Effect of induced hypotensive anaesthesia vs isovolaemic haemodilution on blood loss and transfusion requirements in orthognathic surgery: a prospective, single-blinded, randomized, controlled clinical study.

Induced hypotensive anaesthesia and isovolaemic haemodilution are well-established blood-sparing techniques in major surgery. This prospective study compared them for blood loss, transfusion requirements, and surgical field quality during standardized orthognathic operations. In a surgeon-blinded trial, 60 healthy patients requiring either Le Fort I osteotomy or bimaxillary surgery were randomly allocated to receive normotensive anaesthesia, induced hypotensive anaesthesia, or induced hypotensive anaesthesia combined with isovolaemic haemodilution. Blood loss and haemoglobin level were measured intraoperatively and calculated on postoperative day 3. The surgeons rated surgical field quality. Mean blood loss was 1021.63, 392.38 (p<0.05) and 1191.65ml in the normotensive, hypotensive and haemodilution groups, respectively. Mean haemoglobin level immediately after surgery was 9.3, 10.3, and 7.4g/dl (p<0.05), respectively. No hypotensive group patients received transfusions; four normotensive group patients required allogenic transfusions; seven haemodilution group patients needed autogenous retransfusions (p<0.05). Surgical field quality was significantly better in the hypotensive than in the normotensive (p<0.05) or haemodilution (p<0.05) groups. In orthognathic surgery, hypotensive anaesthesia significantly reduces blood loss and transfusion requirements and minimizes allogenic transfusions risks. Induced hypotensive anaesthesia combined with isovolaemic haemodilution has no additional blood-sparing effects but impairs surgical field quality.

[Treatment modalities for conjunctival melanoma]. / Therapeutische Optionen in der Behandlung des malignen Melanoms der Bindehaut.

BACKGROUND: Because of high local recurrence rates after excision of conjunctival melanoma adjuvant local chemotherapy employing mitomycin C (MMC) or irradiation is recommended. Brachytherapy is possible with ruthenium-106-plaques ((106)Ru) or with the strontium-90-plaques ((90)Sr). PATIENTS AND METHODS: Fifty-six patients received an excision and adjuvant radiotherapy of conjunctival melanoma between 1992 and 2007. The mean follow-up was 42 months (12 - 151 months). Mean age was 62 (28- 86) years. As an adjuvant radiotherapy 15 patients received X-ray irradiation, 12 patients received (106)Ru-brachytherapy, 4 patients received proton beam therapy and 16 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. Four patients received proton beam irradiation and in 13 patients an exenteratio was performed. RESULTS: Twelve patients (21 %) developed tumour recurrences in or adjacent to the irradiated area. Thirteen patients (22 %) showed a recurrence distant from the primary site. Ten patients (18 %) developed systemic metastasis during follow-up. Seven patients (46 %) had no recurrence during the follow-up. Three patients (20 %) had a recurrence in the treated or adjacent areas. Eight patients (53 %) developed new tumours in non-treated areas. CONCLUSIONS: Adjuvant radiotherapy allows an acceptable local tumour control rate after excision of conjunctival melanoma. No obvious differences regarding tumour control or systemic metastasis could be seen between the different modes of radiotherapy used.

Screening for oesophageal neoplasia in patients with head and neck cancer.

Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3 cm throughout the entire length of the squamous oesophagus. Low- or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group.

Primary thinning of the myocutaneous vastus lateralis flap.

To expand the indicational spectrum of the myocutaneous vastus lateralis flap, which is often too voluminous for intraoral application, primary thinning of the fat and muscle component of this microsurgical transplant was performed in 14 patients. The surgical technique includes subfascial localization of at least one myocutaneous perforating vessel of the lateral circumflex femoral artery and its dissection through the fascia, muscles and fatty tissue up to the skin. The epifascial fatty tissue is completely removed except for a 1-2 cm wide cuff around the perforating vessel. The thinning technique was used for covering 10 intraoral and 4 extraoral defects and enabled the raising of skin flaps with a thickness of 4 mm even in obese patients. The vessel pedicle length of the thinned flaps was between 12 and 16 cm; flap size varied between 4x5 and 9x15 cm and the donor sites were directly closed. In one case, there was a partial necrosis (20%), but the other flaps healed without complications. The described method allows the raising of thick myocutaneous as well as thin skin flaps from the same donor region.

De novo expression of vascular endothelial growth factor in human pancreatic cancer: evidence for an autocrine mitogenic loop.

BACKGROUND & AIMS: The role of vascular endothelial growth factor (VEGF) and its receptors in tumor angiogenesis has been well established. We analyzed the expression pattern and biologic significance of VEGF and its receptors in human pancreatic cancer. METHODS: VEGF, KDR/flk-1, and flt-1 expression were examined by immunohistochemistry, in situ hybridization, reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and receptor phosphorylation. VEGF-stimulated mitogenesis was investigated by mitogen-activated protein kinase (MAPK) phosphorylation, transactivation of a c-fos promoter reporter construct, DNA synthesis assays, and stable transfection of a dominant-negative flk-1 complementary DNA (cDNA) construct. RESULTS: Compared with normal pancreas and chronic pancreatitis, VEGF and its receptors were overexpressed in pancreatic cancer. KDR and flt-1 were detected not only in endothelial cells but also in tumor cells. VEGF expression was observed in all human pancreatic tumor cell lines examined, and the KDR/flk-1 and flt-1 receptor was detected in 2 cell lines. VEGF treatment results in phosphorylation of MAPKs, transactivation of a c-fos promoter construct, and growth stimulation in KDR/flk-1-expressing cell lines, which could be blocked by VEGF antagonists. Furthermore, stable transfection of a dominant-negative flk-1 cDNA significantly inhibited tumor cell growth. CONCLUSIONS: These results not only support the important role of the VEGF/VEGF receptor system in pancreatic tumor biology but also suggest the existence of an autocrine/paracrine mitogenic loop for pancreatic cancer cells.

A novel function for the tumor suppressor p16(INK4a): induction of anoikis via upregulation of the alpha(5)beta(1) fibronectin receptor.

The tumor suppressor gene p16(INK4a) inhibits the kinase activity of the cyclin-dependent kinase 4-6/cyclin D complexes and subsequent phosphorylation of critical substrates necessary for transit through the G1 phase of the cell cycle. Recent studies suggested that control of the G1/S boundary might not be the sole biological function of p16(INK4a). We hypothesized that p16(INK4a) might influence hitherto unknown critical features of a malignant epithelial phenotype, such as anchorage dependence. Here we provide evidence that stable transfection of p16(INK4a) restitutes apoptosis induction upon loss of anchorage (anoikis) in a variety of human cancer cells. Anoikis in p16(INK4a)-transfected cells was evidenced by DNA fragmentation and poly(ADP-ribose) polymerase cleavage upon cultivation on polyhydroxyethylmethacrylate-coated dishes and was associated with suppression of anchorage-independent growth as well as complete loss of tumorigenicity. p16(INK4a)-mediated anoikis was due to selective transcriptional upregulation of the alpha(5) integrin chain of the alpha(5)beta(1) fibronectin receptor as detected by FACS((R)) analysis, immunoprecipitation, Northern blotting, and nuclear run-on assays. Addition of soluble fibronectin and inhibitory alpha(5) antibodies to nonadherent cells completely abolished p16(INK4a)-mediated anoikis, whereas laminin was ineffective. Furthermore, antisense-induced downregulation of the alpha(5) integrin chain in p16(INK4a)-transfected cells restored resistance to anoikis. These data suggest a novel functional interference between a cell cycle-regulating tumor suppressor gene and membrane-bound integrins, thus regulating a hallmark feature of an epithelial transformed phenotype: susceptibility to anoikis.

[Primary thinning and de-epithelialization of microsurgical transplants from the lateral thigh]. / Primäre Ausdünnung und Entepithelisierung mikrochirurgischer Transplantate vom lateralen Oberschenkel.

To expand the indicational spectrum of the myocutaneous vastus lateralis flap, which is often too voluminous for intraoral application, we performed extreme, primary thinning of the fat and muscle component of this microsurgical transplant in 14 patients. After subfascial localization of the 0.5- to 1.0-mm-thick perforating vessel, it is exposed through the fascia and muscles up to its exit from the descending branch of the lateral circumflex femoral artery. After isolating the perforating vessel, it is no longer necessary to include parts of the vastus lateralis muscle in the flap. The fatty tissue of the remaining epifascial fat component is completely removed except for a ca. 1- to 2-cm-wide cuff of fatty tissue and fascia around the perforating vessel. When performing this primary radical removal of the subcutaneous fatty tissue, care should be taken not to injure the deep subdermal vascular plexus. In addition to the thinning procedure, de-epithelialization of the skin was performed using scalpel blade dissection (five patients) or carbon dioxide laser (6 W, five patients). This thinning technique was used for covering ten intraoral and four extraoral defects and enabled the raising of skin flaps with a thickness of 3-5 mm even in obese patients. The vessel pedicle length of thinned flaps was between 12 and 16 cm; flap size varied between 4 x 5 and 9 x 15 cm, and the donor sites were directly closed. In one case, there was a partial necrosis (20%), but the remaining flaps healed without complications. On the intraoral flaps, a thin, smooth and pliable surface developed after re-epithelialization within 3-6 weeks. The described method expands the application possibilities of the myocutaneous vastus lateralis flap for a large number of intraoral and flat defects with minimal donor-site morbidity.

Interferon-alpha inhibits chromogranin A promoter activity in neuroendocrine pancreatic cancer cells.

Interferon-alpha (IFN-alpha) treatment can suppress the hypersecretion syndrome associated with functional neuroendocrine tumors. Chromogranin A (CgA) is a matrix protein of neuroendocrine secretory vesicles and appears to be essential for an appropriate neuroendocrine secretory function. To test the hypothesis that IFN-alpha can directly interfere with CgA gene transcription, we performed transient transfection studies in pancreatic neuroendocrine tumor cells employing CgA-luciferase reporter gene constructs showing that IFN-alpha inhibited basal and protein kinase C-dependent CgA promoter activity. Using 5'-deletion constructs in combination with mutational analysis of the proximal CgA core promoter, a cyclic AMP response element (CRE) at -71 to -64 bp was identified as the IFN-alpha response element of the CgA gene. Furthermore, functional studies indicated that IFN-alpha exerts its effect on the CgA promoter via interference with CRE binding protein (CREB)/CREB binding protein (CBP)-dependent transactivation of the CgA-CRE.

Sp1 and CREB mediate gastrin-dependent regulation of chromogranin A promoter activity in gastric carcinoma cells.

Chromogranin A (CgA) is a multifunctional acidic protein that in the stomach is expressed predominantly in enterochromaffin-like cells (ECL cells) where it is regulated by gastrin. In order to investigate the transcriptional response of the mouse CgA (mCgA) promoter to gastrin stimulation, we studied a 4.8-kilobase mCgA promoter-luciferase reporter gene construct in transiently transfected AGS-B cells. 5'-Deletion analysis and scanning mutagenesis of mCgA 5'-flanking DNA showed that a Sp1/Egr-1 site spanning -88 to -77 base pairs (bp) and a cyclic AMP-responsive element (CRE) at -71 to -64 bp are essential for gastrin-dependent mCgA transactivation. Gastrin stimulation increased cellular Sp1 protein levels and Sp1-binding to the mCgA -88 to -77 bp element, as well as binding of CREB to its consensus motif at -71 to -64 bp. Gastrin also stimulated CREB Ser-133 phosphorylation, and abundance of cellular CREB protein levels. Overexpression of either Sp1 or phosphorylated CREB transactivated the mCgA promoter dose dependently, while coexpression of both transcription factors resulted in an additive mCgA promoter response. mCgA -92 to -64 bp, comprising the Sp1/Egr-1 site and the CRE motif, conferred gastrin responsiveness to a heterologous thymidine kinase promoter system, and therefore functions as a "true" enhancer element. This report demonstrates that Sp1 and CREB mediate CCK-B/gastrin receptor-dependent gene regulation, and that the effect of gastrin on the CgA gene is brought about by cooperative action of both transcription factors.

[Basal cell adenocarcinoma of the minor salivary glands of the palate. Case report and review of the literature]. / Basalzelladenokarzinom der kleinen Speicheldrüsen des Gaumens. Kasuistik und Literaturübersicht.

Basal cell adenocarcinoma was first introduced as an entity in the second edition of the WHO's "Histologic Typing of Salivary Gland Tumours" in 1991. This tumor was first described in 1990 by Ellis and Wiskovitch from the Armed Forces Institute of Pathology (AFIP). Basal cell adenocarcinoma accounts for about 2.9% of all salivary gland malignancies. More than 90% of the tumors are situated in the parotid gland. Intraoral manifestations are known from case reports only. Tumors of the palate have been mentioned in three cases. Histologically this tumor can be easily confused with basal cell adenoma and the solid basaloid subtype of adenoid cystic carcinoma. The case presented here is a middle-aged white woman with a basal cell adenocarcinoma of the palate. Therapy consisted of surgical extirpation with three-dimensional safety margins and histologically proven clear resection margins. Knowledge at this point indicates that basal cell adenocarcinoma has a rather high probability of local recurrence (up to 50%) and a mostly lymphogenous metastatic potential for as long as 10 years after removal of the primary tumor. Ten year survival is around 75%.

[Syringomatous carcinoma of the facial skin. Case report of a rare tumor entity]. / Syringomatöses Karzinom der Gesichthaut. Kasuistik einer seltenen Tumorentität.

A rare case of well-differentiated syringomatous carcinoma of the nose, at first histologically misdiagnosed as morpheiform basal cell carcinoma, presented as an ulcerated nasal mass. Recurrence of the tumor and repeated histological examination of tissue specimens led to revision of the primary diagnosis. The histological features of the two entities are compared. The clinician should be aware that knowledge of the biological behavior of this tumor is sparse (based on less than 100 cases) and that the tumor possesses some features of malignancy, requiring a very careful and close follow-up.

[Manifestation of a highly malignant B-cell lymphoma simulating osteomyelitis of the mandible]. / Manifestation eines hochmalignen B-Zell-Lymphoms unter dem klinischen Bild einer Osteomyelitis des Unterkiefers.

A case of precursor B-cell lymphoma of unusual location in the mandible is presented. Clinical features as well as technical examinations led to the misdiagnosis of chronic osteomyelitis. Only immunohistological examination of intraoperatively taken biopsies was able to reveal the true diagnosis. High-dose chemotherapy was started and full remission could be achieved.

[Synovial chondromatosis (chondrometaplasia). Contribution to the differential diagnosis of temporomandibular joint diseases]. / Synoviale Chondromatose (Chondrometaplasie). Beitrag zur Differentialdiagnose von Kiefergelenkerkrankungen.

A rare case of synovial chondromatosis of the temporomandibular joint with unspecific symptoms is presented. This causes difficulties in classifying the different clinically and technically acquired features at differential diagnosis. The concept of chondrometaplasia as being triphasic and self-limiting is strongly supported and extreme care should be taken during therapy in order to avoid any unnecessary destruction and mutilation. This case seems to indicate that chronic parafunctional overload was the initiating stimulus for this reactive metaplastic process. Nonphysiologic overstrain of any cause should be diagnosed and corrected.

[Comparison of laparoscopically assisted vaginal hysterectomy with abdominal hysterectomy. Technique and results]. / Vergleich der laparoskopisch assistierten vaginalen Hysterektomie (LAVH) mit der abdominalen Hysterektomie. Technik und Ergebnisse.

Technique and Results: The aim of this prospective randomised study was to compare laparoscopy-assisted vaginal hysterectomy (LAVH, group A) with abdominal hysterectomy (abd. HE, group B). Therefore, 35 hysterectomies due to non-malignant diseases such as uterine fibroma were performed in each group. A rather simple technique of LAVH was developed. In respect of the indication for hysterectomy, mean duration of operation and the size of the excised uteri there were no statistical differences between the two groups. One severe complication of haemorrhage was observed after LAVH in a patient suffering from a coagulopathy. The requirements for analgesics were significantly lower after LAVH compared to abd. HE during the postoperative period. A significantly lower serum concentration of the c-reactive protein on the first and third days after operation was found in group A. The patients of group A were discharged on the average 5 days after operation and 11 days in group B, respectively. Hence LAVH should replace abd. HE in most cases with the advantages of shorter hospitalisation, minimised requirements for analgesics and cost reduction.

Pathologic fracture of the mandible caused by intraosseous metastasis of oesophageal squamous cell carcinoma: a case report.

A rare case of oesophageal squamous cell carcinoma metastasizing to the mandible and causing a pathologic fracture is described. The relevant literature is reviewed.

[Origin of increased postoperative growth after laser surgical intervention in the peritoneal cavity--an experimental animal study]. / Zu den Ursachen vermehrter postoperativer Verwachsungen nach laserchirurgischen Eingriffen im Bauchraum--Eine tierexperimentelle Untersuchung.

This work deals with the localization and chronology of the appearance of tissue-plasminogen-activator (t-pa) in coagulated and vaporized peritoneal lesions. 21 female WISTAR-rats were laparotomized, similar areas of the parietal peritoneum being vaporized and coagulated. The excision of these lesions was done at seven preset time intervals from 0 to 48 hours postoperatively. The occurrence of t-pa and fibrin was shown by immunohistochemical staining of cryo- and plastic-embedded sections. The differentiation of cells was done with immuno- and enzymhistochemical techniques. The inflammatory response of vaporized lesions shows to be more intense, i.e. exsudation of more fibrin, higher amount of inflammatory cells and a strongly emphasized tendency of adhesion-formation. There is a very low amount of t-pa-reactive cells up to 12 hours postoperatively, increasing after 24 and 48 hours but staying low in relationship to the total amount of cells. In coagulated lesions there is a steady increase of t-pa-reactive cells up to 12 hours postoperatively. Adjacent undamaged peritoneal areas in both types of lesions show a significant t-pa-reactivity. The visible reactivity to t-pa can be localized almost exclusively around monocytes and peritoneal macrophages. Both types of lesions do contain closely the same number of KiM2R-reactive mononuclear cells. There is an increased number of mastcells in vaporized lesions. There is more research needed to be done on the influence of different traumatic impacts on the peritoneum in order to find a causal approach to prevention of adhesions. Right now the only causal way to minimize the incidence of iatrogenic postoperative adhesions is the use of the Semm's well known Endo-coagulation-Technique.