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

Purpose To investigate patient-reported quality of life (QoL) and associated factors in vulvar cancer patients treated surgically by vulvar field resection (VFR) without adjuvant radiation. Methods We retrospectively evaluated patient-reported QoL as part of the prospective monocentric VFR trial using the 30-item European Organization for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30) supplemented by a question assessing sexual activity. All patients had been treated by VFR and no participant had received adjuvant radiotherapy. The gynecologic cancer lymphedema questionnaire (GCLQ) was used to determine the presence of lymphedema. Structured telephone interviews were conducted to assess postoperative sequelae and long-term complications. Results Forty-three VFR patients (median age 63 years) were available for QoL assessment. Thirty-eight (88%) had received inguinal lymph-node dissection in addition to VFR. Mean global QoL (global health status) rating among all patients was 66.1 (± 25.5) on a scale from 0 to 100 with higher scores indicating better QoL. Higher GCLQ scores were significantly associated with lower global QoL scores (Spearman's rank correlation ρ =− 0.7, p p p Conclusion Overall, VFR patients exhibit good quality of life postoperatively. The presence of lymphedema, wound-healing complications, and preoperative morbidities were associated with reduced QoL. Prospective longitudinal studies have to confirm our findings in the future.

Previous findings from our centre suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. We aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumour control without the need for adjuvant radiotherapy.We did the final clinical and histopathological evaluation of data from, the single-centre, observational, cohort study, the Leipzig School Mesometrial Resection Study. Patients of any age with stage IB1, IB2, IIA1, IIA2, or IIB cervical cancer (according to 2009 International Federation of Gynecology and Obstetrics [FIGO]) had total mesometrial resection or extended mesometrial resection and therapeutic lymph node dissection, done on the basis of ontogenetic cancer fields. We defined sentinel node, first-line, second-line, and third-line lymph node regions as progressive regional cancer fields. Primary outcomes were disease-specific survival and recurrence-free survival, and treatment-related morbidity (assessed with the Franco-Italian glossary). Applying Cox proportional hazard models, ontogenetic local (T) and regional (N) tumour staging was compared with pathological T and N staging. This trial is registered with the German Clinical Trials Register, number DRKS00015171.Between Oct 16, 1999, and June 27, 2017, 523 patients were treated per protocol and followed up for a median of 61·8 months (IQR 49·3-94·8). In 495 patients with cervical cancer treated with cancer field surgery, 5-year disease-specific survival was 89·4% (95% CI 86·5-92·4) and recurrence-free survival was 83·1% (79·7-86·6). In the per-protocol population of 523 patients, treatment-related morbidity comprised 112 (21%) grade 2 and 15 (3%) grade 3 complications. The most common moderate and severe treatment-related complications and sequelae were wound dehiscence (17 [3%]), hydronephrosis (17 [3%]), bowel obstruction (26 [5%]), and lymph oedema (33 [6%]). One patient (1%), who received total mesometrial resection, died from postoperative brain infarction.Total or extended mesometrial resection with therapeutic lymph node dissection based on ontogenetic cancer fields results in good survival outcomes of patients with cervical cancer in our institution, but needs to be investigated further in multicentre trials.Leipzig School of Radical Pelvic Surgery, University of Leipzig Medical School, and the Gynecologic Oncology Research Foundation.

Annual cervical cancer screening is recommended in Germany as a part of the statutory preventive care. Abnormal results can provoke psychological distress and anxiety, compromising women’s adherence. Little is known about how a cervical dysplasia impacts adherence follow-up visits and prevention habits over time. To optimize care strategies, this study aims to identify women at risk for nonadherence to follow-up visits after a screening event. Between November 2015 and May 2017, participants with an abnormal Pap smear at the Heidelberg and Leipzig University Hospitals received a four-part questionnaire (sociodemographic data, PHQ-D, self-designed fear and prevention habit questions) at the first consultation (T1) and subsequently after 3 (T2) and 6 (T3) months; healthy controls completed the questionnaire at T1. 132 women with an abnormal Pap smear [with conization: S1 (n = 68, 51.5%), without intervention: S2 (n = 64, 48.5%)] and healthy controls (K, n = 101) generally adhered to gynecological checkups, except S1 6 months after the first diagnosis (S1/T3 − 0.47, signed rank p

A Retraction to this paper has been published and can be accessed via a link at the top of the paper.

Ovarian carcinomas (OCX) have traditionally been thought to arise from the ovarian surface epithelium. However, recent (immuno-) histopathological and molecular analyses suggest that OCX consist of morphological subtypes with different epidemiologic features and a varying prognosis.The data of 482 OCX from the Clinical Cancer Registry of Leipzig who were surgically treated between 2000 and 2019 and were evaluated regarding incidence, clinico-pathologic characteristics and prognostic factors. Cases were separated into high-grade and non-high-grade serous tumors. Both groups were analyzed regarding the tumor stage, lymph node involvement, site of origin and prognosis.The overall incidence for OCX was 17.9. The most common histological subtype was high-grade serous OCX (57.9%; 279/482). Patients with high-grade were significantly older than those with a non-high-grade serous OCX (63.9 versus 58.5 years; p 0.001), more frequently diagnosed at an advanced stagepT3 (78.5% (219/279) versus 42.8% (87/203); p 0.001) and showed a 2.4-fold higher frequency of lymph node metastases (53.4% vs. 21.2%; p 0.02) with a 4.6-fold higher rate of 1 cm metastatic deposits (pN1b) within the lymph nodes (14.8% vs. 4.6%; p 0.02). Irrespective of tumor stage and morphological subtype, the 1- and 5-year overall survival (OAS) was 72.9% and 40.8%, respectively. Patients with high-grade serous OCX showed a shorter 5-year OAS compared to non-high-grade serous OCX (34.1% vs. 57.0%; p 0.001). This association was reproducible in patients with an advanced tumor stage irrespective of the histopathologic tumor type serous OCX (pT3: 32.4% vs. pT1: 75.1%; p 0.001) as well as within high-grade (pT3: 28.7% vs. pT1: 55.5%; p = 0.003) and non-high-grade serous OCX (pT3: 43.0% vs. 80.0%; p 0.001). There were no differences in OAS depending on the site of origin (fallopian tube, ovary, peritoneum) within the two histologic subgroups.OCX cases from a single institution with uniform surgical treatment and a standardized histopathological workup were evaluated. The poor prognostic outcome of patients with high-grade serous compared non-high-grade serous OCX as well as an advanced stage of the disease was confirmed. This study demonstrates for the first time that the histopathological distinction into high-grade serous and non-high-grade serous tumors may be much more prognostically relevant than the site of origin.

In this case–control study, the impact on quality of life and sexual function in women with cervical dysplasia and conization will be evaluated, in order to address coping with such a premalignant lesion and to improve strategies for salutogenesis. This multicenter case–control study evaluates women at special dysplasia outpatient clinic (T1) as well as 3 (T2) and 6 (T3) months after the diagnosis of a dysplasia. The women were subgrouped upon dysplasia only (S2) or dysplasia with conization (S1). Sexual function as well as cervix-related and general quality of life was assessed using validated instruments (FSFI-d, EORTC-QLQ-CX24, SF-36). Women with dysplasia had a lower sexual functioning than controls (FSFI: S1: 23.8 ± 9.7 (p

Summary Background The incidence of vulvar cancer is increasing, but surgical treatment—the current standard of care—often leads to unsatisfactory outcomes, especially in patients with node-positive disease. Preliminary results at our centre showed that locoregional spread of vulvar carcinoma occurs within tissue domains defined by stepwise embryonic and fetal development (ontogenetic cancer fields and associated lymph node regions). We propose that clinical translation of these insights into practice could improve outcomes of surgical treatment of vulvar cancer. Methods We did a single-centre prospective trial at the University of Leipzig's Cancer Center. Eligible patients were aged 18 years or older, had ontogenetic stage 1–3b histologically proven primary carcinoma of the vulva, and had not undergone previous surgical or radiotherapy treatment for vulvar cancer or any other major perineal or pelvic disease. In view of staged morphogenesis of the vulva from the cloacal membrane endoderm at Carnegie stage 11 to adulthood, we defined the tissue domains of tumour spread according to the theory of ontogenetic cancer fields. On the basis of ontogenetic staging, patients were treated locally with partial, total, or extended vulvar field resection; regionally with therapeutic inguinopelvic lymph node dissection; and anatomical reconstruction without adjuvant radiotherapy. The primary endpoints were recurrence-free survival, disease-specific survival, and early postoperative complications. Analysis of tumour spread and early postoperative surgical complications was done by intention to treat (ie, all patients were included), whereas outcome analyses were done per protocol. This ongoing trial is registered with the German Clinical Trials Register, number DRKS00013358. Findings Between March 1, 2009, and June 8, 2017, 97 consecutive patients were included in the study, of whom 94 were treated per protocol with vulvar field resection, therapeutic inguinopelvic lymph node dissection, and anatomical reconstruction without adjuvant radiotherapy. 46 patients had moderate or severe postoperative complications, especially infectious perineal and inguinal wound dehiscence. 3-year recurrence-free survival in all patients was 85·1% (95% CI 76·9–93·3), and 3-year disease-specific survival was 86·0% (78·2–93·8). Interpretation Our results support the theory of ontogenetic cancer fields for vulvar carcinoma, accord with our previous findings in cervical cancer, and suggest the general applicability of the theory. Application of the concept of cancer field resection could improve outcomes in patients with vulvar carcinoma, but needs to be investigated further in multicentre randomised controlled trials. Funding Leipzig School of Radical Pelvic Surgery and Gynecologic Oncology Research Foundation.

Dental and cervical controls are two established screening programs in Germany. Compliance to orthodontic treatment in childhood is essential for dental health and one of the first health interventions that requires adherent behavior; therefore, it may be associated with participation in further screening programs in adulthood. However, it is not yet known whether early orthodontic treatment influences long-term screening adherence. Using a questionnaire administered during a visit to a special dysplasia outpatient service, this case–control study evaluated women’s personal history of orthodontic care, long-term satisfaction, and dental and gynecological screening adherence. Oral health status and dental anxiety were assessed with validated instruments. Cases were categorized as cervical dysplasia only (S2) or cervical dysplasia with conization (S1) and compared to healthy controls with a normal PAP smear. A study population of 233 participants included 132 cases and 101 controls. The control group had had orthodontic treatment during childhood more often than our study population with abnormal PAP smears (68.3% controls versus 56.1% subjects; p

The established surgical treatment approach to gynecological cancers is based on functional anatomy and on a model of radial isotropic tumor growth. The rational consists of tumor resection with a metrically defined margin of healthy tissue. In many cases, however, this necessitates the resection of functional tissue which increases treatment morbidity. In addition, this treatment strategy often requires adjuvant (chemo)radiation which further increases treatment-related morbidity and relapses still occur. A new concept of tumor resection based on the theory of ontogenetic cancer fields has been introduced by Michael Hockel during the last decades. This theory is based on the assumption, that malignant tumors are the phenotypic correlate of reverse dysmorphogenesis. During this process, developmental programs which are established and silenced subsequently during embryogenesis, are re-activated in a stepwise, retrograde pattern. Ontogenetic cancer fields are domains of potential tumor growth during a given step of malignant progression. This theory has led to the introduction of a new cancer staging system based on ontogenetic anatomy. Curative tumor resection can be achieved by removal of the relevant cancer field. Application of this concept has led to the development of TMMR and PMMR for the surgical treatment of cervical and endometrial cancer.

Preeclampsia and intrauterine growth restriction (IUGR) account for a major part of perinatal and maternal morbidity worldwide and are associated with increased later cardiovascular risk. Both diseases are characterized by a shallow endovascular trophoblast invasion causing a disturbed placental development and are considered as syndromes with numerous vascular, metabolic, immunological and clinical alterations. Their etiology and pathophysiological consequences remain mostly unresolved. Beside others one hypothesis favors oxidative stress as a relevant pathophysiological factor. Oxidative stress as an imbalance between free radicals and the capacity of protective antioxidant systems is thought to be a potent promoter of maternal vascular dysfunction and endothelial damage. As both pregnancy complications furthermore are associated with an increased later cardiovascular risk for mother and child, the pathobiology mediated by oxidative stress may have general and long-term devastating influence on vascular function. Disturbed trophoblast invasion and placental development cause an abnormal uterine perfusion in mid-pregnancy, which is easily detectable by abdominal ultrasound and identifies women at risk for the mentioned pregnancy complications antedating their clinical manifestation. We showed that an abnormal uterine perfusion in pregnancy is characterized by a decreased maternal plasma antioxidant capacity. Even though this reduction is not related to the clinical outcome of these high-risk pregnancies, oxidative stress and uterine perfusion are clearly pathophysiologically connected. In this article, we focus on links between oxidative stress and uterine perfusion and possible implications for the early detection of patients at risk for preeclampsia and IUGR. This might improve our understanding of these relationships, and may become of beneficial impact for the short- and long-term outcome in affected mothers and their children.

Pancreatic cancer is highly aggressive and refractory to most existing therapies. Past studies have shown that connective tissue growth factor (CTGF) expression is elevated in human pancreatic adenocarcinomas and some pancreatic cancer cell lines. To address whether and how CTGF influences tumor growth, we generated pancreatic tumor cell lines that overexpress different levels of human CTGF. The effect of CTGF overexpression on cell proliferation was measured in vitro in monolayer culture, suspension culture, or soft agar, and in vivo in tumor xenografts. Although there was no effect of CTGF expression on proliferation in two-dimensional cultures, anchorage-independent growth (AIG) was enhanced. The capacity of CTGF to enhance AIG in vitro was linked to enhanced pancreatic tumor growth in vivo when these cells were implanted s.c. in nude mice. Administration of a neutralizing CTGF-specific monoclonal antibody, FG-3019, had no effect on monolayer cell proliferation, but blocked AIG in soft agar. Consistent with this observation, anti-CTGF treatment of mice bearing established CTGF-expressing tumors abrogated CTGF-dependent tumor growth and inhibited lymph node metastases without any toxicity observed in normal tissue. Together, these studies implicate CTGF as a new target in pancreatic cancer and suggest that inhibition of CTGF with a human monoclonal antibody may control primary and metastatic tumor growth. (Cancer Res 2006; 66(11): 5816-27)

Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell-cell or cell-matrix interactions) and the extended tumour microenvironment (for example vascularization). Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.

Locally advanced cancer of the uterine cervix covers a broad disease spectrum comprising primary tumours of >4 cm in size or FIGO stage >IIA and all local tumour relapses except the rare cases of small recurrences in a retained cervix. Treatment designs have to consider the probability of pelvic and periaortic lymph node metastases and – albeit less frequent in primary disease – distant metastases. Established treatment standards aiming to achieve pelvic and eventually periaortic tumour control are chemoradiation for locally advanced primary disease as well as post-surgical pelvic recurrences, and pelvic exenteration for post-radiation central relapses. A subset of patients with pelvic side wall relapses can now be successfully treated by laterally extended endopelvic resection as well. Based on the current results it is not evident whether neoadjuvant chemotherapy, radical hysterectomy and eventually adjuvant radiation are comparable or superior treatment alternatives for locally advanced intermediate stage cases. Likewise, the benefit of (laparoscopic) surgical staging including the exstirpation of bulky pelvic and periaortic lymph nodes has not been convincingly demonstrated to date. Both surgical treatment concepts need further well-designed prospective randomized trials for their evaluation. From the surgeon's perspective total mesometrial resection, therapeutic lymph node dissection, laterally extended endopelvic resection and new developments in restoration/substitution of pelvic functions have the potential to improve the therapeutic index for defined cohorts of patients suffering from locally advanced cancer of the uterine cervix.

After surgical resection with microscopically clear margins, solid malignant tumors recur locally in up to 50%. Although the effect of a local tumor recurrence on the overall survival may be low in common cancers such as carcinoma of the breast or prostate, the affected patients suffer from exacerbated fear and the burden of the secondary treatment. With some tumor entities such as carcinoma of the uterine cervix or carcinoma of the head and neck, a local recurrence indicates incurability in the majority of cases. The pathomechanisms of local tumor spread and relapse formation are still unclear and comparatively little research has been devoted to their elucidation. Through the analysis of clinical and molecular data, we propose the concept of two pathogenetically and prognostically different local relapse types (i) in situ recurrences that arise in the residual organ/organ system not involved in the surgery for the primary tumor and (ii) scar recurrences that develop at the site of previous tumor resection. Whereas field cancerization, the monoclonal or multiclonal displacement of normal epithelium by a genetically altered but microscopically undistinguishable homologue, may explain the origin of in situ recurrences, most scar recurrences are regarded as the result of the interaction of minimal residual microscopically occult cancer with the surgical wound environment inside a developmentally defined tissue or organ compartment. The therapeutic implications derived from these concepts and areas of future research aimed to reduce local relapses are discussed in this perspective.

Objective We have suggested to base cancer surgery on ontogenetic anatomy and the compartment theory of tumor permeation in order to improve local tumor control and to lower treatment-related morbidity. Following the validation of this concept for the uterine cervix, proximal vagina and vulva, this study explores its applicability for the distal vagina. Methods Serial transverse sections of female embryos and fetuses aged 8–17weeks were assessed for the morphological changes in the region defined by the deep urogenital sinus–vaginal plate complex. Histopathological pattern analysis of local tumor spread was performed with carcinomas of the lower genital tract involving the distal vagina to test the compartment theory. Results Ontogenetically, the female urethra, urethrovaginal septum, distal vagina and rectovaginal septum represent a morphogenetic unit derived from the deep urogenital sinus–vaginal plate complex. Herein, the posterior urethra, the urethrovaginal septum and the distal vagina form a distinct subcompartment differentiated from the dorsal wall of the urogenital sinus. From 150 consecutive patients with distal vaginectomy as part of their surgical treatment 26 carcinomas of the lower genital tract had infiltrated the distal vagina. All 22 tumors involving the ventral wall invaded the urethra/periurethral tissue. Of the five carcinomas involving the dorsal wall none invaded the rectum/mesorectum. Conclusion The pattern of local tumor permeation of lower genital tract cancer in the distal vagina can be consistently explained with ontogenetic anatomy and the compartment theory.

Summary Background Radical hysterectomy based on empirical surgical anatomy to achieve a wide tumour resection is currently applied to treat early cervical cancer. Total mesometrial resection (TMMR) removes the embryologically defined uterovaginal (Mullerian) compartment except its distal part. Non-Mullerian paracervical and paravaginal tissues may remain in situ despite their possible close proximity to the tumour. We propose that in patients with early cervical cancer, the resection of the Mullerian compartment will lead to maximum local tumour control with low morbidity. We also propose that the relatively high rate of pelvic failure after conventional radical hysterectomy, despite adjuvant radiation, might be a consequence of the incomplete removal of the Mullerian compartment. The aim of our study was to test these hypotheses. Methods We did a prospective trial to assess the effectiveness of TMMR without adjuvant radiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA, and selected IIB cervical cancer. We also generated MRI-based pelvic relapse landscapes from patients who had experienced pelvic failure after conventional radical hysterectomy. Findings 212 consecutive patients underwent TMMR without adjuvant radiation. 134 patients (63%) had high-risk histopathological factors. At a median follow-up of 41 months (5–110), three patients developed pelvic recurrences, two patients developed pelvic and distant recurrences, and five patients developed distant recurrences. Recurrence-free and overall 5-year survival probabilities were 94% (95% CI 91–98) and 96% (93–99), respectively. Treatment-related grade 2 morbidity was detected in 20 (9%) patients, the most common being vascular complications. Resection of the Mullerian compartment resulted in local tumour control irrespective of the metric extension of the resection margins. The pelvic topography of the peak relapse probability after conventional radical hysterectomy indicates an incomplete resection of the posterior subperitoneal and retroperitoneal extension of the Mullerian compartment. Interpretation Resection of the embryologically defined uterovaginal compartment seems to be pivotal for pelvic control in patients with cervical cancer. TMMR without adjuvant radiation has great potential to improve the effectiveness of surgical treatment of early-stage cervical cancer. Funding University of Leipzig, Leipzig, Germany.

For almost a century abdominal radical hysterectomy has been the standard surgical treatment of early-stage macroscopic carcinoma of the uterine cervix. The excessive parametrial resection of the original procedures of Wertheim, Okabayashi, and Meigs has later been "tailored" to tumor extent. Systematic pelvic and eventually periaortic lymph node dissection is performed to identify and treat regional disease. Adjuvant (chemo)radiation therapy is liberally added to improve locoregional tumor control when histopathological risk factors are present. The therapeutic index of the current surgical treatment, particularly if combined with radiation, appears to be inferior to that of primary chemoradiation as an oncologically equivalent therapeutic alternative. Several avenues of new conceptual and technical developments have been used since the 1990s with the goal of improving the therapeutic index. These are: surgical staging, including sentinel node biopsy and nodal debulking; minimal access and recently robotic radical hysterectomy; fertility-preserving surgery; nerve-sparing radical hysterectomy; total mesometrial resection based on developmentally defined surgical anatomy; and supraradical hysterectomy. The superiority of these new developments over the standard treatment remains to be demonstrated by controlled prospective trials. Multimodality therapy including surgery for locally advanced disease represents another area of clinical research. Both neoadjuvant chemotherapy followed by radical surgery, with or without adjuvant radiation, and completion surgery after (chemo)radiation are feasible and have to be compared to primary chemoradiation as the new nonsurgical treatment standard. Surgical treatment of postirradiation persisting or recurrent cervical carcinoma has been traditionally limited to pelvic exenteration for central disease. Applying the principle of developmentally derived anatomical compartments increases R0 resectability. The laterally extended endopelvic resection allows even the extirpation of a subset of visceral pelvic side wall tumors with clear margins. Many questions regarding the indication for these "ultraradical" operations, the surgery of irradiated tissues, and the optimal reconstructive procedures are still open and demand multi-institutional controlled trials to be answered.

Current treatment of neoplastic disease that involves the external female genitalia aims to achieve local disease control, but not to restore form and function of these organs. Despite a growing trend to reduce the extent of surgical resection, impaired quality of life after surgery due to severe sexual dysfunction and disturbed body image is common. We postulate that the integration of surgical techniques for vulvar and vaginal reconstruction into primary treatment would improve aesthetic and functional results and therefore quality of life. We systematically searched the literature for surgical procedures designed and validated for vulvovaginal reconstruction. Various skin flaps, both with random vascularisation and those based on vascular territories (ie, axial pattern, fasciocutaneous, musculocutaneous, and bowel flaps), can restore important parts of vulvovaginal form and function with acceptable morbidity at the donor and recipient sites. Appropriate vulvovaginal reconstruction cannot be achieved by doing a few standardised procedures; rather, it necessitates specialists who are familiar with general principles of reconstructive surgery to master many techniques to select the optimum procedure for the individual patient. Vulvovaginal reconstructive surgery has limitations, particularly achievement of functional restoration in irradiated tissue. Physicians who treat women with neoplastic disease of the external genitalia should be aware of the current state of vulvovaginal reconstructive surgery. Prospective controlled clinical trials are warranted to assess the effect of vulvovaginal reconstruction on morbidity and quality of life after treatment.

Pelvic exenteration has been used for 60 years to treat cancers of the lower and middle female genital tract in radiated pelves. The mainstay for treatment success in terms of locoregional control and long-term survival is resection of the pelvic tumour with clear margins (R0). New ablative techniques based on developmentally derived surgical anatomy and laterally extended endopelvic resection have raised the number of R0 resections done, even for tumours that extend to the pelvic side wall, which were traditionally judged a contraindication for exenteration. Although mortality has fallen to less than 5%, treatment-related severe morbidity of pelvic exenteration still exceeds 50%, possibly because of compromised healing of irradiated tissue and use of complex reconstructive techniques. The benefits of exenteration for patients who have advanced primary disease or recurrent tumours after surgery, versus those who have chemoradiotherapy, are not proven by results of controlled trials, but can be assumed from retrospective data. Comparative findings are missing, and arguments are unconvincing to favour pelvic exenteration over less extensive treatments and best supportive care for palliation of cancer symptoms in most patients.

Obesity before and during pregnancy is associated with several obstetrics risk factors for both mother and fetus. The aim of this retrospective study was to analyze the influence of BMI before pregnancy on distinct perinatal parameters.The study includes 5067 singleton pregnancies from 2001 to 2004 at the Department of Obstetrics and Gynecology, University of Leipzig. The study group was divided into BMI groups:18.5,or=18.5 to25,or=25 to30,or=30 to35,or=35 to40, andor=40 kg/m(2). Analysis of perinatal data included rate of intrauterine death, rate of cesarean section and shoulder dystocia, time of hospital stay for mother and newborn, and gestational age of delivery. Neonatal outcome variables included percentage of newborns weighing4000 grams, rate of umbilical cord pH7.10, and rate of 1-, 5-, and 10-minute Apgar scores of8.There was no difference in the gestational age at delivery among the groups. In the group with BMIor=30 kg/m(2), the cesarean section rate was significantly elevated to 25.1%, with a more dramatic increase up to 30.2% in the group with BMIor=35 kg/m(2) and 43.1% in the group with BMIor=40 kg/m(2), mainly because of a higher number of secondary cesarean sections. Although newborns of obese women showed worse initial neonatal adaptation, the 10-minute Apgar values did not differ among the groups. The higher rate of operative deliveries and the trend to an increased rate of shoulder dystocia did not influence duration of the hospital stay for mothers and newborns or morbidity of both.A high pre-pregnancy BMI is clearly associated with a higher rate of cesarean section deliveries. However, under the compensating conditions of a tertiary perinatal center, overall morbidity of mothers and newborns seems not to be increased.

BACKGROUND: Vulvectomy is a disfiguring operation detrimental to self-esteem and female identity, but surgical techniques for anatomical reconstruction are not routinely performed. CASES: Anatomical reconstruction of the vulva is illustrated in 1) a patient with superficial vulvectomy, 2) a patient with deep anterior vulvectomy, and 3) a patient with extended radical vulvectomy. Random skin flaps and axial-pattern skin flaps based on the deep external and the internal pudendal arteries were used. All patients had good postoperative results. CONCLUSION: Established reconstructive procedures can be used to restore the labial folds, vestibulum, posterior commissure, and perineum. We advocate reconstruction of the anterior commissure with clitoral protrusion after superficial and deep vulvectomy.

4150 Background: Connective Tissue Growth Factor (CTGF) is a member of the CCN family of cysteine- rich secreted glycoproteins and is a novel factor recently implicated in tumor progression of seve...