Ulf-Dietrich Braumann

Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis

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 (Müllerian) compartment except its distal part. Non-Müllerian 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 Müllerian 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 Müllerian 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 Müllerian 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 Müllerian 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.

Three-dimensional reconstruction and quantification of cervical carcinoma invasion fronts from histological serial sections

The analysis of the three-dimensional (3-D) structure of tumoral invasion fronts of carcinoma of the uterine cervix is the prerequisite for understanding their architectural-functional relationship. The variation range of the invasion patterns known so far reaches from a smooth tumor-host boundary surface to more diffusely spreading patterns, which all are supposed to have a different prognostic relevance. As a very decisive limitation of previous studies, all morphological assessments just could be done verbally referring to single histological sections. Therefore, the intention of this paper is to get an objective quantification of tumor invasion based on 3-D reconstructed tumoral tissue data. The image processing chain introduced here is capable to reconstruct selected parts of tumor invasion fronts from histological serial sections of remarkable extent (90-500 slices). While potentially gaining good accuracy and reasonably high resolution, microtome cutting of large serial sections especially may induce severe artifacts like distortions, folds, fissures or gaps. Starting from stacks of digitized transmitted light color images, an overall of three registration steps are the main parts of the presented algorithm. By this, we achieved the most detailed 3-D reconstruction of the invasion of solid tumors so far. Once reconstructed, the invasion front of the segmented tumor is quantified using discrete compactness.

Local spread of cervical cancer revisited: A clinical and pathological pattern analysis

BACKGROUND Local tumor spread of cervical cancer is currently considered as radial progressive intra- and extracervical permeation. For radical tumor resection or radiation the inclusion of a wide envelope of tumor-free tissue is demanded. However, this concept may lead to considerable treatment-related morbidity and does not prevent local relapse. We propose an alternative model of local tumor propagation involving permissive compartments related to embryonic development. METHODS We analyzed local tumor spread macroscopically and microscopically in consecutive patients with advanced cervical cancer and post-irradiation recurrences. RESULTS Macroscopically, all 33 stage I B (>2cm) tumors, 40 of 42 stage II tumors and 32 of 44 stage III B tumors were confined to the embryologically defined uterovaginal (Müllerian) compartment. Local tumor permeation deformed the uterovaginal compartment mirroring the mesenchyme distribution of the Müllerian anlage at the corresponding pelvic level in cases of symmetrical tumor growth. Tumor transgression into adjacent compartments mainly involved the embryologically related lower urinary tract. Compartmental transgression was associated with larger tumor size, paradox improvement in oxygenation and an increase in microvessel density. Post-irradiation pelvic relapse landscapes were congruent with the inflated Müllerian compartment. Microscopically, all locally advanced primary cancers and post-irradiation recurrences were confined to the uterovaginal and lower urinary tract compartments. CONCLUSION Cervical cancer spreads locally within the uterovaginal compartment derived from the Müllerian anlage. Compartment transgression is a relatively late event in the natural disease course associated with distinct phenotypic changes of the tumor. Compartmental tumor permeation suggests a new definition of local treatment radicality.

Determination of pore size distribution at the cell-hydrogel interface

BackgroundAnalyses of the pore size distribution in 3D matrices such as the cell-hydrogel interface are very useful when studying changes and modifications produced as a result of cellular growth and proliferation within the matrix, as pore size distribution plays an important role in the signaling and microenvironment stimuli imparted to the cells. However, the majority of the methods for the assessment of the porosity in biomaterials are not suitable to give quantitative information about the textural properties of these nano-interfaces.FindingsHere, we report a methodology for determining pore size distribution at the cell-hydrogel interface, and the depth of the matrix modified by cell growth by entrapped HepG2 cells in microcapsules made of 0.8% and 1.4% w/v alginate. The method is based on the estimation of the shortest distance between two points of the fibril-like network hydrogel structures using image analysis of TEM pictures. Values of pore size distribution determined using the presented method and those obtained by nitrogen physisorption measurements were compared, showing good agreement. A combination of these methodologies and a study of the cell-hydrogel interface at various cell culture times showed that after three days of culture, HepG2 cells growing in hydrogels composed of 0.8% w/v alginate had more coarse of pores at depths up to 40 nm inwards (a phenomenon most notable in the first 20 nm from the interface). This coarsening phenomenon was weakly observed in the case of cells cultured in hydrogels composed of 1.4% w/v alginate.ConclusionsThe method purposed in this paper allows us to obtain information about the radial deformation of the hydrogel matrix due to cell growth, and the consequent modification of the pore size distribution pattern surrounding the cells, which are extremely important for a wide spectrum of biotechnological, pharmaceutical and biomedical applications.

Neural Architecture for Gesture-Based Human-Machine-Interaction

We present a neural architecture for gesture-based interaction between a mobile robot and human users. One crucial problem for natural interface techniques is the robustness under highly varying environmental conditions. Therefore, we propose a multiple cue approach for the localisation of a potential user in the operation field, followed by the aquisition and interpretaion of its gestural instructions. The whole approach is motivated in the context of a reliable operation scenario, but can be extended easily for other applications, such as videoconferencing.

User localisation for visually-based human-machine-interaction

Recently there is an increasing interest in video based interface techniques, allowing more natural interaction between users and systems than common interface devices do. We present a neural architecture for user localisation, embedded within a complex system for visually-based human machine interaction (HMI). User localisation is an absolute prerequisite to video based HMI. Due to the main objective, the greatest possible robustness of the localisation as well as the whole visual interface under highly varying environmental conditions, we propose a multiple cue approach. This approach combines the features of facial structure, head shoulder contour, skin color and motion, with a multiscale representation. The selection of the image region most likely containing a possible user is then realised via a WTA-process within the multiscale representation. Preliminary results show the reliability of the multiple cue approach.

Characteristics and management of diaphragm involvement in patients with primary advanced-stage ovarian, fallopian tube, or peritoneal cancer.

Objectives: The aim of this study was to determine the frequency of diaphragm involvement (DI) in cases of International Federation of Gynecology and Obstetrics (FIGO) stage IIIC and IV primary epithelial ovarian, fallopian tube, or peritoneal cancer; the frequency of use of different surgical techniques in managing diaphragm implants; and the procedure-associated morbidity. Methods: A retrospective analysis of consecutive patients undergoing primary surgery by a single surgical team between January 2005 and June 2007 was accomplished. Patients with tumors of low malignant potential and nonepithelial histologic diagnosis and those who received neoadjuvant chemotherapy were excluded. Results: Thirty-three patients met the inclusion criteria. Diaphragm involvement was found in 91% of the cases. Whereas the left hemidiaphragm is never involved alone, the right side is significantly affected more extensively (P = 0.002) and frequently (alone, 20%; both sides, 80%). The frequency of use of procedures varies considerably in the literature, whereas full-thickness diaphragm resection (DR) had to be performed in 53% of our patients with DI. Diaphragm resection at the left hemidiaphragm and bilateral DRs are very rare in primary cases. A specific histopathologic examination of the DR preparation is desirable. A simple 4-tiered classification of the infiltration depth is proposed. The most frequent complication is serothorax, but a generous indication for intraoperative chest tube placement is solely recommended in cases of DR. Conclusions: Surgical effort in achieving an optimum cytoreduction could be evaluated more precisely with parameters of DI and diaphragm-related treatment procedures. The usual quality criteria for ovarian cancer surgery, such as residual tumor state and morbidity, are more marked by subjectivity and inconsistent definitions.

Influence of the boundary conditions on the result of non-linear image registration

The focus of many non-parametric image registration algorithms lies on the solution of non-linear partial differential equations. We offer a simple solution procedure therefor based on discrete Fourier transform. Boundary conditions can strongly influence the result of the registration. The issue is investigated on the example of non-linear curvature-based registration.

Combined serial section-based 3D reconstruction of cervical carcinoma invasion using H&E/p16INK4a/CD3 alternate staining†

Malignant growth and invasiveness of cancers is a function of both intratumoral and stromal factors. The accessibility to nutrients, oxygen and growth factors, the stromal composition, and the interference with the immune system all shape the tumor invasion front. A recent study has shown a prognostic difference with respect to different invasion patterns analyzed on histological specimens of cervical cancers. The present study analyzes the spatial organization of a cervical cancer and the relation of the tumor invasion front and the infiltration with CD3+ T‐cells.

Quantitative analysis of astrogliosis in drug-dependent humans.

Drug addiction is a chronic, relapsing disease caused by neurochemical and molecular changes in the brain. In this human autopsy study qualitative and quantitative changes of glial fibrillary acidic protein (GFAP)-positive astrocytes in the hippocampus of 26 lethally intoxicated drug addicts and 35 matched controls are described. The morphological characterization of these cells reflected alterations representative for astrogliosis. But, neither quantification of GFAP-positive cells nor the Western blot analysis indicated statistical significant differences between drug fatalities versus controls. However, by semi-quantitative scoring a significant shift towards higher numbers of activated astrocytes in the drug group was detected. To assess morphological changes quantitatively, graph-based representations of astrocyte morphology were obtained from single cell images captured by confocal laser scanning microscopy. Their underlying structures were used to quantify changes in astroglial fibers in an automated fashion. This morphometric analysis yielded significant differences between the investigated groups for four different measures of fiber characteristics (Euclidean distance, graph distance, number of graph elements, fiber skeleton distance), indicating that, e.g., astrocytes in drug addicts on average exhibit significant elongation of fiber structures as well as two-fold increase in GFAP-positive fibers as compared with those in controls. In conclusion, the present data show characteristic differences in morphology of hippocampal astrocytes in drug addicts versus controls and further supports the involvement of astrocytes in human pathophysiology of drug addiction. The automated quantification of astrocyte morphologies provides a novel, testable way to assess the fiber structures in a quantitative manner as opposed to standard, qualitative descriptions.