[Application and control of intravenous fluids in German intensive care units : A national survey among critical care physicians]. / Die Applikation und Steuerung von intravenösen Flüssigkeiten auf deutschen Intensivstationen : Eine nationale Umfrage unter Intensivmediziner:innen.

BACKGROUND: The administration of intravenous fluids includes various indications, e.g., fluid replacement, nutritional therapy or as a solvent for drugs and is a common routine in the intensive care unit (ICU); however, overuse of intravenous fluids can lead to fluid overload, which can be associated with a poorer outcome in critically ill patients. OBJECTIVE: The aim of this survey was to find out the current status of the use and management of intravenous fluids as well as the interprofessional cooperation involving clinical pharmacists on German ICUs. METHODS: An online survey with 33 questions was developed. The answers of 62 participants from the Scientific Working Group on Intensive Care Medicine of the German Society for Anesthesiology and Intensive Care Medicine were evaluated. RESULTS: Fluid overload occurs "frequently" in 62.9% (39/62) and "very frequently" in 9.7% (6/62) of the ICUs of respondents. An established standard for an infusion management system is unknown to 71.0% (44/62) of participants and 45.2% of the respondents stated that they did not have a patient data management system. In addition, the participants indicated how they define fluid overload. This was defined by the presence of edema by 50.9% (28/55) and by positive fluid balance by 30.9% (17/55). According to the participants septic patients (38/60; 63.3%) and cardiological/cardiac surgical patients (26/60; 43.3%) are most susceptible to the occurrence of fluid overload. Interprofessional collaboration among intensive care physicians, critical care nurses, and clinical pharmacists to optimize fluid therapy was described as "relevant" by 38.7% (24/62) and "very relevant" by 45.2% (28/62). Participants with clinical pharmacists on the wards (24/62; 38.7%) answered this question more often as "very relevant" with 62.5% (15/24). CONCLUSION: Fluid overload is a frequent and relevant problem in German intensive care units. Yet there are few established standards in this area. There is also a lack of validated diagnostic parameters and a clear definition of fluid overload. These are required to ensure appropriate and effective treatment that is tailored to the patient and adapted to the respective situation. Intravenous fluids should be considered as drugs that may exert side effects or can be overdosed with severe adverse consequences for the patients. One approach to optimize fluid therapy could be achieved by a fluid stewardship corresponding to comparable established procedures of the antibiotic stewardship. In particular, fluid stewardship will contribute to drug safety of intravenous fluids profiting from joined expertise in a setting of interprofessional collaboration. An important principle of fluid stewardship is to consider intravenous fluids in the same way as medication in terms of their importance. Furthermore, more in-depth studies are needed to investigate the effects of interprofessional fluid stewardship in a prospective and controlled manner.

Preservation of the mesureter to reduce urinary complications: analysis of data from the observational Leipzig School MMR study.

OBJECTIVE: To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN: Retrospective cohort study with historic control. SETTING: Single tertiary academic centre. POPULATION: Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD: We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES: The occurrence of urological and specifically ureteral complications. RESULTS: Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re-operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero-vaginal fistulas. CONCLUSION: The mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage. TWEETABLE ABSTRACT: Surgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.

Simultaneous [18F]FDG-PET/MRI: Correlation of Apparent Diffusion Coefficient (ADC) and Standardized Uptake Value (SUV) in Primary and Recurrent Cervical Cancer.

OBJECTIVES: Previous non-simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment. METHODS: We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body 18F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV. RESULTS: 92 lesions were detected. We found a significant inverse correlation between SUVmax and ADCmin (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = -0.362, p = 0.05) and between SUVmean and ADCmin (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUVmax and ADCmin (r = -0.747, p = 0.002) and SUVmean and ADCmin (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05). CONCLUSIONS: Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.

Lacking hypoxia-mediated downregulation of E-cadherin in cancers of the uterine cervix.

BACKGROUND: Experimental studies have established a causal connection between tumour hypoxia, hypoxia-associated proteome changes and downregulation of E-cadherin, the final common pathway of epithelial-to-mesenchymal transition (EMT). Our study aimed at elucidating the interrelationship of these processes in cancers of the uterine cervix in vivo. METHODS: Tumour oxygenation was assessed in 48 squamous cell carcinomas (SCC) of the uterine cervix using polarographic needle electrodes. The expression pattern of E-cadherin was investigated by immunohistochemistry and western blotting, and was compared with that of the hypoxia-inducible proteins glucose transporter (GLUT)-1 and carbonic anhydrase (CA) IX in biopsy specimens of the oxygenation measurement tracks. RESULTS: The majority of cervical cancers (52%) were E-cadherin positive, with a complete absence of the antigen in only 10% of the tumours. No correlation was found between the level of E-cadherin expression and the oxygenation status (mean pO(2), median pO(2) and hypoxic fractions). In patients showing partial expression of E-cadherin (38%), staining was not preferentially diminished in GLUT-1- or CA IX-positive areas, and loss of E-cadherin occurred independently of tumour cell scattering. CONCLUSION: Our data provide no evidence in favour of a hypoxia-induced EMT as a mechanistic basis of cervical cancer invasiveness.

[Oncological pelvic surgery from a gynecological perspective]. / Onkologische Beckenchirurgie unter gynäkologischen Gesichtspunkten.

The established gynecological cancer operations are based on functional anatomy derived from the mature organism and on a model of radial progressive tumor permeation. Surgical treatment aims to resect the tumor with a metrically defined radial margin of tissue microscopically free of neoplastic or dysplastic disease. However, despite adequate surgical performance local tumor relapses still occur. In the presence of histopathological risk factors adjuvant radiation is therefore recommended which increases treatment-related morbidity. The Leipzig School of Radical Pelvic Surgery has developed new gynecological cancer operations from a different perspective on anatomy and local tumor spread. Tissue mapping is deduced by following the organism's development from the stage of tissue deposition to maturity (ontogenetic anatomy) to define permissive compartments for cancer permeation. The variants of mesometrial resection (TMMR, PMMR) and vulva field resection (VFR) achieve very high (>95%) local control rates in stages I and II cancer of the lower and middle female genital tract without adjuvant radiation. Laterally extended endopelvic resection (LEER) provides sustained tumor control even in locally advanced and recurrent disease as well as cancer of the distal vagina.

Anxiety and depression in cancer patients compared with the general population.

The objective of this study was to compare the prevalence of anxiety and depression in cancer patients with the prevalence found in the general population, using the Hospital Anxiety and Depression Scale (HADS). Participants were 1529 cancer patients treated between 2002 and 2004 in Germany and 2037 persons from the German general population. In the cancer patients, the risk of psychiatric distress was nearly twice that of the general population. While for older age groups (61 years and above) there were only small differences between cancer patients and the general population, the differences in both scales were high for young persons. There were differences between the HADS mean scores of the patients with different tumour localisations, with high values for brain cancer and low scores for prostate cancer. The influence of the tumour stage on anxiety and depression was weak. However, depression scores of patients with a survival time less than 1 year were elevated. The results show that large sample sizes are necessary to evaluate the psychological situation of cancer patients, and that age and gender differences must be taken into account when several samples are compared.

Quality of care and emotional support from the inpatient cancer patient's perspective.

BACKGROUND: Patient satisfaction and emotional support are crucial elements of cancer care. Little is known, however, about which areas of care are important from the patient's perspective and the roles emotional distress and support play in this context. METHODS: Multicenter prospective study was conducted (n = 396 cancer patients; t1 = after admission to hospital, t2 = before discharge). Quality of care was measured with the quality of care from the patient's perspective questionnaire, and emotional distress was measured with the hospital anxiety and depression scale. Additional questions regarding emotional support wished (at t1) and provided (at t2) were administered. RESULTS: The patients reported that the domains of care most important to them were as follows: respect and commitment of the physicians, information before procedures, care equipment, and medical care. The areas where improvements are most obviously needed were nutrition, participation, clarity about who is responsible for personal care, and having the possibility of speaking in private with nurses and psycho-oncologists. Fifty-six percent of the patients were highly emotionally distressed, 84% wanted support from physicians, 76% from nurses, 33% from psychologists, and 7% from a pastor. CONCLUSION: Emotional support is a crucial part of patient satisfaction and should be provided by several members of the oncological team, especially the patients' physicians. In turn, it is crucial that medical professionals be equipped with good communication skills.

[Pathoanatomical preparation and reporting for dysplasias and cancers of the cervix uteri: cervical biopsy, conization, radical hysterectomy and exenteration]. / Pathologisch-anatomische Aufarbeitung und Befundung von Dysplasien und Karzinomen der Cervix uteri. Zervixbiopsien, Konisationen, radikale Hysterektomien und Exenterate.

A careful macroscopic description with selection of representative tissue for histological examination is required for quality assurance, for assessing prognostic factors and for answering legal questions in (pre)cancerous lesions of the cervix uteri. Exact and standardized gross inspection and preparation are decisive for the quality of the histopathological statement. The extent of cervical carcinomas should be given in three dimensions, including the relative depth of invasion into the cervical wall. The report should include size, type (according to the WHO classification) and grading of the tumor, the presence of lymphatic as well as blood vessel invasion and perineural involvement. The statement for resection margins should include the vaginal, parametrial, rectal and vesical directions. It is also mandatory to document the number of lymph nodes with metastatic disease in relation to the total number of nodes investigated. The staging should follow the TNM system. In the handling of conisation specimens, it is important to appropriately document localization, horizontal expansion, depth of invasion including microinvasion of any dysplastic or malignant lesions. Clockwise dissection of the conisation specimen, total submission, and step sections are recommended. The preparation of exenteration specimens is a highly skilled job: the exact tumor dimension should be given in its relation to all resected organs and structures with special focus on resection margins.

Different T-cell receptor (TCR) zeta chain expression in cervical cancer and its precursor lesions.

OBJECTIVE: Cervical cancer is associated with infection of epithelial cells with the human papillomavirus (HPV) type 16 and HPV18. A functional signalling machinery in T-cells is required in order to successfully fight and eradicate HPV16+ transformed epithelial cells. One of the key signalling molecules associated with the T-cell receptor (TCR) is the homodimeric zeta chain molecule. MATERIAL AND METHODS: 28 formalin fixed und paraffin embedded samples of cervical tissue with cervical intraepithelial lesions CIN I (n = 3), CIN III (n = 7), invasive cervical carcinoma (CC) (n = 13) and normal cervical tissue (n = 5) has been evaluated for HPV-PCR und zeta chain immunohistochemistry. For immunohistochemistry a monoclonal IgG1 anti TZR zeta chain-antibody (mAb) has been used (clone 6B 10.2, Santa Cruz, Heidelberg, Germany). According to the performed Western-Blot analysis on peripheral blood monocytes (PBMCs) the used mAb has specifically recognized TCR zeta chains. RESULTS: We show reduced protein zeta chain expression associated with invasive cervical cancer, but not with pre-invasive HPV16-positive lesions or HPV16-negative normal cervix tissue. CONCLUSIONS: Thus, reduced TCR zeta chain expression is not necessarily linked to a chronic viral infection, nor to the presence of transformed cells, but rather to the stromal invasion of the cancer lesion.

Circulating endothelial progenitor cells are inversely correlated with the median oxygen tension in the tumor tissue of patients with cervical cancer.

Tumor hypoxia leads to adaptive responses in cancer cells, including an induction of vasculogenesis initiated by circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs). The aim of the present study was to correlate the number of EPCs and CECs with the oxygenation of cervical cancer. Blood concentrations of EPCs were detected by FACS analysis with antibodies for CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). CECs were evaluated by double staining for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Di-LDL) and lectin in a cell culture assay. Ten patients with cervical cancer were compared with ten healthy volunteers. Intratumoral oxygen tension was assessed polarographically with the computerized Eppendorf histography system. Analysis of CEC numbers revealed no difference between patients and controls. However, patients had lower concentrations of CD34-positive hematopoietic stem cells (HSCs) but a significantly higher fraction of EPCs related to the number of HSCs (1.09% versus 0.53%). This fraction was significantly inversely correlated to the median oxygen tension (r = -0.74, p = 0.015). Our study shows for the first time a significant inverse correlation between the fraction of EPCs and intratumoral oxygen tension. We conclude that the fraction of EPCs should be further evaluated as a useful and convenient marker in the prediction of tumor tissue oxygenation.

Hypoxia and expression of the proapoptotic regulator BNIP3 in cervical cancer.

Hypoxia plays a major role in the malignant progression of tumors. Here, we investigate the expression of Bcl-2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), a proapoptotic Bcl-2 family member, and its relationship to hypoxia in cervical cancer cell lines and clinical samples of cervical cancer. Cervical cancer cell lines were grown under hypoxia or normoxia, and BNIP3 mRNA expression was examined by Northern blot analysis. In 50 patients with cervical cancer, intratumoral oxygen measurement with the Eppendorf electrode and needle biopsies of the tumor were performed. The obtained tissue was subsequently analyzed by immunohistochemistry with an anti-BNIP3 antibody. Cervical cancer tissue collected upon surgery was used for Northern blot analysis of in vivo BNIP3 mRNA expression. BNIP3 mRNA is strongly induced under hypoxic conditions in all cervical cancer cell lines investigated. Furthermore, Northern blot analysis revealed that BNIP3 mRNA is expressed in cervical cancer tissue. Using immunohistochemistry, we demonstrated that BNIP3 protein is expressed in 82% of the investigated cervical cancers and that more advanced tumor stages showed significantly stronger BNIP3 expression. However, we observed no correlation between BNIP3 expression and intratumoral hypoxia. In conclusion, BNIP3 is expressed in different cervical cancer cell lines as well as in clinical samples of cervical cancer. Although BNIP3 is clearly hypoxia-inducible in vitro, our results suggest additional mechanisms of BNIP3 regulation in vivo. Our findings therefore highlight a discrepancy between in vitro models of tumor hypoxia and the complexity of human cancer.

Ultra-radical compartmentalized surgery in gynaecological oncology.

AIMS: To describe "ultra-radical" surgery in gynaecological oncology. This is multivisceral pelvic resection aimed at the eradication of locally advanced and recurrent gynaecologic cancer with microscopically tumour-free margins (R0). METHODS: Up-dated analysis of a prospective trial evaluating oncologic outcome and treatment-related morbidity of ultra-radical compartmentalized surgery carried out by the author. RESULTS: From 8/1996 until 9/2005 74 patients with locally advanced and recurrent gynaecologic tumours have been treated with ultra-radical compartmentalized surgery. Eighteen patients with central disease underwent exenteration as multimesovisceral excision, 56 patients with pelvic side wall disease received laterally extended endopelvic resection. In 72 of the patients the tumours were removed with microscopically free margins (R0). Two patients with advanced age and extensive comorbidity respectively, died during the early postoperative period. Moderate and severe treatment-related morbidity was 66%. At a median follow-up period of 29 months (1-112 months) 5-year overall and recurrence-free survival probabilities are 56% (95% CI: 42-69) and 56% (42-70). CONCLUSION: Ultra-radical compartmentalized pelvic surgery may salvage selected patients with locally advanced and recurrent gynaecologic malignancies including those with pelvic side wall disease traditionally not considered for surgical therapy.

Oxygenation status of primary and recurrent squamous cell carcinomas of the vulva.

INTRODUCTION: Cancers of the vulva are relatively rare and, therefore, little is known about the pathophysiological role of tumor oxygenation in this entity. METHODS: Data are presented on the oxygenation status of primary (n = 15) and recurrent (n = 19) cancers of the vulva, as measured by the Eppendorf pO2 histography system. RESULTS: Contrary to other tumor entities, no significant differences in the oxygenation status between primary (median pO2 = 13 mmHg; hypoxic fraction < or = 5 mmHg = 37%) and recurrent (median pO2 = 11 mmHg; hypoxic fraction < or = 5 mmHg = 45%) tumors were found. Oxygenation was significantly lower in cancers of the vulva than in the subcutis. Anemic patients had significantly poorer tumor oxygenation compared with patients whose cHb values were within the normal range (p = 0.02). CONCLUSIONS: The oxygenation of vulvar cancers is similar to other tumor entities, but does not show more severe hypoxia in recurrent cases. Anemia is associated with a poorer oxygenation status in vulvar cancers, whereas in the normal tissue no impact of cHb values on the median pO2 was observed.

Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome.

OBJECTIVE: BNip3 and its homologue Nix are pro-apoptotic factors of the Bcl-2-family and are expressed in malignant tumors. In vitro, this expression was shown to be mediated by hypoxia. Recently, it has been shown that placental hypoxia as well as apoptosis are pathogenetic factors for pregnancy-induced hypertensive diseases and intrauterine growth retardation (IUGR). The aim of the study was to analyze placental expression of BNip3 and Nix in pregnancies complicated by preeclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and IUGR. MATERIAL AND METHODS: Placental tissue was sampled from 10 pregnancies each with preeclampsia, HELLP syndrome, IUGR and gestational age-matched controls. The placental expression of BNip3/Nix has been investigated with immunohistochemistry by the use of specific human BNip3/Nix antibodies. RESULTS: In cytotrophoblastic cells, the BNip3 expression was strong in the control placentas, but only mediate in the placentas from pregnancies with preeclampsia, IUGR or HELLP syndrome. The intensity of the Nix staining showed a similar pattern. In the syncytiotrophoblast, there was a weak BNip3 staining observable in the control as well as IUGR samples, whereas BNip3 was undetectable in preeclamptic placentas or those with HELLP syndrome. For Nix, only in the preeclampsia a weak staining was detectable, whereas all other probes were negative. CONCLUSIONS: Our study shows for the first time that the pro-apoptotic proteins BNip3 and Nix are expressed in the human placenta. Pregnancies with placental dysfunction and hypertensive pregnancy disorders with different clinical manifestations are characterized by a significantly decreased expression of BNip3 and Nix. These results suggest that the hypothesis of generally increased placental apoptosis in pregnancy-induced hypertensive disorders caused by disturbed trophoblast invasion has to be partly reconsidered.

[Topographical anatomy of the female pelvis in ultrasound]. / Die sonomorphologische Topographie des weiblichen Beckens.

AIM: Achieving a high quality gynaecological ultrasound examination requires thorough knowledge of topographic anatomy. To date, there are no guidelines for a standardised course of the examination. The goal of the study was to define exact planes by means of cross-sectional anatomy and then to standardise the gynaecological ultrasound examination with the transabdominal, introital and transvaginal technique. METHOD: We developed a software tool based on IDL (Interactive Data Language) for the female data set of the Visible Human Project which generates free determinable planes in the volume. The organs of the female pelvis were divided into landmark- and target structures according to the ultrasonic visibility and the variability of the position, shape and structure. From this, a course for the gynaecological ultrasound examination was created and verified on 65 patients each with an inconspicuous ultrasound finding. In addition, the average duration of the examination was determined. RESULTS: The landmark structures could be demonstrated in all patients. Five planes were defined for each technique, and the course of the whole examination with 15 exact planes was described. The average duration of the examination was 4.5 minutes. CONCLUSION: As of now, the digitally reconstructed anatomical illustrations have achieved the best image resolution and quality regardless of the position of the plane in the examination volume. The standardised course of the gynaecological ultrasound examination can serve as a basis for the improvement of training quality and the evaluation of a general gynaecological ultrasound screening.

[Recommendations for the handling and oncologic pathology report of lymph node specimens submitted for evaluation of metastatic disease in gynecologic malignancies]. / Pathologisch-anatomische Aufarbeitung und Befundung von Lymphknoten bei gynäkologischen Malignomen.

The nodal status is one of the strongest prognostic factors in gynecologic malignancies. Metastatic involvement of regional and distant lymph nodes represents the selection basis for adjuvant therapy in a large number of solid neoplasms. The number of resected lymph nodes is one of the most important parameters in the quality control of the surgical procedure, in particular with respect to radicality. The present paper provides recommendations for gross dissection, laboratory procedures and reporting for lymph node biopsies, lymph node dissections and sentinel lymph node biopsies (SLN) for cancers of the vulva, vagina, uterine cervix, endometrium, Fallopian tubes and the ovaries, submitted for the evaluation of metastatic disease. The pathologic oncology report should include information about the number and size of resected lymph nodes, the number of involved lymph nodes with the maximum size of metastases and the presence of paranodal infiltration. In addition, the detection of isolated tumor cells should be reported, particularly with respect to the detection method (immunostains or molecular methods). In cases of metastatic disease and carcinoma of unknown primary (CUP-syndrome), information should be given regarding the primary tumor.

[New concepts for surgical therapy of cervical carcinoma]. / Neue Konzepte für die operative Therapie des Zervixkarzinoms.

Abdominal radical hysterectomy (Wertheim operation) is the current standard of surgical therapy of cervical carcinoma. It is based on historical concepts of female pelvic anatomy and locoregional tumor spread. This surgical therapy - depending on the individual radicality of the operation - leads to damage of essential structures not involved by the tumor, e.g. the autonomic pelvic nerves. Despite of its supposed radicality the Wertheim operation has to be combined with adjuvant radiotherapy in case of histopathological high risk factors to reach acceptable rates of tumor control. The total mesometrial resection (TMMR) uses new insights in pelvic anatomy and local tumor spread derived from developmental biology for a new concept of radicality achieving a high regional control rate with minimal treatment-related morbidity without adjuvant radiotherapy.

Total mesometrial resection: high resolution nerve-sparing radical hysterectomy based on developmentally defined surgical anatomy.

Total mesometrial resection (TMMR) is characterized by: i). the en bloc resection of the uterus, proximal vagina, and mesometrium as a developmentally defined entity; ii). transection of the rectouterine dense subperitoneal connective tissue above the level of the exposed inferior hypogastric plexus; and iii). extended pelvic/periaortic lymph node dissection preserving the superior hypogastric plexus. Since July 1998 we have studied prospectively the outcome in patients treated with TMMR for cervical carcinoma FIGO stages IB, IIA, and selected IIB. By July 2002, 71 patients with cervical cancer stages pT1b1 (n = 48), pT1b2 (n = 8), pT2a (n = 3), pT2b (n = 12) had undergone TMMR without adjuvant radiation. Fifty-four percent of the patients exhibited histopathologic high risk factors. At a median observation period of 30 months (9-57 months) two patients relapsed locally, two patients developed pelvic and distant recurrences and two patients only distant recurrences. Three patients died from their disease. Grade 1 and 2 complications occurred in 20 patients, no patient had grade 3 or 4 complications. No severe long-term impairment of pelvic visceral functions related to autonomic nerve damage was detected. Based on these preliminary results, we believe TMMR achieves a promising therapeutic index by providing a high probability of locoregional control at minimal short and long-term morbidity.

Surgical treatment of locally advanced and recurrent cervical carcinoma: overview on current standard and new developments.

The current standard treatment of locally advanced carcinoma of the uterine cervix is chemoradiation. Whether new developments such as laparoscopic surgical staging or neoadjuvant systemic and regional chemotherapy, preoperative chemoradiation and intraoperative radiation combined with radical hysterectomy will improve recurrence- free and overall survival is yet unproven. Until recently, surgical treatment of locally advanced and recurrent cervical carcinoma was performed only with a central disease location. The required operation, pelvic exenteration, was contraindicated for tumors fixed to the pelvic wall. The laterally extended endopelvic resection (LEER) now allows the exstirpation of a subset of mesenteric pelvic side-wall tumors with clear margins and opens up a 50% chance of long-term survival for the affected patients.