Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
Geburtshilfe Frauenheilkd ; 83(8): 919-962, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37588260

ABSTRACT

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

2.
Geburtshilfe Frauenheilkd ; 83(8): 963-995, 2023 Aug.
Article in English | MEDLINE | ID: mdl-39296646

ABSTRACT

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat low-risk women with endometrial cancer prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 2 of this short version of the guideline provides recommendations on the treatment of precancerous lesions and early-stage endometrial cancer, surgical treatment, radiotherapy and drug-based therapy, follow-up, recurrence, and metastasis of endometrial cancer as well as the state of psycho-oncological care, palliative care, patient education, rehabilitative and physiotherapeutic care.

3.
Geburtshilfe Frauenheilkd ; 81(4): 447-468, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33867563

ABSTRACT

Purpose Positioning injuries are relatively common, forensically highly relevant complications of gynecologic surgery. The aim of this official AWMF S2k-guideline is to provide statements and recommendations on how to prevent positioning injuries using the currently available literature. The literature was evaluated by an interdisciplinary group of experts from professional medical societies. The consensus on recommendations and statements was achieved in a structured consensus process. Method The current guideline is based on the expired S1-guideline, which was updated by a systematic search of the literature and a review of relevant publications issued between February 2014 and March 2019. Statements were compiled and voted on by a panel of experts. Recommendations The guideline provides general and specific recommendations on the prevention, diagnosis and treatment of positioning injuries.

4.
Cancers (Basel) ; 12(9)2020 Aug 25.
Article in English | MEDLINE | ID: mdl-32854222

ABSTRACT

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

5.
Oncotarget ; 8(20): 32461-32475, 2017 May 16.
Article in English | MEDLINE | ID: mdl-28427147

ABSTRACT

BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features. BRCA1 depletion stabilizes HMMR abundance and disrupts cortical asymmetry of NUMA-dynein complexes in dividing cells such that polarity cues provided by cell-matrix adhesions were not able to orient division. We also show that immortalized mammary cells carrying a mutant BRCA1 allele (BRCA1 185delAG/+) reproduce many of these effects but in this model, oriented divisions were maintained through cues provided by CDH1+ cell-cell junctions. These findings reveal a previously unknown effect of BRCA1 suppression on mechanisms that regulate the cell division axis in proliferating, non-transformed human mammary epithelial cells and consequent downstream effects on the mitotic integrity and phenotype control of their progeny.


Subject(s)
BRCA1 Protein/metabolism , Breast Neoplasms/genetics , BRCA1 Protein/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Differentiation/physiology , Cell Division/physiology , Epithelial Cells/pathology , Female , HeLa Cells , Humans , Phenotype , Ploidies
6.
Cell Cycle ; 13(14): 2248-61, 2014.
Article in English | MEDLINE | ID: mdl-24875404

ABSTRACT

Construction of a mitotic spindle requires biochemical pathways to assemble spindle microtubules and structural proteins to organize these microtubules into a bipolar array. Through a complex with dynein, the receptor for hyaluronan-mediated motility (RHAMM) cross-links mitotic microtubules to provide structural support, maintain spindle integrity, and correctly orient the mitotic spindle. Here, we locate RHAMM to sites of microtubule assembly at centrosomes and non-centrosome sites near kinetochores and demonstrate that RHAMM is required for the activation of Aurora kinase A. Silencing of RHAMM delays the kinetics of spindle assembly, mislocalizes targeting protein for XKlp2 (TPX2), and attenuates the localized activation of Aurora kinase A with a consequent reduction in mitotic spindle length. The RHAMM-TPX2 complex requires a C-terminal basic leucine zipper in RHAMM and a domain that includes the nuclear localization signal in TPX2. Together, our findings identify RHAMM as a critical regulator for Aurora kinase A signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic progression through the integration of biochemical and structural pathways.


Subject(s)
Aurora Kinase A/metabolism , Cell Cycle Proteins/metabolism , Extracellular Matrix Proteins/metabolism , Hyaluronan Receptors/metabolism , Microtubule-Associated Proteins/metabolism , Nuclear Proteins/metabolism , Spindle Apparatus/enzymology , Aurora Kinase A/genetics , Cell Cycle Proteins/genetics , Enzyme Activation , Extracellular Matrix Proteins/genetics , HeLa Cells , Humans , Hyaluronan Receptors/genetics , Kinetics , Microtubule-Associated Proteins/genetics , Mitosis , Nuclear Proteins/genetics , Protein Binding , Protein Interaction Domains and Motifs , Protein Stability , Protein Transport , RNA Interference , Signal Transduction , Transfection
7.
Langenbecks Arch Surg ; 399(3): 343-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24515267

ABSTRACT

PURPOSE: This study was aimed to investigate incidence, circumstances and consequences of acute compartment syndrome (CS) of the lower extremity after gynecological operations in lithotomy position by collecting data from departments of Obstetrics and Gynecology in Germany. DESIGN: Retrospective observational study. SETTING: Departments of Obstetrics and Gynecology in the area of North Rhine (Germany) METHODS: A 24-item questionnaire was sent to 168 gynecological departments. In addition, cases anonymously reported to the Expert Committee for Medical Malpractice Claims of the Medical Association of North Rhine between 2002 and 2012 were analyzed. MAIN OUTCOME MEASURE: Incidence of acute CS after gynecological operations. RESULTS: A total of 59 questionnaires (35 %) were returned for analysis, reporting 21 cases of CS. Based on the collected data, we calculated an incidence of postoperative CS ranging between 0.067 % and 0.28 %. All reported cases of postoperative CS occurred after surgeries in lithotomy position, 57.1 % of cases occurred after laparoscopic procedures and 76.2 % after procedures longer than 4 h. Overall, 61.0 % of departments do not routinely inform about the risk of this complication when they get patients' informed consent. Reported prevention strategies were inconsistent and ranged from none to multiple measures. CONCLUSION: CS is a complication clearly associated with long lasting gynecological operations in Lithotomy position. Despite a relatively high incidence, so far no guidelines on perioperative management and medicolegal aspects exist and preventive measures are heterogeneous among institutions. The need for guidelines and recommendations by an expert committee has been identified.


Subject(s)
Compartment Syndromes/epidemiology , Gynecologic Surgical Procedures/adverse effects , Lower Extremity , Acute Disease , Adult , Aged , Female , Germany , Humans , Incidence , Laparoscopy/adverse effects , Middle Aged , Operative Time , Patient Positioning/adverse effects , Retrospective Studies , Risk Factors , Young Adult
8.
Eur J Obstet Gynecol Reprod Biol ; 173: 7-12, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24290432

ABSTRACT

Compartment syndrome (CS) of the lower leg is a rare but severe complication of operations in the lithotomy (LT) position after urologic, gynecologic and general surgery. A delay in diagnosis and treatment can lead to loss of function and even life-threatening complications. The pathophysiology is still not fully understood but it is believed that ischemia as a result of increased compartment pressure and decreased perfusion pressure may lead to CS. The type of leg support and the intraoperative hypotension have been discussed as risk factors but evidence is mainly based on case reports and expert opinion. Studies suggest that time spent in the LT position and the addition of head-down tilt are associated with CS. As these positions are routinely applied during various gynecologic procedures, forensically CS has to be considered as a specific complication of gynecologic surgery in the LT position. Despite the low incidence there is a need for prospective studies and guidelines for its prevention. Sixteen case reports describing 19 cases of CS following gynecologic surgery in lithotomy position were found during a literature search. This review is based on 14 of these case reports (17 cases), which describe a postoperative compartment syndrome in a previously healthy leg. We summarize the reported cases and literature on CS after gynecologic procedures in order to increase awareness among medical staff and to give careful recommendations regarding perioperative management based on available information.


Subject(s)
Compartment Syndromes/etiology , Gynecologic Surgical Procedures/adverse effects , Patient Positioning/adverse effects , Female , Humans
9.
Oncol Lett ; 3(3): 530-534, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22740945

ABSTRACT

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment.

10.
J Cancer Res Clin Oncol ; 138(4): 603-10, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22209976

ABSTRACT

PURPOSE: Targeted oncolytic adenoviruses capable of replication selectively in cancer cells are an appealing approach for the treatment of various cancer types refractory to conventional therapies. The aim of this study was to evaluate the effect of Ad5/3MDR1E1, a multidrug resistance gene 1 (MDR1)-targeted fiber-modified replication-competent adenovirus for the therapy of platinum-pretreated ovarian cancer in combination with cytostatic agents. METHODS: MDR1-specific tumor cell killing of Ad5/3MDR1E1 was systematically evaluated in chemotherapy naïve and pretreated ovarian cancer cells in vitro. Combinations of Ad5/3MDR1E1 and cytostatic agents were studied in vivo and in vitro. An in vivo hepatotoxicity model was used to evaluate liver toxicity. RESULTS: We demonstrate efficient oncolysis of Ad5/3MDR1E1 in chemotherapy-resistant ovarian cancer cells as well as therapeutic efficacy in an orthotopic mouse model. Further, combining Ad5/3MDR1E1 with paclitaxel resulted in greater therapeutic benefit than either agent alone. CONCLUSION: These preclinical data suggest that a fiber-modified adenovirus vector under the control of the MDR1 promoter represents a promising treatment strategy for platinum-pretreated ovarian cancer as a single agent or in combination with conventional anticancer drugs.


Subject(s)
Oncolytic Virotherapy/methods , Oncolytic Viruses/physiology , Ovarian Neoplasms/therapy , Paclitaxel/pharmacology , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Adenoviridae/genetics , Adenoviridae/physiology , Animals , Antineoplastic Agents/pharmacology , Capsid Proteins/genetics , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Cisplatin/pharmacology , Combined Modality Therapy , Drug Resistance, Neoplasm , Female , Humans , Mice , Mice, Inbred C57BL , Oncolytic Viruses/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/virology , Promoter Regions, Genetic/genetics , Survival Analysis , Treatment Outcome , Virus Replication , Xenograft Model Antitumor Assays
11.
Case Rep Neurol ; 3(1): 54-61, 2011 Feb 21.
Article in English | MEDLINE | ID: mdl-21490714

ABSTRACT

We report a 66-year-old woman with slowly progressive ataxia due to cerebellar atrophy. Imaging studies revealed multiple lesions in both the lungs and dorsal subpleural space. A biopsy identified the lesions as metastases of a low-grade endometrial stromal sarcoma containing sex-cord elements. The histological appearance was identical to a uterine tumor the patient was treated for with hysterectomy 16 years before. The metastases were removed surgically, and after 3 months ataxia had regressed. We conclude that the presenting cerebellar degeneration in this patient resulted from the metastatic recurrence of the endometrial tumor.

12.
Integr Biol (Camb) ; 1(1): 80-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-20023794

ABSTRACT

We have built a novel computational microscopy platform that integrates image acquisition, storage, processing and analysis to study cell populations in situ. This platform allows high-content studies where multiple features are measured and linked at multiple scales. We used this approach to study the cellular composition and architecture of the mouse mammary gland by quantitatively tracking the distribution and type, position, proliferative state, and hormone receptor status of epithelial cells that incorporated bromodeoxyuridine while undergoing DNA synthesis during puberty and retained this label in the adult gland as a function of tissue structure. Immunofluorescence was used to identify label-retaining cells, as well as epithelial cells expressing the proteins progesterone receptor and P63. Only 3.6% of luminal cells were label-retaining cells, the majority of which did not express the progesterone receptor. Multi-scale in situ analysis revealed that luminal label-retaining cells have a distinct nuclear morphology, are enriched 3.4-fold in large ducts, and are distributed asymmetrically across the tissue. We postulated that LRC enriched in the ventral mammary gland represent progenitor cells. Epithelial cells isolated from the ventral versus the dorsal portion of the gland were enriched for the putative stem cell markers CD24 and CD49f as measured by fluorescence activated cell sorting. Thus, quantitative analysis of the cellular composition of the mammary epithelium across spatial scales identified a previously unrecognized architecture in which the ventral-most, large ducts contain a reservoir of undifferentiated, putative stem cells.


Subject(s)
Aging/metabolism , Aging/pathology , Gene Expression Profiling/methods , Mammary Glands, Animal/cytology , Mammary Glands, Animal/metabolism , Microscopy/methods , Receptors, Somatotropin/metabolism , Animals , CD24 Antigen/metabolism , Female , Integrin alpha6/metabolism , Mice
13.
Gynakol Geburtshilfliche Rundsch ; 49(3): 117-25, 2009.
Article in German | MEDLINE | ID: mdl-19525618

ABSTRACT

For 20 years laparoscopic pelvic and para-aortal lymph node dissection has become increasingly popular as part of minimally invasive surgical treatment concepts for women suffering from gynaecological malignancies. Especially patients suffering from early-stage cervical or endometrial cancers can benefit from the general advantages of a minimally invasive procedure if a comparable degree of radical surgery is achieved. The feasibility and case-control studies published so far suggest comparable indicators of radicality, such as the number of dissected lymph nodes, but also demonstrate potential advantages like a lower intra-operative blood loss, shorter hospital stay and lower postoperative complication rate in comparison with the conventional approach. Regarding long-term survival, reliable data from prospective randomized studies are still lacking but can be expected to be available in the near future.


Subject(s)
Genital Neoplasms, Female/secondary , Genital Neoplasms, Female/surgery , Laparoscopy/trends , Lymph Node Excision/methods , Female , Genital Neoplasms, Female/pathology , Humans , Lymphatic Metastasis
14.
Maturitas ; 62(2): 176-8, 2009 Feb 20.
Article in English | MEDLINE | ID: mdl-19121901

ABSTRACT

UNLABELLED: Endometrial carcinoma is the most common genital cancer in women. While patients usually present with vaginal bleeding, in 10-20% this characteristic symptom is absent. Endometrial thickness (double layer) is measured by transvaginal sonography and thickening indicates an increased risk of malignancy or other pathology (hyperplasia or polyps). OBJECTIVE: We sought to correlate hysteroscopic and pathological findings in asymptomatic postmenopausal women with sonographically thickened endometrium (>6mm). STUDY DESIGN: A prospective observational study in a university hospital of 304 postmenopausal women referred between 1996 and 2006 because of a sonographically thickened endometrium in the absence of abnormal bleeding, who underwent continuous flow hysteroscopy (4.5mm Storz hysteroscope) and fractionated curettage of the uterine cervix and corpus (D & C) in addition to vaginal sonography (5MHz probe). RESULTS: The mean age of the women was 64.8 (range 57.7-71.9) years. Average endometrial thickness measured by ultrasound was 12mm+/-6.7mm. Hysteroscopy suggested the presence of endometrial polyps in 226 women (74.3%), simple endometrial hyperplasia in 34 (11.2%), atrophic endometrium in 18 (5.9%), complex endometrial hyperplasia in 2 (0.7%), atypical hyperplasia in 3 (1%) and leiomyoma in 9 (3.0%). In 12 women (3.9%), the hysteroscopic appearance suggested malignancy and histology revealed endometrial adenocarcinoma. All hysteroscopic results were confirmed by histological examination. CONCLUSION: Hysteroscopy represents an easy, safe and effective method for the investigation of asymptomatic women with a thickened endometrium found with transvaginal ultrasound. The commonest pathology was endometrial polyps.


Subject(s)
Endometrial Hyperplasia/diagnosis , Endometrial Neoplasms/diagnosis , Hysteroscopy , Uterine Neoplasms/diagnosis , Aged , Atrophy/diagnosis , Endometrial Hyperplasia/pathology , Endometrium/diagnostic imaging , Endometrium/pathology , Female , Humans , Hysteroscopy/methods , Leiomyoma/diagnosis , Middle Aged , Polyps/diagnosis , Postmenopause , Prospective Studies , Risk Factors , Ultrasonography , Uterine Diseases/diagnosis
15.
Cancer Res ; 68(20): 8304-11, 2008 Oct 15.
Article in English | MEDLINE | ID: mdl-18922902

ABSTRACT

Radiation-induced genomic instability, in which the progeny of irradiated cells display a high frequency of nonclonal genomic damage, occurs at a frequency inconsistent with mutation. We investigated the mechanism of this nontargeted effect in human mammary epithelial cells (HMEC) exposed to low doses of radiation. We identified a centrosome-associated expression signature in irradiated HMEC and show here that centrosome deregulation occurs in the first cell cycle after irradiation, is dose dependent, and that viable daughters of these cells are genomically unstable as evidenced by spontaneous DNA damage, tetraploidy, and aneuploidy. Clonal analysis of genomic instability showed a threshold of >10 cGy. Treatment with transforming growth factor beta1 (TGFbeta), which is implicated in regulation of genomic stability and is activated by radiation, reduced both the centrosome expression signature and centrosome aberrations in irradiated HMEC. Furthermore, TGFbeta inhibition significantly increased centrosome aberration frequency, tetraploidy, and aneuploidy in nonirradiated HMEC. Rather than preventing radiation-induced or spontaneous centrosome aberrations, TGFbeta selectively deleted unstable cells via p53-dependent apoptosis. Together, these studies show that radiation deregulates centrosome stability, which underlies genomic instability in normal human epithelial cells, and that this can be opposed by radiation-induced TGFbeta signaling.


Subject(s)
Breast/radiation effects , Genomic Instability/radiation effects , Neoplasms, Radiation-Induced/etiology , Animals , Apoptosis/drug effects , Breast/metabolism , Cells, Cultured , Centrosome/drug effects , Centrosome/metabolism , Centrosome/radiation effects , Dose-Response Relationship, Radiation , Epithelial Cells/radiation effects , Female , Humans , Mice , Mice, Inbred BALB C , Signal Transduction/radiation effects , Transforming Growth Factor beta/pharmacology , Tumor Suppressor Protein p53/physiology
16.
J Minim Invasive Gynecol ; 14(3): 293-9, 2007.
Article in English | MEDLINE | ID: mdl-17478358

ABSTRACT

STUDY OBJECTIVE: In this study we investigated whether teaching advanced laparoscopic procedures like laparoscopic-assisted surgical staging (LASS) for endometrial cancer negatively affects the learning curve of the attending surgeon. DESIGN: Retrospective study (Canadian Task Force classification II-3.) SETTING: Department of Obstetrics and Gynecology, University of Arizona, Tucson. PATIENTS: One hundred twenty-four patients undergoing LASS for endometrial cancer at our institution from 1992 through 2004 were included for analysis. INTERVENTIONS: Cases were classified into 3 groups. Group A comprised the initial learning phase where 2 attending gynecologic oncologists used other faculty as assistants (first 30 cases). Groups B and C comprised procedures after the learning phase involving attendings (n = 27, group B) or obstetrics and gynecology residents (n = 67, group C) as trainees. Groups were compared with respect to general outcome parameters and disease-free survival. MEASUREMENTS AND MAIN RESULTS: Patients within all groups were comparable with respect to age and height or body mass index. In the subgroup analysis, a decrease in blood loss and length of stay occurred mainly during the group B series. Pelvic lymph node yield reached oncologic standards during the initial learning curve (median 12-13) and remained stable during both teaching phases. Intraoperative and postoperative complications occurred in 2.4% and 13.7% of cases, respectively. Ninety percent of intraoperative and 64% of postoperative complications occurred within the first half of the series and were not correlated with type of assistance. Survival data were obtainable in 65% of cases with a median follow-up of 3.6 years. Disease free-survival was 92.5% in stage I disease and without significant difference among the groups. CONCLUSION: After gaining proficiency in the procedure, more or less surgically experienced trainees can be actively included without hampering the progress of the attending's learning curve.


Subject(s)
Endometrial Neoplasms/surgery , Gynecologic Surgical Procedures/education , Laparoscopy/statistics & numerical data , Aged , Aged, 80 and over , Arizona , Disease-Free Survival , Endometrial Neoplasms/pathology , Female , Germany , Gynecologic Surgical Procedures/mortality , Humans , Middle Aged , Neoplasm Staging , Retrospective Studies , Teaching , Treatment Outcome
17.
Microsc Res Tech ; 69(12): 964-72, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16941664

ABSTRACT

Centrosomes are small organelles that organize the mitotic spindle during cell division and are also involved in cell shape and polarity. Within epithelial tumors, such as breast cancer, and some hematological tumors, centrosome abnormalities (CAs) are common, occur early in disease etiology, and correlate with chromosomal instability and disease stage. In situ quantification of CA by optical microscopy is hampered by overlap and clustering of these organelles, which appear as focal structures. CA has been frequently associated with Tp53 status in premalignant lesions and tumors. Here the authors described an approach to accurately quantify centrosome frequencies in tissue sections and tumors, independently of background or noise levels. Applying simple optical rules in nondeconvolved conventional 3D images of stained tissue sections, the authors showed that they could evaluate more accurately and rapidly centrosome frequencies than with traditional investigator-based visual analysis or threshold-based techniques. The resulting population-based frequency of centrosomes per nucleus could then be used to approximate the proportion of cells with CA in that same population. This was done by taking into account baseline centrosome amplification and proliferation rates measured in the tissue. Using this technique, the authors showed that 20-30% of cells have amplified centrosomes in Tp53 null mammary tumors.


Subject(s)
Algorithms , Centrosome , Epithelial Cells/ultrastructure , Mammary Glands, Animal/ultrastructure , Mammary Neoplasms, Animal/ultrastructure , Animals , Cell Nucleus/ultrastructure , Female , Fluorescent Antibody Technique , Image Processing, Computer-Assisted , Mammary Glands, Animal/cytology , Mice , Mice, Inbred BALB C , Tumor Suppressor Protein p53/deficiency
18.
Endocr Relat Cancer ; 13(2): 379-400, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16728569

ABSTRACT

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary glands. This review will address the role of TGF-beta in regulating hormone-dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition, will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.


Subject(s)
Cell Transformation, Neoplastic/metabolism , Endocrine Gland Neoplasms/metabolism , Hormones/metabolism , Transforming Growth Factor beta/physiology , Animals , Cell Transformation, Neoplastic/genetics , Drug Design , Endocrine Gland Neoplasms/drug therapy , Endocrine Gland Neoplasms/genetics , Homeostasis , Hormones/genetics , Humans , Mice , Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/genetics
20.
Eur J Obstet Gynecol Reprod Biol ; 123(2): 224-9, 2005 Dec 01.
Article in English | MEDLINE | ID: mdl-16102887

ABSTRACT

OBJECTIVE: With the present study we wanted to evaluate the effect of a radical resection of bowel and bladder endometriosis with respect to relief of pain symptoms and long-term effects. STUDY DESIGN: Retrospectively we analyzed 23 patients undergoing bowel or bladder resection for infiltrating endometriosis between 1995 and 2004. Chart review was performed and data were analyzed with respect to pain symptoms, fertility, type of surgery, operative morbidity and mortality. At 1, 3 and 5 years of follow-up patients were asked to evaluate their symptoms based on a visual analogue pain scale (0: no pain, 10: most severe pain). Results were compared using the Student's t-test. RESULTS: Leading symptoms were chronic pelvic pain (17/23, 73.9%), dysmenorrhea (11/23, 47.8%), dyspareunia (6/23, 26.1%), infertility (4/23, 17.4%) and dyschezia (4/23, 17.4%). Three patients (13%) had abdominal hysterectomy, 5 (21.7%) LSO (n = 2) or BSO (n = 3), 18 (78.3%) anterior rectal resection, 4 (17.4%) sigmoid resection, 2 (8.6%) segmental bladder resection and one patient (4.3%) cecal resection. Major complications requiring re-operation occurred in three patients (2x postoperative bleeding, 1x anastomosis break-down). During follow-up (mean 40.5 months) 21 of the 23 patients (91.3%) had a persistent improvement of symptoms, 8 of the 23 (34.8%) had recurrent symptoms with a mean symptom-free interval of 40.4 months after surgery (24-60 months). No patient developed dyspareunia or dyschezia during follow-up. Overall cure rate was 73.9%. Four patients became pregnant (23%). Average pain scores increased during follow-up period but still remained significantly below the initial score (p < 0.001). CONCLUSION: Radical surgery for deep endometriosis with bowel or bladder involvement leads to a reliable and persistent relief of pain symptoms. Especially deep dyspareunia and dyschezia might be eliminated by this procedure.


Subject(s)
Endometriosis/surgery , Intestinal Diseases/surgery , Urinary Bladder Diseases/surgery , Adult , Endometriosis/complications , Female , Follow-Up Studies , Humans , Intestinal Diseases/etiology , Pain/diagnosis , Pain/etiology , Pain/surgery , Pain Measurement , Retrospective Studies , Surgical Procedures, Operative , Treatment Outcome , Urinary Bladder Diseases/etiology
SELECTION OF CITATIONS
SEARCH DETAIL