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Biomedical subjects

G Schüder

Publications and source records attributed to G Schüder.

At least 19 recordsLinked to original sources

Complete shutdown of microvascular perfusion upon hepatic cryothermia is critically dependent on local tissue temperature.

Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze-thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0 degrees C-front at 11.7 mm (single freeze-thaw cycle) and 12.1 mm (double freeze-thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 +/- 1.63 degrees C and 9.07 +/- 0.24 degrees C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0 degrees C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation.

Animals↗

Epi-illumination fluorescent light microscopy for the in vivo study of rat hepatic microvascular response to cryothermia.

To elucidate the hepatic microvascular response to cryothermia, we studied the liver microcirculation of Sprague-Dawley rats after one and two 4-minute freeze-thaw cycles using intravital fluorescence microscopy. Irrespective of the number of freeze-thaw cycles applied, the nature of hepatic microvascular injury was characterized by complete stasis of sinusoidal blood flow within the central part of the cryolesions and heterogeneous sinusoidal perfusion in a critically perfused border zone located at the periphery of the lesions. Analysis over time (2 hours) revealed a successive shutdown of sinusoidal perfusion within this critically perfused border zone, which was caused by intravascularly lodging cell aggregates, blocking the lumen of individual sinusoids. The aggregates consisted of parenchymal cells and cell fragments, but did not include leukocytes or platelets. Strikingly, microvascular perfusion failure was associated with Ito cell disintegration and marked dilation of sinusoids (15.6 +/- 0.8 microm vs. 8.8 +/- 0.8 microm; P <.05). This excludes sinusoidal constriction as the cause of nutritive perfusion failure, and may indicate dysfunction of Ito cell-regulated vasomotor control by cryothermia. However, because circulating cell aggregates were frequently observed plugging individual microvessels, dilation of sinusoids may just be the result of passive distension caused by outflow blockade. Analysis of hepatic tissue at 8 weeks after cryothermia did not reveal regeneration and microvascular remodeling, but loss of hepatic tissue, which corresponded well with the tissue area presenting with sinusoidal perfusion failure during the initial observation period after cryothermia. The fact that there was no recovery of sinusoidal perfusion over the initial 2-hour observation period, but loss of tissue after 8 weeks, supports the view that cryothermia induces injury not only by direct low-temperature-mediated action, but also through ischemia caused by irreversible deterioration of the microcirculation.

Animals↗

[Cryosurgery--renaissance or real progress?].

The development and improvement of the cryosurgical technique in combination with intraoperative ultrasonographic imaging enables reliable destruction of liver tumors--although not free of complications--given that tried and tested rules of cryosurgical research are obeyed. In this respect, we can speak of real progress. On the basis of a 3-year testing phase with the CRYO6 cryosurgical apparatus from ERBE, a protocol for the cryosurgical technique for liver tumors is introduced. The spectrum of indications for cryosurgery includes the destruction of irresectable hepatic secondaries or primary tumors with curative intention and the freezing of insufficient or incomplete resection margins. The preliminary results of this treatment modality are encouraging. However, there remains a need for further clinical research to allow final judgement of the cryosurgical method.

Clinical Trials as Topic↗

Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair.

OBJECTIVE: To characterize the impact of abdominal aortic aneurysm repair (AAAR) on spontaneous as well as lipopolysaccharide (LPS)-induced gene expression of pro- and anti-inflammatory cytokines. DESIGN: Prospective, controlled in vivo/ex vivo study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Whole blood from 14 consecutive patients undergoing AAAR withdrawn prior to surgery (T1), at the end of ischemia (T2), 90 min after declamping (T3) and on the first postoperative day (T4) was cultured in the absence or presence of LPS. Five patients undergoing elective inguinal hernia repair served as controls. MEASUREMENTS AND RESULTS: While tumor necrosis factor (TNF), Interleukin (IL)-1 and IL-10 plasma concentrations did not increase significantly, IL-6 was elevated at each time point, as compared with T1. Despite the spontaneous release of trace amounts of IL-6, the ability of cultured whole blood to mount a cytokine response in vitro to LPS was impaired for all cytokines studied at T2 (TNF-62%, IL-1-51%, IL-6 -20%, IL-10-51%). The stimulated IL-6 response was restored early after declamping (T3: +56 %) and enhanced 1 day after operation (T4: +144%). In contrast, stimulated TNF and IL-1 responses remained depressed at T3 (TNF -48%, IL-1-64%) and T4 (TNF-40%, IL-1-24%). A biphasic pattern was observed for IL-10 with initial depression at T3 (-51%) and restoration at T4 (+40%). Among the different cytokines monitored, only impaired TNF responsiveness at early reperfusion (T3) correlated with the postoperative course, as reflected by APACHE II. Cytokine response to LPS was maintained or even increased during and after surgery in the whole blood from patients undergoing hernia repair. CONCLUSIONS: Despite consistent development of clinical signs of systemic inflammatory response syndrome (SIRS) and spontaneous release of IL-6 abdominal aortic aneurysm repair produces a state of impaired pro-inflammatory cytokine response upon a subsequent in vitro Gram-negative stimulus. This early impairment of TNF responsiveness seems to correlate with an unfavorable postoperative course.

Aged↗

[Symptomatic abdominal aortic aneurysm and left-sided infrarenal vena cava].

Coincidence of an abdominal aortic aneurysm and abnormalities of the inferior vena cava is a rare condition but has significance for surgical therapy. By the preoperative use of various imaging techniques and adapted surgical procedure the risk of the operation is decreasing to a minimal level. A case of symptomatic abdominal aneurysm and left-sided infrarenal vena cava is presented and the importance of preoperative examinations and operative strategy is discussed.

Aged↗

Decreased expression of CD44 splicing variants in advanced colorectal carcinomas.

CD44v6 expression appears to be associated with adverse prognosis and propensity for metastasis in patients with colorectal cancer. However, expression of CD44 variants in different tumour stages has been poorly characterised. CD44 variant expression was investigated in normal colonic mucosa (n = 36), colorectal adenomas (n = 15), carcinomas (n = 62) and metastases (n = 6) by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting with exon-specific probes. High frequencies of CD44 standard (CD44s) and CD44 epithelial (CD44e) were observed in normal and neoplastic tissue. CD44v2 was seen predominantly in adenomas (27%) and UICCI carcinomas (29%). CD44v5 expression was low in normal mucosa (3%), higher in adenomas and carcinomas (29-33%), independent of tumour stage. CD44v6 expression was low in normal mucosa (6%) and higher in adenomas (47%) and carcinomas (42%). Surprisingly, a significant decrease of CD44v6 was observed in metastatic primary tumours (8%) and metastases (17%) (UICCIV) (P < or = 0.05). Therefore, the concept of CD44v6 conferring metastatic potential to malignant cells cannot be supported by our data.

Adenoma↗

[Temperature distribution pattern in liver tissue in freezing procedures with new cryoprobes].

The performance of new cryoprobes was studied by measuring the spatial and temporal patterns of the temperature distribution in liver tissue around one to three active cryoprobes. After 15 min of maximal freezing a tissue region 22 mm in diameter was frozen to temperatures below - 50 degrees C by one active cryoprobe. With three cryoprobes, using the synergistic cooling effect, a tissue region 45 mm in diameter was cooled to temperatures below - 50 degrees C. Optimal placement of the cryoprobes was found to be of critical importance.

Animals↗

[Elective lymph node dissection in malignant melanoma--status of color Doppler findings].

Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 < 1 mm tumor thickness). In comparison with a historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).

Adult↗

[Experimental approach to left laparoscopic pancreas resection preserving the spleen].

The pancreas has been excluded from laparoscopic surgery ever since. The technical possibilities of laparoscopic left resection of the pancreas in pigs are examined in this study. Mobilization of the left pancreatic segment up to the confluence area (splenic vein and upper mesenteric vein) was possible preserving the spleen. Sectioning of the organ was performed by ultrasound dissector and selective clipping of the pancreatic duct in 4 animals, in 2 animals this was achieved by Endo-GIA. The size of resected segments was 10-15 cm in length, 2-4 cm in width and the segments weighed 30 gr. Laparoscopic left resection of the pancreas with preservation of the spleen is technically possible in pigs. Postoperative complications have to be further examined in survival studies.

Animals↗

[Technique and quality of laparoscopic hand-sewn intestinal anastomoses in an experimental procedure].

In conventional surgery running suture of all intestine layers is used commonly. Therefore we have tested the following manual running suture technics for laparoscopic surgery using animal experiments. 1. Turnover technic: suture of front and back-wall from outside by using holding sutures. 2. Non-turnover-technic: special holding sutures to fix the back-wall and sewing from the inside followed by the front-wall from outside. 3. Clamp-technic: By using two special parallel closing clamps (Endo-Gauge) with a suture from inside and outside. The ends of the anastomosis are well fixed without additional suture. All animals (n = 15) survived without complications, without leakage of the anastomosis and only one third developed intraabdominal fusions. The main difference was in time performing the anastomosis: 64 min. for the turnover technic, 52 min. for the non-turnover technic and only 25 min for the clamp technic without holding sutures. According to this results, we start to design a new bowel-clamp for sewing laparoscopic anastomosis. Therefore it is possible to perform a laparoscopic manual running suture in a reasonable amount of time. Furthermore the laparoscopic manual suture is a good alternative to the stapler technic because it is much less expensive and leaves no foreign materials.

Anastomosis, Surgical↗

[Endosonography of the esophagus and mediastinum].

It was only the endoscopic ultrasonography that allowed the esophagus and posterior mediastinum to be accessible to ultrasonography. The esophageal wall may be presented in its different anatomic layers to a degree of precision unattained by any other imaging procedure. Being important in the esophagus, both the upper rim of the tumor and the infiltration depth can this way be prognosed correctly to about 85%. In consequence, this allows proceedings appropriate to the tumor stage within the bounds of a multimodal therapeutic concept of esophagus carcinomas. Impressions of the esophagus caused by mediastinal tumors are safely distinguished from intramural tumors. Multiple biopsies to get an examination specimen from a deeper layer should be performed under no other conditions than after endoscopic ultrasonographic examination and just for special questions. In the differential diagnosis of achalasia and peptic stenosis of the esophagus, endoscopic ultrasonography proved to be less efficient. As for bronchial carcinomas, conclusive hints may be drawn from transesophageal and intratracheal ultrasonography. However, due to limited possibilities of judgment caused by air-containing structures these methods are not firmly established in the preoperative staging.

Carcinoma, Bronchogenic↗

Expression pattern of breast-cancer-associated protein pS2/BCEI in colorectal tumors.

Recently, several carcinomas of the gastrointestinal tract were tested for pS2/BCEI activity, a gene isolated from breast-cancer cells and coding for a small secreted peptide. In the latter tumors, its activity is under estrogen control; surprisingly, it was also found expressed in carcinomas of the stomach, biliary tract and pancreas. We have now investigated the expression of this gene in 64 colorectal carcinomas, 31 adenomas and 13 polyps in comparison with their matrix tissues by applying molecular (RNA analysis) and immunohistochemical (pS2 antibody) techniques. Positive pS2 immunostaining (ranging from focal to strong immunoreaction) was noted in 89% of human colon cancers, while 11% remained negative. Furthermore, all 40 transitional mucosae were strongly positive, whereas normal mucosa was negative. Of hyperplastic polyps, 68.2% displayed a significant immunoreaction, and 80.6% of adenomas were focally positive. Finally, 6 out of 16 cases showed significant pS2 transcription in Northern blot analysis. These data clearly indicate that the breast-cancer-associated pS2 protein also plays an as yet undetermined role in the tumorigenesis of human colorectal carcinomas.

Breast Neoplasms↗

Preoperative staging of rectal and colonic cancer.

In rectal cancer, endosonography assesses the tumor penetration depth, EUS T1 to EUS T3, with a sensitivity of 96% and a specificity of 89%. The evaluation of lymph nodes is less accurate, at 79%. The surgical strategy is different in the three parts of the rectum, and depends on the endosonographic tumor stage: upper third of the rectum--anterior resection for all tumor stages; middle third of the rectum--EUS T1 N0: transanal endoscopic microsurgery for "low-risk" carcinomas; EUS T1-2: anterior resection; EUS T3: anterior resection with complete excision of the mesorectum, reconstruction with coloanal pouch; lower third of the rectum--EUS T1 N0: transanal endoscopic microsurgery for "low-risk" carcinomas; EUS T1-2: anterior or intersphincteric resection with complete excision of the mesorectum, reconstruction with colon pouch; EUS T3: abdominoperineal excision. With the impact of endosonography, the proportion of abdominoperineal excisions has dropped from 46% to 15% during the last five years. Laparoscopic technology is likely to have an increasing impact on surgical procedures that have previously required an open approach. The following treatment policy derived from the endosonographic staging of colon tumors is proposed: EUS T1, laparoscopic segmental resection; EUS T2, laparoscopic oncological resection; EUS T3, conventional open surgery.

Colonic Neoplasms↗