ABSTRACT
BACKGROUND: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. METHODS: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). RESULTS: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives. CONCLUSION: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.
Subject(s)
Emigrants and Immigrants , Matched-Pair Analysis , Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Despite goal-directed hemodynamic therapy, vascular function may deteriorate during surgery for advanced abdominal tumor masses. Fluid administration has been shown to be associated with distinct changes in serum levels of functional proteins. We sought to determine how serum total protein and angiopoietin (ANG) levels change during major abdominal tumor surgery. In addition, ex vivo endothelial nitric oxide synthase (eNOS) activation as well as NO bioavailability in vivo were assessed. METHODS: 30 patients scheduled for laparotomy for late-stage ovarian or uterine cancer were prospectively included. Advanced hemodynamic monitoring as well as protocol-driven goal-directed fluid optimization were performed. Total serum protein, ANG-1, -2, and soluble TIE2 were determined pre-, intra-, and postoperatively. Phosphorylation of eNOS was assessed in microvascular endothelial cells after incubation with patient serum, and microvascular reactivity was determined in vivo by near-infrared spectroscopy and arterial vascular occlusion. RESULTS: Cardiac output as well as preload gradually decreased during surgery and were associated with a median total fluid intake of 12.8 (9.7-15.4) mL/kg*h and a postoperative fluid balance of 6710 (4113-9271) mL. Total serum protein decreased significantly from baseline (66.5 (56.4-73.3) mg/mL) by almost half intraoperatively (42.7 (36.8-51.5) mg/mL, p < 0.0001) and remained at low level. While ANG-1 showed no significant dilutional change (baseline: 12.7 (11.9-13.9) ng/mL, postop.: 11.6 (10.8 -13.5) ng/mL, p = 0.06), serum levels of ANG-2 were even increased postoperatively (baseline: 2.2 (1.6-2.6) ng/mL vs. postop.: 3.4 (2.3-3.8) ng/mL, p < 0.0001), resulting in a significant shift in ANG-2 to ANG-1 ratio. Ex vivo phosphorylation of eNOS was decreased depending on increased ANG-2 levels and ANG-2/1 ratio (Spearman r = - 0.37, p = 0.007). In vivo, increased ANG-2 levels were associated with impaired capillary recruitment and NO bioavailability (Spearman r = - 0.83, p = 0.01). CONCLUSIONS: Fluid resuscitation-associated changes in serum vascular mediator profile during abdominal tumor surgery were accompanied by impaired eNOS activity ex vivo as well as reduced NO bioavailability in vivo. Our results may explain disturbed microvascular function in major surgery despite goal-directed hemodynamic optimization.
Subject(s)
Angiopoietins , Nitric Oxide Synthase Type III/blood , Nitric Oxide , Ovarian Neoplasms/surgery , Uterine Neoplasms/surgery , Angiopoietin-2 , Angiopoietins/blood , Endothelial Cells , Female , Gynecologic Surgical Procedures , Humans , Prospective StudiesABSTRACT
BACKGROUND: Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as 'foreign') cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016. METHODS: During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment. RESULTS: No significant differences regarding the patients' survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis. CONCLUSIONS: In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression.
Subject(s)
Genital Neoplasms, Female/ethnology , Genital Neoplasms, Female/mortality , Head and Neck Neoplasms/ethnology , Head and Neck Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Genital Neoplasms, Female/therapy , Germany/ethnology , Head and Neck Neoplasms/therapy , Humans , Kaplan-Meier Estimate , Male , Matched-Pair Analysis , Middle Aged , Progression-Free Survival , Retrospective Studies , White People , Young AdultABSTRACT
BACKGROUND: Cytoreductive surgery (CS) in late-stage ovarian cancer patients is often challenging due to extensive volume shifts, and high fluid intake may provoke postoperative complications. Expression of vasoactive mediators is altered in cancer patients, which may affect systemic vascular function. We sought to assess how serum levels of vasoactive markers and mediators change during CS in ovarian cancer. METHODS: Following IRB approval and informed consent, pre- and postoperative serum samples were analyzed in 26 late-stage ovarian cancer patients using multiplex protein arrays and ELISA. RESULTS: The proinflammatory cytokines and chemokines IL-6, IL-8, and CCL2 were significantly elevated after 24 hrs compared to the baseline values, with IL-6 and IL-8 being most prominently increased. While ANGPT1 remained unchanged after surgery, its competitive antagonist ANGPT2 was significantly increased. In contrast, serum levels of the ANGPT receptor TIE2 were decreased to 0.6 of the baseline values. While VEGF-D, E-selectin, P-selectin, ICAM-1, and PECAM-1 remained unchanged, serum activity of both thrombomodulin and syndecan-1 was significantly increased following surgery. CONCLUSION: We identified a regulatory network of acute-phase reaction during CS in late-stage ovarian cancer. This suggests that IL-6 exerts positive regulation of other proinflammatory mediators and, by upregulating ANGPT2 and suppressing ANGPT1, induces a serum profile that promotes vascular leakage. This may contribute to the observed hemodynamic alterations during CS procedures.
Subject(s)
Inflammation/metabolism , Ovarian Neoplasms/immunology , Ovarian Neoplasms/surgery , Aged , Chemokine CCL2/blood , Cytoreduction Surgical Procedures , Female , Humans , Inflammation/blood , Interleukin-6/blood , Interleukin-8/blood , Kinetics , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/bloodABSTRACT
OBJECTIVE: To analyze the types of treatment of abnormally invasive placenta (AIP) and to investigate the self-reported physical and mental short- and long-term sequelae. METHODS: This single-center observational study was performed between 2003 and 2017. Women with prenatal or intrapartum diagnosis of AIP were identified through the departmental database. Classification was performed according to the time of diagnosis establishment and the type of treatment. Medical complications overall and according to the type of treatment were analyzed. Data about women's perception of diagnosis, treatment, and short- and long-term sequelae were gathered by questionnaire. RESULTS: Cases were classified into four groups: prenatal diagnosis, cesarean hysterectomy (A, n = 10); prenatal diagnosis, expectant management (B, n = 19); intrapartum diagnosis, cesarean hysterectomy (C, n = 6); intrapartum diagnosis, conservative therapy (D, n = 20). Depth of invasion, total units of transfused red blood cells, and the need for reoperation differed between the treatment groups. Expectant management was successful in 94.7% of cases. Irrespective of the treatment group, 73.3% of women perceived the condition as serious or life-threatening; 30.0% utilized psychological support; and 36.7% reported persistent pain or problems. 37.5% of women after uterine preservation had another live birth, AIP recurred in 44.4% of cases. CONCLUSION: Conservative management of AIP is feasible in selected cases. The condition is perceived as life-threatening and has a lasting impact on the physical, mental, and reproductive health of those affected. This finding merits further investigation. AIP continues to be a condition with high morbidity.
Subject(s)
Cesarean Section/methods , Placenta Accreta/surgery , Placenta Diseases/surgery , Adult , Female , Humans , Placenta Diseases/psychology , Pregnancy , Self ReportABSTRACT
PURPOSE: Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized. METHODS: This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA). RESULTS: Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail. CONCLUSIONS: This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.
Subject(s)
Antigens, Surface/metabolism , Breast Neoplasms/metabolism , Glutamate Carboxypeptidase II/metabolism , Adult , Aged , Aged, 80 and over , Antigens, Surface/genetics , Biomarkers , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Female , Gene Expression , Glutamate Carboxypeptidase II/genetics , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Radioisotopes/therapeutic use , Survival Analysis , Treatment OutcomeABSTRACT
Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of value in discriminating benign and malignant cervical diseases. Carcinoembryonic antigen and alpha-fetoprotein distinguished precancerous breast and vulva diseases from healthy controls. These findings show that luminescent oxygen channeling immunoassays-based tumor marker assays provide reliable results in routine diagnostics.
Subject(s)
Biomarkers, Tumor/blood , CA-125 Antigen/blood , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Genital Neoplasms, Female/blood , Mucin-1/blood , alpha-Fetoproteins/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/blood , Case-Control Studies , Female , Genital Neoplasms, Female/pathology , Humans , Immunoassay/methods , Middle Aged , ROC Curve , Sensitivity and Specificity , Young AdultABSTRACT
OBJECTIVES: Extensive surgical efforts to achieve an optimal debulking (no residual tumor) in primary surgery of ovarian cancer are today's criterion standard in gyneco-oncologic surgery. However, it is controversial whether extensive surgery, including resections of metastases in the upper abdomen and bowel resections, is justifiable in patients with not completely operable lesions. METHODS: All patients who had undergone surgery for ovarian cancer in the years 2002 to 2013 at our institution were viewed (n = 472). We retrospectively identified 278 operations for primary ovarian cancer. Ninety-six (35%) of the 278 patients showed postoperative tumor residuals and were included in this study. RESULTS: Fifty-five (57%) of 96 patients underwent bowel resection, showing significantly higher complication rates (64% vs 39% minor complications, P = 0.017; 31% vs 9.8% severe complications, P = 0.013) compared with patients without bowel resections as well as no improvement in progression-free or overall survival (median overall survival, 19.5 vs 32.9; P = 0.382). Multiple anastomoses (≥2) were associated with higher rates for anastomotic leakage (16.7% vs 2.6%, P = 0.02) and a higher mortality (16.7% vs 0%, P = 0.04) compared with patients with only 1 anastomosis. Extensive surgery of the upper abdomen was not associated with a significant increase in complication rates. CONCLUSIONS: Because of the increased morbidity of bowel resections without any evidence for improvement of survival, we suggest to restrain from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumor bulk.
Subject(s)
Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial , Female , Humans , Middle Aged , Neoplasm Staging , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: To analyze the trends and developments among journals in the specialty of obstetrics and gynecology. METHODS: Using the Journal Citation Reports from 2007 to 2013, we analyzed the impact factor (IF), Eigenfactor® Score (ES), and Article Influence® Score (AIS) of 43 journals in the field of obstetrics and gynecology published in this time period. RESULTS: From 78 journals of the Journal Citation Report 2013, 43 were selected for this study. The mean IF grew from 1.68 ± 0.97 in 2007 to 2.12 ± 1.05 in 2013, the ES from 0.0113 ± 0.0169 to 0.0114 ± 0.0140, and the AIS from 0.513 ± 0.302 to 0.663 ± 0.359. Differences in the IF, ES, and AIS between journals from the United States versus Europe could be observed. In most cases, the IF, ES, and AIS increased between 2007 and 2013. Strong correlations could be found between IF, AIS, and ES. CONCLUSIONS: The overall mean IF for obstetrical and gynecological journals increased over the analyzed time period. The IF remains the standard measure to compare scientific journals. It correlates well with two major alternative measures of scientific impact, the ES and especially the AIS. Other measures are evolving and might show superior usage in the future.
Subject(s)
Gynecology/trends , Journal Impact Factor , Obstetrics/trends , Periodicals as Topic/statistics & numerical data , Publishing/trends , Bibliometrics , Female , Humans , Pregnancy , Publishing/statistics & numerical data , United StatesABSTRACT
PURPOSE: The management of cervical cancer in pregnancy persists to be challenging. Therefore, identification of factors that influence the choice of therapeutic management is pivotal for an adequate patient counseling. METHODS: We present a literature review of 26 studies reporting 121 pregnancies affected by cervical cancer. Additionally, we add a retrospective case series of five patients with pregnancy-associated cervical cancer diagnosed and treated in our clinic between 2006 and 2013. RESULTS: The literature review revealed that the therapeutic management during pregnancy varies according to the gestational age at diagnosis, while in the postpartum period no influence on the treatment choice could be detected. Also in our case series the choice of oncologic therapy was influenced by the gestational age, the wish to continue the pregnancy and the risks of delaying definitive treatment. CONCLUSIONS: There are no standardized procedures concerning the treatment of cervical cancer in pregnancy. Therefore, in consultation with the patient and a multidisciplinary team, an adequate individualized treatment plan should be determined.
Subject(s)
Colposcopy/methods , Lymph Nodes/pathology , Neoadjuvant Therapy/methods , Pregnancy Complications, Neoplastic/pathology , Pregnancy Complications, Neoplastic/therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Adult , Female , Humans , Lymph Node Excision/methods , Neoplasm Staging , Postpartum Period , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Outcome , Retrospective Studies , Treatment Outcome , Uterine Cervical Neoplasms/diagnosisABSTRACT
This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced , Neoplasm Recurrence, Local/therapy , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Adult , Aged , Carcinoma, Ovarian Epithelial , Cisplatin/adverse effects , Cisplatin/analysis , Cisplatin/pharmacokinetics , Combined Modality Therapy , DNA Adducts/analysis , Female , Humans , Middle AgedABSTRACT
Several authors question the potential benefit of preoperative magnetic resonance imaging (MRI) against the background of possible overdiagnosis, false-positive findings, and unnecessary resections in patients with newly diagnosed breast cancer. In order to reveal a better selection of patients who should undergo preoperative MRI after histological confirmed breast cancer, the present analysis was implemented. We aimed to evaluate the influence of preoperative breast MRI in patients with newly diagnosed breast cancer to find subgroups of patients that are most likely to benefit from preoperative MRI by the detection of occult malignant foci. A total of 1102 consecutive patients who underwent treatment for primary breast cancer between 2002 and 2013 were retrospectively analyzed. All patients underwent triple assessment by breast ultrasound, mammography, and bilateral breast MRI. MRI findings not seen on conventional imaging that suggested additional malignant disease was found in 344 cases (31.2 %). Histological confirmed malignant foci were found in 223 patients (20.2 %) within the index breast and in 28 patients (2.5 %) in the contralateral breast. The rate of false-negative biopsies was 31 (2.8 %) and 62 (5.6 %), respectively. Premenopausal women (p = 0.024), lobular invasive breast cancer (p = 0.02) as well as patients with high breast density [American College of Radiology (ACR) 3 + 4; p = 0.01] were significantly associated with additional malignant foci in the index breast. Multivariate analysis confirmed lobular histology (p = 0.041) as well as the co-factors "premenopausal stage" and "high breast density (ACR 3+4)" (p = 0.044) to be independently significant. Previous studies revealed that breast MRI is a reliable tool for predicting tumor extension as well as for the detection of additional ipsilateral and contralateral tumor foci in histological confirmed breast cancer. In the present study, we demonstrate that especially premenopausal patients with high breast density as well as patients with lobular histology seem to profit from preoperative MRI.
Subject(s)
Breast Neoplasms/diagnosis , Magnetic Resonance Imaging , Preoperative Care , Adult , Aged , Biomarkers, Tumor , Breast Neoplasms/metabolism , Breast Neoplasms/surgery , Female , Humans , Magnetic Resonance Imaging/methods , Mammography , Middle Aged , Neoplasm Grading , Neoplasm Staging , Risk Factors , Ultrasonography, MammaryABSTRACT
OBJECTIVE: Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. METHODS: To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. RESULTS: A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. CONCLUSIONS: Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma.
Subject(s)
Adenocarcinoma/immunology , Endometrial Neoplasms/immunology , Macrophages/immunology , T-Lymphocytes, Regulatory/immunology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/immunology , Disease-Free Survival , Endometrial Neoplasms/pathology , Female , Forkhead Transcription Factors/immunology , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymph Nodes/pathology , Lymphatic Metastasis , Lymphatic Vessels/pathology , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Receptors, Cell Surface/immunology , Retrospective StudiesABSTRACT
Background: The surgical treatment of advanced ovarian cancer is associated with extensive tissue trauma, prolonged operating times and a considerable volume shift. It, therefore, represents a challenge for anaesthesiological management. Aim: The aim of this single-centre, retrospective, observational study was to investigate whether intraoperative extensive volume supply influences postoperative outcomes and long-term survival. Methods: The study included 73 patients with a mean (SD) age of 63 (13) years who underwent extensive tumour-reducing surgery for ovarian cancer between 2012 and 2015. The effect of the intraoperative fluid balance on postoperative complications, such as anastomotic insufficiency or pleural effusions, was investigated using logistic regression. Further, the influence of fluid balance, lactate and creatinine levels on 5-year survival was analysed in a Cox regression model. Associations between anaesthesia time and the intraoperative fluid balance were examined using Spearman's rank correlation coefficients. Results: The mean (SD) postoperative fluid balance in the considered patient cohort was 9.1 (3.4) litres (l) at a mean (SD) anaesthesia time of 529 (106) minutes. Cox regression did not reveal a statistically significant effect of the fluid balance, but it did reveal a statistically significant association between the lactate level 24 h following surgery and the 5-year survival (HR [95%-CI] fluid balance: 0.97 [0.85, 1.11]; HR [95%-CI] lactate: 1.79 [1.24, 2.58]). According to logistic regression, the intraoperative fluid balance was associated with an increased chance of postoperative complications in the considered patient cohort (OR [95%-CI] 1.28 [1.1, 1.54]). Conclusions: We could not detect a negative impact of an increased fluid balance on 5-year survival, but a negative impact on postoperative complications was found in our patient cohort.
ABSTRACT
BACKGROUND: The feasibility of neoadjuvant chemotherapy (NAC) and the outcome in patients with Federation of Gynecology and Obstetrics (FIGO) IIIC and IV ovarian cancer were assessed. PATIENTS AND METHODS: 67 patients undergoing interval debulking surgery (IDS) and ≥ 4 courses of platinum-based NAC were analyzed for survival, perioperative morbidity and mortality. RESULTS: The median follow-up was 30 months. The median progression-free survival (PFS) was 17 months, the overall survival (OS) 34 months. The PFS of patients without residual disease (n = 23; 34.3%) was 31 months (p = 0.003), the OS 65 months (p = 0.001). PFS and OS were significantly longer in patients with no residual disease than in patients with 1-10 mm (n = 34; 47.9%) (p = 0.005 and p = 0.0001, respectively) residual disease. No survival benefit was seen for patients with 1-10 mm compared to > 1 cm (n = 12; 16.9%) residual disease (PFS p = 0.518; OS p = 0.077). 1 patient (1.4%) died; 12 patients needed interventional treatment or operation (16.9%) within the first 30 days postoperatively. Out of these, 5 patients (7.0%) had residual or lasting disability. CONCLUSIONS: NAC and IDS are safe and feasible in this series of patients with unfavorable prognosis. IDS does not change the goal of complete cytoreduction and therefore does not compensate for a less radical surgical approach.
Subject(s)
Chemotherapy, Adjuvant/mortality , Gynecologic Surgical Procedures/mortality , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/prevention & control , Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Germany/epidemiology , Humans , Middle Aged , Prevalence , Risk Factors , Survival Analysis , Survival Rate , Treatment Outcome , Young AdultABSTRACT
AIM: To analyze the spectrum of cardiovascular diseases occurring during pregnancy and delivery at a tertiary referral center. METHODS: All patients presenting at our institution with pre-existing or first diagnosis of cardiac disease were recruited. Cardiac and obstetric complications and maternal and neonatal outcomes were recorded. RESULTS: Fifty-two pregnancies in 49 women, including three pregnancy terminations were analyzed. Cardiac lesions were congenital in 26 (53.1%) and acquired in nine (18.4%); six patients (12.2%) had cardiomyopathies, eight (16.3%) ar-rhythmic conditions. A total of 42 women (85.7%) had a pre-existing cardiac condition and seven (14.3%) presented with first manifestation. Overall 22 cardiac complications occurred: five in pregnancy, eight around parturition, nine during follow-up. They included >1 New York Heart Association functional class deterioration (n=5), congestive heart failure/cardiomyopathy (n=5), valve replacement (n=4), sustained arrhythmia (n=3), cerebral insult, aortic dissection, transplantation (one case each), and death (n=2). Mean gestational age at delivery was 36+6. The cesarean section rate was 77.5%; 31.6% were performed for cardiac indications. Obstetric complications happened in 23 pregnancies (46.9%). There was no perinatal loss; cardiac defects were diagnosed in 9.3% (n=5) of offspring. CONCLUSION: Cardiovascular diseases occurring during pregnancy and parturition comprise a heterogeneous spectrum of conditions. Established scores aid in the identification of high-risk patients; however, in our series 14.3% women had been healthy previously.
Subject(s)
Parturition , Pregnancy Complications, Cardiovascular , Pregnancy Outcome , Aortic Diseases/diagnosis , Aortic Diseases/epidemiology , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/epidemiology , Cesarean Section/statistics & numerical data , Female , Germany/epidemiology , Gestational Age , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Valve Diseases/diagnosis , Heart Valve Diseases/epidemiology , Heart Valve Diseases/surgery , Humans , Infant, Newborn , Postpartum Period , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Complications, Cardiovascular/epidemiology , Pregnancy Complications, Cardiovascular/mortality , Pregnancy Outcome/epidemiologyABSTRACT
Preoperative neoadjuvant chemotherapy (NAC) can significantly reduce tumour burden in patients with primarily unresectable chemosensitive tumours, allowing a more complete cytoreduction during debulking surgery and facilitating evaluation of tumour chemosensitivity, identification of appropriate treatment options and improvement of intervention protocols. In this study, we investigate, using immunohistochemistry, the impact of platinum/taxane-based NAC (NAC) on tumour-infiltrating lymphocytes (TILs) in advanced epithelial ovarian cancer (EOC) and their relationship with clinical outcome. All patients had clinical response, as shown by ascites volume and CA125 levels compared to pre-treatment findings. NAC intervention significantly increased CD4(+), CD8(+) and granzyme B(+) infiltration while Foxp3(+) accumulation remained unaffected. TILs were prognostically neutral for both progression-free survival (PFS) and overall survival (OS) before NAC. In contrast, after NAC, elevated granzyme B(+) infiltration displayed a tendency for improved PFS (log-rank 0.064). Further, low Foxp3(+) cell density was associated with longer PFS, as compared with strong Foxp3(+) infiltration (median 20.94 vs. 11.24 months; log-rank 0.0001) and with improved OS (median 30.75 vs. 16.04 months, respectively; log-rank 0.056), demonstrating clear prognostic significance for PFS. In addition, high granzyme B(+)/Foxp3(+) ratio post-NAC strongly correlated with improved PFS compared to low granzyme B(+)/Foxp3(+) cell ratio (median 17.88 vs. 11.24 months, respectively), and showed to be a favourable prognostic factor for PFS (log-rank 0.014). Our findings indicate that NAC elicited an immunologic profile in which low immunosuppressive Foxp3(+) infiltration and elevated numbers of activated granzyme B(+) cells were significantly associated with EOC-specific PFS, suggesting a contribution of immunologic effects to improved clinical outcome.
Subject(s)
Neoadjuvant Therapy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/biosynthesis , Cell Movement/drug effects , Cell Movement/immunology , Disease Progression , Female , Forkhead Transcription Factors/biosynthesis , Granzymes/biosynthesis , Humans , Immunohistochemistry , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Middle Aged , Ovarian Neoplasms/pathology , Ovarian Neoplasms/physiopathology , Platinum Compounds/administration & dosage , Platinum Compounds/adverse effects , Prognosis , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate changes in Ki-67 expression during neoadjuvant chemotherapy (NACT) in advanced ovarian cancer. MATERIALS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage IIIC or IV and large-volume ascites were treated with NACT within a phase 2 trial. The expression of Ki-67 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells. Survival curves were plotted using the Kaplan-Meier method. RESULTS: Comparison of 40 individual paired results from pretreatment and posttreatment samples revealed a median difference of -0.11 in the Ki-67 index (95% confidence interval, -0.20 to -0.01; P = 0.005, signed rank test). Univariate analysis identified a high Ki-67 index as well as an increasing Ki-67 index after NACT as significant prognostic markers for progression-free survival (P = 0.004 and P = 0.001; log-rank test). Six of 12 patients with an increased Ki-67 index after NACT developed recurrence within 6 months after therapy. CONCLUSIONS: Changes of the Ki-67 index during NACT are associated with progression-free survival. If confirmed in prospective trials, an increasing Ki-67 index during preoperative treatment may serve as an indicator for resistance to chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Papillary/drug therapy , Cystadenocarcinoma, Serous/drug therapy , Endometrial Neoplasms/drug therapy , Ki-67 Antigen/metabolism , Neoadjuvant Therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carcinoma, Papillary/metabolism , Carcinoma, Papillary/mortality , Cell Proliferation , Clinical Trials, Phase II as Topic , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/mortality , Docetaxel , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/mortality , Female , Humans , Immunoenzyme Techniques , Middle Aged , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/mortality , Prospective Studies , Randomized Controlled Trials as Topic , Survival Rate , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
Backround: Due to extensive surgical intervention for macroscopic complete cytoreduction in epithelial ovarian cancer (EOC) patients, severe complications in the postoperative course are possible. PATIENTS AND METHODS: A total of 345 EOC patients who underwent cytoreductive surgery were retrospectively evaluated regarding risk factors for an unfavorable postoperative course. Possible pre-, intra- and postoperative risk factors were statistically analyzed performing multivariate ordinal logistic regression. RESULTS: A total of 345 EOC patients underwent cytoreductive surgery. There were no complications in 114 patients, mild complications in 114 patients and severe complications in 117 patients. The risk factor evaluation identified age (p=0.049), smoking (p=0.032) and duration of surgery (p<0.0001) as significant factors for severe postoperative morbidity. CONCLUSION: In EOC patients age, smoking and the duration of surgery have significant impact on the postoperative course. Only the duration of surgery can be positively influenced by a well-trained EOC team.