Adipose tissue: a new target for electroporation-enhanced DNA vaccines.

DNA vaccines delivered using electroporation (EP) have had clinical success, but these EP methods generally utilize invasive needle electrodes. Here, we demonstrate the delivery and immunogenicity of a DNA vaccine into subcutaneous adipose tissue cells using noninvasive EP. Using finite element analysis, we predicted that plate electrodes, when oriented properly, could effectively concentrate the electric field within adipose tissue. In practice, these electrodes generated widespread gene expression persisting for at least 60 days in vivo within interscapular subcutaneous fat pads of guinea pigs. We then applied this adipose-EP protocol to deliver a DNA vaccine coding for an influenza antigen into guinea pigs. The resulting host immune responses elicited were of a similar magnitude to those achieved by skin delivery with EP. The onset of the humoral immune response was more rapid when the DNA dose was spread over multiple injection sites, and increasing the voltage of the EP device increased the magnitude of the immune response. This study supports further development of EP protocols delivering gene-based therapies to subcutaneous fat.

[Topical therapy of inflammatory dermatoses, pruritus and pain, as well as hyperhidrosis]. / Topische Therapie von entzündlichen Dermatosen, Juckreiz und Schmerz sowie Hyperhidrose.

In this review, substances suitable for the topical treatment of inflammatory dermatoses, pruritus, pain and hyperhidrosis are presented. Both non-specific and specific topical treatments are discussed with respect to their mode of action, indications and side effects; included are corticosteroids, calcineurin inhibitors, dithranol, coal tar, liquor carbonis detergens, vitamin D analogues, metronidazole, azelaic acid, retinoids, and benzoyl peroxide. Additionally, practical directions for the treatment of these common skin diseases are provided.

[Topical treatment of infections, tumors and hyperkeratotic disorders]. / Topische Therapie von Infektionen, Hauttumoren und Hyperkeratosen.

In this review substances for the topical treatment of skin infections, skin tumors and hyperkeratotic disorders are presented. Substances with specific actions as topical antimycotic, antibiotic, antiseptic, antiviral and antiparasitic agents as well as diclofenac in hyaluronic acid, 5-fluoruracil, imiquimod, ingenol mebutate, bexarotene, mechlorethamine, BCNU, alitretinoin, silicone gel, salicylic acid and urea are discussed with respect to their mode of action, indication and side effects.

[Critical incidents in preclinical emergency airway management : Evaluation of the CIRS emergency medicine databank]. / Kritische Zwischenfälle im Atemwegsmanagement der präklinischen Notfallmedizin : Auswertung der Datenbank CIRS-Notfallmedizin.

BACKGROUND: Many patients are victims of disastrous incidents during medical interventions. One of the obligations of physicians is to identify these incidents and to subsequently develop preventive strategies in order to prevent future events. Airway management and prehospital emergency medicine are of particular interest as both categories frequently show very dynamic developments. Incidents in this particular area can lead to serious injury but at the same time it has never been analyzed what kind of incidents might harm patients during prehospital airway management. MATERIALS AND METHODS: The German website http://www.cirs-notfallmedizin.de (CIRS critical incident reporting systems) offers anonymous reporting of critical incidents in prehospital emergency medicine. All incidents reported between 2005 and 2012 were screened to identify those which were concerned with airway management and four experts in this field analyzed the incidents and performed a root cause analysis. RESULTS: The database contained 845 reports. The authors considered 144 reports to be airway management related and identified 10 root causes: indications for intubation but no intubation performed (n = 8), no indications for intubation but intubation attempt performed (n = 7), wrong medication (n = 25), insufficient practical skills (n = 46), no use of alternative airway management (n = 7), insufficient handling before or after intubation (n = 27), defect equipment (n = 28), lack of equipment (n = 31), others (n = 18) and factors that cannot be influenced (n = 12). CONCLUSIONS: The incidents that were reported via the website http://www.cirs-notfallmedizin.de and that occurred during airway management in prehospital emergency medicine are described. To improve practical airway management skills of emergency physicians are one of the most important tasks in order to prevent critical incidents and are discussed in the article.

[Effectiveness of radiofrequency ablation of lung tumours ]. / Radiofrequenzablation von Lungentumoren : Eine wirklich effektive Therapiemassnahme?

BACKGROUND: There has been great success in the treatment of primary and secondary tumours of the liver using radiofrequency ablation (RFA) therapy, resulting in this method being used for other solid tumours such as in the lung. However, concerning lung cancer only few data are available about the histomorphological effects of this method. The aim of this study was to analyse the effects of RFA therapy in tumours of the lung. PATIENTS AND METHODS: Eleven patients with non-small-cell lung cancer and one with a lung metastasis (primary tumour identified as urothelial carcinoma) underwent RFA therapy followed by resection of the affected lobe. One patient with a metastasis of the liver was included for comparison of treatment effects. Histomorphological analysis of the collected material was used to measure the amount of necrosis. RESULTS: None of the treated tumours of the lung showed complete necrosis after applying RFA therapy. In contrast, this method with the control metastasis of the liver resulted in complete thermal destruction. CONCLUSION: Our results indicate that RFA therapy is not adequate for successful induction of necrosis in tumours of the lung. Therefore the use of this method has to be considered extremely carefully as a palliative treatment option in tumours of the lung.

Preexistence and evolution of imatinib mesylate-resistant clones in chronic myelogenous leukemia detected by a PNA-based PCR clamping technique.

Recently, various mutations within the Abl sequence have been described that negatively affect imatinib binding to Bcr/Abl resulting in cellular resistance of chronic myeloid leukemia (CML) cells. So far, little is known as to whether these mutations are preexisting or develop under imatinib therapy as current mutation analyses are limited by a low sensitivity of approximately 1:2 (50%) to 1:5 (20%). By combining peptide nucleic acid (PNA)-based DNA clamping with a fluorescence hybridization probe assay, we developed a new and highly sensitive technique for the detection of known mutations within the Bcr/Abl kinase domain. With this approach we investigated 19 cases of CML refractory to imatinib treatment before and during therapy. By clamping of wild-type Abl through PNA we could effectively enhance the detection sensitivity for the Bcr/Abl mutations Thr315Ile, Glu255Lys, and Tyr253His such that 1 mutant cDNA molecule could be detected in 500 negatives (0.2%). We observed in one case that a Gly255Lys mutation was detectable before treatment. By DNA analysis of buccal swaps, a genetic polymorphism could be excluded. In two cases clonal evolution of known mutations developed gradually under treatment. In another case an initially detectable Tyr253His mutation disappeared after therapy onset but was again observed after 6 weeks of imatinib treatment. Preexisting and evolving Bcr/Abl mutations associated with an unfavorable prognosis could be safely detected by the presented technique. This may facilitate risk stratification in CML and may serve as a model for individualized molecular monitoring and therapeutic strategies in other malignant diseases.

[Pulmonary blastoma--a rare malignant lung tumor]. / Das pulmonale Blastom--ein seltener maligner Lungentumor.

Pulmonary blastoma is a rare non-small-cell lung cancer. In a statistically significant proportion of cases it is combined with cystic lung disease in children. The biphasic pulmonary blastoma and the well-differentiated fetal adenocarcinoma are the most frequent manifestations of pulmonary blastoma. If metastatic disease is ruled out, surgical therapy should be guided by the principles for radical therapy of NSCLC. There are no sufficient recommendations yet for therapy of stage IIIb and IV (UICC 1997) disease.

[Discontinuity resection in therapy of complicated sigmoid diverticulitis]. / Die Diskontinuitätsresektion in der Therapie der komplizierten Sigmadivertikulitis.

A total of 112 patients were operated on for severe complicated sigmoid diverticulitis, Hartmann's procedure was performed due to local or generalised peritonitis, 80% to them as emergency surgery. There was a mortality of 18.8% due to the sepsis or other complications. Sixty-two of the remaining 80 patients underwent a restorative procedure without any mortality and low morbidity (11 died after discharge not related to the colon disease). Resection and primary anastomsis is always the first choice, but in cases of severe peritonitis there is no discomfort or risk for the patient if Hartmann's procedure with restorative surgery is chosen.

[Extensive surgery of colorectal carcinoma in the elderly--a justified therapy approach]. / Erweiterte Colorectale Carcinomchirurgie im Alter--ein berechtigter Therapieansatz.

Over a 5-year period 1232 patients were operated on for carcinoma of the colon or rectum, 828 had curative surgery without and only 69 with resection of other organs. About half of the patients were 70 or more years old, but the older patients, especially in the extended resected cases, had the same or better 5-year survival and the same rate of complications or mortality. The overall prognosis depends on the complete resection of the tumor, the involvement of lymph nodes and the number of general risk factors, but not on the age of the patient.

[Lymph- and haemangiosis carcinomatosa--an important prognostic factor in non-small-cell bronchial carcinoma (NSCLC)]. / Lymph- und Haemangiosis carcinomatosa--ein wichtiger Prognosefaktor beim nicht-kleinzelligen Bronchialkarzinom (NSCLC).

Between 1 Jan 1984-1 Jan 1990, 199 patients underwent curative (R0) surgery for non-small cell lung cancer. The pathohistological findings showed that a carcinomatous lymphangiosis and haemangiosis (L/H pos.) were present in 26 patients. In six patients, no lymph node metastases were detected. The median (22 mo. vs. 74 mo.) and 5-year survival (25% vs. 41%) were significantly (p < 0.001) higher compared to patients with and without lymphangiosis and haemangiosis carcinomatosa (L/H neg.). There were also significant (p < 0.05) differences in the survival time between pNO L/H neg. and pNO L/H pos. patients (median 74 mo. vs. 15 mo.-5 years 43% vs. 0%).

[The significance of lymph- and hemangiosis carcinomatosa in colorectal carcinoma]. / Die Bedeutung der Lymph- und Hämangiosis carcinomatosa beim colorectalen Carcinom.

Between 1.1.1988 and 31.12.1989 306 patients underwent curative surgery for colorectal cancer at the surgical center of Nurnberg City hospital. The pathohistological findings showed that a carcinomatous lymphangiosis and hemangiosis (LH+) was present in 57 (18.6%) cases. The rate of metachronic metastases of the liver was significantly higher (38.2% vs. 19.6% p < 0.001) compared to patients without lymphangiosis and hemangiosis (LH-). There were also significant differences between the survival rates (5-year survival rate 50% vs. 63% p < 0.02). Analysing the lymph node stage and LH+ situation it was found that carcinomatous lymphangiosis and hemangiosis were already present in 7.2% of patients who didn't have tumorous infiltration of the lymph nodes (p NO/LH+). The 5-year survival rate was bad in both groups (54% vs. 49%).

[Repeat liver resection in colorectal liver metastases]. / Wiederholte Leberresketion bei kolorektalen Lebermetastasen.

For patients with recurrent operable liver metastases from colorectal cancer operative resection is the only chance of getting rid of their tumorous disease for a longer time. As there are not therapeutic alternatives more and more authors are reporting on repeated resections of liver metastases. From 1986 to 1994 we performed 12 recurrent liver resections with curative intent in 8 patients suffering from liver metastases of colorectal cancer: 4 synchronous and 4 metachronous metastases were removed, the primary procedure being anatomic hemihepatectomy in 5 cases and segmentectomy or bisegmentectomy in 3 cases. The mean time interval between the first and the second resections was 14 (4-23) months. Two patients underwent 4 consecutive liver resections because of recurrent metastases. In these cases the interval between the second, third and fourth procedures was 10 months. The postoperative complication rate was 16% and not a single patient died in hospital. Three patients died an average of 28 (9-54) months after the last liver resection, and the other 5 patients are still alive after an average of 14 (4-28) months: 3 are free of tumor and 2 have recurrent metastases in the liver. Compared with untreated or only locally treated cases, patients in whom operative risk is low can achieve prolonged survival times after resections of colorectal metastases to the liver.

[Multivisceral resection of advanced colorectal cancer]. / Multiviszerale Resektion des forgeschrittenen kolorektalen Karzinoms.

From 1 September to 1 January 1990, a total of 1232 patients underwent surgery for colorectal cancer. Resection was performed on 1112 (90.3%) patients. It was curative in 917 cases and palliative in 195. Multivisceral resection was necessary 82 times because of tumour infiltration of adjacent organs (curative: 69 cases; palliative: 13 cases). The complication rate (26.7% vs 27.5%) and mortality rate (3.4% vs 2.9%) were similar to those for curative resections without multivisceral extension. The 5-year survival rate was also similar in the two groups (58% vs 55%). These results show that curative multivisceral resections can lead to the same long-term results as conventional curative resections. These data are encouraging, and tumour infiltration of neighbouring organs should not be taken to demonstrate inoperability.

[Multivisceral resection of advanced stomach cancer]. / Die multiviszerale Resektion des fortgeschrittenen Magenkarzinoms.

From 1985 to 1990, 589 patients with gastric cancer were operated upon. Gastric resection was performed on 416 patients (71%); it was curative in 330 cases and palliative in 86 cases. Multivisceral resection was necessary in 61 patients (i.e. 15% of the resected patients) because of distant metastases or T4 tumors (curative: 43 cases--palliative: 18 cases). Compared to the group of curative resections without multivisceral extension, the complication rate (27% vs 26%) and 30-day lethality (5.2% vs 3.3%) were similar, whereas the 5-year survival rate was lower (22% vs 48%). However, the survival rate (21%) was nearly identical for T3 tumors in the group without multivisceral extension. These results show that curative gastric resections of T4 tumors lead to the same long-term results as resections of T3 tumors and the complication rate and lethality are equal.

[Indication for chemoembolization of liver tumors. An interdisciplinary concept and initial results]. / Indikation zur Chemoembolisation maligner Lebertumoren. Ein interdisziplinäres Konzept und erste Ergebnisse.

We present a new concept after Schultheis which is based on the results of experimental studies on cell cultures. Local chemoembolization in liver tumours including liver metastases is usually performed via the angiographic route. Embolisation of the most peripheral branches of the hepatic artery prevents early formation of collateral vessels. The method also comprises the additional infusion of cytostatic agents via the portal vein. The procedure is usually repeated after an interval of about four weeks. In this paper we will describe our method in liver metastases and present the preliminary results obtained from 19 patients treated to date.

[Chemoembolization of colorectal liver metastases]. / Chemoembolisation kolorektaler Lebermetastasen.

In the Center of Surgery of the Justus-Liebig-University Giessen and in the General Hospital in Nuremberg from 1983 to 1987 21 patients with metastases of a colorectal carcinoma were treated with chemoembolization (CHE). The on average survival period of patients treated with chemoembolization after non-successful application of regional chemotherapy amounted to 6 months. The total survival period of these patients amounted to 17.4 months. Since March 1987 chemoembolization has been applied as initial therapy. The on average survival period of the patients, initially treated with cheomoembolization at present amounts to 14 months. 4 of these patients additionally got chemotherapy by the portal vein after CHE. The survival period of 2 patients, having been resected several times after CHE, at present comes to 27 months. These results are the base for a clinical study, in which CHE is combined with the portal venous infusion of a cytostatic agent (Folin acid 5-FU).

[Laser therapy of colorectal tumors]. / Lasertherapie bei kolorektalen Tumoren.

Between Jan. 1, 1986 and March 31, 1988 a total of 128 patients with tumours of the colon and rectum were treated by Nd-Yag laser at Nürnberg City Hospital. There were 36 benign and 92 malignant lesions. The indications for laser therapy were stenosis, bleeding, spasms of the pelvic floor and increased mucous production. Initial control of these problems could be achieved in 105 patients (82%), however, the symptoms recurred in 50% of the malignant and 47% of the benign tumours. Complications of laser treatment were encountered in 13 patients necessitating an operative intervention in 6. In all, 34 patients underwent additional surgery after laser treatment. Most frequently, a diverting colostomy had to be provided (n = 18) while 12 patients underwent anterior resection; in three an abdomino-perineal resection was performed and in one patient a Hartman procedure was necessary. The median observation time of patients with benign tumours is, at present, 16 months with 72% being free of disease. In malignant tumours the median survival time of patients with laser therapy only is 4.5 months; those with additional surgical treatment survived a median of 17.5 months.

[Differential surgical treatment of ileus of the large intestine]. / Chirurgische Differentialtherapie des Dickdarmileus.

This is a report about 191 patients with colonic obstruction who were operatively treated between 1984 and 1988. A resection of the tumour was carried out in 106 cases while the other patients underwent palliative surgical treatment for various reasons. - A traditional surgical concept proved to be most satisfactory despite the modern forms of treatment such as primary subtotal colectomy, intraoperative lavage of the colon with resection and primary anastomosis, the internal bypass or preoperative laser dilatation. According to this concept tumours of the right half of the colon are primarily resected in the form of a right hemicolectomy; tumours of the left flexure undergo a two stage and those distal to the left flexure a three stage procedure. These principles were consistently applied in our patients and this resulted in an operative mortality of 0% after excluding patients who had a primary septic condition. In contrast, the operative mortality in the patients who were septic because of a colonic perforation (n = 23) was 47.8%. The worst prognosis could be found in cases with a perforation away from the tumour in the oral overdistended bowel such as coecum and ascending (n = 12). Here, the mortality was even 75% while true tumour perforations - which were usually sealed off - had a mortality of only 10% (n = 10). The main problem in the treatment of colonic obstruction, therefore, seems to be the patients who have a concomitant septic condition.