, mean Glu (5.08 mM) and NA (6.31 mM) were decreased. For the cuneus gyrus, no difference in metabolite concentrations between groups was observed. Trend analysis of the precentral gyrus metabolite concentrations revealed significant increases in Cho and Ins and decreases in NA and Glu with respect to the severity of clinical UMN signs. Metabolic changes were greater in the subset of ALS patients with precentral gyrus signal changes on imaging, and significantly increased Ins was associated with cortical hypointensity on fast spin-echo images. CONCLUSION: Mean metabolite concentrations determined from precentral gyrus spectra reflect clinical and pathologic changes that occur in ALS. Imaging findings, while related to the spectral and clinical results, are not specific to ALS.

Proton MR spectroscopy of the brain in 14 patients with Parkinson disease.

PURPOSE: To determine whether the proton spectra from patients with clinically diagnosed Parkinson disease differ from the spectra of age-matched healthy subjects with respect to the major cerebral metabolite resonances as well as lactate. METHODS: Fourteen patients with Parkinson disease (38 to 81 years of age) and 13 healthy control subjects (37 to 81 years of age) were studied using image-guided, single-voxel (27-cm3 volume) proton MR spectroscopy of the occipital lobe. RESULTS: The peak area ratios of N-acetyl aspartate to creatine and N-acetyl aspartate to choline for Parkinson patients did not show a statistically significant difference from the corresponding ratios for control subjects. There was a very significant increase in the ratio of lactate to N-acetyl aspartate for patients with Parkinson disease, with the greatest increase (threefold) manifested by the subgroup (n = 4) with dementia. The difference in N-acetyl aspartate to choline between women (n = 7) with Parkinson disease and healthy women (n = 9) approached significance. No dependence of the peak ratios on age, duration of Parkinson disease, or medication (L-dopa) regimen was found. CONCLUSION: Preliminary results indicating an increase in cerebral lactate in patients with Parkinson disease support the hypothesis that Parkinson disease is a systemic disorder characterized by an impairment of oxidative energy metabolism. The larger increases for Parkinson patients with dementia may be diagnostically useful in assessing clinical course and in differentiating Parkinson disease from other causes of dementia. Additional studies are needed, though, to quantitate lactate changes and identify potential contributions from lipid resonances better.

Radical vulvectomy and bilateral inguinal-femoral lymphadenectomy through separate incisions-experience with 100 cases.

Over a 6-year period 100 patients with vulvar cancer were treated by radical vulvectomy and bilateral inguinal femoral lymphadenectomy performed through separate incisions. The average age of the patients was 68.8 years. Ninety patients had squamous carcinoma, six had melanoma and four had other vulvar malignancies. FIGO staging was stage 1-46, stage II-25, and stage III-23, and stage IVa-6. Twenty-seven patients were found to have spread of tumor to groin nodes, 21 unilateral and six bilateral. For patients with squamous carcinomas, groin nodes were positive in four of 45 (8.9%) with tumor diameter < 2 cm vs. 17 of 42 (40.5%) with tumors> 2 cm. In 60 patients with unilateral squamous tumors, no isolated contralateral node metastases were found, however two of 13 patients (15.4%) with positive ipsilateral nodes had positive contralateral nodes also. One patient with negative nodes developed bilateral recurrent tumor in the skin bridges and subsequently died. Overall 5-year survival corrected for death from intercurrent illness was 74.6%. Corrected survival by stage for squamous carcinomas was as follows: stage I-96.7%, stage II-85%, stage III-45.8% and stage IV-50%.

The impact of loop diathermy on management of early invasive cervical cancer.

Large loop excision of the transformation zone (LLETZ) allows complete histologic assessment of cervical neoplasia. However, selective colposcopically directed punch biopsy followed by local ablation allows the possibility of inappropriate local ablation of early invasive lesions missed at punch biopsy. The onus of accurate diagnosis lies on the colposcopist. We have studied 1143 patients managed with loop diathermy and identified 35 invasive squamous carcinomas and 9 invasive adenocarcinomas. The data show that the cut-off for accurate colposcopic detection of invasive squamous lesions is not breach of the basement membrane but invasion up to a depth of 1 mm. On the other hand, colposcopy is an unreliable guide for the diagnosis of early adenocarcinoma. Diagnosis based on loop excision allows accurate, rational individualization of management for the unexpected diagnosis of colposcopically occult early invasive disease whilst retaining the logistic benefits of a 'see and treat' policy.

The case for early intervention ('see and treat') in patients with dyskaryosis on routine cervical screening.

'See and treat' colposcopy using an excisional technique (usually LLETZ) is very attractive to patients and practitioners. It is therapeutically effective, efficient and cost-effective within the context of the screening programme. It is, of course, inappropriate to excise the transformation zone of any woman who attends the clinic with an abnormal smear. The question should however be, 'Is there a reason why I should not see and treat', rather than 'why should I see and treat'. Reasons for avoiding 'see and treat' comprise patients' preference and young age coupled with minor cytological or histological abnormalities (i.e. mild dyskaryosis or less and CIN 1 or less). This is because many minor problems will resolve without therapy and because long-term data collection may show effects about which we know nothing. I would argue that for patients with mild abnormalities who are older or their fertility is not an issue, 'see and treat' is appropriate because the treatment morbidity is so low and they are at higher risk of having significant lesions than young women. Finally, for patients with more severe abnormalities, the timing of the treatment is irrelevant, and the only argument against 'see and treat' is patient preference.

Langerhans' cells and subtypes of human papillomavirus in cervical intraepithelial neoplasia.

There is strong circumstantial evidence that human papillomavirus is a cofactor in the development of cervical neoplasia. Systemic immunosuppression has also been implicated. A study was therefore carried out examining the relation between subtypes of human papillomavirus and local immunocompetent cells in the cervix. Colposcopically directed punch biopsy specimens were taken from normal cervix and from histologically proved cervical intraepithelial neoplasia for immunohistochemical studies. Human papillomavirus genome probing was performed on the abnormal specimens. A relation was apparent between decreased Langerhans' cells and moderate to high copy numbers of human papillomavirus type 16. The reduction in Langerhans' cells was significant for human papillomavirus type 18 even at low copy numbers. Conversely, the absence of human papillomavirus was associated with increased numbers of Langerhans' cells in cervical intraepithelial neoplasia. These findings suggest that the proposed oncogenic potential of human papillomavirus type 16 and human papillomavirus type 18 in particular may be mediated by a specific effect on the afferent limb of the immune response.

Carcinoma of the vulva. A ten year retrospective study in the West of Scotland (1972-1982).

Vulval carcinoma is a rare and often fatal disease. Little is known about its incidence and distribution in the West of Scotland. This paper records the current distribution and methods of treatment employed in the area and suggests that the results might be improved by a regionally based service.

Proton MR spectroscopy in a 1T open MR imaging system.

(1)H-MR spectroscopy is an established noninvasive MR imaging technique that can be helpful in the diagnosis of brain lesions and in treatment planning. Claustrophobia and body habitus preclude some patients from routine MR imaging in a closed-bore system. The development of (1)H-MR spectroscopy for use in an open MR imaging system would enable a more complete characterization of brain lesions in these patients.

In vivo proton metabolite maps using the MESA 3D technique.

In vivo proton spectroscopy requires excellent static magnetic field homogeneity in order to allow suppression of the water signal. This is usually accomplished by restricting the observed signal to a small volume element, or voxel. However, the disadvantage of all single-voxel techniques is that each experiment results in a spectrum from only a single small region of the patient. This makes it difficult to map metabolite concentrations over extended regions of the patient's anatomy. Standard phase-encoding techniques that cover the entire sensitive volume of the receiver coil can provide metabolite maps but suffer from excessive field inhomogeneity and/or susceptibility problems at interfaces. We report here on a technique which localizes a large voxel within the patient and uses phase encoding within this voxel to obtain metabolite maps over an extended region of the patient's anatomy. Phantom results are presented to demonstrate the performance of the technique. In vivo results on human brains are also presented.

3D multivoxel proton spectroscopy of human brain using a hybrid of 8th-order Hadamard encoding with 2D chemical shift imaging.

Multivoxel 3D localized proton spectroscopy using a hybrid of 1D 8th-order transverse Hadamard spectroscopic imaging (HSI) with 2D chemical shift imaging (CSI) is demonstrated in human brain. The spatially selective HSI pulse incorporates naturally into the PRESS sequence (TE = 135 ms), which then both excites an 8 x 8 x 6 cm parallelepiped volume of interest (VOI) and subdivides it into eight slices. The planes of these slices are further partitioned into 16 x 16 voxel arrays using 2D CSI to yield 8 x 8 x 8 voxels within the VOI. Simultaneous 3D coverage yields good voxel signal-to-noise (8, 12, and 22 for choline, creatine, and N-acetylaspartate, respectively) from these 0.75-ml voxels, in approximately 45 min. The high spatial isolation allows localization to within less than 1 cm from the skull without fat contamination.

The surgical management of cervical carcinoma within the South West of England: progress through an audit loop. Gynaecology Tumour Panel.

OBJECTIVE: To define and use a minimum clinical dataset for prospective data collection in order to audit the surgical management of cervical cancer in the South West of England. To compare this data set with a retrospective audit allowing assessment of the quality of care offered to patients. DESIGN: Prospective collection of a defined dataset on paper forms which were put into a computerised database for analysis. Registrations validated against histopathology databases and hospital coding. SETTING: All 13 hospitals in the South West of England which participated in the retrospective audit. PARTICIPANTS: One hundred and sixty-five women with cervical cancer diagnosed in 1997. MAIN OUTCOME MEASURES: Distribution of cases by hospital and surgeon; workload of individual surgeons; adequacy and accuracy of FIGO staging; adequacy of histological information; and adequacy of surgery. RESULTS: There is a trend to centralisation of cancer care and radical surgery in the region. Prospective collection of data has dramatically improved FIGO staging with 92% of all cases staged. For cases greater than Stage Ia, 98% were staged suggesting that a target of 100% staging is feasible. The histological dimensions of tumours were not measured in a high proportion of cases (20% of tumour diameters and 28% of tumour thicknesses). Apparent inadequacies in surgical management are explored. In 10/165 cases (6%) inappropriate conservative surgery may have been unavoidable, suggesting that a quality standard of 95% for appropriate radical surgical management of cervical cancer can be achieved. An anatomically complete removal of pelvic node-bearing tissue, yielding greater than 10 nodes in more than 95% cases, should be achievable with each surgeon/pathologist achieving a mean of more than 20 nodes. CONCLUSION: Regional audit of cervical cancer management is feasible. It can be used to improve the quality of information on management and guide improved service provision.

Histological and cytological evidence of viral infection and human papillomavirus type 16 DNA sequences in cervical intraepithelial neoplasia and normal tissue in the west of Scotland: evaluation of treatment policy.

Biopsy samples from 27 patients referred to a colposcopy clinic in Glasgow for cervical abnormalities were assessed for the relations among colposcopic appearances, cytological and histological diagnosis, expression of papillomavirus antigen, and the presence of human papillomavirus (HPV) types 6, 11, 16, and 18 deoxyribonucleic acid (DNA) sequences. Specimens were from colposcopically abnormal areas of the transformation zone and from colposcopically apparently normal areas of the zone in the same patients (paired matched internal control tissue). All 27 women referred for abnormal smears had colposcopic abnormalities. HPV-16 or 18 DNA sequences were detected in 20 of the 27 colposcopically abnormal biopsy samples and 13 of the 27 paired normal samples. Twelve samples of colposcopically normal tissue contained histological evidence of viral infection but only four of these contained HPV DNA sequences. The other nine samples of colposcopically normal tissue which contained HPV DNA sequences were, however, histologically apparently normal. HPV-6 and 11 were not detected. Integration of the HPV-16 genome into the host chromosome was indicated in both cervical intraepithelial neoplasia and control tissues. In two thirds of the HPV DNA positive samples the histological grade was classed as normal, viral atypia, or cervical intraepithelial neoplasia grade 1. Papillomavirus antigen was detected in only six of the abnormal and three of the normal biopsy samples, and HPV DNA was detected in all of these. The detection of HPV DNA correlates well with a combination of histological and cytological evidence of viral infection (20 of 22 cases in this series). A poor correlation between the site on the cervix of histologically confirmed colposcopic abnormality and the presence of HPV DNA sequences implies that a cofactor other than HPV is required for preneoplastic disease to develop. A separate study in two further sets of biopsy samples examined the state of HPV DNA alone. The sets were (a) 43 samples from cervical intraepithelial neoplasia and nine external controls and (b) 155 samples from cervical intraepithelial neoplasia, cervical cancer, vulval intraepithelial neoplasia, and vulval cancer and external controls. HPV-11 was found in only two (4.7%) of the 43 specimens from cervical intraepithelial neoplasia, whereas HPV-16 was found in 90 (58%) of the other 155 specimens. These results also suggest that HPV subtype is subject to geographical location rather than being an indicator of severity of the lesion or of prognosis.

Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment.

OBJECTIVE: To quantify and analyse the influence of a histological report of incomplete excision of CIN after LLETZ on frequency of detection of residual CIN. DESIGN: Review of a computerised database of sequential women treated by LLETZ. Initial follow-up was three months post-treatment. SETTING: The Colposcopy Clinic, Regional Department of Gynaecological Oncology, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK. SUBJECTS: 721 women with CIN diagnosed histologically on LLETZ specimens. RESULTS: In spite of a first time treatment success rate of 95% at 3 months, only 56% of the women were reported to have complete histological excision of CIN. A report suggesting incomplete excision was more likely with more severe CIN, extensive lesions and involvement of the endocervical canal. Furthermore, 21% with residual CIN had apparent complete excision of CIN at LLETZ. CONCLUSIONS: A histological report of incomplete excision of CIN at LLETZ does not equate with residual disease. The high treatment success rate of LLETZ means that a report of incomplete excision should stimulate close colposcopic and cytologic follow-up to identify the small number of women with residual CIN after therapy.

The Royal College of Obstetricians and Gynaecologists micro-invasive carcinoma of the cervix study: preliminary results.

OBJECTIVES: To determine how micro-invasive carcinoma of the cervix is diagnosed and treated in the United Kingdom. To record the frequency of the various pathological features which comprise the histological diagnosis of micro-invasion, and to assess their relevance to outcome. DESIGN: Prospective observational study. SETTING: Hospitals throughout the United Kingdom. SUBJECTS: Two hundred and eighty-six cases were submitted for entry into the study. Following independent review of the histological material 116 cases were excluded: 41 were not accompanied by histological slides for review, 55 had no evidence of invasive disease, 17 had invasive disease greater than FIGO Stage 1a, and three were adenocarcinomas. The remaining 170 cases were registered for the study but follow up was incomplete in 18. This report concerns the 152 women with complete follow up to 1991. RESULTS: The age of the 152 women ranged from 22 to 65 years (median 36 years). In 116 women (76%) the diagnosis was made by cone biopsy (cold knife, loop diathermy, or laser) or wedge biopsy, in 9 women (6%) the diagnosis was made by hysterectomy, and in 27 women (18%) punch biopsy suggested an invasive lesion and subsequent excisional treatment (including radical hysterectomy with node dissection in three) demonstrated micro-invasion. The depth of invasion was up to 3 mm in 142 women (93%) and 3.1 to 5 mm in 10 women (7%). Capillary-like space involvement was present in 12 women (8%). Treatment methods used were local cervical surgery in 79 women (52%), simple hysterectomy in 63 (41%), and radical hysterectomy in 10 (7%). There was only one known recurrence and death due to cervical carcinoma. CONCLUSION: There is no uniformity in the management of micro-invasive carcinoma of the cervix. The frequency of recurrence, lymph metastases, and death is low. Nonradical surgery appears to give satisfactory results.

Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: a multicenter study.

BACKGROUND: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue V was injected intradermally shortly before surgery. Routine groin lymph node dissection and radical vulvectomy were performed. During the surgery, blue lymph vessels and lymph nodes were identified, and the blue lymph nodes were sent separately for histologic examination. The negative predictive value of the blue lymph nodes for the absence of metastases was assessed by histologic examination of the groin lymph node specimens. RESULTS: Fifty-one patients in whom 93 groin lymph node dissections were performed were entered. One or more blue lymph nodes were detected in only 52 groins (56%). Nine (17%) of these were tumor positive, and 6 blue lymph nodes were the only tumor positive lymph nodes in the specimen in which they were found. There were two false-negative blue lymph nodes. The negative predictive value was 0.953. CONCLUSIONS: It was shown in this multicenter study that sentinel lymph node detection in vulvar carcinoma patients with blue dye only is not feasible because its negative predictive value is too low. Further studies involving the use of a combination of radioactive labeled technetium and blue dye are warranted.