Perinatal outcomes after previable preterm premature rupture of membranes before 24 weeks of gestation.

OBJECTIVE: A current descriptive assessment of perinatal outcomes in pregnancies complicated by previable preterm premature rupture of membranes (pPPROM) at <24 weeks of gestation, after expectant treatment. STUDY DESIGN: Maternal and short-term neonatal data were collected for patients with pPPROM. RESULTS: Seventy-three patients with 93 fetuses were hospitalized with pPPROM at 15-24 weeks' gestation. Among these patients, 27.4% (n=20) chose pregnancy termination, 27.4% (n=20) miscarried and 45.2% (n=33) proceeded to live births. After a median latency period of 38 days, ranging from 1 to 126 days, 24 singletons and 20 multiples were live-born, of whom 79.5% (n=35) survived the perinatal period. The main neonatal sequelae were pulmonary hypoplasia (29.5%; n=13), connatal infection (56.8%; n=25), intraventricular hemorrhage (25%; n=11; resulting in five neonatal deaths) and Potter's syndrome (15.9%; n=7). Nine newborns died, within an average of 2.8 days (range, 1-10 days). The overall neonatal survival rate was 51.5% - including miscarriages but not elective terminations. The intact survival rate was 45.5% of all live-born neonates. CONCLUSIONS: Even with limited treatment options, overall neonatal survival is increasing. However, neonatal mortality and morbidity rates remain high. The gestational age at membrane rupture does not predict neonatal outcome.

Shame in Medical Education: A Randomized Study of the Acquisition of Intimate Examination Skills and Its Effect on Subsequent Performance.

THEORY: Although medical students are exposed to a variety of emotions, the impact of emotions on learning has received little attention so far. Shame-provoking intimate examinations are among the most memorable events for students. Their emotions, however, are rarely addressed during training, potentially leading to withdrawal and avoidance and, consequently, performance deficits. However, emotions of negative valance such as shame may be particularly valuable for learning, as they might prompt mental rehearsal. We investigated the effect of shame on learning from the perspective of cognitive load theory. HYPOTHESES: We hypothesized that (a) training modality determines state shame, (b) state shame directly affects the quality of a clinical breast examination as one example of a shame-provoking exam, and (c) students who experience shame during training outperform those who just discuss the emotion during subsequent performance assessments. METHOD: Forty-nine advanced medical students participated in a randomized controlled, single-blinded study. After a basic, low-fidelity breast examination training, students were randomized to further practice either on a high-fidelity mannequin including a discussion of their emotions or by examining a standardized patient's real breasts. Last, all students conducted a breast examination in a simulated doctor's office. Dependent variables were measures of outcome and process quality and of situational shame. RESULTS: Students training with a standardized patient experienced more shame during training (p < .001, d = 2.19), spent more time with the patient (p = .005, d = 0.89), and documented more breast lumps (p = .026, d = 0.65) than those training on a mannequin. Shame interacted with training modality, F(1, 45) = 21.484, p < .001, η2 = 0.323, and differences in performance positively correlated to decline in state shame (r = .335, p = .022). CONCLUSIONS: Students experiencing state shame during training do reenact their training and process germane load-in other words, learn. Furthermore, altering simulation modality offers a possibility for educators to adjust the affective component of training to their objectives.

A simulated night shift in the emergency room increases students' self-efficacy independent of role taking over during simulation.

BACKGROUND: Junior doctors do not feel well prepared when they start into postgraduate training. High self-efficacy however is linked to better clinical performance and may thus improve patient care. What factors affect self-efficacy is currently unknown. We conducted a simulated night shift in an emergency room (ER) with final-year medical students to identify factors contributing to their self-efficacy and thus inform simulation training in the ER. METHODS: We simulated a night in the ER using best educational practice including multi-source feedback, simulated patients and vicarious learning with 30 participants. Students underwent 7 prototypic cases in groups of 5 in different roles (leader, member and observer). Feeling of preparedness was measured at baseline and 5 days after the event. After every case students recorded their confidence dependent of their role during simulation and evaluated the case. RESULTS: Thirty students participated, 18 (60 %) completed all surveys. At baseline students feel unconfident (Mean -0.34). Feeling of preparedness increases significantly at follow up (Mean 0.66, p = 0.001, d = 1.86). Confidence after simulation is independent of the role during simulation (F(2,52) = 0.123, p = 0.884). Observers in a simulation can estimate leader's confidence independent of their own (r = 0.188, p = 0.32) while team members cannot (r = 0.61, p < 0.001). CONCLUSIONS: Simulation improves self-efficacy. The improvement of self-efficacy is independent of the role taken during simulation. As a consequence, groups can include observers as participants without impairing their increase in self-efficacy, providing a convenient way for educators to increase simulation efficiency. Different roles can furthermore be included into multi-source peer-feedback.

Cervical sonoelastography for improving prediction of preterm birth compared with cervical length measurement and fetal fibronectin test.

AIM: Accurate prediction of the risk of spontaneous preterm birth is crucial for the clinical management of patients with preterm labor. The aim of the study was to investigate whether cervical sonoelastography improves prediction of spontaneous preterm birth compared with cervical length measurement and a fetal fibronectin (fFN) test. METHODS: A prospective cohort study was conducted including 64 patients with preterm labor at 23-34 weeks of gestation. Patients had an fFN test and transvaginal cervical length measurement, followed by real-time cervical sonoelastography. The ratio of nondeformable tissue to the total area of a designed region of interest was analyzed and related to the gestational week of delivery. RESULTS: Cervical sonoelastography and fFN test show a significant correlation with spontaneous preterm delivery (P=0.007, P=0.001), resulting in 72.7%/36% sensitivity and 73%/95% specificity. The positive predictive value (PPV) was 61.5%/81.8% and the negative predictive value was 81.8%/70%. The cervical length was not different in cases with and without term delivery (P=0.165). CONCLUSIONS: Cervical sonoelastography is a promising technique that can complement routine diagnostic procedures to improve prediction of preterm birth. The PPV is improved by an fFN test.

In vivo high-resolution magnetic resonance elastography of the uterine corpus and cervix.

OBJECTIVES: To apply 3D multifrequency MR elastography (3DMMRE) to the uterus and analyse the viscoelasticity of the uterine tissue in healthy volunteers considering individual variations and variations over the menstrual cycle. METHODS: Sixteen healthy volunteers participated in the study, one of whom was examined 12 times over two menstrual cycles. Pelvic 3DMMRE was performed on a 1.5-T scanner with seven vibration frequencies (30-60 Hz) using a piezoelectric driver. Two mechanical parameter maps were obtained corresponding to the magnitude (|G (*) |) and the phase angle (φ) of the complex shear modulus. RESULTS: On average, the uterine corpus had higher elasticity, but similar viscosity compared with the cervix, reflected by |G (*) |uterine corpus = 2.58 ± 0.52 kPa vs. |G (*) |cervix = 2.00 ± 0.34 kPa (p < 0.0001) and φ uterine corpus = 0.54 ± 0.08, φ cervix = 0.57 ± 0.12 (p = 0.428). With 2.23 ± 0.26 kPa, |G (*) | of the myometrium was lower in the secretory phase (SP) compared with that of the proliferative phase (PP, |G (*) | = 3.01 ± 0.26 kPa). For the endometrium, the value of |G (*) | in SP was 68% lower than during PP (PP, |G (*) | = 3.34 ± 0.42 kPa; SP, |G (*) | = 1.97 ± 0.34 kPa; p = 0.0061). CONCLUSION: 3DMMRE produces high-resolution mechanical parameter maps of the uterus and cervix and shows sensitivity to structural and functional changes of the endometrium and myometrium during the menstrual cycle. KEY POINTS: MR elastography provided for the first time spatially resolved viscoelasticity maps of uterus. Uterine corpus had a higher elasticity, but similar viscosity compared with cervix. The stiffness of both endometrium and myometrium decreases during the menstrual cycle.

Benefits of early and prolonged fulvestrant treatment in 848 postmenopausal advanced breast cancer patients.

Response to fulvestrant and survival in postmenopausal hormone-sensitive advanced breast cancer was investigated within a non-randomized, In-Practice Evaluation Program, with the aim of optimizing treatment decisions. 848 patients (median age 64 years; 52% co-morbidity; 78% prior palliative therapy; median 4 prior regimens) received monthly fulvestrant injections (250 mg/month) and were followed-up three-monthly for 9 months. Clinical benefit (PFS ≥ 24 weeks) occurred in 532/848 (62.7%); stable disease (SD) in 627/848 patients (74%), including 62 complete and 177 partial responses. Best response was delayed in 115 patients. Estimated 9-month overall survival (OS) was 89%; 9-month event-free survival (EFS) was 71%. Indicators of disease aggressiveness affected response and survival, but number of fulvestrant cycles was the key OS and EFS determinant. The patients with SD at 3 months benefitted from continued fulvestrant. Excluding deaths, 7 serious adverse events occurred (none attributable to fulvestrant). No new or unexpected safety issues arose; 90% of the patients and physicians rated fulvestrant tolerability as "very good" or "good". In the largest prospective, fulvestrant-treated cohort to date, advanced breast cancer patients achieving SD or better after 3 months of treatment gained survival benefit by prolonging fulvestrant therapy-independent of disease and treatment history.

Optimized pro-active management of anemia by Epoetin alpha in pre-operative chemotherapy for primary breast cancer.

This prospective study quantifies the response of hemoglobin and other blood factors to Epoetin alpha (EPO) administration in the course of pre-operative chemotherapy in breast cancer. Blood count time series were analyzed in 38 primary breast cancer patients with/without EPO during the course of pre-operative chemotherapy with epirubicin and paclitaxel. EPO injections improved blood counts in 'anemic' patients (< or =12.0 g/dl) receiving chemotherapy, but had little effect when administered to patients with higher hemoglobin concentrations. On the average, without chemotherapy, hemoglobin concentrations drifted toward about 11.1 g/dl without EPO but could be maintained at near 12.0 g/dl with EPO. In conclusion, there is potential for improved anemia management using EPO during pre-operative chemotherapy, which not only benefits quality of life but could also influence long-term survival in breast cancer through improved tumor oxygenation.

Circulating vascular endothelial growth factors and their soluble receptors in pre-invasive, invasive and recurrent cervical cancer.

AIM: To study the impact of circulating vascular endothelial growth factors (VEGF) -A, -C and -D and their soluble receptors VEGFR-1/-2 on disease invasion and progression in patients with pre-invasive (CIN), invasive (PCC) and recurrent (RCC) cervical cancer. PATIENTS AND METHODS: Blood samples were obtained from 125 women, including 50 cases of CIN, 51 of PCC and 24 of RCC, before treatment. Soluble (s) biomarker levels were determined by ELISA and tested for correlation with histopathological factors. RESULTS: With disease progression, sVEGF-A (p = 0.007) and sVEGFR-2 (p = 0.014) significantly increased, while sVEGF-D (p = 0.046) decreased. sVEGFR-2 levels were increased in node+ patients (p = 0.024) and in metastatic disease (p = 0.003). sVEGF-A values were higher in HPV+ cases (p = 0.019). In detecting disease invasiveness, sensitivity and specificity were 76% and 48% for sVEGF-A, 52% and 32% for sVEGF-D, 25% and 94% for sVEGF-C, 93% and 6% for sVEGFR-1 and 73% and 34% for sVEGFR-2, respectively. CONCLUSION: In cervical neoplasia, a switch from a lymphangiogenic phenotype towards a hemangiogenic phenotype occurs with disease invasion and progression. The sensitivity and specificity values, however, seem not convincing enough to establish these factors as clinical markers for disease invasiveness in cervical cancer.

Can acoustic structural quantification be used to characterize the ultrasound echotexture of the peripheral zone of breast lesions?

BACKGROUND: Besides mammography, breast ultrasound is the most important imaging modality for women with suspected breast cancer. New software tools bear high potential for improved detectability and specification of malignant breast lesions. OBJECTIVE: To compare the halo depicted around malignant breast lesions by ultrasound using Acoustic Structure Quantification (ASQ) of raw image data with the echogenic rim seen in B-mode ultrasound. METHODS: This retrospective study included 37 women for whom conventional B-mode ultrasound of the breast and ASQ were available as well as histopathology findings for comparison. Software tools were used to measure the halo area or echogenic rim and tumor area and calculate halo-to-lesion ratios for the two ultrasound modes. Six inexperienced readers characterized the breast lesions based on this information. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. ANOVA, the Wilcoxon test, and ROC curve analysis were performed. RESULTS: There was a linear relationship between ASQ-based and B-mode-based halo-to-lesion ratios; however, a systematic error was also noted. ASQ-derived ratios tended to be higher for breast lesions with lymphangioinvasion (p = 0.051, n.s.) and higher N-stages (p > 0.925, n.s.), while there was no correlation with other markers. Because of the significantly greater conspicuity of peritumoral halos in the ASQ mode, inexperienced readers achieved greater sensitivity (78% vs. 74%) and specificity (75% vs. 71%) and higher NPVs (75% vs. 71%) and PPVs (78% vs. 74%) compared with B-mode images. Greater halo conspicuity affected the identification of malignant lesions with both modes; ASQ was found to be particularly well suited (FBimage (1,100) = 19.253, p < 0.001; FASQ (1,100) = 52.338, p < 0.001). The inexperienced readers were significantly more confident about their diagnosis using the ASQ maps (z = -3.023, p = 0.003). CONCLUSIONS: We conclude that the halo in ASQ and the echogenic rim in B-mode ultrasound are attributable to different morphologic correlates. ASQ improves diagnostic accuracy and confidence of inexperienced examiners because of improved halo visibility.

Postoperative sense of well-being and quality of life in breast cancer patients do not depend on type of primary surgery.

BACKGROUND: In primary breast cancer, breast conserving surgery and mastectomy are equal options with regard to patient survival. We therefore investigated whether and how the type of surgery has impact on the patients' quality of life (QoL) in order to support individualized surgical concepts in treatment of breast cancer. 3 types of surgery are compared: breast-conserving surgery; modified radical mastectomy with or without primary reconstruction. PATIENTS AND METHODS: 91 out of 114 consecutive patients diagnosed with histologically confirmed primary breast cancer agreed to answer the QoL questionnaires within the first 2 years of their follow-up care. 2 recognized questionnaires on sense of well-being and QoL were used: Multidimensional Mood Questionnaire and QoL SF-12. RESULTS: No significant correlation between sense of well-being and type of operation or tumor stage was found. With regard to health-related QoL, we saw no significant correlation with type of surgery. However, low tumor stage was significantly correlated with better physical (p = 0.012) but not psychological well-being. CONCLUSION: Within the first 2 years after primary surgery for breast cancer, we did not find significant differences in sense of well-being or QoL dependent on type of surgery.

Treatment strategies that effectively reduce early recurrence risk in postmenopausal women with endocrine-sensitive breast cancer: AIs upfront vs. switching.

Several large, well-controlled clinical trials have now established that the aromatase inhibitors (AIs), including letrozole, anastrozole, and exemestane, are more effective than tamoxifen when used as adjuvant endocrine therapy in postmenopausal women with breast cancer. Yet, it is an open question as to how these drugs should be best integrated into the adjuvant treatment regimen. Both letrozole and anastrozole have shown efficacy over tamoxifen when used as initial adjuvant therapy (initiated just following surgery for breast cancer), while exemestane and anastrozole have been used as switching adjuvant therapy, i.e., following 2-3 years of initial adjuvant tamoxifen therapy, with proven efficacy over continued tamoxifen. Studies demonstrate that recurrence risk peaks in the early period after surgery, and that distant metastases in particular, accounting for most of the early recurrences, have worse survival rates when compared with other types of recurrences. Treatments that reduce recurrences, especially distant metastases, in this early period are therefore likely to improve overall survival (OS) and reduce mortality from breast cancer. In this review, we discuss early recurrence risk among postmenopausal women with successfully treated early breast cancer, the efficacy of the different AIs in reducing early recurrences and distant metastases when incorporated into adjuvant therapy, and the evidence for increased OS when AIs are used as initial or switch adjuvant therapy.

Impact of tumor biological factors on response to pre-operative epirubicin and paclitaxel chemotherapy in primary breast cancer.

BACKGROUND: The objective of this study was to determine the predictive impact of several established tumor biological factors (progesterone receptor, estrogene receptor, HER2/neu, and Ki-67) on response to pre-operative combination chemotherapy with epirubicin and paclitaxel in a representative group of primary breast cancer patients. PATIENTS AND METHODS: Thirty-eight primary breast cancer patients (metastasis-negative) received pre-operative chemotherapy with epirubicin and paclitaxel. The response characteristics analyzed included pathological complete response and partial remission determined by 3D ultrasound, as well as down-staging and breast conserving surgery. RESULTS: Pathologically complete response occurred in six patients. Overexpression of HER2/neu, low (negative) hormone receptors and high Ki-67 were all significant positive predictive factors for response to pre-operative chemotherapy. CONCLUSION: HER2/neu overexpression is predictive for response not only to trastuzumab, but also to epirubicin and paclitaxel.

Epidermal growth factor receptor (EGFR) mutation does not correlate with platinum resistance in ovarian carcinoma. Results of a prospective pilot study.

BACKGROUND: Different studies have demonstrated epidermal growth factor receptor (EGFR) status as an independent prognostic factor for ovarian cancer (OC). Recent studies in non-small cell lung cancer suggest that the presence of a clinical response to tyrosine kinase inhibitors correlates with somatic mutations in the kinase domain of EGFR, exons 18-21. For patients with OC, data are not available on EGFR gene mutation. MATERIALS AND METHODS: Shock-frozen samples from 32 patients with OC were screened for L858R deletion mutations of EGFR within exon 21 of the kinase domain and 15 bp deletion in exon 19. Additionally, nine commercially available OC cell lines and 32 established OC lines were analysed. RESULTS: In cell lines, as well as in tumor samples, stratified to platinum-free therapy interval, no mutation of the EGFR gene was observed. CONCLUSION: Mutations in the kinase domain of the EGFR, exons 19 and 21, are absent or very infrequent in patients with OC.

Transrectal broadband-Doppler sonography with intravenous contrast medium administration for prostate imaging and biopsy in men with an elevated PSA value and previous negative biopsies.

UNLABELLED: THE AIM of this study was to determine the prostate cancer detection rate of targeted biopsy using contrast-enhanced ultrasound (US) in patients with elevated prostate specific antigen (PSA) levels and previous negative biopsy. PATIENTS AND METHODS: A total of 114 patients initially underwent ultrasonography using transrectal ultrasound (TRUS) and power Doppler. All the patients had at least one previous biopsy series negative for prostate carcinoma. Ninety-five of the patients were examined with a new broadband Doppler technique, advanced dynamic flow (ADF), after i.v. injection of the echo enhancer (2.4 ml, SonoVue). The systematic biopsies were also obtained supplemented by removal of two targeted tissue cores in all the patients with a suspicious area in the inflow phase or late phase. RESULTS: Histology confirmed prostate cancer in 30 of the 95 patients. Sensitivity for the detection of prostate cancer by contrast-enhanced US was 100% and specificity was 48%. Suspicious areas were identified in 48 cases including 40 hypervascularized areas and 14 hypoechoic areas after 60 sec. Targeted biopsy identified 24 of the 30 carcinomas. Randomized octant biopsy identified only 8 of the 30 carcinomas. All 65 patients with negative histology were prostate cancer free at 12-month follow-up. The ADF US scans were degraded by fewer artifacts than the power Doppler images. CONCLUSION: Contrast-enhanced ADF Doppler allows reliable differentiation of prostate cancer and normal prostate tissue with a high sensitivity in patients with previous negative biopsy and fewer artifacts than power Doppler images, thus providing a good basis for targeted prostate biopsy instead of systematic biopsy.

Real-time sonoelastography of the cervix: tissue elasticity of the normal and abnormal cervix.

RATIONALE AND OBJECTIVES: First study to investigate the basic tissue elastic properties of the cervix in pre- and postmenopausal healthy women and to compare these normal findings with the results in a group of patients with focal pathology of the cervix. MATERIALS AND METHODS: A total of 113 patients underwent transvaginal ultrasound, among them 24 with cervical pathology. The real-time elastography (Hitachi) information was color-coded and superimposed on the B-mode scan. The elastography images were analyzed by means of a software tool to identify thresholds for the colors red (soft), blue (hard), and green (medium hard), and the percentages of the three colors of the total area were determined. The results were correlated with age. In addition, scans were evaluated subjectively on an analogue scale from 1 (definitely normal) to 5 (definitely abnormal). Statistical analysis was performed using Anova, Wilcoxon's test, and Pearson's correlation. RESULTS: Computer-assisted generation of the color spectrum showed green to be predominant in both the normal group (67+/-13 %) and in the group with cervical pathology (64+/-15 %) without a significant difference between both groups (p=>0.05). Significant differences (p<0.05) in the blue color spectrum (hard tissue) were found between the 13 cervical tumor patients (34+/-15 %) and the normal group (26+/-13 %) but not between the CIN patients and normal women (19+/-12 %) (p>0.05). Subjective tumor characterization also showed significant differences (p<0.05) among the groups and good correlation with the histologic diagnosis (r2=0.744). There were no significant changes in color distribution with patient age (p>0.05). CONCLUSION: Computer-assisted and subjective evaluation of cervical elastography allows differentiation of malignancy from normal findings. CIN cannot be identified with this modality. Elastographically, cervical tissue is of medium hardness and does not change with age.

Tissue Doppler and strain imaging for evaluating tissue elasticity of breast lesions.

RATIONALE AND OBJECTIVES: Sonoelastography depicts the intrinsic elastic properties of a tissue which are characterized by the strain applied to achieve tissue deformation and the velocity at which tissue deformation occurs. The present study served to investigate whether the specificity of B-mode ultrasound (US) can be improved by combining B-mode imaging with tissue Doppler imaging (TDI) and offline analysis of tissue strain imaging (TSI). MATERIALS AND METHODS: Fifty women, 25 with malignant and 25 with benign focal breast lesions, were examined by US with a linear transducer (9 MHz, Aplio, Toshiba, Otawara, Japan). B-mode US views of the lesions were overlaid with color-coded TDI information and area quotients (AQ = area B-mode view/area TDI) were calculated. TSI views were reconstructed offline from the source data. This was done by placing a region of interest (ROI) in the target lesion and color-encoded display of the information. In addition, tissue elasticity was evaluated using a scale of 1-5 corresponding to the BI-RADS categories. Maximum strain (strain factor, SF) was determined in the ROI. All patients also underwent mammography. Sensitivities and specificities were calculated and statistical analysis was performed using Wilcoxon's test. RESULTS: Sensitivity/specificity was 96%/68% for B-mode US, 100%/40% for combined B-mode US and mammography, and 96%/80% for TSI. The AQ of benign and malignant lesions was significantly different (p = .00008) as was the difference in SF (p = .0004). The readers considered TSI a feasible technique. CONCLUSION: Evaluation of elasticity based on the quantification of strain factors improves characterization of focal breast lesions, especially the differentiation of BI-RADS 3 and 4 lesions. Surprisingly, significant results in characterizing breast lesions were obtained with the simple technique of TDI, showing a lower tissue displacement in malignant cases.

Improvement of safety profile of docetaxel by weekly administration in patients with metastatic breast cancer.

BACKGROUND: This is a retrospective cohort study on the safety and efficacy profiles of weekly docetaxel at varying doses in patients with pretreated metastatic breast cancer. PATIENTS AND METHODS: Twenty-five anthracycline-pretreated patients received docetaxel administered on a weekly basis, as a one-hour infusion, at various dosage levels (25, 30, 35, 40 mg/m2) depending on their baseline Karnofsky index. Each 8-week cycle consisted of 6 weeks of drug infusion, followed by a 2-week rest period. RESULTS: Of the 25 patients investigated, none achieved complete response (CR), while 9 patients showed partial response (PR), which corresponds to an overall response rate of 36%. Five patients (20%) maintained stable disease (SD), whereas 11 patients (44%) suffered tumor progression (PD) during treatment. Clinical response (defined as PR+SD) was achieved in 14 patients (56%). Median time to progression was 231 days (95% CI, 187-275). The baseline Karnofsky index was 87% +/- 9% (range: 70-100). Patients pretreated with anthracyclines only tended to have a better response than anthracycline/paclitaxel-pretreated patients (n = 6, p = 0.054). Higher dosages were associated with neurotoxicity, skin/nail toxicity, leukopenia, nausea/vomiting, fatigue/asthenia, peripheral edema, but not with diarrhea and alopecia. The cumulative dose per patient was largest for a weekly docetaxel dosage of 35 mg/m2 and almost as large for 30 mg/m2. CONCLUSION: Balancing toxicity vs. efficacy/cumulative dosage delivered, our results support weekly administration of docetaxel at dosages of 30-35 mg/m2 in metastatic breast cancer. Response in patients pretreated with anthracyclines and taxanes may be poorer than in those pretreated with anthracyclines only.

Chemotherapy treatment options for elderly women with breast cancer.

Due to improved life expectancy and the increase in incidence of breast cancer in old age, ever more older women are developing this disease. Although there is only limited evidence-based data from randomized trials on the treatment, older patients are still under-represented in clinical studies, and currently there is no clear consensus on chemotherapy treatment for older women with breast cancer. Adjuvant therapy strategies, in particular, suffer from a lack of uniform standards and reflect a generally less aggressive treatment. Recently published studies have shown that older women suffering from breast cancer can also profit from a treatment based on therapeutic standards and consensus guidelines. In spite of developments in adjuvant chemotherapy using increased amounts of therapeutic agent to improve survival, many older patients receive instead reduced quantities of chemotherapeutic agent. Thus, the questions arise, whether undertreatment of older patients with breast cancer can lead to a poorer outcome or whether new therapy strategies (e.g., dose-intensive chemotherapy) can be used with older patients. A common reason for dose reductions is neutropenia, but studies have shown that it is manageable by using granulocyte colony-stimulating factors (G-CSFs). In this review, the current status of clinical research in the area of adjuvant treatment and the necessity for clinical studies that take into account the special therapeutic requirements of older women are discussed.

Options and limits of surgery after pre-operative chemotherapy in breast cancer.

The primary administration of chemotherapy leads to a reduction in size of tumors, increasing the possibility of breast-conserving surgery in both locally advanced, inoperable and primary operable mamma carcinomas. This, however, increases the rate of local relapse and the rate of mastectomy over the course of the disease, even although the EUSOMA guidelines are not exceeded. Whether the pre-surgical administration of chemotherapy with pathological complete remission actually increases the disease-free rate and overall survival remains to be determined. Further clinical studies are required to establish the reliability of sentinel lymph-node biopsy; currently, axillary lymphadenectomy is still the standard therapy. The response of the tumor to therapy, in correlation with predictive factors and the molecular-genetic profile, could make more individualized treatment regimes possible in the future.

Postoperative therapy modalities for cervical carcinoma.

Currently, the standard therapy for cervical carcinoma of FIGO stage IIB following adequate radical surgery is simultaneous radiochemotherapy with a platinous chemotherapeutic agent. According to the current state of scientific knowledge, all patients of FIGO stages IIA-IB with at least one additional risk factor (adenocarcinoma, pN1, L1, V1, pT1b2) also benefit from adjuvant radiochemotherapy. Various studies have shown that it is possible to successfully carry out a platinous radiochemotherapy. However, one disadvantage is that a number of patients have to break off therapy because of treatment-related toxicities. It has also been proven that a low hemoglobin level during radiochemotherapy is a negative prognostic factor for overall survival. The data regarding a possible survival advantage following an increase in the hemoglobin content in the blood of cancer patients by erythropoietin administration is still contradictory. As a result, the administration of new cytostatics, platinous combination chemotherapies, sequential instead of simultaneous regimens and appropriate supportive therapies have to be taken into account. Several studies are currently being conducted into the effectiveness of such new therapies on both life expectancy and quality of life (e.g., Cervix-NOGGO-AGO-Uterus 7-study).