Analysing the serum levels of tumour markers and primary tumour data in stage III melanoma patients in correlation to the extent of lymph node metastases--a prospective study in 231 patients.

BACKGROUND: Serum tumour markers correlate with biological tumour behaviour and prognosis of patients. We collected prospective data of melanoma patients in tumour stage III before radical lymph node dissection. MATERIALS AND METHODS: Between 2003 until 2007 we collected 231 tumour stage III patients and analysed the preoperative serum tumour markers S100 (S100 calcium binding protein), NSE (Neuron specific enolase, Enolase 2), Albumin, LDH (Lactate dehydrogenase) and CRP (C-reactive protein) and evaluated the correlation to clinical and pathological data. We divided patients into a group with only a positive sentinel lymph node (group 1; n = 109) and a second with further lymph node metastases (group 2; n = 122). RESULTS: Patients of group 2 had a significant higher T level (p < 0.0001) and Breslow index (p < 0.0001). Patients with a higher Breslow index had a higher S100 serum level (p = 0.021). Patients of group 2 displayed a significant higher level of serum S100. The serum level of CRP correlated with increasing number of lymph node metastases. CONCLUSIONS: A higher Breslow index in tumour stage III patients seems to have an influence on lymph node metastases and on S100 serum level. Patients with more than a positive sentinel lymph node do have a higher S100 level.

Influence of surgical complications on the level of pain after radical inguinal/iliacal lymph node dissection.

BACKGROUND: We collected the data of 288 patients with malignant skin tumours. We analysed the postoperative pain assessed by a visual analogue scale (VAS) to evaluate the quality of our standard peri-operative pain therapy after a radical inguinal and iliacal lymph node dissection (RILND) as well as the influence of postoperative surgical complications on the level of pain. MATERIALS AND METHOD: The postoperative level of pain of 85 patients with malignant skin tumours who underwent a RILND between August 2003 and December 2007 was recorded prospectively. Patients received a standardised perioperative pain therapy according to level I or II of the World Health Organisation (WHO) ladder of pain. The efficiency of our pain therapy was registered via VAS in the morning of the first three postoperative days. RESULTS: Using our standard pain therapy, we determined a VAS < 30 in rest during the first three postoperative days, but significantly more pain (VAS median 50-30) (p < 0.001) under stress. Patients with surgical complications in the postoperative period (n = 71) had significantly more pain in the postoperative period compared to patients with a regular postoperative course (p = 0.047). CONCLUSIONS: Immediately after a RILND, an analgesic therapy according to level I or II of the WHO pain ladder does not seem to be effective enough. Postoperative surgical complications lead to a higher VAS level of pain in the postoperative period.

[Surgical technique and postoperative morbidity following radical inguinal/iliacal lymph node dissection--a prospective study in 67 patients with malignant melanoma metastatic to the groin]. / Technik und Morbidität der radikalen inguinal / iliakalen Lymphknoten-dissektion--eine prospektive Untersuchung an 67 Patienten mit lymphogen metastasiertem malignen Melanom.

BACKGROUND: The surgical radical inguinal / iliacal lymph node dissection (RLND) is the procedure of choice in patients presenting with lymphatic metastasis of melanoma of the lower extremity or the lower part of the trunk. The perioperative morbidity of patients includes not only local wound complications, seroma formation or lymphatic fistula but also leg oedema, deep venous thrombosis and neuralgic disorders postoperatively. The aim of this prospective study was the evaluation of postoperative morbidity in patients undergoing radical inguinal/iliacal RLND in a standardised surgical fashion. PATIENTS AND METHODS: 67 patients suffering from malignant melanoma of the lower extremity or the lower trunk with metastatic lymph nodes in the groin or the iliacal region underwent a combined RLND of the inguinal / iliacal region or the groin alone between 2003 and 2006. All operations were performed in a standardised technique. The main criterion of the study was the incidence of postoperative wound complications. Minor endpoints included the incidence of lymphatic fistula, the length of hospital stay, and the development of temporary or permanent leg oedema. RESULTS: 64 patients underwent inguinal / iliacal and 3 patients only inguinal LND (lymph node dissection). All patients tolerated the procedure well. The overall wound complication rate was 34 %. One patient died on the 21st postoperative day due to a pulmonary embolism and a simultaneous cerebral apoplexy. Lymphatic fistula occurred in 22 (33 %) patients whereas seroma resulted in 23 (34 %) patients. The length of hospital stay was 15 (3-41) days. A relevant leg oedema was observed in 9 (13 %) patients. CONCLUSION: Even with a proper perioperative management and a precise wound care management, one-third of the patients undergoing radical inguinal / iliacal lymphadenectomy suffer from a complication requiring medical or interventional treatment. Our data demonstrate that most of these complications can be treated sufficiently by conservative treatment. A fitted surgical support hose could prevent long-term complications.

In vitro and in vivo antitumor activity of a novel immunomodulatory drug, leflunomide: mechanisms of action.

Leflunomide, a novel immunomodulatory drug, has two biochemical activities: inhibition of tyrosine phosphorylation and inhibition of pyrimidine nucleotide synthesis. In the present study, we first showed that A77 1726 [N-(4-trifluoromethylphenyl-2-cyano-3-hydroxycrotoamide)], the active metabolite of leflunomide, was more effective at inhibiting the tyrosine kinase activity of platelet-derived growth factor (PDGF) receptor than that of epidermal growth factor (EGF) receptor, and had no effect on the tyrosine kinase activity of the fibroblast growth factor receptor. In the presence of exogenous uridine, A77 1726 was more effective at inhibiting the PDGF-stimulated proliferation of PDGF receptor-overexpressing C6 glioma than the EGF-stimulated proliferation of EGF receptor-overexpressing A431 cells. In vivo studies demonstrated that leflunomide treatment strongly inhibited the growth of the C6 glioma but had only a modest effect on the growth of the A431 tumor. Uridine co-administered with leflunomide did not reverse the antitumor activity of leflunomide on C6 and A431 tumors significantly. Quantitation of nucleotide levels in the tumor tissue revealed that leflunomide treatment significantly reduced pyrimidine nucleotide levels in the fast-growing C6 glioma but had no effect on the relatively slow-growing A431 tumor. Whereas uridine co-administration normalized pyrimidine nucleotide levels, it had minimal effects on the antitumor activity of leflunomide in both tumor models. Immunohistochemical analysis revealed that leflunomide treatment significantly reduced the number of proliferating cell nuclear antigen-positive cells in C6 glioma, and that uridine only partially reversed this inhibition. These results collectively suggest that the in vivo antitumor effect of leflunomide is largely independent of its inhibitory effect on pyrimidine nucleotide synthesis. The possibility that leflunomide exerts its antitumor activity by inhibition of tyrosine phosphorylation or by a yet unidentified mode of action is discussed.

Do angiogenesis and growth factor expression predict prognosis of esophageal cancer?

A retrospective study of surgically resectable esophageal cancers was undertaken to determine the relationship between angiogenesis score and growth factor expression with tumor size, histology, degree of differentiation, depth of invasion, nodal disease, and the presence of Barrett's esophagus. The office and hospital charts of 27 patients who had esophageal resection for carcinoma between 1990 and 1995 at Rush-Presbyterian-St. Luke's Medical Center were reviewed. Data collection included patient demographics, survival, tumor size, histology, differentiation, depth of invasion, nodal metastases, and the presence of Barrett's esophagus. The pathology specimens were immunostained for von Willebrand factor (factor VIII-related antigen). Immunostaining was also performed for vascular endothelial growth factor and transforming growth factor alpha. Twenty normal esophageal specimens served as controls. Angiogenesis score was determined by counting vessels under conventional light microscopy at x200 magnification, and growth factor expression was graded on a scale of 1 to 4. Cancers had higher angiogenesis and growth factor expression than controls (P = 0.01). Patient age, tumor size, histology, differentiation, depth of invasion, and Barrett's esophagus did not correlate with angiogenesis score or tumor growth factor expression. Lymph node status did correlate with both angiogenesis score and growth factor expression (P < or = 0.02). We conclude that high angiogenesis score and growth factor expression correlate with the presence of lymph node metastases. This may help select patients for preoperative radiation and chemotherapy or determine the extent of surgery performed for esophageal carcinoma.

Epigallocatechin gallate can significantly decrease free oxygen radicals in the reperfusion injury in vivo.

OBJECTIVE: There is experimental evidence that oxygen-derived free radicals (Superoxide (O(2)(-))) play a key role in tissue damage in ischemia-reperfusion injury. Among various antioxidants tested in vitro, natural polyphenols like Epigallocatechine gallate (EGCG) show a 164-fold higher scavenging activity for O(2)(-) than ascorbic acid We therefore conducted an animal study in order to investigate the impact of EGCG on O(2)(-) production during reperfusion after defined periods of ischemia in the muscle tissue of the rat, using a recently developed cytochrome c-based biosensor for on-line in vivo monitoring of O(2)(-). MATERIALS AND METHODS: Femoral artery and vein were dissected below the inguinal ligament in male Wistar rats. The cytochrome c-based biosensor was placed in the gastrocnemius muscle. Ischemia was induced by clamping the femoral vessels. Ischemia times were either 60 (n = 14) or 120 (n = 14) minutes. Six animals in each group received 4 mg/kg body weight EGCG intravenously at the time of reperfusion, another six animals in each group served as controls (no treatment). Additionally, two animals in each group received the same volume of saline instead of EGCG. The current response of the biosensor corresponding to the O(2)(-) concentrations in vivo was recorded on a PC. The gastrocnemius muscles were harvested for histological evaluation. RESULTS: The average maximum O(2)(-) concentration after 60 minutes of ischemia was 188, 18 nmol/L (23 pA) compared to 90 nmol/L (11 pA) (P <.01) with EGCG application. The mean O(2)(-) value after 120 minutes was 220 nmol/L (27 pA) versus 135 nmol/L (16.5 pA) (P <.01) with EGCG, respectively. Histological analysis showed advanced muscle cell injury and neutrophil infiltration in the group without EGCG. No O(2)(-) reduction could be verified administering saline instead of EGCG. CONCLUSION: For the first time the scavenging activity of an antioxidant was verified in vivo on-line. EGCG significantly diminished O(2)(-) tissue concentrations after 60 or 120 minutes of ischemia by an average of nearly 50%, suggesting its therapeutic potential.

[Keloid of the earlobe after ear piercing. Not only a surgical problem]. / Keloidbildung des Ohrläppchens nach Ohrlochstechen. Nicht nur ein chirurgisches Problem.

Earlobe keloids are benign, fibrous proliferations that show a high rate of recurrence of up to 80% following surgical excision. Traumas to the earlobe such as ear piercing, burns or surgical interventions are important in the pathogenesis of the disease. In addition to surgical keloid excision and reconstruction of the earlobe, several adjuvant therapeutic concepts have been described to prevent recurrence. Here we present the case of a female patient who suffered from severe bilateral keloid development after piercing of both ears. The report gives an overview of the relevant therapeutic concepts in the treatment of earlobe keloids and their possible complications. In addition, the question of written informed consent before ear piercing is discussed.

[Leflunomide reduces the angiogenesis score and tumor growth of subcutaneously implanted colon carcinoma cells in the mouse model]. / Leflunomid reduziert den Angiogenesescore und das Tumorwachstum subkutan implantierter Kolonkarzinomzellen im Mausmodell.

BACKGROUND: The inhibition of tumorangiogenesis may be of importance in the additive treatment of various cancers. Leflunomide, a drug which has been approved in Germany for the therapy of rheumatoid arthritis, inhibits the activity of several growth factors in vitro. The aim of this study was to investigate the effects of the drug on tumor angiogenesis in a nude mouse model. MATERIALS AND METHODS: A total of 40 nude mice were injected with human colon carcinoma cells. Following randomization in 4 groups, therapy started on day five. Group 1 was treated daily with orally administered Leflunomide (35 mg/kg) dissolved in 1.5% Carboxymethylcellulose (CMC). Group 2 served as a control group and received 1 ml CMC orally per day. The animals of group 3 were treated daily with 35 mg Leflunomide/kg KG and 500 mg Uridine/kg dissolved in 1 ml Nacl 0.9% intraperitoneally. The 4th group again served as a control group and received only 500 mg Uridine/kg intraperitoneally each day. The main outcome criterion was the angiogenesis score (AS). In addition, the tumor volume and tumor weight were also assessed. The AS was determined by immunohistochemistry using an antibody against factor VIII related antigen. RESULTS: All animals tolerated the procedure well. In the Leflunomide and the Leflunomide/Uridine group the angiogenesis score (p < 0.01), the tumor volume (p < 0.01) and the tumor weight (p < 0.01) were lower compared to the respective control groups. CONCLUSION: The administration of Leflunomide leads to a significant reduction of tumor weight and tumor volume following subcutaneous injection of human colon carcinoma cells in a nude mouse model. This could be due to the reduction of tumor angiogenesis. Following further experimental and clinical studies, Leflunomide may come to play a role in the additive treatment of colonic carcinoma.

A prospective randomized trial: the influence of intraoperative application of fibrin glue after radical inguinal/iliacal lymph node dissection on postoperative morbidity.

BACKGROUND: Effects of intraoperative application of fibrin glue following combined radical inguinal and iliacal lymph node dissection (RILND) on the amount of postoperative lymphatic secretion are discussed controversially. To detect whether fibrin glue application results in a decreased lymphatic secretion following RILND a randomized patient blinded clinical trial was conducted. METHOD: Between September 2003 and September 2006 58 patients with stage IV melanoma underwent therapeutic RILND and were randomized into two groups. 29 Patients received 4 cc fibrin glue after RILND whereas 29 patients were only irrigated with saline 0.9 percent. Postoperatively all patients received two inguinal and one iliacal closed suction drain. The main outcome criteria were the duration of drain placement in the wound. Minor criteria were the total amount of secretion and the length of hospital stay. RESULTS: There was no difference between the treatment and the control group in the duration of drain placement (fibrin group: 4 days (1-27); control group 5 days (1-26); p=0.64). The total amount of fluid was 310 cc (30-6005) in the fibrin group vs. 365 cc (30-3945 cc) in the control group (p=0.9) and the length of hospital stay 10 days (3-41) (group 1) compared to 11 days (3-41) (p=0.99) were not different between both groups either. CONCLUSION: Intraoperative application of 4 cc fibrin glue does not reduce the length of drain placement, drain output or hospitalisation of patients undergoing RILND with melanoma metastasis to the lymph node basin.

Esophageal necrosis and perforation of the left main bronchus following photodynamic therapy of esophageal carcinoma.

Photodynamic therapy is an effective palliative treatment of esophageal cancer. Minor complications associated with this therapy include pleural effusions, fever or esophageal strictures. In addition to this major complications such as respiratory-esophageal fistula and bronchus perforation have been described. We report here our experience with a patient who developed a complete esophageal necrosis and perforation of the left main bronchus following photodynamic therapy. The surgical and intensive care management of the patient is described and the literature discussed.

Long-term survival of a patient with small-cell lung cancer (SCLC) following treatment with thalidomide and combination chemotherapy.

Thalidomide, an angiogenesis inhibitor is currently used in clinical trials in the US and Europe in combination with chemotherapy for the treatment of various solid tumors. The prognosis of patients suffering from small-cell lung cancer (SCLC) is poor. A 73-year-old female with extensive disease of SCLC was given six courses of chemotherapy with adriamycine, cyclophasphamide and oncovine, which led to complete remission of the disease. Following written informed consent, the patient has been treated with thalidomide 200 mg orally on a daily basis for 2 years and 5 months. There has been no sign of tumor recurrence during the follow-up. This case underlines the possible role of additional treatment with angiogenesis inhibitors in combination with traditional chemotherapy in the therapy of SCLC. Although there is no proof that thalidomide contributed to this good outcome and no conclusions can be drawn from this treatment in a single patient, further studies may determine the role of thalidomide as an adjuvant antiangiogenic agent in the therapy of SCLC.

In a pig model ePTFE grafts will sustain for 6 weeks a confluent endothelial cell layer formed in vitro under shear stress conditions.

OBJECTIVE: to investigate in a pig model whether small diameter ePTFE grafts will sustain a confluent endothelial cell layer formed in vitro under shear stress conditions. MATERIALS AND METHODS: thirteen ePTFE (4 mm) grafts were implanted end to end in the right femoral artery of; 8 grafts had been endothelialized in vitro. Grafts were left in situ for 6 weeks then evaluated with ultrasound and histology. RESULTS: seven endothelialized graft were patent with confluent endothelial cell lining. None of the control grafts were patent or showed evidence of an endothelial lining. CONCLUSION: in this pig model ePTFE grafts sustained for 6 weeks a confluent endothelial cell layer formed in vitro under shear stress.

[High pressure injection injuries of the hand with surfacer]. / Hochdruckeinspritzverletzung der Hand mit Spachtelmasse.

The most commonly injected materials in high-pressure injection injury to the hand include paint, automotive grease, solvents and diesel oil. High-pressure injection injuries are a frequently mismanaged problem, as they are often not recognized and treated early, which may result in a compromised function of the hand or even the amputation of a digit. Early diagnosis is an important factor, as well as the type and amount of injected material and the injection pressure at appliance. We present one case of high-pressure injection injury to the hand with the surfacer Caparol Accord. This report describes the principles of treatment and gives an overview of the literature about tissue injuries caused by components of different substances encountered in high-pressure injection injuries.

Re-opened foramen ovale--a rare cause of postoperative dyspnea following pneumonectomy.

Dyspnea and hypoxemia are common postoperative problems following pneumonectomy. Platypnea, the increased dyspnea in the erect position relieved by assuming a prone position, has been reported as a result of right to left inter-atrial shunt. We report here on our experience with a patient who had severe platypnea with remarkable positional arterial desaturation following right pneumonectomy. After establishing the diagnosis with contrast-enhanced transesophageal echocardiography of the preoperatively undetected interatrial right-left shunt, cardiac surgery led to clinical improvement and resumption of platypnea. Given the rarity of the diagnosis, we think interatrial shunt, based on an open foramen ovale, should be taken into consideration when platypnea occurs in patients as a postoperative complication following lung surgery. Transesophageal echocardiography may be helpful in detecting patients with "anatomical closed but functional open" foramen ovale or genuine inter-atrial septal defect prior to lung surgery.

Mechanical, histologic, and biochemical effects of canine rectal formalin instillation.

UNLABELLED: Instillation of 4 percent formalin effectively treats radiation hemorrhagic proctitis; however, little is known regarding its side effects. PURPOSE: The study contained herein was undertaken to determine rectal compliance and collagen content, mucosal and vascular histologic changes, and kinetics of formalin absorption following instillation. METHODS: Fifteen mongrel dogs (50-60 pounds) were randomized into five experimental groups according to time elapsed from formalin treatment: control, acute, one week, two weeks, and four weeks. Formalin was instilled in 30-ml aliquots to a total volume of 400 ml. Rectal compliance (closed manometry system) was assessed pre-formalin and post-formalin at the designated time interval. Serum formalin metabolites were determined at time 0, 0.5, 1, and 3 hours. A segment of rectal wall was analyzed for collagen content, mucosal injury, and blood vessel density. RESULTS: Serum formalin levels peaked within 30 minutes, returning to normal by 3 hours. With the exception of one dog, toxic levels were not reached at any time during the study. No dogs experienced sepsis, fever, or altered gastrointestinal function. Acute and one-week dogs showed mild diffuse proctitis and mucosal slough, which healed within two weeks. Rectal compliance and collagen content were unchanged. Mucosal blood vessels decreased in number early (P = 0.03). CONCLUSIONS: Instillation of 4 percent formalin in sequential aliquots of a small volume that is kept in contact for a short period of time is safe. Serum formalin levels generally do not reach toxic levels, and the slight elevation in formalin concentration that was seen returns to normal within three hours. Formalin-induced proctitis heals within two weeks, and no long-term changes in rectal compliance or collagen content were seen.