Ovarian cancer prevention by opportunistic salpingectomy is a new de facto standard in Germany.

PURPOSE: The most prevalent and aggressive subtype of epithelial ovarian carcinoma (EOC), high-grade serous carcinoma (HGSC), originates in many cases from the fallopian tubes. Because of poor prognosis and lack of effective screening for early detection, opportunistic salpingectomy (OS) for prevention of EOC is being implemented into clinical routine in several countries worldwide. Taking the opportunity of a gynecological surgery in women at average cancer risk, extramural fallopian tubes are completely resected preserving the ovaries with their infundibulopelvic blood supply. Until recently, only 13 of the 130 national partner societies of the International Federation of Obstetrics and Gynecology (FIGO) have published a statement on OS. This study aimed to analyze the acceptance of OS in Germany. METHODS: (1) Survey of German gynecologists in 2015 and 2022 by the Department of Gynecology of the Jena University Hospital in co-operation with the Department of Gynecology at Charité-University Medicine Berlin with support of NOGGO e. V. and AGO e. V. (2) Salpingectomy numbers in Germany for years 2005-2020 as retrieved from the Federal Statistical Office of Germany (Destatis). RESULTS: (1) Survey: Number of participants was 203 in 2015 and 166 in 2022, respectively. Nearly all respondents (2015: 92%, 2022: 98%) have already performed bilateral salpingectomy without oophorectomy in combination with benign hysterectomy with the intention to reduce the risk for malignant (2015: 96%, 2022: 97%) and benign (2015: 47%, 2022: 38%) disorders. Compared to 2015 (56.6%), considerably more survey participants performed OS in > 50% or in all cases in 2022 (89.0%). Recommendation of OS for all women with completed family planning at benign pelvic surgery was approved by 68% in 2015 and 74% in 2022. (2) Case number analysis: In 2020, four times more cases of salpingectomy were reported by German public hospitals compared to 2005 (n = 50,398 vs. n = 12,286). Of all inpatient hysterectomies in German hospitals in 2020, 45% were combined with salpingectomy, and more than 65% in women at the age of 35 to 49 years. CONCLUSION: Mounting scientific plausibility regarding involvement of fallopian tubes in the pathogenesis of EOC led to change of clinical acceptance of OS in many countries including in Germany. Case number data and widespread expert judgment demonstrate that OS has become a routine procedure in Germany and a de facto standard for primary prevention of EOC.

Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.

"Locus minoris resistentiae" and connective tissue weakness in older women: a case report and literature review on pelvic organ prolapse with inguinal bladder hernia.

BACKGROUND: Conditions such as genital prolapse and hernia are known to be related to connective tissue dysfunction. In this report on cases of the rare simultaneous finding of large genital prolapse and post-prolapse repair female inguinal bladder hernia, we aim to contribute to the discussion of a possible clinical definition of connective tissue weakness, for its clinical assessment and preoperative patient counselling. CASE PRESENTATION: Three cases of medial third-grade (MIII, Aachen classification) inguinal bladder hernia developing or enlarging after successful stage-IV pelvic organ prolapse (POP) repair at a university pelvic floor centre are presented. All patients were aged ≥ 80 years with long-standing postmenopausal status. One patient was followed for 5 years and two patients were followed for 6 months. In all patients, ultrasound revealed that the hernia sac contained the urinary bladder, which had herniated through the inguinal hernia orifice. A literature search revealed only one case report of direct female inguinal bladder hernia and few investigations of the simultaneous occurrence of POP and hernia in general. CONCLUSION: The simultaneous occurrence of inguinal hernia and female POP can lead to bladder herniation following prolapse surgery in the sense of a "locus minoris resistentiae". Clinical examination for simultaneous signs of connective tissue weakness and counselling prior to pelvic reconstructive surgery could help to increase patients' compliance with further surgical treatment for hernia.

Inverse correlation between urethral length and continence before and after native tissue pelvic floor reconstruction.

Urethral length was evaluated retrospectively in patients with prolapse undergoing anterior native-tissue repair. Effects of age, prolapse stage, defect pattern, urodynamic and clinical stress test findings, and tension-free vaginal tape (TVT) surgery indication were analyzed using Mann-Whitney and Wilcoxon tests and linear and logistic regression. Of 394 patients, 61% had stage II/III and 39% had stage IV prolapse; 90% of defects were central (10% were lateral). Median pre- and postoperative urethral lengths were 14 and 22 mm (p < 0.01). Preoperative urethral length was greater with lateral defects [p < 0.01, B 6.38, 95% confidence interval (CI) 4.67-8.08] and increased stress incontinence risk (p < 0.01, odds ratio 1.07, 95% CI 1.03-1.12). Postoperative urethral length depended on prolapse stage (p < 0.01, B 1.61, 95% CI 0.85-2.38) and defect type (p = 0.02, B - 1.42, 95% CI - 2.65 to - 0.2). Postoperatively, TVT surgery was indicated in 5.1% of patients (median 9 months), who had longer urethras than those without this indication (p = 0.043). Native-tissue prolapse repair including Kelly plication increased urethral length, reflecting re-urethralization, particularly with central defects. The functional impact of urethral length in the context of connective tissue aging should be examined further.

Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment.

PURPOSE: First evaluation of dual-phase vaginal Er:YAG laser to omit hormonal treatment for atrophy-related symptoms in post-menopausal breast cancer survivors following prolapse surgery. METHODS: Patients with a history of breast cancer at the time of surgery for pelvic organ prolapse were offered non-hormonal vaginal Er:YAG laser treatment when complaining of atrophy-related genitourinary syndrome of menopause. A single 10-min course of dual-phase protocol of pulsed Er:YAG laser (2940 nm, fractional ablative and thermal mode, fluence according to tissue thickness). Follow-up included subjective satisfaction, vaginal pH, vaginal health index (VHI), and complications after 6 weeks. RESULTS: A total of 16 breast cancer survivors (age 71 years, SD 7) had been seeking treatment for pelvic floor symptoms related to vaginal atrophy at follow-up visits after prolapse surgery. All ablative vaginal Er:YAG laser outpatient procedures were successfully completed, all patients returned to daily activities without a need for analgetic medication. Evaluation was performed after 8.3 (SD 2.5) weeks. Pre-laser VHI scored 16 (SD 4.6) and post-laser VHI 20 (SD 3) with p = 0.01. Patients were satisfied in 94% (n = 15) regarding symptom relief. CONCLUSIONS: Breast cancer survivors with atrophy-related complaints after pelvic floor surgery may benefit from vaginal application of this innovative dual protocol of Er:YAG laser technology as a non-hormonal treatment approach.

Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial.

Background: Primary breast cancer (BC) patients with extensive axillary lymph-node involvement have a limited prognosis. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) trial compared intense dose-dense (idd) adjuvant chemotherapy with conventionally scheduled chemotherapy in high-risk BC patients. Here we report the final, 10-year follow-up analysis. Patients and methods: Enrolment took place between December 1998 and April 2003. A total of 1284 patients with 4 or more involved axillary lymph nodes were randomly assigned to receive 3 courses each of idd sequential epirubicin, paclitaxel and cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by paclitaxel (EC â†’ P) q3w. Event-free survival (EFS) was the primary end point. Results: A total of 658 patients were assigned to receive iddEPC and 626 patients were assigned to receive EC â†’ P. The median duration of follow-up was 122 months. EFS was 47% (95% CI 43% to 52%) in the standard group and 56% (95% CI 52% to 60%) in the iddEPC group [hazard ratio (HR) 0.74, 95% CI 0.63-0.87; log-rank P = 0.00014, one-sided]. This benefit was independent of menopausal, hormone receptor or HER2 status. Ten-year overall survival (OS) was 59% (95% CI 55% to 63%) for patients in the standard group and 69% (95% CI 65% to 73%) for patients in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P = 0.0007, two-sided). Nine versus two cases of secondary myeloid leukemia/myelodysplastic syndrome were observed in the iddEPC and the EC â†’ P arm, respectively. Conclusion: The previously reported OS benefit of iddEPC in comparison to conventionally dosed EC â†’ P has been further increased and achieved an absolute difference of 10% after 10 years of follow-up.

Gynaecological Prolapse Surgery in Very Old Female Patients: A Case-Control Study on Co-Morbidity and Surgical Complications.

BACKGROUND: The aim of this study is to compare very elderly female patients with a younger control group after prolapse surgery with regard to co-morbidity and complications. METHOD: In a case-control design, the consecutive data of patients after prolapse surgery at the age of over 80 years and those of a control group were analysed by means of the Clavien-Dindo (CD) classification of surgical complications, the Charlson Comorbidity Index and the Cumulative Illness Rating Scale Geriatrics (CIRS-G). Statistics: Student's t, Fisher's exact and Mann-Whitney U tests. RESULTS: The analysis comprised n = 57 vs. n = 60 operations. In the very elderly patients there was often a grade IV prolapse (p < 0.001), apical fixations were more frequent (p < 0.001), but the operating times were not different. In the very elderly patients 21 % CD II+III complications were observed, in the control group 6.6 % (p = 0.031). No CD IV and V complications occurred in either group, the duration of inpatient stay amounted to 5 (± 1) vs. 4.1 (± 0.8; p < 0.001) days, the very elderly patients needed an inpatient follow-up more frequently (p < 0.001). The co-morbidities of the very elderly patients differed from those of the control group in number (median 2.0 vs. 1.5; p < 0.001), in CIRS-G (4.1 ± 2.2 vs. 2.4 ± 1.7; p < 0.01) and in Charlson Index (1.6 ± 1.6 vs. 0.5 ± 0.7; p < 0.001). CONCLUSIONS: A prolapse in very elderly women can be safely managed by surgery. In no case did the complications require intensive care treatment nor were they life-threatening, but they did lead to a longer duration of hospital stay and more frequently to further treatment geriatric or inpatient internal medicine facilities.

Risk index for pelvic organ prolapse based on established individual risk factors.

PURPOSE: To identify known risk factors for pelvic organ prolapse (POP) in a hospital cohort and to develop a prolapse risk index (PRI). METHODS: Risk factors for POP were recorded in women who underwent surgery with symptomatic POP (n = 500) or non-POP gynaecological conditions (n = 236). Descriptive statistics were determined by Chi-squared and Mann-Whitney U tests. Stepwise multivariate regression analysis was performed for all patients and subgroups by age (<60 and ≥60 years). Primary outcome measures were variables with the strongest impact on prolapse and PRI development. Secondary: specificity, sensitivity, positive and negative predictive values (PPV and NPV, respectively), and Cohen's kappa statistic (κ). RESULTS: Stepwise multivariate regression analysis (n = 736) showed difficult obstetric history [odds ratio (OR) 10.04], family history of POP (OR 7.28), and ≥10 years since menopause (OR 4.53) were independent risk factors for prolapse (P < 0.001). When one of the three variables with the strongest influence on POP development was present, the PRI for all women showed a PPV of 82%, NPV of 68%, and κ of 0.47 for predicting symptomatic POP requiring treatment. In women under 60 years (n = 349), logistic regression revealed difficult obstetric history (OR 9.108), positive family history (OR 8.016), and body mass index (OR 2.274) as independent risk factors. CONCLUSIONS: Eighty-seven percent of our patient cohort with symptomatic POP requiring therapy could be identified by the PRI, which may be useful for counselling and education.

Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I.

OBJECTIVE: In 2008 GROINSS-V-I, the largest validation trial on the sentinel node (SN) procedure in vulvar cancer, showed that application of the SN-procedure in patients with early-stage vulvar cancer is safe. The current study aimed to evaluate long-term follow-up of these patients regarding recurrences and survival. METHODS: From 2000 until 2006 GROINSS-V-I included 377 patients with unifocal squamous cell carcinoma of the vulva (T1, <4 cm), who underwent the SN-procedure. Only in case of SN metastases an inguinofemoral lymphadenectomy was performed. For the present study follow-up was completed until March 2015. RESULTS: Themedian follow-up was 105 months (range 0­179). The overall local recurrence ratewas 27.2% at 5 years and 39.5% at 10 years after primary treatment, while for SN-negative patients 24.6% and 36.4%, and for SN-positive patients 33.2% and 46.4% respectively (p = 0.03). In 39/253 SN-negative patients (15.4%) an inguinofemoral lymphadenectomy was performed, because of a local recurrence. Isolated groin recurrence rate was 2.5% for SN-negative patients and 8.0% for SN-positive patients at 5 years. Disease-specific 10-year survival was 91% for SN-negative patients compared to 65% for SN-positive patients (p b .0001). For all patients, 10-year disease-specific survival decreased from 90% for patients without to 69% for patients with a local recurrence (p b .0001).

Standardised Registration of Surgical Complications in Laparoscopic-Gynaecological Therapeutic Procedures Using the Clavien-Dindo Classification.

Introduction: The registration of complications represents an important component in the evaluation of surgical therapeutic procedures. The aim of the present study was to examine the frequency of occurrence as well as the severity of surgical complications after laparoscopic-gynaecological operations in a standardised manner using the Clavien-Dindo system. Material and Methods: Altogether 7438 treatment courses after laparoscopic-gynaecological interventions by 9 working groups were evaluated. Covariates recorded were the technical complexity of the operation, type of study cohort, study size, data acquisition as well as study centre. Target variables recorded were the surgical morbidity rate, subdivided into mild (Clavien-Dindo grade I-II) and severe complications (Clavien-Dindo grade III-V). In addition, a binary logistic regression analysis for the mentioned covariates and the occurrence of surgical complication was carried out. Results: 946 complications were recorded (overall complication rate: 13 %). These included 664 mild complications (8.9 %) and 305 severe complications (4.1 %). A correlation was found between the covariates technical complexity (relative risk [rR] 1.37; p < 0.01), study size (rR: 0.35; p < 0.01) and study centre (rR 0.19; p < 0.01) and the occurrence of surgical complications. Conclusion: By means of a standardised registration of complications using the Clavien-Dindo classification it appears to be possible to limit the methodologically caused underestimation of surgical morbidity in the retrospective evaluation of gynaecological-endoscopic therapeutic procedures. Factors decisively influencing the surgical morbidity of gynaecological-laparoscopic therapeutic procedures are the respective operative experience of the treating facility as well as the technical complexity of the intervention.

Long-term risk of fibroid recurrence after laparoscopic myomectomy.

OBJECTIVE: The use of laparoscopic myomectomy as a surgical treatment for uterine leiomyoma is associated with low intraoperative morbidity and short hospitalization. Limited data about the long-term outcome of this surgical approach are available. The aims of this study were to estimate the risk of uterine fibroid recurrence after laparoscopic myomectomy and to identify factors contributing to the rate of fibroid relapse. STUDY DESIGN: Between 1996 and 2003, 331 patients underwent laparoscopic myomectomy to treat uterine leiomyoma in our hospital; 224 of these patients consented to participate in our 2009 follow-up survey. Clinical symptomatic uterine leiomyoma recurrence was defined as relapse. Recurrence rates at 24 and 60 months post-operatively were calculated for the study population. Fisher's exact tests were used to examine the impacts of factors previously linked to an increased risk of fibroid recurrence, including (1) patient age at the time of initial surgery, (2) pre-operative body mass index, (3) number and localization of uterine leiomyoma removed, and (4) pregnancy and (5) delivery after laparoscopic myomectomy on fibroid recurrence in our study cohort. RESULTS: We observed 75 recurrences in 224 patients. The cumulative risk of recurrence was 4.9% at 24 months and 21.4% at 60 months post-operatively. An age of 30-40 years and the presence of more than one fibroid at the time of initial laparoscopic myomectomy were identified as factors significantly increasing the risk of symptomatic recurrence after laparoscopic myomectomy (31.25% and 38.71%, respectively; both p<0.01). CONCLUSION: Patients with multiple uterine leiomyoma and those in the third decade of life should be counselled thoroughly about the risk of recurrence prior to laparoscopic myomectomy. The low observed recurrence rate in peri- and postmenopausal patients in our study may support the use of laparoscopic myomectomy as a uterus-preserving surgical alternative beyond the reproductive period.

Prophylactic bilateral salpingectomy (PBS) to reduce ovarian cancer risk incorporated in standard premenopausal hysterectomy: complications and re-operation rate.

PURPOSE: Hysterectomy for benign conditions can be combined with bilateral salpingectomy to prevent re-intervention for malignant or benign fallopian tube pathologies. The objective of this study was to evaluate the benefit of prophylactic bilateral salpingectomy (PBS) in standard hysterectomy in premenopausal women. METHODS: This retrospective cohort study included all premenopausal patients at our institution who underwent laparoscopically assisted vaginal hysterectomy (LAVH) without oophorectomy for benign pathologies between 2001 and 2007 [PBS group (LAVH + PBS), 2006-2007; non-PBS group (LAVH without PBS), 2001-2005]. Electronic and paper-based files as well as questionnaire responses were analyzed. In 2010, a survey on patients of a non-BRCA background with and without PBS was requested to complete a standardized questionnaire. Data were analyzed for differences between both subgroups regarding surgical outcome and adnexal pathologies as reported in the postoperative follow-up. RESULTS: Surgical outcomes of 540 patients (PBS: 127; non-PBS: 413) revealed no difference between groups. No preneoplastic or malignant lesions were diagnosed in the fallopian tubes. Follow-up (non-PBS 92 months, PBS 55 months; p < 0.01) responses from 295 (54.6 %) patients showed a higher incidence of benign adnexal pathologies in the non-PBS group (26.9 vs. 13.9 %; p = 0.02). The rate of LAVH-related surgical re-intervention was higher in the non-PBS group (12.56 vs. 4.16 %; p = 0.04). No malignant neoplasm was reported in the cohort. CONCLUSIONS: PBS did not increase the complication rate and reduced the incidence of adnexal pathologies requiring surgical re-intervention. Prospective trials should clarify the impact of PBS on cancer mortality.

Sonographic discrimination between benign and malignant adnexal masses in premenopause.

PURPOSE: The aim of this study was to assess the diagnostic value of sonographic pattern recognition by experts, a standardized morphological scoring system, the risk malignancy index (RMI) and CA 125 assay for the preoperative assessment of ovarian lesions in premenopausal patients. MATERIAL AND METHODS: Diagnostic work-up of 1320 patients who underwent surgical exploration due to an adnexal mass at a tertiary referral center were included. We assessed the discriminative value of pattern recognition, a sonographic morphological scoring system, RMI and CA 125 by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa for each diagnostic approach while using histopathology as the reference standard. RESULTS: Pattern recognition showed the highest discriminative power with an observed kappa of 0.53. Sensitivity and specificity yielded 0.76 and 0.97 respectively. Combining pattern recognition with CA 125 serum measurement in the context of a triage system diminished the diagnostic value (kappa: 0.24; sensitivity: 0.29 specificity: 0.97). For the RMI we observed a sensitivity of 0.54 and a specificity of 0.96 and estimated kappa value yielded 0.37. Omitting the CA 125 assay and using a morphological sonographic assessment system increased the kappa value to 0.45 with sensitivity and specificity observed at 0.61 and 0.97 respectively. CONCLUSION: Expert pattern recognition was found to be the method with the highest discriminative power in assessing an adnexal mass during premenopause. Additional assessment of serum CA 125 diminished the diagnostic accuracy. Standardized morphological sonographic assessment resulted in a moderate diagnostic accuracy. Supplementing the morphological sonographic assessment with CA 125 by using the RMI algorithm did not improve the diagnostic value.

Liver resection in selected patients with metastatic breast cancer: a single-centre analysis and review of literature.

PURPOSE: Despite the development of modern chemotherapeutics and target-specific drugs as well as improved surgical techniques, prognosis of metastatic breast cancer remains poor. Only a small number of selected patients will be eligible for liver resection and/or alternative metastatic ablation. Data on prognostic factors for patients with surgically resectable liver metastases of breast cancer are scarce at present. METHODS: From 1997 to 2010, 50 patients with hepatic metastases of breast cancer have undergone laparotomy with the intention to undergo a curative liver resection at our institution. Data from these patients were collected in a prospectively maintained standardized liver resection data base. RESULTS: Liver resection was performed in 34 patients. Resection margins were clear in 21 cases (R0). Nine patients lived for more than 60 months after liver resection. The observed 5-year survival rate was 21% for all 50 patients, 28% for resected patients and 38% after R0-resection. On univariate analysis, survival rates of the resected patients were statistically significantly influenced by R-classification, age, extrahepatic tumour at the time of liver resection, size of metastases and HER2 expression of liver metastases. Multivariate analysis revealed absence of HER2 expression, presence of extrahepatic tumour and patient's age ≥50 years as independent factors of poor prognosis. CONCLUSIONS: Breast cancer patients younger than 50 years with technically resectable hepatic metastases, minimal extrahepatic tumour and positive HER2 expression appear to be suitable candidates for liver resection with curative intent. An aggressive multi-disciplinary management of those patients including surgical treatment may improve long-term survival.

Laparoscopic lymphocele fenestration in gynaecological cancer patients after retroperitoneal lymph node dissection as a first-line treatment option.

OBJECTIVE: To evaluate laparoscopic lymphocele fenestration (LLF) as a first-line treatment in gynaecological cancer patients with a history of retroperitoneal lymph node dissection (LND). DESIGN: Retrospective cohort study. SETTING: A tertiary referral centre. POPULATION: Patients who underwent LLF between January 2001 and December 2010 for a symptomatic lymphocele following retroperitoneal LND. METHODS: Surgical outcomes of 102 patients who underwent LLF at our hospital between January 2001 and December 2010 were analysed. Patients were identified using hospital database search software, and hand-written and electronic charts were reviewed. MAIN OUTCOME MEASURES: Outcomes included operating time, blood loss, conversion rate, intra- and postoperative complication rates, hospital stay and relapse rate. RESULTS: A total of 132 lymphoceles were fenestrated in 102 patients. The mean duration of surgery was 115.6 minutes and the average intraoperative blood loss per patient was 146 ml. The overall conversion rate to laparotomy was 7.8%. Intra- and postoperative complication rates were estimated at 9.8 and 5.9%, respectively. The rate of intraoperative and postoperative complications was significantly higher in patients after pelvic plus paraaortic LND (23.8%), compared with those after pelvic LND only (3.6%; P > 0.01). The mean follow-up time was 60.4 months and a total of seven symptomatic recurrences of lymphoceles were observed (a recurrence rate of 6.9%). CONCLUSIONS: For the treatment of symptomatic lymphoceles, LLF has previously been established as an efficient first-line treatment option in a post-transplant context. Our data suggest that these favourable results for LLF may be transferable to gynaecological cancer patients.

Combined staging at one stop using MR mammography: evaluation of an extended protocol to screen for distant metastasis in primary breast cancer - initial results and diagnostic accuracy in a prospective study.

PURPOSE: Accurate staging of primary breast cancer is essential for the therapeutic approach. Modern whole-body MR scanners would allow local and distant staging during a single examination. Accordingly, we designed a dedicated protocol for this purpose and prospectively evaluated the diagnostic accuracy. MATERIALS AND METHODS: 65 consecutive breast cancer patients underwent pre-therapeutic MRI (1.5 T). A bilateral breast protocol (axial: T1w/GRE dynamic contrast-enhanced, T2w/TSE; TA: 10 min) was extended to screen for distant metastasis at one stop without repositioning (coronal: T2w/HASTE, T1w/VIBE; FOV: thorax, abdomen and spine; TA: 90 sec; multichannel surface coils). The standard of reference was S3 guideline-compliant staging examinations. Global assessment regarding the presence of distant metastasis was performed independently by two experienced and blinded radiologists (five-level confidence score). Inter-rater agreement (weighted kappa) and observer scoring were analyzed (contingency tables). RESULTS: The prevalence of synchronous metastases was 7.7 % (n = 5). The protocol enabled global assessment regarding the presence of distant metastasis with high accuracy (sensitivity: 100 %; specificity: 98.3 %) and inter-rater agreement (kappa: 0.92). CONCLUSION: Applying the extended MRI protocol, accurate screening for distant metastasis was possible in combination with a dedicated breast examination.

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study.

BACKGROUND: Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity. PATIENTS AND METHODS: An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m(2)) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m(2)/week) (arm-B) in patients with stage IB-IIB CC after surgery. Primary objective was progression-free survival (PFS). RESULTS: Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2% (95% CI 81.2-93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001). CONCLUSIONS: Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.

Efficacy control of therapy using circulating epithelial tumor cells (CETC) as "liquid biopsy": trastuzumab in HER2/neu-positive breast carcinoma.

PURPOSE: The majority of targeted personalized cancer therapies are effective only in part of the patients, and most of these drugs are excessively expensive. Therefore, methods are urgently required, which reveal already early during treatment, whether the therapy is effective. In the present report, monitoring of circulating epithelial tumor cells (CETC) was used as a timely control of trastuzumab therapy in patients with HER2/neu-positive breast cancer. METHODS: Seventy-nine sequential HER2/neu-positive breast cancer patients, 35 without trastuzumab, and 36 treated with 1 year of trastuzumab treatment were included. CETC from unseparated white blood cells stained with FITC-anti-EpCAM were analyzed repeatedly during chemotherapy and between 2 and 10 times during 1 year of maintenance treatment or observation. RESULTS: Patients treated with trastuzumab had a better relapse-free survival than patients without trastuzumab treatment during the first 2-4 years of follow-up. Decrease in numbers or no change versus highly variable numbers or increase (fivefold or more) allowed to discriminate highly significantly and clearly (P < 0.0001, hazard ratio 5.5) between patients with a low or high risk of relapse. An increase in CETC was accompanied by an increasing portion of cells containing a very high number of HER2/neu gene amplificates. CONCLUSIONS: Analysis of the behavior of CETC can, in the future, contribute to evaluate the efficacy of targeted therapy early during the course of the disease, sparing patients unnecessary treatment but also to reduce the costs for the health system and to downsize the extent and length of clinical studies.

Potential of MR mammography to predict tumor grading of invasive breast cancer.

PURPOSE: Tumor grading (TG) is one of the most widely used prognostic factors in the case of breast cancer. This study aims to identify the potential of magnetic resonance mammography (MRM) to non-invasively assess TG. MATERIALS AND METHODS: 399 invasive breast cancers were included (IRB approval; standardized clinical MRM protocols). All breast cancers were prospectively evaluated by two experienced (> 500 MRM) and blinded radiologists in consensus. In every cancer a set of 18 previously published MRM descriptors was assessed. These were assessed by univariate and multivariate analysis to identify the potential of MRM to predict TG (X2 statistics; binary logistic regression; area under the ROC curve [AUC]). RESULTS: 8 of 18 MRM descriptors were associated with TG, e. g. internal structure, edema (p < 0.001), as well as skin thickening and destruction of the nipple line (p < 0.05). MRM was feasible to predict TG by multivariate analysis (p < 0.001). The highest potential could be identified to predict well differentiated breast cancers with good prognosis (AUC = 0.930). CONCLUSION: MR mammography was able to non-invasively assess tumor grading in a standard protocol. Since tumor grading is a surrogate for overall survival, these results provide further evidence to the clinical application of MR mammography as a noninvasive prognostic tool.

[Space-occupying tumor of the temporal region with facial nerve palsy, vestibular dysfunction and hearing loss]. / Raumforderung der Regio temporalis bei Fazialisparese, vestibulärem Ausfall und Hörminderung.

A 73-year-old female patient complained of right-sided facial pain, progressive loss of hearing, giddiness when changing position, a pre-auricular swelling and lack of facial expression. Clinically there was a right-sided indolent and immovable swelling approximately 7 cm in size and an incomplete ipsilateral acute peripheral facial paralysis. Magnetic resonance tomography revealed a space-occupying lesion approximately 75 mm in diameter right temporal and multilocular metastases in the pelvis, spinal column, clavicle and skull. Histology showed this to be a well to moderately differentiated adenocarcinoma with centers of positive immune response to GCDFP-24 (gross cystic disease fluid protein). The subsequent computed tomography of the thorax and mammography located the approximately 25 mm in size primary tumor in the left breast. After surgery and radiation therapy the TNM classification was a tubular adenocarcinoma of the left breast grade 2, T2N0M1 (OSS multiple osseous, BRA brain) stage IV.