Morbidity after pelvic exenteration for gynecological malignancies: a retrospective multicentric study of 230 patients.

ObjectiveOur study purpose was to evaluate morbidity and postoperative mortality in patients who underwent pelvic exenteration (PE) for primary or recurrent gynecological malignancies.MethodsWe identified 230 patients who underwent PE, referred to the gynecological oncology units of 4 institutions: Charitè University in Berlin, Friedrich-Schiller University in Jena, S. Orsola-Malpighi University in Bologna, and Catholic University in Rome and in Campobasso.ResultsThe median age was 55 years. The tumor site was the cervix in 177 patients, the endometrium in 28 patients, the vulva in 16 patients, and the vagina in 9 patients. Sixty-eight anterior, 31 posterior, and 131 total PEs were performe…

Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions

Background Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions. Methods We obtained biopsies from peritoneal endometriotic lesions (n = 60) and peritoneal sites distant from the endometriotic lesion (n = 60), as well as healthy peritoneum from patients without endometriosis (control tissue, n = 10). These controls were hysterectomy specimens from patients without endometriosis or adenomyos…

Laparoscopic Management of External Iliac Artery Injury Using Yasargil Clamps and Intracorporeal Suture

Presented is a case report of laparoscopic repair of an external iliac artery injury using titanium Yasargil clamps and intracorporeal suture during lymphadenectomy. Yasargil clamps were introduced and placed, 1 distal and 1 proximal to the lesion. The vascular injury site was identified and repaired using intracorporeal sutures. Laparoscopic staging was completed successfully. No sign of thrombosis or vascular occlusion was detected. The patient was discharged on postoperative day 4 to receive adjuvant therapy. Laparotomy is the accepted way of managing major vascular injuries during laparoscopy. However, in controlled circumstances, with availability of Yasargil clamps and a surgeon exper…

Optimized culture conditions for tissue explants of uterine leiomyoma

Background Uterine leiomyomas are the most common benign tumours in women, which arise from smooth muscle cells of the uterine myometrium and usually are multicentric. In spite of their frequency pathogenesis is widely unknown, mainly due to the absence of a suitable model system. We describe the systematic optimization of culturing leiomyoma tissue explants in an economical and effective ex vivo system. Methods Different concentrations of oxygen, different media, sera, hormones, and growth factor supplements were tested. Immunohistochemical stainings with antibodies against hormone receptors as well as specifying proliferation and apoptotic indices and real-time PCR were performed. Results…

Validity of the Colposcopic Criteria Inner Border Sign, Ridge Sign, and Rag Sign for Detection of High-Grade Cervical Intraepithelial Neoplasia

OBJECTIVE: To evaluate the association of three patho-gnomonic criteria, inner border, ridge sign, and rag sign with high-grade cervical intraepithelial neoplasia (CIN) using video exoscopy. METHODS: Retrospective evaluation of video recordings of 335 patients, referred for diagnostic colposcopy, who underwent cervical biopsies, and, if indicated loop excisions, was performed. The most severe histologic diagnosis was recorded. Sensitivity, specificity, positive, negative predictive value, and likelihood ratios for highgrade CIN were calculated. RESULTS: In 285 patients (85%), a single colposcopy directed biopsy was taken; 50 patients (15%) underwent two biopsies. One hundred sixty-two patie…

Imbalance between sympathetic and sensory innervation in peritoneal endometriosis

To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n= 40) and healthy peritoneum (n= 12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleuki…

A multicentric randomized study comparing two techniques of magnification assisted loop excision of high-grade cervical intraepithelial neoplasia: video exoscopy and colposcopy.

Purpose: To compare loop excisions of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) under video exoscopy, or colposcopic guidance, with respect to safety and effectiveness. Methods: Prospective multicentric randomized trial of 300 patients, undergoing loop excision for CIN 2+ either under video exoscopy (group A) or colposcope (group B) guidance. Intra- and post-operative complications, resection margins, and removed cervical volume in both groups were evaluated. Results: 19.3% of patients in video exoscopy group and 15.5% in colposcopy group (p = 0.67) had transformation zone (TZ) 3. 45/151 (29.8%) of group A patients and 48/149 (32.2%) of group B patients underwent top-hat …

Neuroimmunomodulatory Alterations in Non-Lesional Peritoneum Close to Peritoneal Endometriosis

<b><i>Objectives:</i></b> An imbalance in the ratio of sensory to sympathetic nerve fibre (NF) density in peritoneal endometriotic lesions (pEL) has recently been demonstrated and leads to the assumption that this preponderance of the sensory pro-inflammatory milieu is a major cause of pain in endometriosis. Therefore, the density of sensory and sympathetic NFs was determined in distal unaffected peritoneum of endometriosis patients to be able to detect possible alterations in unaffected peritoneum. <b><i>Methods:</i></b> In serial pEL sections (n = 40), lesional and matching unaffected peritoneum as well as healthy peritoneum (HP) from patien…

Eutopic endometrium from women with endometriosis does not exhibit neurotrophic properties

The role of neurotrophins in eutopic endometrium from endometriosis-patients was investigated in a prospective study using immunofluorescence-staining, Western blot and a neuronal growth assay. The nerve growth factor is expressed in primary endometrial cell culture from women with and without endometriosis. Western blot analysis of endometrial biopsies or uterine fluid from patients with and without endometriosis shows no difference in the neurotrophin expression. We could not find a difference between patients with and without endometriosis with regards to the neurite outgrowth of sensory ganglia when treated with conditioned cultured medium or uterine fluid. This result refutes the assum…

Prospective Comparison of Loop Excision under Colposcopic Guidance versus Vitom Guidance.

Background: Aim of the study was to compare the quality of loop excision using a colposcope with results using the VITOM system. Results compared included cervical volume removed, intra- and postoperative complications, and positive resection margins. Methods: A total of 200 patients with histologically confirmed high-grade cervical premalignant lesions, persistent atypical cytological results and/or suspicious colposcopic findings, and cytological and histological discrepancies were included in the study. In transformation zone type 1 (T1) only a superficial cone biopsy was done, in zones type 2 and 3 (T2 and T3) a superficial outside cone biopsy or a deeper inside cone biopsy were done re…

High Lymph Vessel Density and Expression of Lymphatic Growth Factors in Peritoneal Endometriosis

To investigate the occurrence of lymph vessels and lymphangiogenic growth factors in peritoneal lesions, we performed immunohistochemical staining of peritoneal lesions of 37 patients with antibodies against podoplanin (D2-40), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero homeobox protein 1 (Prox-1), vascular epithelial growth factor (VEGF)-C/VEGF-D. Overall, 10 lesions were double stained against D2-40 and von Willebrand factor. The lymph vessel density in peritoneal lesion was significantly higher in comparison with healthy peritoneum. All lymph vessel makers could be detected, whereby the lymph vessel density of LYVE-1- and Prox-1-positive lymph vessels was signi…

Laparoscopic Sentinel Lymph Node Detection After Hysteroscopic Injection of Technetium-99 in Patients With Endometrial Cancer

Background and Objectives Endometrial cancer (EC) has an increasing incidence worldwide. Despite the unequivocal prognostic importance of nodal status, systematic lymphadenectomy is associated to elevated morbidity. Sentinel lymph node (SLN) biopsy is designed to avoid extensive nodal dissection and provide crucial oncologic information. The goal of this prospective study was to determine the feasibility, safety, and accuracy of laparoscopic SLN biopsy in EC obtained through hysteroscopic injection of technetium-99 (Tc-99). Methods From January 2008 to December 2012, a total of 42 women with EC were included in the study. We injected 20 mBq of Tc-99 hysteroscopically underneath the tumor mi…

Tertiary cytoreduction in the setting of recurrent ovarian cancer (Review)

Ovarian cancer is the most lethal gynecological malignancy, with aggressive surgical debulking and adjuvant chemotherapy as the main treatment modalities. Optimal debulking during the primary surgery is significantly correlated with prolonged survival. As surgical techniques and chemotherapeutic agents improve, more patients with prolonged survival may face secondary and tertiary recurrences. The role of surgical debulking in secondary cytoreduction (SC) is not clearly defined and is based on retrospective series. The treatment of patients with primary or secondary recurrences generally consists of second-line chemotherapy, but may be performed on medically fit patients in certain circumsta…

Laparoscopic temporary clipping of uterine artery during laparoscopic myomectomy

Purpose: Our aim is to study the feasibility and effect of bilateral laparoscopic temporary occlusion of uterine arteries by special vascular clamps on blood loss during laparoscopic myomectomy. Methods: Of 166 women with symptomatic uterine myomas necessitating surgical intervention who wished to retain their uteri, 80 underwent laparoscopic uterine artery clipping and myomectomy (experimental group) and 86 received laparoscopic myomectomy only (control group). Main outcome measures were operating time, number and weight of leiomyomas, blood loss, Doppler examination of the uterine arteries and complications of procedure. Results: In the experimental group the median hemoglobin drop measur…

Laparoscopic excision of a benign peritoneal cystic mesothelioma

Benign cystic peritoneal mesothelioma is a rare tumor and most commonly occurs in women in the reproductive age group. It is very rare in women of postmenopausal age. We present a rare case of a postmenopausal woman with benign peritoneal cystic mesothelioma removed at laparoscopy.

Laparoscopic pelvic lymphadenectomy in 32 pregnant patients with cervical cancer: Rationale, description of the technique, and outcome

ObjectiveIndividualized treatment of pregnant patients with cervical cancer is mandatory; hence, information on nodal status is pivotal to allow a waiting strategy in early-stage disease.We aimed to verify the oncological safety and surgical reproducibility of a standardized laparoscopic pelvic lymphadenectomy in pregnant patients with cervical cancer.MethodsWe standardized laparoscopic pelvic lymphadenectomy during the first and second term of gestation in 32 patients with cervical cancer since 1999. According to gestational week (GW) of less than 16 GWs or more than 16 GWs, 2 different techniques were used.ResultsThe International Federation of Gynecology and Obstetrics stages were IA in …

Invasive cervical cancer during pregnancy: laparoscopic nodal evaluation before oncologic treatment delay

Introduction. Cervical cancer is the most frequently encountered malignancy during pregnancy. Presence of nodal metastasis is the most important negative prognostic factor and its assessment represents a crucial parameter to decide if pregnancy can safely continue. We describe the results of 18 pregnant patients with cervical cancer who had their nodal status proved by means of laparoscopy. Material and methods. Eighteen patients with cervical cancer who underwent laparoscopic pelvic lymphadenectomy during pregnancy at Charit-University Berlin and Friedrich-Schiller-University Jena between 1999 and 2010 were analyzed retrospectively. Results. The mean age at diagnosis was 32 years (26-40) a…

Vaccination against HPV-Associated Neoplasias

Neoplasias associated with anogenital human papilloma viruses (HPV) are characterised by high patient morbidity and mortality and by appreciable limitations in the patientʼs quality of life. Each year 530,000 women worldwide and 4800 women in Germany develop cervical cancer 1, 2. Biomolecular and epidemiological studies carried out in the past 25 years have demonstrated causal link between persisting infections with HPV 16 and HPV 18 and at least 11 other so-called high-risk HPVs (HR-HPVs) and the development of cervical cancer and its precursor lesions (so-called dysplasias or, respectively, cervical intraepithelial neoplasias – CIN). HPV 16, HPV 18 and other HR-HPVs are also the causes of…

Evidence of neurotrophic events due to peritoneal endometriotic lesions

To investigate the neurotrophic properties of endometriosis, as well as the involvement of neurotrophic factors in the development of chronic pelvic pain in patients with endometriosis, we performed a prospective clinical study. The presence of neurotrophins was investigated in the peritoneal fluid (PF) of patients with peritoneal endometriotic lesions or adenomyosis, as well as from women with non-endometriotic adhesions and from women without endometriosis/adenomyosis/adhesions. The PF from patients with peritoneal endometriotic lesions was divided in three groups: asymptomatic endometriosis, minimal pain and severe pain. PF from patients with adenomyosis or with non-endometriotic adhesio…

Influence of nerve growth factor in endometriosis-associated symptoms

To investigate the role of the nerve growth factor (NGF) in the development of dysmenorrhea/pelvic pain in patients with endometriosis, we performed a prospective, clinical, blind study. Peritoneal fluids (PFs) were obtained from patients with histologically proven endometriosis. Patients with endometriosis were divided into 7 different groups depending on their preoperative pain score and symptomatology: patients with no pain, patients with minimal pain (dysmenorrhea, pelvic pain, or both), and patients with severe pain (dysmenorrhea, pelvic pain, or both) and were used for the neuronal growth assay with cultured chicken dorsal root ganglia (DRG) and for Western blot analyses. Dorsal root …

Clinical Recommendation Radical Trachelectomy for Fertility Preservation in Patients With Early-Stage Cervical Cancer

Radical trachelectomy (RT) is a fertility-sparing procedure with the aim to provide adequate oncological safety to patients with cervical cancer while preserving their fertility. In the current review, indications, development of the procedure, technical aspects, preoperative and postoperative management, and oncological, fertility, and obstetric outcomes are discussed and studied with respect to whether the procedure is performed abdominally or vaginally. Complications of RT, staging, and more conservative alternatives to RT are discussed as well. A systematic MEDLINE search was performed, which yielded 218 articles, of which 75 were selected for further analysis based on the number of pat…

Validity of Laparoscopic Staging to Avoid Adjuvant Chemoradiation following Radical Surgery in Patients with Early Cervical Cancer

<b><i>Purpose:</i></b> To determine the rate of unavoidable adjuvant chemoradiation (RCTX) due to histologic results after radical surgery in patients with early cervical cancer. <b><i>Patients and Methods:</i></b> Between May 2004 and July 2011, 448 consecutive patients diagnosed with invasive cervical cancer stage IA1 L1 to IIA underwent laparoscopic staging at the Department of Gynecology and Gynecologic Oncology at Charité Berlin. Only in patients without lymph node metastases (n = 394) on frozen section, radical operation was continued either by laparoscopic radical hysterectomy (n = 228) or by radical vaginal trachelectomy (n = 166). The…

Prevalence of lymph nodes in the parametrium of radical vaginal trachelectomy (RVT) specimen

Objective: In order to evaluate radicality in fertility preserving surgery in women with early invasive cervical cancer we analyzed the parametrium of specimens of patients treated by radical vaginal trachelectomy for the presence of lymph nodes. We tried to identify morphologic factors associated with the presence of parametrial lymph nodes. Methods: We analyzed surgical specimens of 112 patients who underwent radical trachelectomy between June 2004 and April 2009 at the Department of Gynecologic Oncology at Charité Campus Benjamin Franklin and Campus Mitte. All parametrial tissue was step sectioned and a total of 1878H&E stained histological sections were analyzed. Results: In 8 patients …

Clinical relevance of objectifying colposcopy.

Purpose: To evaluate the clinical value of four objective colposcopic criteria inner border, ridge sign, cuffed crypt openings and rag sign to diagnose cervical intraepithelial neoplasia grade 2 or worse (CIN 2+), using video exoscopy and to compare it to subjective graduating signs. Methods: Retrospective evaluation of video recordings of 444 patients, referred for diagnostic colposcopy, who underwent cervical biopsies, and if indicated loop excisions. Most severe histological diagnosis was recorded. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) with 95 % confidence interval, for CIN 2+ were calculated. Results: Singl…

Survival after curative pelvic exenteration for primary or recurrent cervical cancer a retrospective multicentric study of 167 patients

ObjectiveEvaluate the survival of patients who underwent pelvic exenteration (PE) with curative intent for primary persistent or recurrent cervical cancer.MethodsWe retrospectively investigated 167 consecutive patients, referred to the gynecological oncology units of 4 centers in Germany or Italy, who underwent PE. Data regarding surgery, histology, and oncologic outcomes were collected and statistically evaluated. Survival was determined from the day of exenteration until last follow-up or death.ResultsThe median age was 51 years. Twenty-seven patients (16.2%) underwent PE owing to advanced primary tumors (group A), 34 patients (20.4%) underwent PE owing to persistent cancer after chemothe…

Perioperative morbidity and rate of upstaging after laparoscopic staging for patients with locally advanced cervical cancer: results of a prospective randomized trial.

Objective The International Federation of Gynecology and Obstetrics (FIGO) staging for cervical cancer is based on clinical examination. Previous studies have demonstrated significant upstaging with surgical staging. However, no randomized trial has ever shown a survival benefit when radiation combined with chemoradiation (RCTX) is modified according to surgical staging. The objective of the study was to evaluate the feasibility and outcomes of surgical staging prior to radical RCTX treatment among patients with locally advanced cervical cancer in the setting of a larger, prospective, randomized study (the Uterus-11 study of the German Gynecologic Oncology Group). Study Design Between 2009 …

Impfprävention HPV-assoziierter Neoplasien : Empfehlungen aus der aktuellen S3-Leitlinie des HPV-Management-Forums der Paul-Ehrlich-Gesellschaft für Chemotherapie e. V. – AWMF Leitlinien-Register Nr. 082-002 (Kurzfassung), gültig bis 31.12.2018

A region on human chromosome 4 (q35.1→qter) induces senescence in cell hybrids and is involved in cervical carcinogenesis

Human papillomavirus (HPV) types 16 and 18 are known to play a major role in cervical carcinogenesis. Additional genetic alterations are required for the development and progression of cervical cancer. Previously, we showed that the introduction of an entire human chromosome 4 into HPV-immortalized cells by microcell-mediated chromosome transfer (MMCT) can induce senescence in cell hybrids. In the present study, we established eight new murine donor cell lines harboring different fragments of the human chromosome 4. These were tested for their ability to induce senescence by MMCT into HPV16-immortalized keratinocytes (HPK II) and cervical carcinoma cells (HeLa). By exclusion, we could ident…

Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3).

Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A …

Implication of the Examining Pathologist to Meet the Oncologic Standard of Lymph Node Count after Laparoscopic Lymphadenectomy

<i>Objective:</i> The lymph node number as benchmark in oncologic operations depends on the patient’s anatomy, surgeon’s skill and pathologist’s accuracy. The influence of the pathologist is barely evaluated. <i>Methods:</i> A retrospective analysis of lymph node numbers after 700 laparoscopic lymphadenectomies in correlation to the examining pathologists was done. Three surgeons from the same department performed all operations at 2 campi, where 2 separate pathology institutions exist. Lymph node specimens were assigned randomly to any of the 62 involved pathologists. <i>Results:</i> The mean number of lymph nodes was equal for all surgeons. Lymph node s…

Laparoscopic lymph node dissection should be performed before fertility preserving treatment of patients with cervical cancer

Objective: The aim of this study is to assess our results of treatment of women with stage I cervical cancer > 2 cm in diameter seeking fertility preservation. Treatment consisted of Laparoscopic Pelvic and Paraaortic Lymphadenectomy (LPPLND), and when no nodal metastasis was detected, neoadjuvant chemotherapy (NACT) followed by radical vaginal trachelectomy (RVT). Patients with positive lymph nodes underwent primary chemoradiation. Methods: A cohort of women younger than 40 years of age with stage I disease > 2 cm who underwent LPPLND and either NACT and RVT or chemoradiation. Oncological outcome was evaluated prospectively. Results: Eighteen women were eligible for this study. Twelve (67%…

Overexpression of nerve growth factor in peritoneal fluid from women with endometriosis may promote neurite outgrowth in endometriotic lesions

To investigate the role of the nerve growth factor (NGF) in the endometriosis-associated innervation in the development of endometriosis- associated symptoms, 41 peritoneal fluid samples (PF) from patients with surgically and histologically proven endometriosis and 20 PF from patients with other gynecologic conditions were analyzed with Western blot and a novel in vitro model using dorsal root ganglia (DRG) to show neuronal outgrowth; endometrial cells also were analyzed. The results suggest that the PF of endometriosis patients and endometriotic lesions have neurotropic properties, because the Western blot analysis and the cell culture stainings showed NGF expression, and the neurite outgr…

Radical vaginal trachelectomy (RVT) combined with laparoscopic lymphadenectomy: Prospective study of 225 patients with early-stage cervical cancer

Objective: The aim of the study was to prove the surgical and oncological safety of radical vaginal trachelectomy (RVT) and laparoscopic lymphadenectomy for patients with early-stage cervical cancer who are seeking parenthood. Methods: A database of 225 patients with early-stage cervical cancer and intention to treat by RVT after laparoscopic lymphadenectomy was prospectively maintained. A total of 212 patients were treated according to the protocol. The procedure was preformed in a standardized manner, and life table analysis was applied. Results: In the cohort of patients treated according to protocol, 8 recurrences occurred and 4 patients died from recurrence. The median follow-up time w…

Pelvic exenteration for recurrent endometrial adenocarcinoma: a retrospective multi-institutional study about 21 patients.

ObjectiveThe aim of our study was to evaluate morbidity, mortality, and long-term survival of patients who underwent pelvic exenteration (PE) with curative intent for recurrence of endometrial adenocarcinoma during a single decade.MethodsWe defined a cohort of 21 patients who met our inclusion criteria, referred to 4 cooperating gynecologic oncology settings in Germany and Italy between 2000 and 2011. Data regarding surgery, histology, and oncologic outcomes were collected and statistically evaluated. Survival was determined from the day of exenteration until the last follow-up or death.ResultsThe median age was 66 years. A total of 42.9% of the patients had major complications, and a compl…