Gestational and Non-gestational Trophoblastic Neoplasia. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 032/049, April 2022).

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Clinico-pathologic characteristics and prognostic factors of ovarian carcinoma with different histologic subtypes - A benchmark analysis of 482 cases.

PURPOSE: Ovarian carcinomas (OCX) have traditionally been thought to arise from the ovarian surface epithelium. However, recent (immuno-) histopathological and molecular analyses suggest that OCX consist of morphological subtypes with different epidemiologic features and a varying prognosis. METHODS: The data of 482 OCX from the Clinical Cancer Registry of Leipzig who were surgically treated between 2000 and 2019 and were evaluated regarding incidence, clinico-pathologic characteristics and prognostic factors. Cases were separated into high-grade and non-high-grade serous tumors. Both groups were analyzed regarding the tumor stage, lymph node involvement, site of origin and prognosis. RESULTS: The overall incidence for OCX was 17.9. The most common histological subtype was high-grade serous OCX (57.9%; 279/482). Patients with high-grade were significantly older than those with a non-high-grade serous OCX (63.9 versus 58.5 years; p < 0.001), more frequently diagnosed at an advanced stage >pT3 (78.5% (219/279) versus 42.8% (87/203); p < 0.001) and showed a 2.4-fold higher frequency of lymph node metastases (53.4% vs. 21.2%; p < 0.02) with a 4.6-fold higher rate of > 1 cm metastatic deposits (pN1b) within the lymph nodes (14.8% vs. 4.6%; p < 0.02). Irrespective of tumor stage and morphological subtype, the 1- and 5-year overall survival (OAS) was 72.9% and 40.8%, respectively. Patients with high-grade serous OCX showed a shorter 5-year OAS compared to non-high-grade serous OCX (34.1% vs. 57.0%; p 0.001). This association was reproducible in patients with an advanced tumor stage irrespective of the histopathologic tumor type serous OCX (pT3: 32.4% vs. pT1: 75.1%; p 0.001) as well as within high-grade (pT3: 28.7% vs. pT1: 55.5%; p = 0.003) and non-high-grade serous OCX (pT3: 43.0% vs. 80.0%; p 0.001). There were no differences in OAS depending on the site of origin (fallopian tube, ovary, peritoneum) within the two histologic subgroups. CONCLUSION: OCX cases from a single institution with uniform surgical treatment and a standardized histopathological workup were evaluated. The poor prognostic outcome of patients with high-grade serous compared non-high-grade serous OCX as well as an advanced stage of the disease was confirmed. This study demonstrates for the first time that the histopathological distinction into high-grade serous and non-high-grade serous tumors may be much more prognostically relevant than the site of origin.

Increase of fallopian tube and decrease of ovarian carcinoma: fact or fake?

PURPOSE: Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube. METHODS: Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes. RESULTS: The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology. CONCLUSION: The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

Endocervical adenocarcinoma in situ (AIS) with ovarian and pulmonary involvement: report of a case and review of the literature suggesting a "seed and soil hypothesis".

PURPOSE: Cervical cancer metastases to the ovary may occur with advanced tumor stage, deep cervical stromal involvement and corpus involvement. Endocervical adenocarcinoma in situ (AIS) with ovarian involvement is exceptionally rare with about twelve reported cases. METHODS: Here we present a case of endocervical AIS with ovarian and pulmonary involvement 39 months after the initial diagnosis. The characteristics of that case were compared and summarized with the eleven previously published cases. RESULTS: The patients' age ranged between 30 and 40 years (median 37.4 years). The time interval between the diagnosis of AIS and ovarian involvement was 26.7 months (range 2-84 months). Majority of the patients are alive without evidence of disease after a median time of 63.4 months (range 9-156 months). All reported cases were positive for high-risk HPV which was associated with strong p16 expression on immunohistochemistry. CONCLUSIONS: The ovarian involvement by endocervical AIS suggests the concept of a transtubal spread of the neoplastic cervical cells with or without previous colonization within the endometrium without evidence of invasive growth, suggesting a seed and soil spread of the disease. In cases with ovarian involvement by the AIS and without additional extragenital spread, the prognosis may be favorable.

Psychometric Properties of the Fatigue Questionnaire EORTC QLQ-FA12 in a Sample of Female Cancer Patients.

CONTEXT: Cancer patients frequently suffer from fatigue. Recently, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life group developed a new 12-item fatigue assessment instrument. OBJECTIVES: The aim of this study was to psychometrically test this questionnaire in comparison with the three-item fatigue scale of the EORTC QLQ-C30. METHODS: A sample of 354 patients who were being treated for breast cancer or gynecologic cancer were examined using the new fatigue questionnaire EORTC QLQ-FA12 and the EORTC QLQ-C30 during their hospital stay (t1) and three months after hospital discharge (t2). Confirmatory factorial analyses, item analyses, test-retest reliability analyses, and correlation analyses were performed. RESULTS: The analyses roughly supported the three-factorial structure of the FA12, which comprised the subscales physical, emotional, and cognitive fatigue. The fit indices of the confirmatory factorial analysis were worse than those of the original article but nevertheless acceptable. Cronbach alpha of the total scale was 0.92; the coefficients of the subscales were between 0.79 and 0.93. The correlation between the EORTC QLQ-FA12 total scale and the fatigue scale of the EORTC QLQ-C30 was 0.69 and the correlation between the t1 and t2 scores was 0.45 for the EORTC QLQ-FA12 total scale and between 0.37 and 0.47 for the subscales. CONCLUSION: The psychometric coefficients justify the calculation of a sum score, which can be used by clinicians to assess the general degree of fatigue. Although the three-item fatigue scale of the EORTC QLQ-C30 stresses the physical aspect of fatigue, the new EORTC QLQ-FA12 covers its emotional and cognitive aspects as well.

Effects of stepped psychooncological care on referral to psychosocial services and emotional well-being in cancer patients: A cluster-randomized phase III trial.

OBJECTIVE: Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. METHODS: In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and emotional well-being half a year after baseline, measured with the Hospital Anxiety and Depression Scale. A secondary endpoint was uptake of outpatient health care. Analysis employed mixed-effects multivariate regression modeling. RESULTS: Thirteen wards were randomized; 1012 patients participated. With stepped care (N = 570; 7 wards), 22% of the patients were referred to CL services and 3% with standard care (N = 442; 6 wards; odds ratio [OR] 10.0; P < .001). Well-being 6 months after baseline was 9.5 after stepped care (N = 341) and 9.4 after standard care (N = 234, ß -0.3; P = .71). After stepped care, patients with psychiatric comorbidity went more often to psychotherapists (OR 4.0, P = .05) and to psychiatrists (OR 2.3, P = .12), whereas patients without comorbidity used psychiatrists less often (OR 0.4, P = .04) than in standard care. CONCLUSIONS: Stepped care resulted in better referral to CL services. The patients' emotional well-being was not improved, but uptake of outpatient psychiatric help was increased in patients with psychiatric comorbidity and decreased in patients without.

Management of Primary Retroperitoneal Mucinous Tumors: A Retrospective Meta-Analysis.

OBJECTIVE: Primary retroperitoneal mucinous tumors (PRMTs) are rare epithelial neoplasms arising in the retroperitoneal space whose pathogenesis is poorly understood. To date, only single-case reports and small case series on diagnosis and management of these tumors exist. The aim of this first-time meta-analysis was to provide more reliable data to inform the management of PRMTs. METHODS: Database searches were conducted to identify case reports and case series between the years of 1975 and 2015. Two cases of patients treated at our institution were also included. Diagnostic, radiographic, surgical, and follow-up data were gathered. Regression modeling was used to identify factors aiding preoperative diagnosis and affecting treatment. Survival analysis including Cox regression modeling was performed to provide insights into treatment effects on the prognosis of female patients with PRMTs. RESULTS: One hundred forty-four cases of PRMTs were included in this analysis. Eighty-nine percent occurred in women. Most of the PRMTs were found to be malignant (53%). No preoperative factors predicting tumor dignity were identified by multiple regression analysis. Five-year disease specific survival of patients with benign and borderline tumors was excellent, reaching 100%, whereas it was only 68% for patients with malignant disease. Adjuvant surgical treatments including hysterectomy, salpingoophorectomy, and lymph node dissection were not associated with a statistically significant survival advantage. However, there was a nonsignificant association of hysterectomy with improved survival (hazard ratio, 0.42; 95% confidence interval, 0.09-2.07; P = 0.285). Adjuvant chemotherapy was associated with reduced survival (hazard ratio 3.791; 95% confidence interval, 1.509-9.526; P = 0.0046). CONCLUSIONS: A reliable diagnosis of a PRMT can only be made by pathological examination of the tumor. Surgical excision is thus necessary to facilitate diagnosis while it also remains the mainstay of treatment. There is no conclusive evidence supporting the role of adjuvant surgical procedures or chemotherapy.

Optimism, pessimism and self-efficacy in female cancer patients.

OBJECTIVE: The aim of this examination was to study whether psychological resource variables (optimism and self-efficacy) decrease when cancer is present and to test the predictive power of these variables for anxiety, depression and quality of life (QoL). METHODS: The patient sample was comprised of 354 German women suffering from breast cancer or gynecological cancer. Participants filled in the resource assessment tools Life Orientation Test-Revised and the General Self-Efficacy Scale as well as the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-4 and the QoL instrument EORTC QLQ-C30 at two time points: (t1) during patients' hospital stay and (t2) 3 months later. RESULTS: The mean scores for optimism (total score: M = 16.2) and self-efficacy (M = 29.8) were even somewhat higher than the corresponding means of the general population. Optimism and self-efficacy were positively correlated with QoL (r between 0.15 and 0.17, P < 0.01) and negatively associated with anxiety and depression (r between -0.17 and -0.36, P < 0.01). However, only optimism was predictive of the t2 anxiety, depression and QoL scores when statistically taking into account the baseline levels of the outcome variables. CONCLUSIONS: Having cancer does not generally reduce optimism and self-efficacy on the level of patients' mean scores. Cancer patients with a high level of habitual optimism will adapt to their disease better than pessimistic patients, even if the baseline levels of the outcome variables have been accounted for.

Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.

Socio-economic disparities in long-term cancer survival-10 year follow-up with individual patient data.

PURPOSE: Reasons for the social gradient in cancer survival are not fully understood yet. Previous studies were often only able to determine the socio-economic status of the patients from the area they live in, not from their individual socio-economic characteristics. METHODS: In a multi-centre cohort study with 1633 cancer patients and 10-year follow-up, individual socio-economic position was measured using the indicators: education, job grade, job type, and equivalence income. The effect on survival was measured for each indicator individually, adjusting for age, gender, and medical characteristics. The mediating effect of health behaviour (alcohol and tobacco consumption) was analysed in separate models. RESULTS: Patients without vocational training were at increased risk of dying (rate ratio (RR) 1.5, 95% confidence interval (CI) 1.1-2.2) compared to patients with the highest vocational training; patients with blue collar jobs were at increased risk (RR 1.2; 95% CI 1.0-1.5) compared to patients with white collar jobs; income had a gradual effect (RR for the lowest income compared to highest was 2.7, 95% CI 1.9-3.8). Adding health behaviour to the models did not change the effect estimates considerably. There was no evidence for an effect of school education and job grade on cancer survival. CONCLUSIONS: Patients with higher income, better vocational training, and white collar jobs survived longer, regardless of disease stage at baseline and of tobacco and alcohol consumption.

Ultrasound plays a key role in imaging and management of genital angiomyofibroblastoma: a case report.

INTRODUCTION: Angiomyofibroblastoma is a benign, rare mesenchymal tumor arising from the genital tract of both men and women and was first described by Fletcher and colleagues in 1992. The tumor needs to be distinguished from other, similar lesions, such as deep and superficial aggressive angiomyxoma and cellular angiofibroma, because aggressive angiomyxoma demands much more extensive treatment. The vast majority of angiomyofibroblastomas arise from the vulva and appear as solid cystic masses on ultrasound images. CASE PRESENTATION: We report a case of a 35-year-old Caucasian woman with an angiomyofibroblastoma arising from the vagina. She presented with a painless mass of about 5cm in diameter that had a rather homogeneous, hypoechoic appearance on ultrasound images. The patient underwent surgical resection of the mass, which was subsequently diagnosed as angiomyofibroblastoma. We present sonographic and magnetic resonance imaging findings, intraoperative and histologic images, and a thorough review of the literature. CONCLUSIONS: In our opinion, ultrasonography is the most valuable tool to establish a preoperative diagnosis of this tumor entity, differentiate it from other lesions of the female genital tract, and plan surgery accordingly. Even though it is a rare tumor, gynecologists should be able to recognize it and to differentiate it from other tumor entities that demand more aggressive treatment. We describe a different sonographic appearance of this tumor than previously reported.

Effect of a structured psycho-oncological screening and treatment model on mental health in cancer patients (STEPPED CARE): study protocol for a cluster randomized controlled trial.

BACKGROUND: High levels of emotional distress in cancer patients often goes unnoticed in daily clinical routine, resulting in severe undertreatment of mental health problems in this patient group. Screening tools can be used to increase case identification, however, screening alone does not necessarily translate into better mental health for the patient. Doctors play a key role in providing basic emotional support and transferring the patients in need of such specific support to mental health professionals. This study investigates whether a stepped care model, combining screening, doctor consultation and professional psycho-oncological service in a structured way, improves the emotional wellbeing of cancer patients. METHODS/DESIGN: This study is a cluster randomized trial with two parallel groups (intervention vs. care as usual), set in an academic hospital. Participants are cancer patients, a total of 1,000 at baseline. The intervention consists of stepped psychosocial care. Step one: screening for distress, step two: feedback of screening results to the doctor in charge of the patient and consultation with the patient, and step three: based on a shared patient-doctor decision, either transferal to the consultation liaison (CL) service or not. The outcome will be emotional well-being half a year after baseline, ascertained with the Hospital Anxiety and Depression Scale. Randomization will be done by the cluster randomization of wards. DISCUSSION: Mental health problems not only cause emotional suffering but also direct and indirect costs. This calls for timely and adequate psychosocial support, especially as we know that such support is effective. However, not every cancer patient can and must be treated by a mental health professional. Allocating limited resources most sensibly and economically is of crucial importance for our healthcare system to ensure the best quality of care to as many patients as possible. It is the hope of the STEPPED CARE trial that this model is both effective and efficient, and that it can be implemented in other hospitals as well, if proven to be effective. TRIAL REGISTRATION: Clinical Trials Register (Clinicaltrials.gov) identifier: NCT01859429 registration date 17 May 2013.

Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

A cut-off value of 2 cm in tumor size is of prognostic value in surgically treated FIGO stage IB cervical cancer.

OBJECTIVES: Limited knowledge exists about the value of tumor size in surgically treated cervical cancer (CX) using a tumor size of 2 cm as cut-off value. METHODS: A total of 366 cases of CX FIGO stage IB who received upfront surgery were evaluated regarding tumor size, the prediction of pelvic lymph node involvement, and recurrence-free and overall survival during a median follow-up time of 94 months. Tumors ≤2.0 cm were defined as small, tumors 2.1-4.0 cm as medium sized and those larger than 4 cm as bulky disease. RESULTS: Small tumors were seen in 28.7%, medium sized in 52.5% and bulky tumors in 18.9%. There was a significant higher frequency of pelvic lymph node involvement with increasing tumor size (13.3% vs. 23.4% vs. 43.5%, respectively; p<0.001) and an increase of recurrent disease (6.7% vs. 18.8% vs. 29.4%, respectively; p<0.001). The 5-year overall survival rate was significantly reduced with increasing tumor size (94.0% vs. 85.1% vs. 69.9%, respectively; p<0.001). Pelvic lymph node involvement and maximal tumor size were independent prognostic factors for both recurrence-free and overall survival in multivariate analysis. CONCLUSIONS: The results support that tumor size is of prognostic impact in FIGO stage IB cervical carcinomas. A further substaging is suggested for tumors up to 4.0 cm maximum dimension using a cut-off value of 2.0 cm as discriminator. Patients with tumors ≤2.0 cm may represent low risk disease.

CD34(low) and SMA(high) represent stromal signature in uterine cervical cancer and are markers for peritumoral stromal remodeling.

Peritumoral desmoplastic stromal reaction (DSR) with myofibroblastic phenotype may be of prognostic impact in uterine cervical carcinoma. The present study evaluates the immunostaining (CD34 and smooth muscle actin; SMA) of 97 squamous cell cancers. Staining was scored as low/negative (<5% stroma positive), moderate (patchy/focal expression, 5%-50%), or high (diffuse expression throughout peritumoral stroma, >50%) and DSR as negative/weak and moderate/strong. The staining results were correlated to patient survival. Of the cases, 78.3% showed a decreased of CD34 (<5% stromal positivity) and 71.9% an increased SMA staining with more than 50% SMA positive stromal cells. Tumors representing moderate/strong DSR showed a significant decreased CD34 (P=.001) and an increased but not statistically significant SMA staining (P=0.345). Cases with low CD34 and high SMA staining showed reduced 5-year overall survival when compared to cases with high CD34 and low SMA positivity (59.9 vs 81.0%; P=0.025 and 64.6 vs 81.1%; P=0.243). Peritumoral stromal response in cervical carcinoma is immunohistochemically characterized by CD34(low)/SMA(high) and associated reduced overall survival.

The course of fatigue in patients with gynecologic and breast cancer.

OBJECTIVE: The objective of this study is to examine the course of fatigue in female cancer patients during the first months after treatment. METHODS: We examined a sample of 110 patients suffering from gynecological or breast cancer. Fatigue was assessed with two questionnaires, the Multidimensional Fatigue Inventory (MFI) and the fatigue scale of the quality of life questionnaire European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30). Participants were tested during their stay in the hospital (t1), two weeks after discharge (t2), and three months after discharge (t3). RESULTS: Fatigue in the patients' sample was markedly higher than the general population reference values. At t1, the effect sizes are d=0.81 (MFI) and d=1.21 (EORTC QLQ-C30 fatigue scale). Age and tumor stage had no significant influence on fatigue, but patients with a long time since diagnosis had higher fatigue levels than patients with a shorter time since diagnosis. From t1 to t3, fatigue mean scores decreased. The correlations between the t1 and the t3 fatigue scores were weak, with correlation coefficients of only about 0.30. CONCLUSION: Though the mean scores of fatigue, averaged across all patients, decreased over the first three months, the individual courses could not be predicted from the t1 score.

Serous tubal in situ carcinoma (STIC) in primary peritoneal serous carcinomas.

Recent new data in the pathogenesis of serous pelvic cancer and the introduction of serous tubal in situ carcinoma (STIC) and its precursors have raised the question that whether all primary peritoneal cancers (PPC) are in fact of tubal origin. Therefore, the present study evaluates the frequency of STIC and its precursor lesions in cases that were diagnosed as PPC using the morphologic criteria of the most recent WHO classification. The present study evaluates immunohistochemically (Ki-67 and p53 staining) the presence of STIC and its precursor lesions (p53 signature, serous tubal intraepithelial lesion [STIL]) in the completely processed Fallopian tubes of 46 consecutive PPCs. STIC was detected in 10 patients (21.7%) and p53 signature in 9 cases (19.6%). No STIL was observed. All except 1 STIC occurred at the fimbriated end of the Fallopian tube, and a bilateral involvement was detected in 2 cases. These precursor lesions were missed during the initial routine screening. Repeated staining for p53 was negative in STIC in 2 cases. STIC and p53 signature as precursor lesions of pelvic serous cancer are detected in some but not all the cases of primary serous peritoneal cancer. There might be the 2 different carcinogenetic pathways within PPC, and further studies are required to identify the source of serous cancer in cases without an STIC lesion.

Health-related quality of life during sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: a multicenter phase ii study of the North Eastern German Society of Gynecological Oncology.

AIM: We describe the impact of a sequential dose-dense schedule of carboplatin and paclitaxel on the quality of life (QoL) of patients with ovarian cancer. PATIENTS AND METHODS: In this multicenter phase II trial, four cycles of carboplatin followed by 12 cycles of weekly paclitaxel were applied after cytoreductive surgery. QoL was assessed using the QoL questionnaires EORTC QLQ-C30 and QLQ-OV28 before chemotherapy (baseline), after four cycles of carboplatin, at the end of treatment (EOT), and after 6, 12, and 24 months. RESULTS: Out of 104 eligible patients 87 (84%) participated in at least one QoL assessment. At baseline, all QLQ-C30 scales and symptoms were significantly worse than age-adjusted values for the general population. Subsequently QoL improved in general. During chemotherapy with paclitaxel, most functioning scales and symptoms worsened slightly (not significantly). However, peripheral neuropathy and chemotherapy-related side-effects increased to clinically important levels. At the end of treatment, most QoL scores were similar to those of the general population, but physical functioning and fatigue were worse. Sexual functioning and peripheral neuropathy remained problematic. CONCLUSION: QoL was affected mainly by the weekly paclitaxel schedule, but effects were in most cases only temporary. A dose-dense regimen using a sequential protocol may be favourable in terms of QoL.

(Laterally) extended endopelvic resection: surgical treatment of locally advanced and recurrent cancer of the uterine cervix and vagina based on ontogenetic anatomy.

OBJECTIVE: Pelvic exenteration is mainly applied as a salvage operation for a subset of patients with persistent and recurrent cervicovaginal cancer. The procedure can also cure locally advanced primary disease not suitable for radiotherapy. However, high operative abortion and intralesional tumor resection rates significantly limit its clinical benefit. To improve locoregional tumor control we have proposed to establish cancer surgery on ontogenetic anatomy and, consequently, we have developed the (Laterally) Extended Endopelvic Resection ((L)EER). METHODS: (L)EER is clinically and histopathologically evaluated with a monocentric prospective observational study. Patients with advanced and recurrent cervicovaginal cancer are treatment candidates if distant metastases and tumor fixation at the region of the sciatic foramen can be excluded. RESULTS: 91 patients with locally advanced primary (n=30) and recurrent or persistent (n=61) carcinoma of the cervix and vagina were treated with (L)EER. 74% of the tumors were fixed to the pelvic wall. No (L)EER treatment was aborted, R0 resection was histopathologically confirmed in all cases. (L)EER definitively controlled the locoregional cancer in 92% (95% CI: 85-99) of the patients. Five year overall survival probability was 61% (95% CI: 49-72). CONCLUSIONS: The results of (L)EER treatment confirm the concept of cancer surgery based on ontogenetic anatomy. In patients with locally advanced and recurrent cervicovaginal cancer (L)EER achieves locoregional tumor control both with central disease and with tumors fixed to the pelvic side wall except at the region of the sciatic foramen.