Clinical impact of FDG PET-CT on the management of patients with locally advanced cervical carcinoma.

AIM: To evaluate the impact of staging FDG PET-CT on the initial management of patients with locally advanced cervical carcinoma (LACC) and any prognostic variables predicting survival. MATERIALS AND METHODS: Retrospective analysis of consecutive patients undergoing FDG PET-CT for staging of LACC in a single tertiary referral centre, between April 2008 and August 2011. Comparison was made between MRI and PET-CT findings and any subsequent impact on treatment intent or radiotherapy planning was evaluated. RESULTS: Sixty-three patients underwent FDG PET-CT for initial staging of LACC. Major impact on management was found in 20 patients (32%), a minor impact in five (8%), and no impact in 38 (60%). In those patients where PET-CT had a major impact, 12 had more extensive local nodal involvement, five had occult metastatic disease, two had synchronous tumours, and one patient had equivocal lymph nodes on MRI characterized as negative. PET-positive nodal status at diagnosis was found to be a statistically significant predictor of relapse-free survival (p < 0.05). CONCLUSION: Staging FDG PET-CT has a major impact on the initial management of approximately one-third of patients with LACC by altering treatment intent and/or radiotherapy planning. PET-defined nodal status is a poor prognostic indicator.

Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy.

The distribution of fibrosis and cellular hypertrophy was studied in the hearts of patients with dilated cardiomyopathy (DC). Transmural sections were removed from the left and right ventricular free walls and the ventricular septum of 9 patients with heart failure and 6 control subjects. These sections were stained with hematoxylin-eosin (to determine cell size) and trichrome (to determine percent fibrosis). The sections were separated into equal areas from epicardium to endocardium in the free walls and right to left across the septum. Percent fibrosis was greater in patients with DC (20 +/- 4%) than control subjects (4 +/- 1%, p = 0.0001). A pattern of increasing fibrosis in the left ventricular free wall from epicardium (14 +/- 6%) to endocardium (22 +/- 9%, p less than 0.05) was documented. Fibrosis was greater on the left (21 +/- 12%) than the right (15 +/- 6%, p less than 0.05) side of the septum. No pattern was evident in the right ventricular free wall or in the control group. Myocardial cell diameter was greater in the heart failure group (22 +/- 5 micron) than the control group (17 +/- 2 micron, p less than 0.05), but no pattern of hypertrophy across the walls was seen. The increased fibrosis, the pattern of fibrosis and the increased cell diameter in patients with DC help to characterize DC.

The reliability of performing a screening cystometrogram using a fetal monitoring device for the detection of detrusor instability.

OBJECTIVE: To determine if a cystometrogram performed using the intrauterine pressure channel of a fetal monitor can be used to screen for detrusor instability in women undergoing evaluation for urinary incontinence. METHODS: Sixty-six women with primary complaints of urinary incontinence were randomized to have a cystometrogram performed at their initial visit with a multichannel electronic cystometer or with the intrauterine pressure channel of a fetal monitor. Subjects underwent a second cystometrogram 1-4 weeks later with the alternative technique. The results were analyzed with chi 2 analysis and correlation coefficients. RESULTS: Twenty-two subjects had detrusor instability diagnosed by the multichannel electronic cystometer. The fetal monitor cystometrogram was 91% sensitive and 86% specific in detecting detrusor instability, and had a 77% positive predictive value and a 95% negative predictive value. The correlation coefficients between the two examinations for bladder volume at first sensation, maximum capacity, volume at first contraction, and intensity of uninhibited detrusor contraction were r = 0.51, r = 0.69, r = 0.87, and r = 0.79, respectively; all of these were statistically significant. CONCLUSION: The intrauterine pressure channel of a fetal monitor can be used reliably to perform a cystometrogram to screen for detrusor instability in patients presenting with complaints of urinary incontinence.

A comparison of stress leak-point pressure and maximal urethral closure pressure in patients with genuine stress incontinence.

OBJECTIVE: To determine the correlation between the maximal urethral closure pressure and the stress leak-point pressure in patients with genuine stress incontinence, and to define a critical stress leak-point pressure value to detect patients with a low-pressure urethra, as defined by a maximal urethral closure pressure less than 20 cm H2O. METHODS: Fifty-nine patients with genuine stress incontinence were evaluated prospectively with multichannel urodynamics. Maximal urethral closure pressures and stress leak-point pressures were determined and correlated. Several stress leak-point pressure values were evaluated by contingency tables to detect a critical level for detecting a low-pressure urethra. RESULTS: There is a statistically significant relationship (P < .0001) between the stress leak-point pressure and the maximal urethral closure pressure. However, a correlation coefficient of 0.56 demonstrates poor clinical relationship. A stress leak-point pressure less than or equal to 45 cm H2O was found to be 80% sensitive and 90% specific in diagnosing a low-pressure urethra. A stress leak-point pressure less than or equal to 60 cm H2O was 90% sensitive and 64% specific in detecting a low-pressure urethra. CONCLUSIONS: The stress leak-point pressure has poor clinical correlation to the maximal urethral closure pressure. A stress leak-point pressure less than or equal to 45 cm H2O has adequate sensitivity and specificity to diagnose a low-pressure urethra. A value less than or equal to 60 cm H2O would be an appropriate cutoff level to screen for those patients at risk of having a low-pressure urethra in need of further evaluation.

Evaluation of current urodynamic testing methods in the diagnosis of genuine stress incontinence.

OBJECTIVE: To determine the sensitivity and specificity of several urodynamic testing methods in the diagnosis of genuine stress urinary incontinence (GSI). METHODS: One hundred eight consecutive patients were evaluated prospectively by history and physical examination, cough stress test, and single and multichannel urodynamics. Sensitivities and specificities in detecting genuine stress incontinence were calculated for: a positive cough stress test with a negative cystometrogram, equalization throughout a cough urethral pressure profile, a positive stress leak-point pressure determination, observed urine loss with cough during multichannel urodynamics, and a pressure transmission ratio of less than 90% for each third of the urethra. RESULTS: Sixty-five patients (60%) were found to have GSI. Observed urine loss with cough during multichannel studies was 91% sensitive and 100% specific. A positive stress leak-point pressure determination had a 78% sensitivity and was 100% specific. A positive cough stress test with a negative cystometrogram was 77% sensitive and 100% specific. Pressure equalization throughout the length of the urethra during a cough urethral pressure profile was 49% sensitive and 98% specific. A pressure transmission ratio of less than 90% in the distal, middle, and proximal urethra had sensitivities and specificities of 54 and 79%, 51 and 65%, and 45 and 58%, respectively. A pressure transmission ratio of less than 90% along the entire length of the urethra was 22% sensitive and 93% specific. CONCLUSION: Observed urine loss with cough during multichannel urodynamics was the best examination for diagnosing GSI in our population.

Comparison of pelvic organ prolapse in the dorsal lithotomy compared with the standing position.

OBJECTIVE: To determine if there is a significant difference in the degree of pelvic organ prolapse assigned during examination in the standing position compared with the dorsal lithotomy position with the patient performing maximal Valsalva maneuver. METHODS: Fifty-one women with symptoms of pelvic organ prolapse were examined in both the dorsal lithotomy position, while performing maximal Valsalva, and in the standing position at the same visit by one of two examiners. Nine site-specific measures and summary stages were recorded, as outlined by the International Continence Society's classification system for pelvic organ prolapse. The data were analyzed by Wilcoxon signed-rank test and correlation coefficients. RESULTS: The mean age was 52 +/- 15 years. Excellent correlation was noted between all six points representing the vaginal prolapse. The R values for point Aa were 0.97, Ba 0.96, C 0.98, Ap 0.97, Bp 0.96, and D 0.97. The total vaginal length, perineal body, and genital hiatus measurements were performed in the dorsal lithotomy position with the patient at rest and were not repeated. The stages were identical in 48 of 51 patients. The average stage in the dorsal lithotomy position was 2.3 and in the standing position, 2.3. There was no statistically significant difference between the stage or any of the measured points in the dorsal lithotomy and standing examinations. CONCLUSION: The degree of pelvic organ prolapse can be assessed adequately in the dorsal lithotomy position with the patient performing maximal Valsalva. It is not necessary to routinely repeat the examination in the standing position.

Test-retest reliability of the cough stress test in the evaluation of urinary incontinence.

OBJECTIVE: To determine the test-retest reliability of the cough stress test in women who present with complaints of urinary incontinence. METHODS: This prospective observational study involved 50 women between the ages of 28 and 78 years with primary complaints of urinary incontinence. All subjects underwent a pelvic examination, cystometrogram, and a cough stress test. The cough stress test was performed in the standing position at a bladder volume of 300 mL or at maximum cystometric capacity if it was less than 300 mL. The results of the cough stress test were recorded as positive if urine loss occurred with a cough or as negative if no urine loss was seen and the bladder volume was recorded. The women returned in 1-4 weeks for a second cough stress test performed at the same bladder volume as at the initial examination. RESULTS: Of the 50 women studied, 45 (90%) had similar results with both cough stress tests. Thirty-five had a positive cough stress test on the initial examination, and 32 of these patients (91%) also had a positive cough stress test at a repeat visit. Fifteen patients had a negative initial cough stress test, and 13 of these 15 (87%) had a negative cough stress test on repeat examination. All 20 patients diagnosed as having pure genuine stress incontinence had a positive cough stress test on initial and repeat examinations. Of the 15 patients diagnosed with detrusor instability or sensory urge incontinence, 13 (86%) had negative cough stress tests on initial and repeat examinations. Of the 15 patients diagnosed with mixed incontinence, 12 (80%) had positive cough stress tests on initial and repeat examinations. CONCLUSION: The cough stress test appears to be a reliable test. The reliability is more consistent in women with a diagnosis of pure genuine stress incontinence.

Stable, stoichiometric delivery of diverse protein functions.

As contemporary "genomics" steadily reveals an increasing number of novel gene sequences, the need for efficient methodologies to functionally characterize these genes in vivo increases significantly. Reliable coupling of target gene expression to a variety of surrogate reporter functions is critical to properly assay novel gene function in complex cell populations. Ideally, independent target and reporter proteins would be derived from a single open reading frame creating a stoichiometric relationship without obscuring subcellular localization. We report here effective strategies for assaying gene function through the stable production of chimeric polyproteins, processed intracellularly by inclusion of an intervening 19-amino-acid sequence from the 2A region of the Foot and Mouth Disease virus. Using drug-resistance and flow cytometry-based assay systems, we demonstrate that diverse protein functions are effectively delivered to various cell types by retroviral constructs as single 2A-cleaved polyproteins. For example, cells infected with a retrovirus encoding a nuclear cell cycle regulator, linked via the 2A-motif to a marker membrane protein, showed a direct correlation between cell cycle arrest and surface marker level. This demonstrates the utility of this methodology for stable and stoichiometric delivery of distinctly localized protein functionalities. In particular, the ability to exploit multiple cellular functions will serve to accelerate the functional characterization of gene products and facilitate novel gene therapy approaches.

The clinical evaluation of pelvic floor dysfunction.

Although Baden concluded that "the pelvic exam is just the pelvic exam," the history and examination are tools of no less merit than the cystometrogram or scalpel for clinicians treating patients with symptomatic pelvic floor dysfunction. An effective history and physical examination provide the basis for effective management of the patient's symptoms.

MR staging of endometrial carcinoma.

Endometrial cancer is the second most common gynaecological malignancy. The usual presentation with post-menopausal bleeding results in an early diagnosis in most cases and thus there is opportunity for cure. Magnetic resonance (MR) imaging is pivotal in the decision-making process regarding treatment options. We present a review of the magnetic resonance (MR) findings to illustrate its role in the staging of endometrial cancer.

The distribution of pelvic organ support in a population of female subjects seen for routine gynecologic health care.

OBJECTIVE: This study was undertaken to describe the distribution of pelvic organ support stages in a population of women seen at outpatient gynecology clinics for routine gynecologic health care. STUDY DESIGN: This was an observational study. Women seen for routine gynecologic health care at four outpatient gynecology clinics were recruited to participate. After informed consent was obtained general biographic data were collected regarding obstetric history, medical history, and surgical history. Women then underwent a pelvic examination. Pelvic organ support was measured and described according to the pelvic organ prolapse quantification system. Stages of support were evaluated by variable for trends with Pearson chi(2) statistics. RESULTS: A total of 497 women were examined. The average age was 44 years, with a range of 18 to 82 years. The overall distribution of pelvic organ prolapse quantification system stages was as follows: stage 0, 6.4%; stage 1, 43.3%; stage 2, 47.7%; and stage 3, 2.6%. No subjects examined had pelvic organ prolapse quantification system stage 4 prolapse. Variables with a statistically significant trend toward increased pelvic organ prolapse quantification system stage were advancing age, increasing gravidity and parity, increasing number of vaginal births, delivery of a macrosomic infant, history of hysterectomy or pelvic organ prolapse operations, postmenopausal status, and hypertension. CONCLUSION: The distribution of the pelvic organ prolapse quantification system stages in the population revealed a bell-shaped curve, with most subjects having stage 1 or 2 support. Few subjects had either stage 0 (excellent support) or stage 3 (moderate to severe pelvic support defects) results. There was a statistically significant trend toward increased pelvic organ prolapse quantification system stage of support among women with many of the historically quoted etiologic factors for the development of pelvic organ prolapse.

The need for standardization of the valsalva leak-point pressure.

The Valsalva leak-point pressure is a new test being advocated for evaluation of urethral sphincter function. However, there is currently no standardized technique for performing the test, and therefore it is difficult to draw conclusions regarding its ability to define the degree of function or dysfunction of the urethral sphincter mechanism. This article reviews the current literature regarding the parameters and techniques for performing the Valsalva leak-point pressure test. Based on what is known, recommendations for testing parameters and conditions under which the test should be performed are provided. This test may play a role in the evaluation of the urethral sphincter and give prognostic information regarding surgical outcomes, but first the technique for performing the test should be standardized and agreed upon. Until this is done no general conclusions can be drawn regarding the usefulness of this test in the evaluation of the incontinent woman.

Gallstone ileus: CT findings.

We describe the CT findings of four consecutive cases of surgically proven gallstone ileus and discuss the pathophysiology of gallstone ileus and the impact of CT on diagnosis of the condition.

Intrasubject variability of the pressure-transmission ratio in patients with genuine stress incontinence.

The aim of the study was to determine the intrasubject variability of the pressure-transmission ratio (PTR) with various cough intensities in subjects with genuine stress incontinence. Thirty-six patients with genuine stress incontinence underwent multichannel urodynamics and had a series of pressure-transmission ratios (PTRs) determined with the urethral transducer placed at the point of the maximal closure pressure. Patients were asked to cough with increasing intensities and three to four different cough-induced PTRs were recorded for each subject. The data were analysed using regression analysis, repeated measures analysis of variance and comparison of variance. The PTRs showed a high degree of variability within subjects. The mean within subject standard deviation was 18.5%. The effect of parity, maximal urethral closure pressure and age were insignificant on the variability. Cough intensities of greater than 90 cmH2O have a lesser degree of variability. The mean PTR across all cough intensities was fairly constant in the 82%-87% range. It was concluded that the PTR in an individual has a high degree of variability independent of cough intensity, and cannot be relied upon as a diagnostic measure in subjects with genuine stress incontinence. However, the PTR for the population as a whole was consistent across all cough intensities.

Case-control study of etiologic factors in the development of severe pelvic organ prolapse.

The aim of this case-control study was to identify etiologic factors predictive for the development of severe pelvic organ prolapse. Three hundred and sixty-eight controls from a database describing pelvic organ support in the general population were identified as having known good pelvic organ support. Eighty-seven cases were identified from a urogynecology clinic with severe pelvic organ prolapse. The risk of severe prolapse was modeled using stepwise multiple logistic regression analysis. Additional analyses using chi2 and two-sample t-tests were conducted to determine differences in means for individual variables. Variables examined included age, gravidity, parity, number of vaginal deliveries, weight of largest infant delivered vaginally, menopause status, race, body mass index prior to pelvic surgery, and medical illnesses. The following four variables were selected in the regression analysis as predicting severe prolapse: age, weight of largest vaginal delivery, hysterectomy and previous prolapse surgery. Other variables that demonstrated statistically significant differences between groups by chi2 and two-sample t-tests were gravidity, parity, number of vaginal deliveries, menopausal status, race, history of incontinence surgery and the presence of hypertension. Variables that did not demonstrate any significant differences were body mass index, the presence of chronic obstructive pulmonous disease and diabetes mellitus. Advancing age, increasing weight of infants delivered vaginally, a history of hysterectomy and a history of previous prolapse surgery were found to be the strongest etiologic predictors of severe pelvic organ prolapse in our population.

Hepatic Doppler perfusion index: measurement in nine healthy volunteers.

Nine healthy volunteers were studied to validate the reproducibility of the Doppler perfusion index--the ratio of hepatic arterial to total liver blood flow--and to evaluate the method of its derivation and the influence of the variable parameters necessary for its calculation. Wide intraobserver variability was observed, and Doppler perfusion index values were consistently outside the previously reported normal range.

Oncogene expression in murine splenic T cells and in murine T-cell neoplasms.

The differential expression of a series of proto-oncogenes has been examined in a group of cultured murine T-cell lymphomas that were induced following virus inoculation into, or X irradiation of, C57BL/6 mice. Two classes of T lymphoma cell lines were studied: growth factor-dependent (autocrine) cells, and growth factor-independent T lymphoma cells. Cell lines that were established from X-irradiation-induced T lymphomas were growth factor dependent, whereas T lymphoma lines grown from virus-induced tumors were generally growth factor independent. Of 18 cellular proto-oncogenes studied, five (c-myc, c-myb, c-abl, c-rasHa, c-rasKi) were consistently expressed in all cell lines tested. Thirteen other proto-oncogenes (c-mos, c-sis, c-rel, c-yes, c-fes3, c-fes4, c-fos, c-fms, c-src, c-erbA, c-erbB, int-1, Pim-1) were not expressed in any of the T lymphoma cells tested. Concanavalin A-stimulated spleen cells, representative of replicating T cells, expressed c-myc, c-abl, and Pim-1, suggesting that the products of these proto-oncogenes are involved in T-cell proliferation. The results indicate no qualitative differences (albeit some quantitative differences) in proto-oncogene expression between the growth factor-dependent and growth factor-independent cells. This suggests that expression of the five proto-oncogenes is in itself not sufficient to induce the progression of the growth factor-dependent cells to their fully growth factor-independent counterparts. Changes in the regulation of one or more of the five active proto-oncogenes, i.e., from an inducible to a constitutive state, and/or additional changes in the expression of other cellular genes may be required to induce the transformation of neoplastic T cells from growth factor dependence to growth factor independence.

Peritoneal carcinomatosis: image-guided peritoneal core biopsy for tumor type and patient care.

PURPOSE: To assess image-guided peritoneal core biopsy for the diagnosis of tumor type and treatment of patients with peritoneal carcinomatosis. MATERIALS AND METHODS: Thirty-five women (age range, 47-85 years; mean age, 69 years) prospectively identified in a gynecologic oncology center underwent 18-gauge core biopsy in omental cake (n = 25), peritoneal (n = 7), or adnexal (n = 3) sites. No complications of biopsy occurred. Standard hematoxylin-eosin analysis of the biopsy cores was supplemented by immunohistochemical markers to CA-125, carcinoembryonic antigen, cytokeratin 7, and cytokeratin 20. Diagnoses were validated with further multidisciplinary review, subsequent surgery, and response to specific chemotherapy. RESULTS: In 27 (77%) of the 35 women, a confident primary site diagnosis was obtained with standard hematoxylin-eosin analysis of core biopsy material from the following sites: ovary (n = 22), breast (n = 2), colon (n = 2), and lymphoma (n = 1). The finding at hematoxylin-eosin analysis in another seven (20%) women was poorly differentiated adenocarcinoma with no definite primary site but with an immunohistochemical profile suggesting ovarian cancer (CA-125 positive, carcinoembryonic antigen negative, cytokeratin 7 positive, cytokeratin 20 negative). There was one false-negative biopsy result. CONCLUSION: Image-guided peritoneal core biopsy with hematoxylin-eosin analysis supplemented with immunohistochemical analysis is a simple, safe, and accurate technique for providing site-specific diagnoses in women with undiagnosed peritoneal carcinomatosis.

Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: a multicenter, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine the efficacy of transvaginal electrical stimulation in treating genuine stress incontinence. STUDY DESIGN: This was a multicenter, prospective, randomized, double-blind, placebo-controlled 15-week trial comparing the use of an active pelvic floor stimulator with a sham device. Thirty-five women used an active unit and 17 control subjects used sham devices. Weekly and daily voiding diaries were recorded throughout the trial. Urodynamic testing, including pad test and subtracted cystometry, was done before and at the end of device use. Pelvic muscle strength was measured at baseline and at the end of the trial. Patients scored their symptoms on visual analog scales and completed quality-of-life questionnaires before and after therapy. RESULTS: Significant improvements from baseline were found in patients using active devices but not in controls. Comparisons of changes from baseline between active-device and control patients showed that active-device patients had significantly greater improvement in weekly (p = 0.009) and daily (p = 0.04) leakage episodes, pad testing (p = 0.005), and vaginal muscle strength (p = 0.02) when compared with control subjects. Significantly greater improvement was also found for both visual analog scores of urinary incontinence (p = 0.007) and stress incontinence (p = 0.02), as well as for subjective reporting of frequency of urine loss (p = 0.002), and urine loss with sneezing, coughing, or laughing (p = 0.02), when compared with controls. Pad testing showed that stress incontinence was improved by at least 50% in 62% of patients using an active device compared with only 19% of patients using sham devices (p = 0.01). Voiding diaries showed at least 50% improvement in 48% of active-device patients compared with 13% of women using the sham device (p = 0.02). No irreversible adverse effects were noted in either group. CONCLUSIONS: Transvaginal pelvic floor electrical stimulation was found to be a safe and effective therapy for genuine stress incontinence.

Interobserver and intraobserver reliability of the proposed International Continence Society, Society of Gynecologic Surgeons, and American Urogynecologic Society pelvic organ prolapse classification system.

OBJECTIVE: Our purpose was to determine the intraobserver and interobserver reliability of site-specific measurements and stages with the proposed international Continence Society, Society of Gynecologic Surgeons, and American Urogynecologic Society 1994 draft prolapse terminology document. STUDY DESIGN: Women who completed informed consent procedures underwent pelvic examinations by two investigators, each blinded to the results of the other's examination. The reproducibility of the nine site-specific measurements and the summary stage and substage were analyzed with Spearman's correlation coefficient (rs) and Kendel tau B Correlation Coefficient (tau b), respectively. Similar analyses were performed on supine and upright examinations performed at two different times by one examiner. RESULTS: Experienced examiners averaged 2.05 minutes per examination and new examiners averaged 3.73 minutes. In the study of interobserver reliability, 48, subjects, mean age 61 +/- 14 years, parity 3 +/- 2, weight 74 +/- 31 kg, comprised the study population. Correlations for each of the nine measurements were substantial and highly significant (rs 0.817, 0.895, 0.522, 0.767, 0.746, 0.747, 0.913, 0.514, and 0.488, p = 0.0008 to < 0.0001). Staging and substaging were highly reproducible (tau b 0.702 and 0.652). In no subject did the stage vary by more than one; in 69% stages were identical. In the study of intraobserver reliability, for 25 subjects correlations for each of the nine measurements were equally strong (rs 0.780, 0.934, 0.765, 0.759, 0.859, 0.826, 0.812, 0.659, 0.431). Measurements from the upright examinations reflected greater prolapse. Staging and substaging were highly reproducible (tau b 0.712 and 0.712). In no subject did the stage vary by more than one; in 64% stages were identical. All stage discrepancies represented an increase in the upright position. CONCLUSIONS: There is good reproducibility of measures with the proposed system. The data suggest that the reliability is independent of examiner experience. Patient position is likely important in maximizing the severity of the prolapse.