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Biomedical subjects

H Koelbl

Publications and source records attributed to H Koelbl.

At least 19 recordsLinked to original sources

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer.

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.

Antineoplastic Agents, Phytogenic↗

Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer.

OBJECTIVE: Docetaxel and carboplatin are active in relapsed ovarian, peritoneal and tubal cancer. Recently, two prospective-randomized trials showed an advantage of carboplatin combination regimen with paclitaxel or gemcitabine over carboplatinum alone in platinum-sensitive cases. The question on the most effective combination with the best tolerable side effects still needs to be answered. METHODS: Eligible patients had recurrent ovarian, peritoneal or tubal cancer (platinum-free interval >6 months), performance status 0-2 and normal bone marrow, renal and hepatic function. 25 patients (age 18-75 years) were enrolled into this phase II trial. Patients with debulking operation of recurrence were excluded from this study. Docetaxel 75 mg/m(2) via 30-min infusion was given on day 1 followed by carboplatin (area under curve [AUC] 5) on day 1. The administration was repeated every 3 weeks over 6 courses. Primary endpoint of this trial was the response rate; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In the intent-to-treat population, there were 16 (64.0%) complete and 2 (8.0%) partial responses resulting in an overall response rate of 72.0%. Three patients (12.0%) showed a stable disease and other 2 patients (8.0%) a progression of cancer. Two patients (8.0%) were not evaluable for response. Neutropenia was the most frequent G3/G4 hematologic toxicity in 15/25 patients (60.0%); but no neutropenic fever occurred in this trial. Diarrhea G3 was the most frequent G3/G4 non-hematologic toxicity in only 3/25 patients (12.0%). Dose-limiting toxicities were hypersensitivity reaction in one and depressive mood alteration requiring therapy in another case. CONCLUSION: Carboplatin in combination with docetaxel is highly active and well tolerated in patients with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Prospective-randomized trials comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer are a possible option for the future to answer the question on the best combination regimen.

Adult↗

Influence of diabetes mellitus and nodal distribution in endometrial cancer and correlation to clinico-pathological prognostic factors.

OBJECTIVE: The aim of this study was to describe the relationships between the distribution of nodal disease, clinico-pathological patterns and recurrence and survival in surgically staged cases of endometrial cancer. METHODS: Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence and survival were collected. The chi square test was used to test associations between variables. The Kaplan-Meier method was used for survival analysis and Cox's proportional hazards model for multiple regression analysis. RESULTS: Sixty-nine out of 181 patients underwent lymph node dissection. Twenty-three had pelvic lymph node dissection, 23 underwent pelvic and paraaortic lymph node dissection and 20 patients had lymph node sampling. The median count of removed lymph nodes was 22.4. Fifty-four lymph node dissections showed negative lymph nodes and in 15 cases there was a minimum of one positive lymph node. Overall survival was in correlation to nodal involvement with a p value of 0.0017. Patients with lymph node involvement showed significantly more recurrence than patients with negative lymph nodes (p = 0.003). The depth of myometrial invasion correlated with lymph node metastasis (p = 0.01) and patients with additional diabetes mellitus showed significantly more nodal involvement (p = 0.02). CONCLUSION: Endometrial cancer showed pelvic lymph node (PLN) and paraaortic lymph node (PALN) involvement. Under-diagnosis of the disease might result if there was only a PLN, but with or without PALN involvement there was no significant difference in overall survival or recurrence. There was an univariate correlation between lymph node involvement and diabetes.

Acanthoma↗

MR-guided intervention in women with a family history of breast cancer.

OBJECTIVE: A study was undertaken to assess the clinical value of magnetic resonance (MR) imaging-guided interventions in women with a family history, but no personal history of breast cancer. METHODS AND PATIENTS: Retrospective review was performed on 63 consecutive women who had a family history, but no personal history of breast cancer. A total of 97 lesions were referred for an MR-guided intervention. Standardized MR examinations (1.0 T, T1-weighted 3D FLASH, 0.15 mmolGd-DTPA/kg body weight, prone position) were performed using a dedicated system which allows vacuum assisted breast biopsy or wire localization. RESULTS: Histologic findings in 87 procedures revealed 9 (10%) invasive carcinomas, 12 (14%) ductal carcinomas in situ, 2 atypical ductal hyperplasias (2.5%) and 2 atypical lobular hyperplasias (2.5%). Sixty-two (71%) benign histologic results are verified by an MR-guided intervention, retrospective correlation of imaging and histology and by subsequent follow-up. In ten lesions the indication dropped since the enhancing lesion was no longer visible. Absent enhancement was confirmed by short-term re-imaging of the noncompressed breast and by follow-up. CONCLUSION: Malignancy was found in 24%, high-risk lesions in 5% of successfully performed MR-guided biopsy procedures. A 57% of MR-detected malignancies were ductal carcinoma in situ. In 10% of the lesions the intervention was not performed, since no enhancing lesion could be reproduced at the date of anticipated intervention. Such problems may be avoided if the initial MRI is performed in the appropriate phase of the menstrual cycle and without hormonal replacement therapy.

Adult↗

Reconstructive surgery following resection of primary vulvar cancers.

OBJECTIVE: This study describes the surgical treatment and follow-up of 213 patients with primary vulvar cancer; particular attention is given to reconstructive surgical procedures. METHODS: The clinical and pathological parameters of the patients were recorded according to standardized procedures, and the data concerning type of operation, surgical reconstruction and postoperative course of disease (recurrence-free and overall survival) were analyzed. RESULTS: In about one-third of the cases, plastic surgery reconstruction involving skin-flaps was performed. In the present group of patients, plastic surgery procedures led to an elevated degree of operability as well as to more satisfactory results in terms of wound healing. For minor cosmetic defects, local (fasciocutaneous) skin-flaps resulted in excellent wound healing and short periods of in-patient treatment, even in patients with larger tumors. In cases exhibiting more severe wounds extending over larger areas of the vulva and its surrounding regions, similarly encouraging results were achieved using regional (myocutaneous) skin-flaps. CONCLUSION: The present study shows that reconstructive surgery of the vulva leads to good results in patients with vulvar cancer. Plastic surgery enlarges the spectrum of available operative therapy in vulvar cancer, especially in large tumors, and its application leads to a favorable oncological outcome as well as excellent cosmetic results in patients with vulvar cancer.

Adult↗

Updated recommendations on ultrasonography in urogynecology.

Ultrasound is a supplementary, indispensable diagnostic procedure in urogynecology; perineal, introital, and endoanal ultrasound are the most recommended techniques. The position and mobility of the bladder neck can be demonstrated. In patients undergoing diagnostic work-up for urge symptoms, ultrasound occasionally demonstrates urethral diverticula, leiomyomas, and cysts in the vaginal wall. These findings will lead to further diagnostic assessment. The same applies to the demonstration of bladder diverticula, foreign bodies in the bladder, and bullous edema. With endoanal ultrasound, different parts of the sphincter ani muscle can be evaluated. Recommendations for the standardized use of urogenital ultrasound are given.

Female↗

A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy.

BACKGROUND: We evaluated the efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support. PATIENTS AND METHODS: Patients (n = 157) were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after doxorubicin and docetaxel chemotherapy (60 mg/m(2) and 75 mg/m(2), respectively). Duration of grade 4 neutropenia, depth of neutrophil nadir, incidence of febrile neutropenia, time to neutrophil recovery and safety information were recorded. RESULTS: A single 6 mg injection of pegfilgrastim was as effective as daily injections of filgrastim for all efficacy measures for all cycles. The mean duration of grade 4 neutropenia in cycle 1 was 1.8 and 1.6 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2-4 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (13% versus 20%, respectively). A single fixed dose of pegfilgrastim was as safe and well tolerated as standard daily filgrastim. CONCLUSIONS: A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim in safely providing neutrophil support during myelosuppressive chemotherapy. Pegfilgrastim may have utility in other clinical settings of neutropenia.

Adult↗

Follow-up of breast lesions detected by MRI not biopsied due to absent enhancement of contrast medium.

Our objective was to follow-up patients in whom scheduled MR-guided vacuum biopsies for suspicious lesions were aborted due to absent enhancement of contrast medium. Thirty-seven of 291 scheduled MR-guided vacuum biopsies were aborted. Six cases were lost to follow-up. Two could be unequivocally identified and were nevertheless biopsied. In 25 of 29 patients absent enhancement was confirmed on subsequent studies without compression. Varying hormonal or inflammatory changes between initial MRI and MR-guided vacuum biopsy most probably explain the findings. Enhancement re-appeared on short-term follow-up <6 months without compression in 4 of the 29 patients. Too strong compression during MR-guided vacuum biopsy explains the absence of enhancement in these patients. Of note, on histology, three of these cases proved malignant. We conclude that short-term follow-up without compression is necessary and recommended for all lesions not visible during scheduled MR-guided vacuum biopsy.

Artifacts↗

Lymphatic mapping of sentinel nodes in early vulvar cancer.

OBJECTIVE: The aim of the study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients suffering from vulvar cancer. METHODS: From May 1998 to November 2000, 26 patients with early vulvar cancer, planned for local wide excision or vulvectomy including groin dissection, were eligible for the study. Two to 3 h before the planned procedure we injected technetium(99) m-labeled microcolloid intradermally at four locations around the tumor. Dynamic and static images were recorded using a gamma camera. SLN locations were marked on the overlying skin. In the operating theater SLNs were identified at the beginning of the procedure using a handheld gamma-detection probe. After resection of suspected SLNs a standard unilateral or bilateral groin dissection was performed, subsequently followed by local wide excision or, if indicated, radical vulvectomy. Sentinel node detection using technetium(99) m-labeled microcolloid was compared with final histopathological and immunohistochemical results. RESULTS: Scintigraphy showed focal uptake in all 26 patients. Intraoperatively we detected all sentinel nodes by handheld gamma probe. In 20 patients, one sentinel node was identified unilaterally, while in 6 patients two or more nodes were identified bilaterally. Histologically positive SLNs were found in 9 patients. In our preliminary series we did not find any false-negative SLN. CONCLUSION: Identification of sentinel nodes in vulvar cancer is feasible with preoperatively administered technetium(99)m-labeled microcolloid. We confirm the results of previous studies and improve the evidence that the SLN procedure could be implemented in future therapy concepts.

Adult↗

SCC antigen in the serum as an independent prognostic factor in operable squamous cell carcinoma of the cervix.

The aim of this study was to retrospectively examine whether the occurrence of squamous cell carcinoma (SCC) antigen tumour marker in the serum has prognostic significance in operable SCC of the cervix at the International Federation of Gynaecology and Obstetrics (FIGO) stages IA2-IIB. A total of 129 patients who had undergone a radical hysterectomy for SCC of the uterine cervix at the Department of Gynecology of the Martin-Luther University, Halle-Wittenberg in 1991-2000 were included. SCC antigen (Ag) was measured by IMx SCC-Ag microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, IL, USA). To assess the prognostic value of SCC antigen in the serum, we used a step-by-step multivariate analysis based on the Cox proportional hazard regression model. Using a cut-off value of 3.0 ng/ml, we detected preoperative SCC antigen in the serum as an independent prognostic factor in SCC of the cervix, both for recurrence-free and overall survival (P=0.003 and 0.0078). In this retrospective analysis the value of the SCC antigen tumour marker correlates with prognosis in operable SCC of the cervix, independent of tumour size, pelvic nodal status, cervical stroma infiltration, parametrial spread and tumour grading.

Adult↗

The clinical value of preoperative wire localization of breast lesions by magnetic resonance imaging--a multicenter study.

To evaluate the clinical value of MRI guided preoperative wire localization of clinically and mammographically occult lesions of the breast. In a multicenter study, we evaluated 132 preoperative MRI guided localizations. Median lesion size evaluated by MRI prior to wire localization was 9mm. MRI guided localization was successfully performed in 96.2% of cases. Median wire deviation from the lesion was 0 (0-10) mm. Moderate bleeding with no further treatment required occurred in three patients. We conclude that MRI guided preoperative wire localization is a safe and accurate procedure in cases of clinically and mammographically occult lesions of the breast.

Adult↗

Sentinel node procedure in Ib cervical cancer: a preliminary series.

The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium(99)m-labelled nanocolloid in each quadrant of the cervix. Dynamic and static images were recorded using a gamma camera. SLNs were identified intraoperatively using a handheld gamma-detection probe. After resection of SLNs a standard radical hysterectomy with pelvic lymph node dissection was performed. Patients and tumour characteristics were compared with sentinel node detection and with final histopathological and immunohistochemical results. Scintigraphy showed focal uptake in 13 of the 14 patients. Intraoperatively we detected 26 sentinel nodes by gamma probe. In 8 of 13 patients, one or more sentinel nodes were identified unilaterally, in 5 women bilaterally. Histologically positive SLNs were found in only 1 patient. We did not find any false-negative SLN in our series. In conclusion identification of sentinel nodes in cervical cancer is feasible with preoperatively administered technetium(99)m-labelled nanocolloid. A larger series will be required to establish sentinel node detection in cervical cancer for further therapy concepts and planning.

Adenocarcinoma↗

Sertoli-Leydig cell tumor.

Sertoli-Leydig cell tumors belong to the group of sex-cord stromal tumors of the ovary. They account for less than 0,5% of all ovarian neoplasms. The majority of these tumors are benign, and almost all are localised unilaterally. Herewith, we describe an ovarian Sertoli-Leydig cell tumor in an 11-year-old girl. Serum levels of estradiol and progesterone were mildly elevated. while testosterone and androstendion levels were raised to around three- and sevenfold upper normal limit respectively on presentation. A left salpingo-oophorectomy was performed. Microscopically, the tumor was intermediately differentiated. At 6 months follow-up, there was neither clinical nor sonographical evidence of recurrence, and almost all sex hormone levels had returned to within normal range. Treatment of this pathological entity has to be individualized according to patient age, stage of tumor and degree of differentiation.

Androstenedione↗

Sacrospinous ligament fixation for vaginal vault prolapse.

INTRODUCTION: To assess intra- and postoperative complications and to look for long term follow-up results in women with sacrospinous ligament fixation. METHODS: Between 1988 and 1999, 200 women (mean age 59.8 years, range 33 to 83 years) underwent vaginal unilateral sacrospinous ligament fixation. 172 patients had had prior hysterectomy. In 28 patients concomitant hysterectomy and sacrospinous ligament fixation was performed. Sacrospinous ligament fixation was combined with the following procedures: 109 enterocele repairs (54.5%), 88 anterior colporrhaphies (44%), 57 reconstructions of urogenital diaphragma (28.5%) and 23 posterior colporrhaphies (11.5%). Additional Burch colposuspension and a Stamey procedure were carried out in 7 (3.5%) and 15 (7.5%) patients, respectively. RESULTS: All 200 patients were analysed for intra- and postoperative complications. Urinary tract infection (n = 16, 8.0%), temporary irritation of the sciatic nerve (n = 15, 7.5%), temporary partial ureteral obstruction (n = 11, 5.5%) and blood loss less than 400 ml (n = 7, 3.5%), occurred in the postoperative phase. Long-term data (range from 6 months to 9 years, mean 4.8 years) exist for 123 patients. 119 were completely cured without any signs of urinary incontinence and prolapse. At follow-up 4 patients (3.25%) showed recurrent vaginal vault prolapse. Recurrent cystoceles, rectoceles, enteroceles, were found in 10 cases (8.1%), one (0.8%) and one (0.8%), respectively. Two patients with complete recurrence of vaginal vault prolapse successfully underwent colpectomy and repeated sacrospinous ligament fixation, respectively. CONCLUSIONS. Sacrospinous ligament fixation is an effective and safe procedure with a low recurrence and complication rate.

Adult↗

Treatment of postoperative urinary retention by elongation of tension-free vaginal tape.

Tension-free vaginal tape elongation with a polypropylene intermediate piece was successfully carried out in a patient with urinary retention after an initial tension-free vaginal tape surgical procedure. This resulted in immediate residual-free voiding and continence, unchanged at 6 months follow-up. Postoperative urinary retention may thus be treated by elongation instead of dissection of the tension-free vaginal tape.

Adult↗