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Gynecologic Oncology 03/2013; · 3.89 Impact Factor
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Gynecologic Oncology 08/2012; · 3.89 Impact Factor
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ABSTRACT: Pelvic exenteration is mainly applied as a salvage operation for a subset of patients with persistent and recurrent cervicovaginal cancer. The procedure can also cure locally advanced primary disease not suitable for radiotherapy. However, high operative abortion and intralesional tumor resection rates significantly limit its clinical benefit. To improve locoregional tumor control we have proposed to establish cancer surgery on ontogenetic anatomy and, consequently, we have developed the (Laterally) Extended Endopelvic Resection ((L)EER).
(L)EER is clinically and histopathologically evaluated with a monocentric prospective observational study. Patients with advanced and recurrent cervicovaginal cancer are treatment candidates if distant metastases and tumor fixation at the region of the sciatic foramen can be excluded.
91 patients with locally advanced primary (n=30) and recurrent or persistent (n=61) carcinoma of the cervix and vagina were treated with (L)EER. 74% of the tumors were fixed to the pelvic wall. No (L)EER treatment was aborted, R0 resection was histopathologically confirmed in all cases. (L)EER definitively controlled the locoregional cancer in 92% (95% CI: 85-99) of the patients. Five year overall survival probability was 61% (95% CI: 49-72).
The results of (L)EER treatment confirm the concept of cancer surgery based on ontogenetic anatomy. In patients with locally advanced and recurrent cervicovaginal cancer (L)EER achieves locoregional tumor control both with central disease and with tumors fixed to the pelvic side wall except at the region of the sciatic foramen.
Gynecologic Oncology 08/2012; 127(2):297-302. · 3.89 Impact Factor
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Gregor Thörmer,
Josephin Otto,
Martin Reiss-Zimmermann,
Matthias Seiwerts,
Michael Moche,
Nikita Garnov,
Toni Franz,
Minh Do,
Jens-Uwe Stolzenburg, Lars-Christian Horn,
Thomas Kahn,
Harald Busse
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ABSTRACT: To evaluate the influence of the choice of b values on the diagnostic value of the apparent diffusion coefficient (ADC) for detection and grading of prostate cancer (PCa).
Forty-one patients with biopsy-proven PCa underwent endorectal 3-T MRI before prostatectomy. Different combinations of b values (0-800 s/mm(2)) were used to calculate four representative ADC maps. Mean ADCs of tumours and non-malignant tissue were determined. Tumour appearance on different ADC maps was rated by three radiologists as good, fair or poor by assigning a visual score (VS) of 2, 1 or 0, respectively. Differences in the ADC values with the choice of b values were analysed using one-way ANOVA.
Choice of b values had a highly (P < 0.001) significant influence on the absolute ADC in each tissue. Maps using b = [50, 800] and [0, 800] were rated best (VS= 1.6 ± 0.3) and second best (1.1 ± 0.3, P < 0.001), respectively. For low-grade carcinomas (Gleason score ≤ 6, 13/41 patients), only the former choice received scores better than fair (VS = 1.4 ± 0.3). Mean tumour ADCs showed significant negative correlation (Spearman's ρ -0.38 to -0.46, P < 0.05) with Gleason score.
Absolute ADC values strongly depend on the choice of b values and therefore should be used with caution for diagnostic purposes. A minimum b value greater than zero is recommended for ADC calculation to improve the visual assessment of PCa in ADC maps.
• Absolute ADC values are highly dependent on the choice of b values. • Absolute ADC thresholds should be used carefully to predict tumour aggressiveness. • Subjective ratings of ADC maps involving b = 0 s/mm ( 2 ) are poor to fair. • Minimum b value greater than 0 s/mm ( 2 ) is recommended for ADC calculation.
European Radiology 04/2012; 22(8):1820-8. · 3.22 Impact Factor
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ABSTRACT: Infrared microspectroscopy (IR-MSP) has been proposed for automated histological tissue differentiation of unstained specimens based on chemical analysis of cell and extracellular constituents. This study aimed to determine the accuracy of IR-MSP-based histopathology of cervical carcinoma sections with complex tissue architecture under practically relevant testing conditions.
In total, 46 regions of interest, covering an area of almost 50 mm(2) on sections derived from paraffin-embedded tissue of radical hysterectomy specimens, were analysed by IR-MSP (nominal resolution ~4.2 μm). More than 2.8 million pixel spectra that were processed using fuzzy c-means clustering followed by hierarchical cluster analysis permitted image segmentation regarding different biochemical properties. Linear image registration was applied to compare these segmentation results with manual labelling on haematoxylin and eosin-stained references (resolution ~0.7 μm). For recognition of nine tissue types, sensitivities were 42-91% and specificities were 79-100%, mostly being affected by peritumoral inflammatory responses. Algorithmic variation of the outline of dysplasia and carcinoma revealed a spatial preference of false values in tissue transition areas.
This imaging technique has potential as a new method for tissue characterization; however, the recognition accuracy does not justify a pathologist-independent tissue analysis, and the application is only possible in combination with concomitant conventional histopathology.
Histopathology 02/2012; 60(7):1084-98. · 3.08 Impact Factor
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Gynecologic Oncology 12/2011; 125(3):765-6; author reply 766-7; discussion 767. · 3.89 Impact Factor
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ABSTRACT: In cervical cancer lymph node dissection is applied for regional tumor staging. Up to now, the use of (chemo)radiation in the nodal positive patient has prevented the exact pattern analysis of regional tumor spread and the evaluation of the therapeutic role of lymph node dissection. New surgical techniques founded on ontogenetic instead of functional anatomy for the treatment of cervical cancer dispensing with adjuvant radiotherapy offer the possibility to accurately determine the topography of regional lymph node metastases which is the prerequisite for optimized diagnostic and therapeutic lymph node dissection.
Patients with cervical cancer FIGO stages IB-IIB were treated with total mesometrial resection (TMMR) and lymph node dissection after exposing the ontogenetic visceroparietal compartments of the female pelvis. Resected lymph nodes were allocated to regions topographically defined by the embryonic development of the iliac, lumbar and mesenteric lymph systems prior to histopathological assessment.
71 of 305 treated patients had lymph node metastases. Topographic distribution of these metastases at primary surgery and analysis of pelvic failures showed a spatial pattern related to the ontogenesis of the abdominopelvic lymphatic system. Five-year locoregional tumor control probability was 96% (95% CI: 94-98) for the whole group and 87% (95% CI: 77-97) for nodal positive patients.
The pattern of regional spread in cervical cancer can be comprehended and predicted from ontogenetic lymphatic compartments. In patients with early cervical cancer lymph node dissection based on ontogenetic anatomy achieves high regional tumor control without adjuvant radiation.
Gynecologic Oncology 12/2011; 125(1):168-74. · 3.89 Impact Factor
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ABSTRACT: PURPOSE: Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor. METHODS: Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n = 44; age 60.64 ± 13.78, mean ± SD) and carcinoma patients (n = 11; age 58.91 ± 12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1-3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR). RESULTS: M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2 > M3 and M3 > M2) were observed, which differed in associated purinergic and histamine receptor expression. CONCLUSIONS: M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.
World Journal of Urology 10/2011; · 2.41 Impact Factor
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Gynecologic Oncology 09/2011; 124(1):173-4; author reply 174-5. · 3.89 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the role of the fimbriated end and nonfimbriated epithelium of fallopian tubes with regard to p53 signature, tubal intraepithelial lesions in transition (TILT), and serous tubal in-situ carcinoma (STIC) in cases of different kinds of serous pelvic cancer. This study immunohistochemically evaluated (by Ki-67 and p53 staining) the presence of p53 signature, TILT lesions, and STIC in 14 consecutive cases of prophylactic salpingo-oophorectomy in women with BRCA-1/2 mutation (bilateral salpingo-oophorectomy), 11 cases of macroscopically inconspicuous adnexae of patients with primary contralateral tubal cancer (TC), 9 cases of primary peritoneal cancer (PPC), and 10 cases of serous ovarian borderline tumors, evaluating the fallopian tubes (using the Sectioning and Extensively Examining the FIMbria protocol), ovarian surface epithelium, and ovarian cortical inclusion cysts. The frequencies of p53 signature, TILT, and STIC were 35.7%, 7.1%, and 0% in cases of prophylactic surgery, 18.2%, 9.1%, and 18.2% in TC, and 11.1%, 0%, and 33.3% in PPC. These precursor lesions were missed during the initial routine screening and were found in the fimbriated end of the fallopian tubes in 94%. In 1 case of PPC, staining for p53 was negative in STIC. The studied adnexal tissue of serous ovarian borderline tumor and ovarian cortical inclusion cysts of all cases showed no alterations according to p53 signature, TILT, or STIC. STIC and p53 signature as precursor lesions of pelvic serous cancer were seen in macroscopically inconspicuous contralateral fallopian tubes in unilateral TC, in patients with elective bilateral salpingo-oophorectomy, and in patients affected by PPC. Therefore, we propose the complete processing of adnexal tissue and the use of step sectioning to establish the correct diagnosis. Immunohistochemistry for p53 and ki-67 may aid in the diagnosis, but is not necessary for routine investigation.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 09/2011; 30(5):417-24. · 2.07 Impact Factor
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Thilo Schwalenberg,
Jens-Uwe Stolzenburg,
Thi Phuc Ho,
Tobias Mallock,
Siegurd Hartenstein,
Henry Alexander,
Gerolf Zimmermann,
Rudolf Hohenfellner,
Stefan Denzinger,
Maximilian Burger, Lars-Christian Horn,
Jochen Neuhaus
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ABSTRACT: Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls.
Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction.
We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients.
The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.
World Journal of Urology 08/2011; 30(3):411-7. · 2.41 Impact Factor
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ABSTRACT: 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.
Serial transverse sections of female embryos and fetuses aged 8-17 weeks 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.
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.
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.
Gynecologic Oncology 05/2011; 122(2):313-8. · 3.89 Impact Factor
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The lancet oncology 05/2011; 12(5):422; author reply 422-3. · 14.47 Impact Factor
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Annals of diagnostic pathology 03/2011; 15(3):216-8.
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ABSTRACT: Perturbation of the normal tissue architecture in solid malignant tumors is perceived to be the consequence of actively migrating cancer cells which invade the adjacent normal host tissue. The opposite, invasion of cancer cell clusters by a vascularized stroma, has not been considered. The latter process should, however, be expected to occur since the hypoxic cores of tumor cell aggregates, under the control of HIF-1, are known to secrete cytokines (e.g., bFGF, VEGF) which attract fibroblasts and induce blood vessel formation. In this study, the expression of glucose transporter (GLUT)-1, a major HIF-1 target gene, was examined in 51 squamous cell carcinomas of the uterine cervix by immunohistochemistry to identify the localization of hypoxic tumor cell areas. The relationship of the expression pattern of GLUT-1 with the localization and morphology of the tumor stroma was analyzed. We identified three recurrent histological signs which represent strong evidence in favor of an invasion of solid tumor masses by actively migrating stromal cells. According to our findings, the histological structure of squamous cell carcinomas of the uterine cervix may in part result from the interplay between the inherent tendency of neoplastic epithelial cells to expand in the form of coherent aggregates and the fragmentation of these aggregates by invading, finger- or wedge-like stromal protrusions which carry new blood vessels, driven by gradients of hypoxia-induced pro-angiogenic, pro-migratory and growth-promoting molecules emanating from the hypoxic core.
International Journal of Oncology 01/2011; 38(1):145-50. · 2.40 Impact Factor
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ABSTRACT: Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.
Advances in Urology 01/2011; 2011:639479.
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European journal of obstetrics, gynecology, and reproductive biology 12/2010; 153(2):229-31. · 1.97 Impact Factor
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ABSTRACT: The study determines morphological features that are associated with perineural invasion (PNI) in patients with cervical carcinoma (CX). Histological slides from 194 patients from surgically treated squamous cell carcinoma were re-examined for PNI and correlated to morphological factors of tumor growth. Material from 68 patients (35.1%) represented PNI. PNI was significantly correlated with advanced tumor stage (P < .001). Patients with deep cervical stromal invasion (>66%) showed more PNI than those with more superficial invasion (41% vs 16.9%; P = .001). Tumors with spray-like PI showed significantly more PNI (48.4%) when compared with finger-like PI (26.7%) and those with pushing borders (18.8%; P = .007). Strong peritumoral desmoplastic stromal reaction and absence of peritumoral inflammation were associated with a higher frequency of PNI (P < .001). PNI is associated with advanced tumor stage, deep cervical stromal invasion (>66%), high grade of tumor cell dissociation (ie, spray-like pattern of invasion), strong peritumoral desmoplastic stromal reaction, and reduced peritumoral inflammation.
International Journal of Surgical Pathology 11/2010; 19(2):159-63. · 1.00 Impact Factor
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ABSTRACT: Current local treatment of vulvar cancer is wide tumor excision and radical vulvectomy based on functional anatomy established from the adult and on the view of radial progressive tumor permeation. Standard surgery is associated with a considerable local failure rate and severe disturbance of the patients' body image. Vulvar field resection (VFR) is based on ontogenetic anatomy and on the concept of local tumor spread within permissive compartments. VFR combined with anatomical reconstruction (AR) is proposed as a new surgical approach to the treatment of vulvar cancer.
A prospective trial was launched to test the compartment theory for vulvar cancer and to assess safety and effectiveness of the new therapy.
In 54 consecutive patients 46 tumors were locally confined to the tissue compartment differentiated from the vulvar anlage. The 8 tumors having transgressed into adjacent tissue compartments of different embryonic origins exhibited signs of advanced malignant progression. 38 patients with vulvar cancer, stages T1-3 were treated with VFR and AR. The perioperative complication rate was low. At 19 (3-50) months follow-up no patient failed locally. 33 patients estimated their body image as undisturbed.
Vulvar cancer permeates within ontogenetic tissue compartments and surgical treatment with VFR and AR appears to be safe and effective. Patients should benefit from the new approach as local tumor control is high and the preserved tissue can be successfully used for restoration of vulvar form and function. Confirmatory trials with more patients and longer follow-up are suggested.
Gynecologic Oncology 10/2010; 119(1):106-13. · 3.89 Impact Factor
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Jens-Uwe Stolzenburg,
Panagiotis Kallidonis,
Do Minh,
Anja Dietel,
Tim Häfner,
Robert Rabenalt,
George Sakellaropoulos,
Roman Ganzer,
Uwe Paasch, Lars-Christian Horn,
Evangelos Liatsikos
Urology 09/2010; 76(3):749. · 2.43 Impact Factor
