Ossi R. Koechli

Morbidity of Sentinel Lymph Node Biopsy (SLN) Alone Versus SLN and Completion Axillary Lymph Node Dissection After Breast Cancer Surgery A Prospective Swiss Multicenter Study on 659 Patients

Objective:To assess the morbidity after sentinel lymph node (SLN) biopsy compared with SLN and completion level I and II axillary lymph node dissection (ALND) in a prospective multicenter study. Summary Background Data:ALND after breast cancer surgery is associated with considerable morbidity. We hypothesized: 1) that the morbidity in patients undergoing SLN biopsy only is significantly lower compared with those after SLN and completion ALND level I and II; and 2) that SLN biopsy can be performed with similar intermediate term morbidity in academic and nonacademic centers. Methods:Patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) were included between January 2000 and December 2003 in this prospective Swiss multicenter study. All patients underwent SLN biopsy. In all patients with SLN macrometastases and most patients with SLN micrometastases (43 of 68) or isolated tumor cells (11 of 19), a completion ALND was performed. Postoperative morbidity was assessed based on a standardized protocol. Results:SLN biopsy alone was performed in 449 patients, whereas 210 patients underwent SLN and completion ALND. The median follow-ups were 31.0 and 29.5 months for the SLN and SLN and completion ALND groups, respectively. Intermediate-term follow-up information was available from 635 of 659 patients (96.4%) of enrolled patients. The following results were found in the SLN versus SLN and completion ALND group: presence of lymphedema (3.5% vs. 19.1%, P < 0.0001), impaired shoulder range of motion (3.5% vs. 11.3%, P < 0.0001), shoulder/arm pain (8.1% vs. 21.1%, P < 0.0001), and numbness (10.9% vs. 37.7%, P < 0.0001). No significant differences regarding postoperative morbidity after SLN biopsy were noticed between academic and nonacademic hospitals (P = 0.921). Conclusions:The morbidity after SLN biopsy alone is not negligible but significantly lower compared with level I and II ALND. SLN biopsy can be performed with similar short- and intermediate-term morbidity in academic and nonacademic centers.

Perineal ultrasound for evaluating the bladder neck in urinary stress incontinence

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 β during straining. Comparisons 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 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.

Sonographic evaluation of the bladder neck in continent and stress-incontinent women☆

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.

Single-use versus reusable laparoscopic surgical instruments : a comparative cost analysis

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.

Improvement of perineal sonographic bladder neck imaging with ultrasound contrast medium

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.

Comparison of paclitaxel and docetaxel (Taxotere) in gynecologic and breast cancer cell lines with the ATP–cell viability assay

The in vitro effects of paclitaxel (Tx) and docetaxel (Taxotere, Txt) are compared in this study using the adenosine triphosphate cell viability assay (ATP-CVA) in 14 cancer cell lines. Eleven cell lines were sensitive and three were partially sensitive to paclitaxel. Nine cell lines were sensitive, three were partially sensitive and two were resistant to docetaxel. Mean IC50s were 3.7-660 ng/ml paclitaxel and 5.4-540 ng/ml docetaxel. In five sensitive cancer cell lines docetaxel was more active than paclitaxel, and in six sensitive cell lines paclitaxel was more active than docetaxel on a concentration basis. Two cell lines were sensitive to paclitaxel and resistant to docetaxel. In one cell line the two compounds had similar activities. In the ATP-CVA, paclitaxel and docetaxel are very active and are partially non-cross-resistant.

Dexamethasone-induced enhancement of resistance to ionizing radiation and chemotherapeutic agents in human tumor cells

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 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.Hintergrund: In der Literatur gibt es verschiedene Berichte über eine dexamethasoninduzierte Erhöhung der Strahlenresistenz. Wir untersuchten deshalb weitere menschliche Tumorzellinien und Fibroblasten auf induzierbare Veränderungen der Wachstumsfähigkeit und der Strahlenempfindlichkeit. Außerdem prüften wir die Wirkung von Dexamethason auf die Sensibilität von Ovarialkarzinomproben gegenüber Carboplatin und Paclitaxel. Material und Methode: Wir untersuchten acht Karzinomzellinien, eine Glioblastomzellinie sowie Hautfibroblasten in Kultur. Die Wirkung auf die Wachstumsfähigkeit der Zellen und auf die Strahlenwirkung wurde unter Verwendung des üblichen Koloniebildungstests bestimmt. Die Wirkung von Dexamethason auf die Effekte der Chemotherapeutika Carboplatin und Paclitaxel wurde an Proben von 13 konsekutiven Ovarialkarzinomen im Rahmen einer klinischen Studie (SAKK 45/94) prospektiv untersucht (ATP cell viability assay). Ergebnisse: Dexamethason stimulierte das Wachstum einer Karzinomzellinie, ohne die Strahlenresistenz zu beeinflussen. Außerdem wurde das Wachstum einer anderen Zellinie vollständig gehemmt, so daß die Wirkung auf die Strahlenempfindlichkeit nicht untersucht werden konnte. Dexamethason bewirkte in einer der übrigen Karzinomzellinien eine erhöhte Resistenz gegenüber Bestrahlung. Wachstumsfähigkeit und Strahlenempfindlichkeit von Glioblastomzellen und Fibroblasten wurden nicht beeinflußt. Außerdem induzierte Dexamethason eine erhöhte Resistenz gegenüber Carboplatin in vier der 13 Ovarialkarzinomproben. Eine erhöhte Resistenz gegenüber Paclitaxel wurde hingegen nicht beobachtet. Schlußfolgerungen: Diese Ergebnisse bestätigen frühere Berichte über dexamethasoninduzierte Resistenz gegenüber Bestrahlung. Einschließlich der in der Literatur publizierten Daten findet sich eine dexamethasoninduzierte Erhöhung der Resistenz in vier von zwölf evaluierbaren Karzinomzellinien (33%), nicht jedoch in den drei Glioblastomzellinien oder in Fibroblasten. Dexamethason erzeugte ähnlich häfuig, nämlich in vier von 13 Proben (31%), eine erhöhte Resistenz gegenüber Carboplatin. Dexamethasongabe könnte sich deshalb negativ auswirken.

Usefulness of ultrasound contrast medium in perineal sonography for visualization of bladder neck funneling—first observations

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.

Characteristics of the combination paclitaxel plus doxorubicin in breast cancer cell lines analyzed with the ATP-Cell Viability Assay

SummaryPreliminary clinical data show promising activity regarding the combination of paclitaxel (TaxolTM) (TAX) and doxorubicin (AdriamycinTM) (ADR) in the treatment of breast cancer. This combination needs both further preclinical and clinical investigations to better understand the drug interaction, and to optimize the dose and schedule of these drugs. This study was done to evaluate the combination effect of TAX and ADR in three human breast cancer cell lines. The ATP-Cell-Viability Assay was used to evaluate the chemosensitivity profiles and to obtain dose response curves. For quantitation of synergism and antagonism the median-effect principle was applied and the corresponding combination index values were calculated. Drug synergism/antagonism was shown to be dose-related; synergism was enhanced at higher fractions affected. From this preclinical data, we have concluded that TAX-ADR is highly effective and partly synergisticin vitro. In spite of severe initial toxicities in early clinical trials in metastatic breast cancer patients, further clinical studies appear to be justified in order to define a tolerable dosage.

Assessment of effect of photosensitizers on cytotoxicity of photodynamic therapy in human breast cancer cell cultures

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-tetrahydroxy-phenylchlorin (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 μg/ml. The calculated inhibition concentration to produce 50% cell kill (IC50) was 4.55 μg/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.