'Loss of pigment epithelium-derived factor enables migration, invasion and metastatic spread of human melanoma'.

Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein that displays broad anti-tumor activity based on dual targeting of the tumor microenvironment (anti-angiogenic action) and the tumor cells (direct anti-tumor action). Here, we show that PEDF expression is high in melanocytes, but it is lost during malignant progression of human melanoma. Using a high-throughput analysis of the data from microarray studies of molecular profiling of human melanoma, we found that PEDF expression is lost in highly invasive melanomas. In paired cell lines established from the same lesion but representing the high and low extremes of malignant potential, abundant PEDF expression was restricted to the poorly aggressive counterparts. We used RNA interference to directly address the functional consequences of PEDF silencing. PEDF knockdown in poorly aggressive melanoma cell lines augmented migration, invasion and vasculogenic mimicry, which translated into an increased in vivo metastatic potential. PEDF interference also significantly enhanced the migratory and invasive capability of normal melanocytes and moderately increased their proliferative potential. Our results show that loss of PEDF enables melanoma cells to acquire an invasive phenotype and, therefore, modulation of this multifunctional factor could be critical for the malignant progression of human melanoma.

[Primary malignant melanoma of the vagina--case report and review of the literature]. / Primares malignes Melanom der Vagina--Fallbericht und Literaturubersicht.

The primary malignant melanoma of the vagina is a very rare tumor with less than 300 cases reported worldwide. Metastatic melanomas of the vagina are even rarer and only 5 cases have been reported so far. We describe the case of patient with a melanoma of the left side of the vagina with a tumor size of 6 cm and a tumor invasion of 2.5 cm. At the time of diagnosis there were no signs of nodal metastases in the positron emission tomography. In the literature, wide local excision with adjuvant radiotherapy is recommended, and radical surgery with adjuvant radiotherapy as second-line therapy. Both procedures show similar 5-year survival rates. To reduce the risk of metastases, we had planned an immunotherapy with interferon-alpha, which has been shown to improve relapse-free and overall survival in patients with high-risk cutaneous melanoma. Unfortunately, the cancer was found to have heavily metastasized 6 months later; the patient therefore received a palliative chemotherapy with dacarbazine and thalidomide.

Baseline staging in cutaneous malignant melanoma.

BACKGROUND: Baseline staging in patients with primary cutaneous malignant melanoma (MM) is routine, but the diagnostic accuracy and the impact on clinical outcome are still unclear. OBJECTIVES: To evaluate the sensitivity and specificity of baseline staging in the early detection of regional lymph node metastases or distant metastases in patients with MM. METHODS: One hundred consecutive patients with MM of Breslow's tumour thickness over 1.0 mm were enrolled. All patients had an extensive baseline staging including physical examination, ultrasound (US) of the abdomen and regional lymph nodes, chest X-ray, whole-body positron emission tomography (PET) and sentinel lymph node biopsy. The sensitivity and specificity of detection of macroscopic or microscopic metastases in the regional lymph nodes or at distant sites were calculated for each method. RESULTS: Sentinel lymph node biopsy was positive in 26 patients. US detected two of 26 histologically tumour-positive sentinel nodes (sensitivity 8%, specificity 88%) and PET two of 26 (sensitivity 8%; specificity 100%). There were three lymph node metastases with a diameter > 4 mm. All of them were found suspect at physical examination. Two of them were detectable with US, two with PET, and all were identified with either US or PET. Nine patients had suspect findings at distant sites, which were all false positive on further investigation (specificity of the combined staging procedures 91%). At 18 (6-37) months' follow-up, five of 26 (19%) patients with a positive sentinel node and four of 74 (5%) of patients with a negative sentinel node had recurrent or progressive disease. CONCLUSIONS: The combination of physical examination and lymph node US detects the great majority of patients with macroscopic lymph node metastasis (approximately 3% of patients at baseline). Only 10% of patients who have a histologically tumour-positive sentinel node are macroscopically detectable. Altogether, approximately 25% of patients have a positive sentinel node biopsy, among 90% microscopic. The value of whole body staging at baseline remains limited, since distant metastases can hardly ever be detected. The survival benefit of baseline staging and surveillance in patients with cutaneous MM remains to be established by comparative prospective trials.

Histological, immunological and molecular features of a nasal mucosa primary melanoma associated with nasal melanosis.

Nasal mucosa melanoma is a rare entity that may occur together with nasal melanosis. The histological and immunological features and loss of heterozygosity analysis of such lesions have not been reported to date. In the study presented here short-term cell cultures were established from the patient's melanoma and subsequent relapses. Histology, immunohistochemistry, reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, human leukocyte antigen analysis, microdissection with subsequent polymerase chain reaction for analysis of loss of heterozygosity were used to characterize the tumour and other cells. Melanoma of the nasal cavity was found, with a surrounding proliferation of atypical melanocytes corresponding to nasal melanosis. Immunoreactivity was found for S-100, gp100, tyrosinase and MelanA protein. Loss of heterozygosity for a p16-flanking marker was found in the tumour and the melanotic cells. Short-term cell cultures expressed tyrosinase and MUC18 at the mRNA level and intercellular adhesion molecule-1 (ICAM-1) and interleukin-12 receptor at the protein level. This is the first time short-term cell cultures have been established and analysed from such a tumour. Melanoma-associated antigens were identified within the tumour. The melanoma and the melanotic cells showed loss of heterozygosity for the p16 gene, which is implicated in melanoma development. This points to a common origin in tumorigenesis. Pathways of tumour escape, such as expression of CD54 and interleukin-10, were observed. The clinical, immunological and molecular features suggest that nasal melanosis should be followed closely.

Optimal regional anaesthesia for abdominal hysterectomy: combined subarachnoid and epidural block compared with other regional techniques.

Regional anaesthesia for abdominal hysterectomy is commonly combined with heavy sedation or light general anaesthesia in order to avoid the occurrence of visceral pain. Our clinical experience has indicated that this pain can be controlled using regional anaesthesia techniques alone. In an effort to find the optimal technique, we randomly assigned 200 ASA and I and II patients who requested regional anaesthesia for abdominal hysterectomy (with or without elective appendicectomy) to one of five groups: 1) subarachnoid bupivacaine; 2) subarachnoid bupivacaine plus intravenous midazolam and buprenorphine; 3) epidural bipivacaine; 4) epidural bupivacaine plus epidural morphine; 5) subarachnoid bupivacaine plus epidural morphine and bupivacaine. The last combination provided by far the best analgesia. Only two of 40 patients complained of slight discomfort, and this was easily controlled. Success rates correlated also with the height of the blockade. It was concluded that the combination of subarachnoid bupivacaine plus epidural morphine and bupivacaine represents an effective and reliable technique for abdominal hysterectomy with or without elective appendicectomy.

[Informative morphogenetic variants--guidelines for the diagnosis of major malformations]. / Nalaz informativnih morfogenetickih varijanti--putokaz u dijagnostici major malformacija.

UNLABELLED: Informative morphogenetic variants are present both in healthy population and in certain diseases and genetic syndromes. They are defined as "structural anomalies with no medical or aesthetic consequences" (1) or "unusual morphologic features with no relevant medical or cosmetic consequences on the carrier" (2). The investigation was initiated when evidences from the foreign literature were found suggesting that children with polythelia more frequently show hereditary and acquired urinary tract malformations than in general population, that is, in children with no IMV. OBJECTIVE: to determine the correlation between the onset of polythelia and hereditary and acquired urinary tract major malformations. On the basis of the results and the discussion we might conclude the following: among the children with polythelia a statistically significant majority has hereditary and acquierd urinary tract major malformations when compared to those with no IMV.

[Is 0.5% bupivacaine solution isobaric?]. / Ist 0,5% ige Bupivacaine-Lösung isobar?

Bupivacaine 0.5% 3 ml was administered by subarachnoid injection to 100 patients. They were divided to four equal groups, according to the body position immediately following the injection: horizontal supine and lateral, sitting and Trendelenburg position. 15 min after the injection was the median dermatome in the later group at T 8.64, and after 60 min at T 7.44 level. The corresponding values for sitting patients were T 5.48 respect. T 3.08. It was concluded that subarachnoidally applied bupivacaine 0.5% shows hypobaric characteristics. This is in agreement with already reported in vitro determinations.

[Avoiding hypoxemia during anesthesia]. / Die Vermeidung der Hypoxämie während der Narkose.

The incidence of unexpected hypoxaemia during general anaesthesia was studied in 230 healthy patients undergoing a peripheral surgical procedure. Measurements of arterial oxygen and carbon dioxide tension (paO2 and paCO2) were performed under rigorously controlled conditions in regard to the age of the patients, their smoking habits, course and type of the anaesthetic and surgery, body position, inspiratory fraction of oxygen (FiO2), expiratory fraction of carbon dioxide (FECO2), respiratory minute volume and inspiratory to expiratory time ratio. 10% of the patients receiving FiO2 of 0.33 and 3.3% of those receiving 0.40 were found to have a paO2 below 80 mm Hg. 25% respect. 0% of older (greater than 60) and 6.7% respect. 4.4% of younger patients (less than 60 years) receiving FiO2 of 0.33 respect. 0.40 were hypoxemic (paO2 less than 80 mm Hg). These figures were compared with the results of an inquiry of practicing anaesthesiologists (in USA, West Germany and Switzerland) and their opinions about the safe FiO2 and paO2 limits. Most of the respondents use under the described conditions of this study an FiO2 of 0.33. At the same time 96% of them expect a paO2 over 80 mm Hg. On the basis of 10% incidence of hypoxaemic values among the patients studied it was concluded that FiO2 of 0.33 can not be considered as safe: increasing FiO2 to 0.40 helps to decrease the incidence of unexpected hypoxaemia especially in the patients over 40 years old.

[Fatal lung embolism following ischemia and peridural anesthesia]. / Tödliche Lungenembolie nach Blutleere und Periduralanaesthesie.

We report the case of a patient who died immediately following repair of a malleolar fracture. Post-mortem examination showed massive central and peripheral pulmonary artery thromboembolism. The possible causative role of peridural anaesthesia and/or ischaemic tourniquet technique are discussed. It is speculated that the combination of both techniques, but especially the last one, might be the provocative factor for such embolism in predisposed patients.

[Phantom phenomena during regional anesthesia]. / Phantom-Erscheinungen während regionaler Anaesthesie.

Phantom phenomena were studied following the administration of peridural (PDA), spinal (SA) and brachial plexus anaesthesia (PB) to 200 patients undergoing a peripheral surgical procedure. 18% of the subjects in PDA, 40% in SA and 63% in the PB group reported a typical, phantom of lower, respect. upper extremities as already described in the literature. Various additional (atypical) forms of phantoms were observed: 10% in PDA, 24% in SA and 6% in PB group. Sex, age, tourniquet, premedication and type of local anaesthetic did not influence substantially the occurrence of phantom. The latter was however directly related to the total dose (mg) of local anaesthetic administered. The appearance of phantom was not always a guarantee of successful block. The possible mechanisms of painless phantoms are discussed.

[Peridural morphine in the treatment of postoperative pain (author's transl)]. / Die peridurale Morphingabe zur Behandlung postoperativer Schmerzen.

The action of peridural morphine (1.5, 3.0 and 5.0 mg) as compared to placebo was studied in the patients who underwent inguinal hernia repair or lower extremity surgery under peridural anaesthesia. Morphine produced a dose-dependent intensive and long lasting segmental analgesia which was statistically significantly superior to placebo at all dosages. This action was however accompanied by a high incidence of urine retention and vomiting. We did not find any respiratory or circulatory depression. Nevertheless, it is accentuated that under different clinical conditions this depression might be highly probable.

Phantom limb pain during peridural anaesthesia.

Report the occurrence of severe phantom leg pain during peridural anaesthesia. The patient had no preoperative pain complaints or neurological deficits and was scheduled for surgical removal of an osteosynthesis plate from his otherwise intact femur. The pain developed parallel with the appearance of phantom sensation during peridural anaesthesia. It was independent of surgical stimulation and vanished towards the end of the operation. Phantom limb pain disappeared completely with dissipation of regional blockade. Some of the possible mechanisms of painless and painful phantoms are discussed. We suggest that investigation of similar cases may help in elucidating phantom limb pain following irreversible pathological deafferentation.

[The luxation of the heart following a blunt trauma to the thorax. A case report (author's transl)]. / Herzluxation nach stumpfem Thoraxtrauma. Ein Fallbericht.

We report a rare complication in a patient who suffered blunt trauma to the thorax. During suturing of the ruptured aorta, distal to the subclavian artery, cardiac arrest occurred. For half an hour the pupils remained fixed and dilated, despite intensive reanimation efforts. It was then realised, that the heart had been displaced through a pericardial defect. Following its reposition the patient recovered without any signs of cerebral damage.