Biomedical subjects
Publications and source records attributed to O R Koechli.
Pelvic exenterations are the most extensive surgeries performed for patients with gynecologic cancer, and the surgical team and patients have to be fully aware of the many issues that come into the discussion. This article discusses the history, indications, surgical techniques, and complications of pelvic exenteration.
OBJECTIVE: We introduce a new multivariate analysis, not yet applied to gynecologic cancer, that includes the creation of a survival tree. The tree structured survival analysis is a statistical method designed to identify meaningful prognostic subsets in a study population, which usually do not emerge from routine proportional hazards analysis. We also applied the scoring systems from other groups to our patients and compared them with our system using a variety of statistical methods. MATERIAL AND METHODS: After excluding patients with microinvasive and small cell carcinoma, data from remaining 301 patients were analyzed. We performed an univariate and multivariate analysis. Significant single parameters and other variables considered important were chosen for multivariate analysis, including the creation of a survival tree. RESULTS: Risk factors to define prognosis best were: Depth of invasion, lymph vascular space involvement, age of 40 years and lymph node metastases. CONCLUSIONS: The presented model separates patients with early stage invasive carcinoma of the cervix into three subgroups with a significant different survival and correlates well with other models. Our new model is easy to apply and only requires depth of invasion, lymph vascular space involvement, node status and age of a patient to define the individual risk.
BACKGROUND: Dexamethasone-induced changes in radioresistance have previously been observed by several authors. Here, we examined effects of dexamethasone on resistance to ionizing radiation in 10 additional human cell lines and strains, and on resistance to carboplatin and paclitaxel in 13 fresh tumor samples. MATERIAL AND METHODS: Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily chosen for these in-vitro studies. Effects on radiosensitivity were assessed using a conventional colony formation assay. Effects on resistance to the drugs were investigated prospectively (ATP cell viability assay) using 13 fresh tumor samples from consecutive patients operated for ovarian cancer within the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94). RESULTS: Dexamethasone promoted proliferation of 1 of the cell lines without affecting radiosensitivity, while it completely inhibited proliferation of another cell line (effects on radiosensitivity could thus not be examined). Furthermore, dexamethasone induced enhanced radioresistance in 1 of the 8 carcinoma cell lines examined. In the glioblastoma cell line, there was no effect on growth or radioresistance, nor in the fibroblasts. Treatment with dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resistance to paclitaxel was observed. CONCLUSIONS: In agreement with previous reports, we found that dexamethasone may induce radioresistance in human carcinoma cells. Including the published data from the literature, dexamethasone induced enhancement in radioresistance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma cell lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ovarian cancer evaluated prospectively (in 4 of 13 samples; 31%). We worry that induction of resistance by corticosteroids given to patients undergoing either radiotherapy or chemotherapy with agents causing DNA damage might be associated with a reduced clinical responsiveness in a significant fraction of patients with a carcinoma.
OBJECTIVE: To evaluate a new sonographic method to measure depth and width of proximal urethral dilation during coughing and Valsalva maneuver and to report its use in a group of stress-incontinent and continent women. METHODS: Fifty-eight women were evaluated, 30 with and 28 without stress incontinence proven urodynamically, with a bladder volume of 300 mL and the subjects upright. Urethral pressure profiles at rest were performed with a 10 French microtip pressure catheter. Bladder neck dilation and descent were assessed by perineal ultrasound (5 MHz curved linear array transducer) with the help of ultrasound contrast medium (galactose suspension-Echovist-300), whereas abdominal pressure was assessed with an intrarectal balloon catheter. Statistical analysis used the nonparametric Mann-Whitney test. RESULTS: The depth and diameter of urethral dilation could be measured in all women. During Valsalva, all 30 incontinent women exhibited urethral dilation. One incontinent woman showed dilation only while performing a Valsalva maneuver, not during coughing. In the continent group, 12 women presented dilation during Valsalva and six during coughing. In continent women, dilation was visible only in those who were parous. Nulliparous women did not have dilation during Valsalva or coughing. Bladder neck descent was visible in continent and incontinent women. CONCLUSION: This method permits quantification of depth and diameter of bladder neck dilation, showing that both incontinent and continent women might have bladder neck dilation and that urinary continence can be established at different locations along the urethra in different women. Parity seems to be a main prerequisite for a proximal urethral defect with bladder neck dilation.
Photodynamic therapy (PDT) is a promising alternative method for clinical cancer treatment. In the present study, cells from four breast carcinomas, seven ovarian carcinomas of various stages of differentiation, and ascites from a diffuse metastatic tumor were treated by PDT in vitro. Tetra(m-hydroxyphenyl)-chlorin (m-THPC) was used as the photosensitizer. Surviving cell rate was evaluated by the ATP-Cell-Viability-Assay (ATP-CVA), which measures light production as an interaction of intracellular ATP with the luciferin-luciferase complex. The most effective PDT of the tumor cells was achieved at an m-THPC concentration of 0.2 microgram/ml following incubation of the cells with photosensitizer for 24 hours. PDT toxicity resulted in a cell survival rate of 1% to 42% compared to untreated control cells (survival rate of control = 100%). The inhibitor concentration IC50 of m-THPC was determined both in the dark (dark toxicity) and in combination with laser irradiation. IC50 was defined as the concentration of photosensitizer which caused 50% of cell death. The IC50 values were heterogeneous in all tumor specimens examined. IC50 values for dark toxicity were on average 0.14 microgram m-THPC/ml for primary ovarian carcinoma, 2.16 micrograms m-THPC ml for refractory ovarian carcinoma and 0.3 microgram m-THPC/ml for breast carcinoma. After PDT, average IC50 value for refractory ovarian carcinoma was 0.04 microgram m-THPC/ml, for primary ovarian carcinoma 0.05 microgram m-THPC/ml and for breast carcinoma 0.03 microgram m-THPC/ml. These data might indicate that clinical PDT of gynecological carcinoma requires individual treatment conditions to achieve optimal results.
OBJECTIVE: To correlate urodynamic with perineal sonographic findings in pressure variations. PATIENTS AND METHODS: In 15 women presenting with urethral pressure variations a urodynamic evaluation with water filling cystometry, urethral pressure at rest and during coughing and uroflowmetry were performed. During water filling cystometry, there were simultaneous perineal video-sonography and urethrocystometry. Video ultrasound images and urodynamic curves were simultaneously monitored on a computer screen. RESULTS: Simultaneous ultrasound and urodynamic evaluation in the 15 patients revealed movements in two areas leading to urethral pressure variations: activity of the pelvic floor muscles and of the urethral sphincter muscles. For the pelvic floor, we found either slow or fast contractions with, respectively, slow (15-30 cm H2O for 3-10 sec) or fast (30-130 cm H2O for 1-3 sec) urethral pressure changes. Urethral sphincter contractions were always fast, resulting in fast pressure changes of 30-170 cm H2O for 1-3 sec. CONCLUSION: Evaluation of simultaneous perineal sonography and urethrocystometry shows the association of urethral pressure variations and muscle activity. Urethral pressure variations are caused by the activity of urethral sphincter or pelvic floor muscles. With ultrasound the activity of the urethral sphincter muscle can directly be seen whereas pelvic floor muscle activity is indirectly visible. Pelvic floor muscle contractions are either fast or slow, whereas the urethral sphincter muscle contractions are always fast contractions.
BACKGROUND: This study was performed to identify a statistical combination of independent pathologic and clinical features that best predict 5-year disease free survival (DFS) in patients with early stage cervical carcinoma treated by radical hysterectomy. The main goal of the study was to identify subsets of patients based on risk factors with maximal differences in DFS. METHODS: Three hundred and seventy patients were found for whom complete clinical and pathologic material, including cone and cervical biopsies, were available for analysis. Variables studied included age, weight, race, marital status, economic status, tumor size (TS), depth of invasion (DI), lymph-vascular space involvement (LVSI), cell type, tumor grade, lymph node metastasis (LNM), and number of lymph nodes removed. Patients with LNM, parametrial involvement, and positive or close surgical margins were offered postoperative radiation. After excluding patients with microinvasive and small cell carcinoma, data from the remaining 301 patients were submitted to univariate and multivariate analyses to define those variables that best predict DFS. RESULTS: Univariate analysis showed that, ranked by degree of significance, DI, TS, LVSI, LNM, tumor volume (TV) and clinical stage were significant in predicting survival. Significant (P < 0.05) single parameters and other variables considered important were chosen for multivariate analysis, including the creation of a survival tree. With this method, DI (< or = 6 mm and > 2 cm), LVSI, age (> or = 40 yrs), and LNM were found to be the best combination of risk factors to define prognosis. CONCLUSIONS: The multivariate survival tree analysis maximally separates patients with early stage invasive carcinoma of the cervix into 3 subgroups with 5-year DFS of 91%, 68%, and 43%, respectively. The authors excluded patients with microinvasive carcinoma (SGO, Society of Gynecologic Oncologists), who have an excellent DFS of 100%, and patients with small carcinoma, who have a poor DFS of 36.4% based on cell type alone, to define independent risk factors that maximally separate the remaining patients by DSF. The survival tree prognostic scoring system is easy to apply, and only requires DI (mm), LVSI (+, -), LNM, and age to assign an individual patient to one of three risk groups.
OBJECTIVES: To assess the efficacy of ultrasound medium when imaging bladder neck anatomy with perineal ultrasound. METHODS: In 10 female patients with urinary stress or stress-urge incontinence, a new echogenic contrast medium (Echovist) was intravesically administered and perineal ultrasound performed. The examination was done with the women in the upright position both without and with ultrasound contrast medium at rest and during pressing, and the pictures of the bladder base, bladder neck, and urethra were compared. RESULTS: With the patient in the upright position, the ultrasound contrast medium enters the urethra during pressing and bladder neck funneling is identified more accurately than without contrast medium. With Echovist, bladder neck funneling was detected in 9 of the 10 cases but without it in only 4 cases. CONCLUSIONS: The use of ultrasound contrast medium results in a better visualization of the bladder neck anatomy. Bladder neck funneling and urinary leakage are seen more distinctly, and this improves the diagnostic reliability in female urinary stress incontinence. This pilot study supports the necessity for further investigations in the use of ultrasound contrast medium as a diagnostic improvement of perineal ultrasound.
This is a report on the fundamentals of perineal ultrasound examination for female incontinence. The measurement method described here enabled us to determine the position of the bladder neck, the size of the retrovesical angle beta and the occurrence of funnelling. In four different investigations, each involving at least 30 patients, we investigated the influence of examination position, bladder filling volume and pressure of the ultrasound probe against the perineum on these measurements and analyzed the difference between coughing and the Valsalva maneuver. The results showed that when the patient is standing, the bladder neck is lower than when the patient is supine. We also observed that excessive pressure on the ultrasound probe displaces the bladder neck cranially and can squeeze the urethra. Increasing the bladder filling volume does not affect the measurement values, but funnelling can be seen better with higher bladder volumes. The best overall image quality was obtained at 300 ml. A comparison between coughing and the Valsalva maneuver showed that during coughing, the bladder neck descends less and remains closer to the symphysis than with the Valsalva maneuver.
The aim of this study was to evaluate the efficacy of tropisetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, versus placebo in the prevention of postoperative nausea and vomiting in patients undergoing general anesthesia for gynecologic surgery. Ten minutes before induction of general anesthesia, 80 patients received in a double-blind manner a single intravenous (IV) injection of either 5 mg tropisetron or a matching placebo. Anesthesia was induced with thiopental and maintained with nitrous oxide and enflurane in oxygen. In the first 24 h postoperatively 7 of 40 patients (17.5%) given tropisetron and 16 of 40 patients (40%) receiving placebo vomited (P < 0.05). The incidence of nausea was 30% (12/40) in the tropisetron group and 52% (21/40) in the placebo group (P < 0.05). A total effective antiemetic response showed 26 patients (65%) in the tropisetron group and 16 patients (40%) in the placebo group (P < 0.05). We conclude that tropisetron given IV prior to gynecologic procedures in general anesthesia significantly reduces postoperative nausea and vomiting when compared to placebo without causing any adverse effect.
BACKGROUND: This study was performed to identify pathologic and clinical features that best correlate with lymph node metastasis and disease free survival among patients with Stage I and II cervical cancer treated by radical hysterectomy. METHODS: Three hundred-seventy patients with complete clinical information and pathologic material, including cone and cervical biopsies, were selected for analysis. Of these patients, 301 with clinical stages I and II disease were the subject of this paper. The results of patients with microinvasive carcinoma of the cervix, as defined by the Society of Gynecologic Oncologists (depth of invasion < or = 3 mm and no lymph node vascular space invasion), were reported previously and excluded from this analysis. Patients with small cell carcinoma of the cervix were found to have a very poor prognosis (disease free 5-year survival of 36%) and were also excluded from this analysis (Sevin BU, Nadji M, Metkoch MW, Lu Y, Averette HE. Unpublished data, 1995). Variables studied were patient age, weight, race, marital status, and economic status; tumor size; depth of invasion; lymph node-vascular space involvement; cell type; tumor grade; lymph node metastasis; and number of lymph nodes removed. The influence of these variables on survival was examined by univariate analysis with use of Cox's regression model and the log rank test for comparison of survival curves. RESULTS: Factors that predict disease free survival, ranked by degree of significance, were depth of invasion, tumor size, lymph node-vascular space invasion, number of positive nodes, tumor volume, clinical stage, and tumor extension to the vagina or surgical margins. CONCLUSIONS: Radical hysterectomy and bilateral lymphadenectomy is standard therapy for patients with Stage IB and IIA carcinoma of the cervix. A variety of surgically defined risk factors predict 5-year disease free survival, and many of these factors are related. Identification of independent risk factors requires a multivariate analysis of data.
Paclitaxel is an exciting chemotherapeutic agent active in a variety of malignant tumors. This study was designed to explore the radiosensitizing potential of paclitaxel in human cervical cancer cell lines. The cell lines ME180, SiHa, and MS751 were evaluated. Experiments were performed in the proliferative phase of growth. Paclitaxel doses were treated at 0.01x, 0.02x, 0.03x, 0.04x, and 0.05x peak plasma concentration (PPC) in ME180 and 0.001x, 0.002x, 0.003x, 0.004x, and 0.005x PPC in SiHa and MS751. Radiation (RT) doses of cobalt-60 were 0, 2, 4, 6, 8, and 10 Gy. In the combination group RT was given 48 hr after paclitaxel treatment. To allow for median effect analyses, combination doses were kept at a fixed ratio: 0.01x/2 Gy, 0.02x/4 Gy, 0.03x/6 Gy, 0.04x/8 Gy, and 0.05x/10 Gy for ME180 and 0.001x/2 Gy, 0.002x/4 Gy, 0.003x/6 Gy, 0.004x/8 Gy, and 0.005x/10 Gy in MS-751 and SiHa. Adenosine triphosphate bioluminescence was performed on Day 7 after treatment and compared to untreated controls. Dose-response data were fit to the linear quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. The median effect principle was used to evaluate the nature of the interaction between the two therapeutic modalities. Paclitaxel increased radiation cytotoxicity in all three cell lines. Mean inactivation D values for RT versus combination were 6.70 (+/- 0.15) and 4.33 (+/- 0.43) (P = 0.004) in ME180, 6.08 (+/- 0.70) and 4.54 (+/- 0.093) (P = 0.033) in MS751, and 7.03 (+/- 0.46) and 5.97 (+/- 0.51) (P = 0.034) in SiHa. The interaction of paclitaxel and RT was found to be supraadditive in ME180 and SiHa and subadditive in MS751. We conclude that paclitaxel has modest radiation-sensitizing effects in cervical cancer cell lines and that further clinical trials should be considered.
BACKGROUND: Photodynamic therapy (PDT) might be of clinical value for patients with breast cancer with local recurrences or metastasis. However, there is a need for improved photosensitizers that are effective in combination with laser light and have few, if any, side-effects. We evaluated in vitro the effectiveness of a second generation photosensitizer by testing the influence of laser light on cell cultures of a human breast carcinoma cell line, incubated with meta-tetrahydroxyphenylchlorin (m-THPC) (= Temoporfin). EXPERIMENTAL DESIGN: Five thousand MCF-7 cells were plated in 96-well plates. Forty-eight hours before laser treatment, the cells were plated to achieve a monolayer configuration. Twenty-four hours after plating, they were incubated with m-THPC. On day 6 after treatment with m-THPC we lysed the cells to extract the intracellular ATP that correlates with the number of living cells. The ATP-CVA was used to assess the cytotoxicity of the tested photosensitizer m-THPC at various concentrations and the relevant laser light alone prior to their combination after six days of culture. RESULTS: We found a dose-response for m-THPC alone ranging from 2 to 16 micrograms/ml. The calculated inhibition concentration to produce 50% cell kill (IC50) was 4.55 micrograms/ml. We also observed a very low cytotoxicity for laser irradiation alone but a very strong cell kill for the combination of m-THPC together with laser light. CONCLUSIONS: PDT gave almost total cell kill at m-THPC concentrations that are not toxic in vitro.
OBJECTIVE: Our purpose was to determine and compare the total annual costs for reusable and single-use laparoscopic instruments. STUDY DESIGN: Records were kept over a 12-month period of all laparoscopic operations (performed only with reusable instrumentation), the surgical instruments used, depreciation costs, and all associated expenses (repairs, maintenance, replacements, cleaning, sterilization, wages). The total cost was then calculated and compared with the total cost (purchase price plus disposal fees) that single-use instruments would have caused for the same operations. RESULTS: The total cost for single-use instruments would have been more than seven times that for reusable instruments. CONCLUSION: We have decided to continue using reusable instruments for most of our laparoscopic operations. However, single-use instruments are used in situations in which they present a definite advantage. A proper balance is thus sought between the importance of cost factors, on the one hand, and the recognition of the need for the best instrument available for certain procedures, on the other.
OBJECTIVE: To assess the reproducibility of a new method for evaluation of the bladder neck with perineal ultrasound and to compare it with lateral chain urethrocystography. METHODS: In the first phase, two investigators examined 40 patients using perineal ultrasound to assess the reproducibility of a new measurement method for the determination of the bladder neck position. In the second phase, 60 patients were evaluated by perineal ultrasound and lateral chain urethrocystography. RESULTS: With perineal ultrasound, there was good interexaminer agreement for determining bladder neck position, funneling, and bladder neck descent at rest and during the Valsalva maneuver, but not for the posterior angle beta during straining. Comparison of sonographic and x-ray assessments showed good agreement for the bladder neck position at rest, but not during Valsalva, whereas the posterior angle, funneling, and bladder base descent differed between the two techniques at rest as well as during Valsalva. CONCLUSION: With our new method for determining the position of the bladder neck, perineal ultrasound is a reliable technique that allows reproducible static and dynamic evaluation. Lateral chain urethrocystography is superior to perineal ultrasound only if bladder neck funneling is the aim of the evaluation; it is inferior if bladder neck mobility during maximal Valsalva is being investigated.
OBJECTIVE: To assess the efficacy of ultrasound contrast medium when imaging bladder neck anatomy in perineal ultrasound. METHODS: In 39 women with clinically and urodynamically proven urinary stress or stress-urge incontinence, a new echogenic contrast medium (Echovist) was administered transurethrally and perineal ultrasound was performed. Women were examined in the upright position both without and with ultrasound contrast medium at rest and during Valsalva maneuver, and the pictures of the bladder base, bladder neck, and urethra were compared. RESULTS: With the subject in the upright position, the contrast medium lay at the lowest point of the bladder and resulted in a reverse picture of the bladder base and bladder neck and clear visualization of these structures. In women with urinary stress incontinence, the ultrasound contrast medium entered the urethra during Valsalva, and bladder neck funneling was identified more accurately than without contrast medium. With Echovist, bladder neck funneling was detected in 38 of the 39 cases, compared with only 19 when it was not used. Furthermore, when the bladder neck, urethra, or bladder base were not visible with plain perineal ultrasound, they were seen when ultrasound contrast medium was used. The contrast agent was well tolerated, and there were no adverse side effects. CONCLUSION: The use of ultrasound contrast medium improves visualization of the bladder neck anatomy. Bladder neck funneling and urinary leakage are seen more distinctly, and this improves the diagnostic reliability in female urinary stress incontinence.
This is the first report on the ATP cell viability assay as a chemosensitivity test system for gestational trophoblastic neoplasms (GTN). We obtained chemosensitivity profiles in two established trophoblastic cell lines and four fresh tumors. Ten drugs were tested in vitro in the two cell lines JAR and JEG-3. The IC50 values of the 10 chemotherapeutic agents tested were very similar for both cell lines. The three most active drugs in these cell lines were VP-16, paclitaxel and vincristine. This is the first report on the activity of paclitaxel in trophoblastic cell lines. We furthermore evaluated this assay for chemosensitivity testing in four fresh malignant GTN tumors: one placental site trophoblastic tumor, one chorocarcinoma and two invasive moles. The placental site trophoblastic tumor specimen revealed to be rather chemoresistant in vitro whereas the other three tumors were chemosensitive. From our cell line data we conclude that the ATP cell viability assay is a practicable assay for chemosensitivity testing of GTN cell lines and gives repeatable results. However, the value of this assay for fresh GTN chemosensitivity testing needs to be defined.
BACKGROUND: This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. METHODS: Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. RESULTS: The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. CONCLUSIONS: Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations.