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Biomedical subjects

M Höckel

Publications and source records attributed to M Höckel.

At least 37 records · Page 2Linked to original sources

[Total mesometrial resection: nerve-sparing extended radical abdominal hysterectomy].

The total mesometrial resection (TMMR) is the first radical hysterectomy procedure based on defined anatomical landmarks with all surgical steps. The new abdominal operation combines maximum resection of the oncologically relevant mesometrium with minimal tissue traumatization and sparing of the pelvic autonomic nervous system. The extended pelvic and low periaortic lymph node dissection which is part of the procedure includes the removal of the lymphatic tissue localized laterally and dorsally of the main vessels. A prospective multidimensional trial is currently under way to evaluate the potential of the total mesometrial resection to improve the therapeutic index in the surgical treatment of carcinoma of the uterine cervix, especially for high risk tumors.

Autonomic Nervous System↗

The pelvic plexus and antireflux surgery: topographical findings and clinical consequences.

PURPOSE: Voiding dysfunction and urinary retention are rare complications of antireflux surgery. As mainly reported after bilateral antireflux surgery with extravesical technique, bladder insufficiency has been suspected to be caused by intraoperative damage to neural structures. We studied the topography of the pelvic plexus and assessed the injury to the plexus resulting from antireflux surgery. MATERIALS AND METHODS: Human cadavers fixed with Thiel solution were used for dissection. The superior hypogastric plexus and hypogastric nerves were identified as the pathway to the pelvic plexus. After dissecting the surrounding fatty tissue the S2 to S4 nerves and efferent nerve bundles from the pelvic plexus were identified. RESULTS: The main portion of the pelvic plexus was located about 1.5 cm. dorsal and medial to the ureterovesical junction. The bundles of the pelvic plexus ended at the distal ureter, trigone and rectum. When simulating an antireflux procedure, there was a high risk of injury to the pelvic plexus and its efferent nerves if dissection was performed distal to the ureter and dorsal trigone. CONCLUSIONS: Careful dissection close to the ureter avoids inadvertent injury to the pelvic plexus. To minimize the risk of voiding dysfunction bilateral antireflux surgery should be performed at 2 sessions unless the operative technique allows preservation of the neural structures.

Aged↗

Inguinovaginal sling procedure for female stress incontinence: introduction of a minimally invasive technique.

PURPOSE: The inguinovaginal sling procedure is well accepted for surgical treatment of female stress urinary incontinence. Although the functional results are excellent, the operative trauma is higher compared to that of more recently used minimally invasive techniques. MATERIALS AND METHODS: A modified inguinovaginal sling procedure was performed in 15 patients with urodynamically diagnosed intrinsic sphincter deficiency. With the assistance of a laparoscope, two fascial strips were dissected using two small suprapubic skin incisions. The pullthrough maneuver of the fascial slings was facilitated by opening the perivesical space with an inflatable balloon. RESULTS: There were no intraoperative or postoperative complications. Mean follow-up of 7.7 months (range 4 to 11) was available in all patients. Stress incontinence was cured in 14 patients; only one woman reported using one pad per day. All patients were able to void spontaneously after a mean of 8 days (range 6 to 10). CONCLUSIONS: The laparoscopically assisted inguinovaginal sling procedure is less invasive than the original technique. Good long-term results are known from the original inguinovaginal sling procedure, and there is no need for allografts or synthetic material.

Aged↗

Biological consequences of tumor hypoxia.

Growing evidence from experimental and clinical studies points to the fundamental, pathophysiologic role of hypoxia in solid tumors. Intratumoral hypoxia is a consequence of a structurally and functionally disturbed microcirculation, with deterioration of the diffusion geometry and of tumor-associated anemia. Hypoxia-induced changes of the proteome in the neoplastic and stroma cells may lead to neoplastic growth impairment through molecular mechanisms, resulting in cellular quiescence, differentiation, and apoptosis. Alternatively, hypoxia-induced proteome changes activating nonspecific stress response, anaerobic metabolism, angiogenesis, tissue remodeling, and change of cell contacts may promote tumor propagation by enabling neoplastic cells to overcome the nutritive deprivation through adaptation or escape from the "hostile" environment. Whether the phenotypic result of hypoxia-induced proteome change is impairment, stasis, or promotion of neoplastic growth is thought to be determined by the genome of the tumor cells and additional microenvironmental factors. Tumor cells with genomic alterations (such as loss of apoptotic potential) allowing their survival under hypoxia will aggravate tumor hypoxia. Sustained hypoxia increases genomic instability, genomic heterogeneity, and the selection pressure of the microenvironment. New variants even better adapted to survive and proliferate under reduced pO2 will be selected through clonal expansion. These variants will further drive the vicious circle of malignant progression which is clinically characterized by an increasing probability of local, perifocal, regional, and distant spread.

Animals↗

Association between host tissue vascularity and the prognostically relevant tumor vascularity in human cervical cancer.

For many human solid tumors including carcinoma of the uterine cervix it has been shown that vascularity is linked to the malignant potential of the neoplasm. However, tumor microvessel density might not just represent the angiogenic potential of the neoplastic cells but could also be influenced by the primary vascularization of the host tissue. Vascular densities were assessed by systematic random sampling of normal cervical stroma and of cervical cancer tissue in surgical specimens of 52 consecutive patients. Spatially defined tumor vascular densities were related to the vascular density of the normal cervix, tumor size and survival probability. Median vascular densities of the normal cervix, tumor periphery and tumor core were 53 (range 16-105), 66 (range 24-181) and 31 (range 3-117) microvessels per mm2, respectively. Vascular densities of the tumor periphery were related to the vascular densities of the normal cervical stroma and did not depend on tumor size, whereas the vascular densities of the tumor core were independent of the vascular densities of the normal cervical stroma and decreased with increasing tumor size. Microvascular 'hot spots' were detected in the tumor periphery in 67% and in the tumor core regions in 33% of the cases. 'Hot spot' vascular densities were independent of tumor size but significantly (p=0.001) correlated with the vascular densities of the normal cervical stroma. Patients with high tumor 'hot spot' vascular densities (> or =40 vessels/counting field) had significantly (p=0.01) poorer survival probability than patients with low tumor 'hot spot' vascular densities (<40 vessels/counting field). Growth of cervical cancer is accompanied by hypervascularity at the periphery and hypovascularity within the tumor core upon comparison with the vascular density of the normal cervical stroma remote from the invasion front. Our study confirms the prognostic relevance of 'hot spot' vascular density in cancer of the uterine cervix. The association between normal cervix microvascular density remote from the tumor and the 'hot spot' vascular density of the tumor suggests an influence of the local host tissue vascularity on the tumor's aggressiveness.

Adenocarcinoma↗

Colon pouch (Mainz pouch III) for continent urinary diversion after pelvic irradiation.

OBJECTIVES: Urinary diversion after previous pelvic irradiation is challenging. The use of irradiated bowel in particular is associated with an increased rate of early and late complications. We therefore performed continent cutaneous urinary diversion using exclusively nonirradiated bowel segments in this group of patients. METHODS: A continent colon pouch for urinary diversion was performed in 44 female patients after pelvic irradiation. The indications were irreparable vesical fistula in 20, local recurrence of gynecologic tumors in 22, and radical cystectomy for bladder cancer in 2 patients. Depending on the length of the nonirradiated bowel segment, a transverse-ascending colon pouch (n = 8) or transverse-descending colon pouch (n = 36) was performed. The efferent segment was created from a tapered bowel segment embedded in the pouch wall. The ureters were implanted using a submucosal (n = 67) or subserosal (n = 17) extramural tunnel. RESULTS: No pouch-related complications were observed during the immediate postoperative period. In long-term follow-up (mean 52.2 months), upper urinary tract dilation was seen in five renal units. All five of these had been dilated preoperatively, and none required ureteral reimplantation. Incontinence occurred in 2 patients; both underwent reoperation with subsequent continence. Umbilical stoma stenosis was observed in 6 patients. CONCLUSIONS: The technique of the colon pouch for continent urinary diversion in previously irradiated patients is safe and has a low complication rate. The use of nonirradiated bowel segments should be the method of choice in this group of patients.

Adult↗

Leptin and pregnancy outcome.

Leptin, a recently discovered hormone that is involved in the regulation of body weight, appears to be one of the hormonal factors that signal the body's readiness for sexual maturation and reproduction to the brain. The present review focuses on clinical and experimental studies that describe the roles of maternal and foetal leptin as predictive factors for the physiological and pathophysiological development of the foetus during pregnancy, assisted reproduction and neonatal life. Through evaluating alterations of maternal serum leptin levels, a physiological hyperleptinaemia has been observed to occur, particularly during the second and third trimesters of pregnancy, which is not associated with a decreased food intake or reduced metabolic activity in the pregnant women. This state of leptin resistance is comparable to the condition in obesity. In contrast, hypoleptinaemia is suggested to be an indicator for the cessation of pregnancy, either naturally at term or as a result of pathology at any time during gestation. Thus, an appropriate maternal leptin level seems to be a prerequisite for a normal pregnancy. The main source of foetal leptin is the still immature foetal adipose tissue. As intrauterine growth has been found to be independently associated with cord blood leptin level, it has been suggested that leptin plays a role as a regulator of foetal growth. During assisted reproduction cycles leptin levels in the follicular fluid of patients may be also of predictive value, with low levels predicting therapeutic failure. Finally, the relevance of leptin to postnatal development is reviewed; leptin may be important for regulation of satiety and peripheral metabolism. In summary, leptin appears to be an important permissive factor that is involved in female reproduction.

Embryonic and Fetal Development↗

Identity testing in cervical carcinoma in case of suspected mix-up.

The histopathologic diagnosis is the cornerstone of modern oncology. But mix-ups of specimens can occur at any stage. The resection of a 1.2 cm polypoid cervical mass in a 25-year-old woman showed a poorly differentiated adenocarcinoma prospectively staged as T1b1 (International Federation of Gynecology and Obstetrics IB1). Even after complete embedding and serial sectioning of the whole cervix of the hysterectomy specimen after radical hysterectomy, only adenocarcinoma in situ, but no invasive tumor, was seen. To exclude a mix-up of the specimens, identity testing of the paraffin-embedded material was performed by microsatellite analysis. For both materials, we established identical results after testing the microsatellite loci HumTH01, HumVWA, HumFGA, HumACTBP2, HumF13B, and HumD8S1132. The resulting probability of identity came to 99.9999%, excluding a mix-up of the specimens. Archival paraffin-embedded specimens can be used to establish identity and can prevent the wrong patient from having major surgery.

Adenocarcinoma↗

[Angiogenesis in cervical cancer].

Angiogenesis is a factor of spread and metastatization. This fact has been established for many malignancies, but the data concerning cervical cancer are rather conflicting. In a study including 42 patients affected by cervical cancer stages IB to IVA, the authors assess the mean capillary density and the correlations between this parameter and the other anatomoclinical parameters: the VEGF expression, tumoral oxygenation and the data obtained from dynamic MRI. The histologic assessment of the capillary density and the data obtained by dynamic MRI enable us at the same time to quantify the tumoral angiogenesis and establish the prognosis. The two methods could be used routinely as markers of prognosis. VGEF surely plays a role in angiogenesis linked with cervical cancer growth, but its regulation is not definitively clear at the moment. The impact of tumoral oxygenation (whose place as a prognostic marker is clearly established) on tumoral angiogenesis and vessels' permeability as well as its control is currently not clearly established. Further studies on larger populations are necessary.

Adult↗

Hypoxic cervical cancers with low apoptotic index are highly aggressive.

There is evidence from experimental work that hypoxia induces apoptosis in apoptosis-sensitive neoplastic cells and that this apoptotic sensitivity is lost during malignant progression. Oxygenation profiles and apoptotic indices in human squamous cell cancer of the uterine cervix have been determined, and a subgroup of tumors has been identified with low apoptotic index despite pronounced hypoxia representing carcinomas that consist of neoplastic cells with diminished apoptotic potential. These hypoxic low-apoptotic tumors show a high probability for lymphatic spread and for recurrence despite adjuvant treatment with radiation or chemotherapy in addition to radical surgery. The clinical results presented strongly support the hypothesis derived from experimental studies that the selection of apoptosis-insensitive neoplastic cell phenotypes in a hypoxic microenvironment is an important mechanism for malignant progression in solid tumors.

Apoptosis↗

Expression of tenascin in human cervical cancer--association of tenascin expression with clinicopathological parameters.

OBJECTIVE: Tenascin is an extracellular matrix glycoprotein, relevant for embryonal and fetal development, which is reexpressed in the stroma of benign and malignant tumors. Little is known about the molecular interaction of tenascin during neoplastic transformation and tumor progression in cervical cancer. METHOD: We studied the expression of tenascin in normal tissue of the cervix uteri, cervical carcinoma in situ, and invasive cervical carcinoma in paraffin sections by immunohistochemistry using a monoclonal antibody. Tenascin immunoreactivity was compared with various prognostic parameters. RESULTS: In normal cervical tissue (n = 5) and in cervical carcinoma in situ (n = 10) only vessel walls showed a weak tenascin cross-reactivity, whereas tenascin was not expressed in the epithelial layer or the underlying connective tissue. In invasive cervical carcinoma (n = 89) tenascin expression was markedly increased. In 84% (n = 75) of the cases examined a strong tenascin immunoreactivity was noted around and within the tumor cell nests. Sixteen percent (n = 14) of infiltrating cervical carcinomas showed no tenascin immunoreactivity. A definite correlation was found between weak or no tenascin expression and slight desmoplastic mesenchymal reactivity (n = 42/91%, P < 0.001), lymphatic space invasion (n = 54/81%, P < 0.001), and lymph node metastases (n = 30/77%, P < 0.05). Tenascin-positive patients had a significantly better prognosis than tenascin-negative patients (mean survival time of 56.5 +/- 4.1 months versus 31.9 +/- 5.6 months, P < 0.05). CONCLUSION: Based on these findings we discuss that the appearance of tenascin is an indicator of an adequate biological defense in cervical cancer patients. The tenascin staining may therefore be useful for detecting a subgroup of invasive cancer patients missing tenascin reactivity with alterations of stromal defense and a poorer prognosis.

Carcinoma in Situ↗

Metastasizing signet ring cell carcinoma of the stomach-mimicking bilateral inflammatory breast cancer.

We describe a case of unusual metastases of a gastric carcinoma to the female breast, there likely to be an inflammatory breast cancer. A 46-year-old woman was admitted to our institution with bilateral breast tumors, not typical for a breast cancer as tumor growth was synchronically bilateral within a very short period of only 2 months. The woman underwent a palliative gastrectomy 3 months before for a poorly differentiated adenocarcinoma with signet ring appearance presenting as linitis plastica. At the time of the first operation the mammary glands were not suspicious. Breast biopsies assured metastases of the gastric cancer. In addition to this case report, a short overview of the literature concerning the very few cases of metastases of gastric cancer to the breast is given.

Breast Neoplasms↗

Laterally extended endopelvic resection: surgical treatment of infrailiac pelvic wall recurrences of gynecologic malignancies.

OBJECTIVE: My purpose was to treat infrailiac pelvic wall recurrences of gynecologic malignancies with extended radical surgery. STUDY DESIGN: On the basis of cadaver dissection studies, I developed the laterally extended endopelvic resection techniques. The new operations were offered to patients with infrailiac sidewall disease during a 3-year feasibility study. RESULTS: Laterally extended endopelvic resections extending the lateral resection plane of pelvic exenteration to the medial aspects of the acetabulum, obturator membrane, sacrospinous ligament, and sacral plexus/piriformis muscle were performed in 18 consecutive patients. After this procedure, all patients had tumor-free intraoperative biopsy specimens taken from the remaining pelvic wall structures within the tumor bed area. The final histopathologic report confirmed clean margins in 6 patients and margins with microscopic tumor extensions only in 12 patients. Severe complications occurred in 4 patients (22%), without treatment-related deaths. CONCLUSION: Laterally extended endopelvic resection allows the complete surgical removal of infrailiac pelvic-side-wall tumors, the most frequent local recurrence of lower genital tract cancer, either with free margins or with potential microscopic residual tumor as a prerequisite for combined operative and radiation treatment.

Combined Modality Therapy↗

Tumor hypoxia in pelvic recurrences of cervical cancer.

We have previously demonstrated in primary cancer of the uterine cervix that tumor hypoxia, as determined polarographically, is strongly associated with clinical malignant progression of the disease. Having applied a similar methodological approach to investigate loco-regional relapses, we found a pronounced shift to more hypoxic oxygenation profiles in the recurrent tumors than in the primary tumors. Median pO2 values in 53 pelvic recurrences were significantly lower than the median pO2 values of 117 primary tumors of comparable sizes (7.1 +/- 1.1 mmHg vs. 12.1 +/- 1.0 mmHg, p = 0.0013). The differences in tumor oxygenation between primary and recurrent tumors mirrored the differences in the patients' 5-year survival probabilities. In the cohort of patients with pelvic relapses, median tumor pO2 < 4 mmHg indicated a significantly shorter median survival time as compared to median tumor pO2 > or = 4 mmHg. Our results further support our thesis that in cervical cancer, tumor hypoxia and clinical aggressiveness in terms of resistance to therapy and tumor dissemination, are interrelated.

Adenocarcinoma↗

Liposuction-assisted nerve-sparing extended radical hysterectomy: oncologic rationale, surgical anatomy, and feasibility study.

OBJECTIVE: Our purpose was to improve the therapeutic index of radical hysterectomy by extending the resection of parametrial tissue without further impairing pelvic autonomic nerve functions. STUDY DESIGN: We studied the topographic anatomy of the parametrial tissue with high-resolution magnetic resonance imaging and by dissection of fresh human cadavers. We then performed a clinical feasibility study of the liposuction-assisted nerve-sparing extended radical hysterectomy. RESULTS: Magnetic resonance imaging demonstrated that the perispinous adipose tissue is retained after type III radical hysterectomy and is a frequent site of tumor recurrence. The perispinous adipose tissue contains the pelvic plexus, the pelvic splanchnic nerves, small blood vessels, and lymphatic tissue. We developed the liposuction-assisted nerve-sparing extended radical hysterectomy and applied it to seven consecutive patients with cervical or vaginal cancer. No intraoperative or postoperative complications occurred. Postoperative magnetic resonance imaging assured us that perispinous adipose tissue was cleared in all cases. A metastatic lymph node was found in the perispinous adipose tissue removed by liposuction from one patient. Suprapubic cystostomies could be removed after a median period of 12 days. CONCLUSION: The nerve-sparing removal of perispinous adipose tissue by liposuction is a feasible addition to wide en bloc parametrectomy in anatomically defined planes.

Adipose Tissue↗

Five-year experience with combined operative and radiotherapeutic treatment of recurrent gynecologic tumors infiltrating the pelvic wall.

BACKGROUND: Whereas 25 to 50% of selected patients with gynecologic tumors who relapse centrally in an irradiated pelvis can be salvaged by exenteration, postirradiation recurrence infiltrating the pelvic side wall generally has been fatal. We have designed the combined operative and radiotherapeutic treatment (CORT) procedure for the treatment of postirradiation recurrence infiltrating the pelvic wall and developed several new techniques for its realization. The aim of the surgery is as follows: (1) total resection of the tumor with only a microscopic margin (R1) at the pelvic wall, preserving the bony pelvis and the neurovascular support of the leg; (2) modulation of the therapeutic index for a second high-dose irradiation of the pelvic wall by transferring autologous tissue from the abdomen or the thigh, and (3) reconstruction of pelvic organ functions lost due to tumor resection. The tumor bed is irradiated postoperatively with brachytherapy through transcutaneous guide tubes implanted at the pelvic wall. METHODS: Between April 1989 and December 1994, we treated 48 patients with postirradiation recurrent or persistent gynecologic malignancies infiltrating the pelvic wall with CORT and followed them prospectively with the following endpoints: tumor control, survival, complications, and quality of life. RESULTS: At a median follow-up of 33 months (range, 3-71 months), the 5-year survival probability calculated with the Kaplan-Meier method was 44%. The overall local control rate was 68%, and 85% in the last 25 patients in the series. The censored severe complication rate at 5 years was 33%. No patient died as a consequence of the treatment. Quality of life was self-assessed with a validated questionnaire by 15 patients without evidence of disease, and was rated with a total of 74% of the maximum score points. Age of the patient, state of resection at the pelvic wall (R1 vs. R2), and recurrent tumor size independently influenced tumor progression after CORT in this series. CONCLUSIONS: CORT appears to be a feasible, innovative treatment with long term survival potential and acceptable quality of life for selected patients with postirradiation gynecologic tumor recurrence infiltrating the pelvic wall. R1 resection of the tumor at the pelvic wall is mandatory; however, the reconstruction options within the pelvis are limited.

Adult↗

Hypoxia and Radiation Response in Human Tumors.

This study demonstrates by an updated analysis of an ongoing prospective study that tumor oxygenation, as measured with a validated standardized polarographic needle electrode method before treatment, powerfully predicts the prognosis of patients receiving radiotherapy for intermediate and advanced stage cancer of the uterine cervix. First evidence for a host component in tumor oxygenation based on a significant correlation between median pO(2) values determined in normal subcutaneous fatty tissue and in cervical cancer is also presented. Further investigations are necessary to clarify whether tumor hypoxia is just a marker of intrinsic tumor aggressiveness or whether the negative impact of tumor hypoxia on survival is related to radiobiological mechanisms caused by hypoxia per se, which may include (1) the reduced oxygen enhancement effect, (2) increased radioresistance due to expression of genes for cell cycle delay and stress proteins, and/or (3) accelerated tumor progression to more radioresistant and metastatic variants by increased genetic heterogeneity.

Journal Article↗