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Michael Höckel

Publications and source records attributed to Michael Höckel.

33 records · Page 2Linked to original sources
PubMed2005

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.

Algorithms↗
PubMed2004

Lack of correlation between expression of HIF-1alpha protein and oxygenation status in identical tissue areas of squamous cell carcinomas of the uterine cervix.

Hypoxia inducible factor-1alpha (HIF-1alpha) has been proposed as a candidate endogenous marker of tumor hypoxia and as a molecular mediator of hypoxia-driven malignant progression and acquired treatment resistance. In this study, HIF-1alpha expression in 68 biopsies of oxygenation measurement tracks from squamous cell carcinomas of the uterine cervix of 38 patients was assessed. Expression of HIF-1alpha was commonly found to increase as a function of distance from microvessels, at the center of tumor cell aggregations, and in the vicinity of necrotic areas. However, there was no correlation of HIF-1alpha expression with median oxygen tension (oxygen partial pressure; pO2) and hypoxic fractions (hypoxic fraction < 2.5 mm Hg, hypoxic fraction < 5 mm Hg). The results indicate that HIF-1alpha should not be used as an endogenous marker of tumor hypoxia in locally advanced squamous cell carcinomas of the uterine cervix. Additionally, no significant prognostic impact of HIF-1alpha expression was found in this group of patients.

Adult↗
PubMed2004

Anatomical reconstruction after vulvectomy.

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.

Adult↗
PubMed2003

Oxygenation gain factor: a novel parameter characterizing the association between hemoglobin level and the oxygenation status of breast cancers.

Tumor hypoxia has been linked to acquired treatment resistance, tumor progression, and poor prognosis. Because anemia is a major causative factor for the development of hypoxia, the association between blood hemoglobin concentration (cHb) and breast cancer oxygenation was examined in this study. In addition, a novel parameter characterizing the relationship between oxygenation status and rising cHb is introduced: the oxygenation gain factor (OGF). In breast cancer patients, median cHb over the range 8.5-14.7 g/dl correlated positively with the median pO(2) (3-15 mm Hg), yielding an average OGF of 2 mm Hg.dl/g. In contrast, in normal tissues (normal breast, subcutis, and skeletal muscle) the median pO(2) values were substantially higher (52 mm Hg, 51 mm Hg, and 37 mm Hg, respectively) and remained constant irrespective of the hemoglobin level over the range from 10 to 16 g/dl (OGF = 0 in grade I anemia and nonanemic patients). Moderately lower median pO(2) values in subcutis and skeletal muscle were only observed in grade II anemia (8 g/dl < cHb < or =10 g/dl), although this would appear to be of no biological relevance. Conversely, in breast cancers, even mild anemia (grade I anemia) is a major causative factor for the development of hypoxia or anoxia.

Adult↗
PubMed2003

Impact of oxygenation status and patient age on DNA content in cancers of the uterine cervix.

PURPOSE: In carcinomas of the uterine cervix, the tumor oxygenation status has been shown to be a prognostic indicator that is independent of treatment modality. In vitro studies suggest gene amplification and polyploidization to be among the major consequences of hypoxia (with or without consecutive reoxygenation) and to be associated with treatment resistance and tumor progression. This study analyzed whether hypoxia alters net DNA content in uterine cervix cancer cells to the extent that it is identifiable by DNA image cytometry. MATERIALS AND METHODS: In 64 patients with primary cervical cancer, tumor oxygenation was assessed polarographically and correlated with cell DNA content (DNA image cytometry) in areas adjacent to the oxygen microsensor tracks in which oxygenation measurements were made. RESULTS: No correlation between DNA content (stemline position, Auer classification, and 2c deviation index) and oxygenation status was observed. However, an association between DNA content and patient age and menopausal status was found. CONCLUSION: Using DNA cytometry, hypoxia-associated genomic changes in uterine cervix cancer cells could not be detected. The impact of tumor hypoxia on the genome may be masked by the effects of alternative mechanisms of genomic instability that can also influence DNA content.

Adult↗
PubMed2003

Laterally extended endopelvic resection. Novel surgical treatment of locally recurrent cervical carcinoma involving the pelvic side wall.

OBJECTIVES: To demonstrate the therapeutic potential of the laterally extended endopelvic resection (LEER) especially for patients with recurrent cervical carcinomas involving the side wall of an irradiated pelvis. These patients, suffering from the most common situation of local failure, have so far no longer been considered for curative therapy. METHODS: Extending the lateral resection plane of pelvic exenteration to the medial aspects of the lumbosacral plexus, sacrospinous ligament, acetabulum, and obturator membrane enables the complete removal of a subset of locally advanced and recurrent tumors of the lower female genital tract fixed to the pelvic wall with free margins (R0). Patients selected for LEER were accrued to a prospective outcome trial. RESULTS: Thirty-six patients with recurrent (n = 29) or primary advanced (n = 7) gynecologic malignancies involving the side wall of the lesser pelvis underwent LEER from July 1996 until October 2002. The majority of the patients suffered from cervical carcinoma (n = 29) and had received previous pelvic irradiation (n = 24). Tumor-free (R0) lateral margins were obtained in 34 patients. Severe postoperative complications occurred in 14 patients with one treatment-related death. Five-year survival probability is 49% for the whole group and 46% for those patients considered only for palliation with current treatment options. Most patients without evidence of disease at least 1 year after LEER achieved good quality of life. CONCLUSIONS: LEER can be offered as novel surgical salvage therapy to a selected subset of patients with locally advanced and recurrent cervical carcinoma involving the pelvic wall.

Adult↗
PubMed2003

Structure and regulation of the murine Mash2 gene.

Transcription factors of the basic helix-loop-helix family such as Mash2 are essential for adequate differentiation of the trophoblast. Disruption of the Mash2 gene leads to early intrauterine death caused by placental insufficiency with an absent spongiotrophoblast and an underdeveloped chorion. The aim of the present study was to analyze the structure of the murine Mash2 gene, to screen a broad spectrum of organs for its expression, and to investigate placental Mash2 expression at different gestational ages. The RNase protection assay identified, in addition to the postulated Mash2 mRNA, two unexpected Mash2 transcripts that could be confirmed by a 5' rapid amplification of cDNA ends. However, all three transcripts were detectable exclusively in murine placenta and not in other organs, such as the ovary, uterus, skin, lung, femur, skeletal muscle, kidney, skull, adrenal gland, tongue, stomach, spleen, skin, testis, or pancreas. Sequence analysis disclosed an additional transcription start site upstream of exon 2. Placental Mash2 mRNA is measurable at all investigated stages of gestation. After its initial detection on Day 8.5 postcoitum (p.c.; set to 100%; 100.0% +/- 28.4%), the Mash2 mRNA concentration increases significantly and reaches a maximum of 812.0% +/- 69.7% on Day 12.5 p.c. The second half of gestation is marked by a more than 8-fold Mash2 decrease by Day 18.5 p.c. (77.0% +/- 28.4%). A 36.9% +/- 4.7% level of placental Mash2 mRNA is measurable at term.

Animals↗
PubMed2002

Oxygenation status of gynecologic tumors: what is the optimal hemoglobin level?

BACKGROUND: Tumor hypoxia has been linked to the development of treatment resistance, tumor progression, and poor prognosis. Since anemia is a major causative factor for the development of hypoxia, the association between blood hemoglobin concentration (cHb) and tumor oxygenation was examined in this study. PATIENTS AND METHODS: Pretreatment O(2) tension (pO(2)) measurements were performed in 59 primary carcinomas of the uterine cervix in which a stringent histopathologic examination of the electrode tracks was mandatory in order to exclude measurements in necrotic, stromal or normal cervical tissue. In addition, pO(2) readings in twelve primary cancers and 17 local recurrences of vulvar cancers were included in this study. cHb was determined at the time of pO(2) measurements. RESULTS: Data presented clearly show that an optimal Hb level with regard to the median pO(2) values of cervical and vulvar cancers should prevail at cHb values of between 12 and 14 g/dl (7.45-8.60 mmol/l). In anemic patients (cHb < 12 g/dl), the deterioration of the tumor oxygenation status can be explained by a reduced O(2) transport capacity. At cHb values > 14 g/dl, a worsening of the tumor oxygenation is apparent, most probably due to a drop in perfusion following a drastic increase in viscous resistance to flow. This pathogenetic mechanism is thought to counteract and finally to abrogate the high O(2) transport capacity in this cHb range. CONCLUSIONS: This study suggests that cHb values of between 12 and 14 g/dl are optimal with regard to the oxygenation status in the tumor entities investigated, a finding which may have far-reaching implications in the clinical setting.

Adult↗