Cold atmospheric pressure plasma for treatment of chronic wounds: drug or medical device?

OBJECTIVE: The use of cold atmospheric pressure plasma (CAPP) as a new therapeutic option to aid the healing of chronic wounds appears promising. Currently, uncertainty exists regarding their classification as medical device or medical drug. Because the classification of CAPP has medical, legal, and economic consequences as well as implications for the level of preclinical and clinical testing, the correct classification is not an academic exercise, but an ethical need. METHOD: A multidisciplinary team of physicians, surgeons, pharmacists, physicists and lawyers has analysed the physical and technical characteristics as well as legal conditions of the biological action of CAPP. RESULTS: It was concluded that the mode of action of the locally generated CAPP, with its main active components being different radicals, is pharmacological and not physical in nature. CONCLUSION: Depending on the intended use, CAPP should be classified as a drug, which is generated by use of a medical device directly at the point of therapeutic application.

Single-Layer Continuous Versus Double-Layer Continuous Suture in Colonic Anastomoses-a Randomized Multicentre Trial (ANATECH Trial).

PURPOSE: Apart from stapling methods, single- or double-layer continuous hand sutures are established techniques for colonic anastomoses. It is unclear which hand suture technique has superior anastomotic safety. This randomized trial evaluated the incidence of postoperative complications depending on anastomosis technique. METHODS: This multicentre randomized trial enrolled adult elective patients between February 2004 and June 2012 in four German university hospitals. Primary endpoint was incidence of clinical anastomotic leakage until 3 months postoperatively. Estimated sample size was 768 randomized patients. Main secondary endpoints were duration of anastomotic suture, postoperative morbidity and stool patterns at 3-month follow-up. Patients and postoperative outcome assessors were blinded to the group assignment. This trial is registered (NCT00996554). RESULTS: Due to slow recruitment, the trial was stopped prematurely. Two hundred fifty-two patients (129 to single-layer suture anastomosis (SLA), 123 to double-layer suture anastomosis (DLA)) were randomized and analysed. Nine patients (3.6 %) were lost during follow-up. Exploratory primary endpoint analysis by intention-to-treat principle showed no significant difference for clinical anastomotic leakage between suturing techniques (SLA, 4 of 129 (3.1 %) vs. DLA, 6 of 123 (4.9 %), p = 0.532). Secondary endpoint analysis showed on average a 6-min shorter suture duration for SLA than DLA (18 min (4-49) vs. 24 min (8-50), p < 0.001). At 3-month follow-up, subjective well-being and stool patterns were not significantly different between groups. CONCLUSIONS: The present study did not reach sufficient power and cannot confirm whether both techniques might be equally or if one technique might be superior. Exploratory analysis suggests that in elective colonic resections, the single-layer continuous hand suture technique may be equally effective as the double-layer technique regarding incidence of anastomotic leakage, length of hospital stay, overall postoperative complications, subjective short-term well-being and stool patterns. Lessons learned from this trial course are summarized. TRIAL REGISTRATION: This trial is registered (Trial registration: NCT00996554). Link: https://clinicaltrials.gov/ct2/show/NCT00996554 .

[Use of Reusable Textile Undergloves for Medical Procedures: A Feasibility Study]. / Einsatz wiederaufbereitbarer textiler Unterziehhandschuhe für medizinische Tätigkeiten: eine Machbarkeitsstudie.

OBJECTIVE: Undergloves are a way to reduce moisture-related skin damage. The aim of this feasibility study was to gain experience with logistics, applicability, acceptability and cost of the routine use of reusable textile undergloves in a hospital setting. METHODS: Undergloves were tested with 18 health-care workers on an intensive care unit over three months. Data on usage as well as logistics were recorded. At baseline, personal data and knowledge and use of cotton undergloves, existing skin problems and the nursing behaviour of the hands by the subjects were determined by means of an input questionnaire. After each wearing, data on usage were collected by a questionnaire. Participants were interviewed by means of a questionnaire with respect to their experience with the use of the undergloves. RESULTS: Acceptance and compliance with the use of undergloves was remarkably good. This was partly due to the properties of the gloves, and partly to the reduction of sweating and very positive effect on the skin of the hands. In the study period 2165 underglove uses were documented, resulting in an average daily consumption of four pairs per person per day. The average wearing time was 28.6 min. The undergloves were suitable for application as well as reprocessing. Reprocessment-related fatigue was relatively low and did not lead to the loss of the properties, only few gloves had to be sorted out. Even if one assumes a complete write-off of the gloves with end of the study, costs for reprocessing were about 0.46 € or 64 % less than the single use. CONCLUSION: The routine use of textile, reprocessable undergloves is feasible. Major challenges for broad usage are within logistics and acceptance by the user.

[Modern treatment of an appendiceal mass]. / Moderne Therapie perityphlitischer Abszesse.

BACKGROUND: The recommendations for the treatment of an appendiceal mass are still controversial. The need for staged appendectomy is still under discussion. PATIENTS AND METHODS: In a retrospective study all patients with the diagnosis appendiceal mass (ICD 10 K35.32) treated in the surgical clinic of the University Clinic in Greifswald between June 1999 and June 2011 were analyzed. RESULTS: A total of 38 patients were included in the study whereby 17 patients (9 male and 8 female) were treated with drainage and antibiotics (group A) and 21 (14 male and 7 female) were treated by immediate surgery (group B). Nonsurgical therapy with drainage of the abscess was found to be efficient. Immediate surgical treatment was also effective and should be performed when signs of peritonitis exist. Interval appendectomy is not indicated.

Induction of M2-macrophages by tumour cells and tumour growth promotion by M2-macrophages: a quid pro quo in pancreatic cancer.

INTRODUCTION: More effective therapies are required to improve survival of pancreatic cancer. Possible immunologic targets include tumour associated macrophages (TAMs), generally consisting of M1- and M2-macrophages. We have analysed the impact of TAMS on pancreatic cancer in a syngeneic orthotopic murine model. METHODS: 6606PDA murine pancreatic cancer cells were orthotopically injected into C57BL6 mice. Tumour growth was monitored using MRI. Macrophages were depleted by clodronate liposomes. Tumours including microvessel density were evaluated using immunohistochemistry, immunofluorescence and/or cytometric beads assays. Naïve macrophages were generated employing peritoneal macrophages. In vitro experiments included culturing of macrophages in tumour supernatants as well as tumour cells cultured in macrophage supernatants using arginase as well as Griess assays. RESULTS: Clodronate treatment depleted macrophages by 80% in livers (p = 0.0051) and by 60% in pancreatic tumours (p = 0.0169). MRI revealed tumour growth inhibition from 221.8 mm(3) to 92.3 mm(3) (p = 0.0216). Micro vessel densities were decreased by 44% (p = 0.0315). Yet, MCP-1-, IL-4- and IL-10-levels within pancreatic tumours were unchanged. 6606PDA culture supernatants led to a shift from naïve macrophages towards an M2-phenotype after a 36 h treatment (p < 0.0001), reducing M1-macrophages at the same time (p < 0.037). In vivo, M2-macrophages represented 85% of all TAMs (p < 0.0001). Finally, culture supernatants of M2-macrophages induced tumour growth in vitro by 63.2% (p = 0.0034). CONCLUSIONS: This quid pro quo of tumour cells and M2-macrophages could serve as a new target for future immunotherapies that interrupt tumour promoting activities of TAMs and change the iNOS-arginase balance towards their tumoricidal capacities.

Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer.

PURPOSE: Tumour-associated macrophages have been shown to promote proliferation, angiogenesis and metastasis in several carcinomas. The effect on colon cancer has not yet been clarified. Furthermore, Kupffer cells in the liver might initiate the formation of metastases by directly binding tumour cells. METHODS: An orthotopic syngeneic mouse model of colon cancer as well as a liver metastases model has been studied, using murine CT-26 colon cancer cells in Balb/c-mice. Macrophages were depleted in both models by clodronate liposomes. Tumour sizes and metastases were determined using 7-Tesla MRI. The macrophage and vascular density in the orthotopic tumours as well as the Kupffer cell density in the livers were evaluated using immunohistochemistry. RESULTS: Animals in the macrophage-depleted group displayed significantly smaller primary tumours (37 ± 20 mm(3)) compared to the control group (683 ± 389 mm(3), p = 0.0072). None of the mice in the depleted group showed liver or peritoneal metastases, whereas four of six control mice displayed liver and five out of six mice peritoneal metastases. The vascular density was significantly lower in the macrophage-depleted group (p = 0.0043). In the liver metastases model, animals of the Kupffer cell-depleted group (14.3 ± 7.7) showed significantly less liver metastases than mice of the two control groups (PBS liposomes, 118.5 ± 28.2, p = 0.0117; NaCl, 81.7 ± 23.2, p = 0.0266). The number of liver metastases correlated directly with the Kupffer cell density (p = 0.0221). CONCLUSION: Macrophages promote tumour growth, angiogenesis and metastases in this orthotopic syngeneic mouse model. Kupffer cells enhance the formation of metastases in the liver.

[Disease-adapted closure of the appendicular stump in laparoscopic appendectomy]. / Stadiengerechte Versorgung der Appendixbasis im Rahmen der laparoskopischen Appendektomie.

The frequency of laparoscopic appendectomy has dramatically increased with it now being the standard procedure for acute appendicitis in many hospitals in Germany. Hence, these hospitals require the personnel, the technique as well as the expertise to guarantee a top standard and quality of appendectomies at all times. Only this will meet the requirements of the high case load and the socio-economical importance of appendectomies. The closure of the appendicular stump is a critical step of this procedure. The three most commonly used techniques consist of the endo-loop, the clip and the endo-stapler. The endo-stapler has the advantage of offering closure and transection of the appendix in one step; it can be employed in all cases of appendicular inflammation; and it allows a partial caecal resection. However, it is quite expensive. The clip and the endo-loop offer the same cost-effectiveness, yet the clip appears to be simpler in use compared to the loop. Also, sharing this feature with the stapler, it offers the possibility of closing and transecting the appendix before dissecting the mesoappendix. A disadvantage of the clip not being shared with the loop is the limitation of clips to appendicular diameters of only up to 16 mm. In summary, we propose a cost-effective disease-adapted closure of the appendicular stump employing the clip in standard appendectomies, with the endo-loop being a good alternative. If clip or loop cannot be applied the stapler is the technique of choice. In particular, it should be used if the base of the appendix is inflamed. Adopting this pathway helps to control the still somewhat higher costs of laparoscopic appendectomies compared to classical open appendectomies.

[Single-port access cholecystectomy is a safe alternative to conventional laparoscopic cholecystectomy: a retrospective comparison of single-port access versus standard laparoscopic cholecystectomy]. / Single-Port-Access-Cholezystektomie als sichere Alternative zum 4-Port-Vorgehen: Ein retrospektiver Vergleich.

PURPOSE: As laparoscopic surgery develops, one current goal is the reduction of scarring and operative trauma to a minimum. Single-port access surgery (SPA) uses a single small incision hidden in the umbilicus. This report describes our experiences with 69 SPA cholecystectomies compared to the conventional laparoscopic approach. METHODS: Within two years 69 SPA cholecystectomies were performed. Data including demographic distribution, incision to closure time, duration of the postoperative hospital stay, rates of intraoperative and postoperative complications, and conversion rates were collected retrospectively. Data for a matched control group treated by standard laparoscopic cholecystectomy were gathered within the same time frame and then compared. RESULTS: There were no significant differences in the rates of intraoperative or postoperative complications in the SPA group when compared to the standard laparoscopy group. The incision-to-closure time strongly depended on the surgeon but did not depend on the method. The duration of postoperative hospital stay was slightly decreased in the SPA group. However, this effect was statistically not significant. CONCLUSIONS: For selected patient groups, SPA cholecystectomy is on par with the conventional laparoscopic method. The cosmetic advantage that it offers does not come at the cost of any loss of safety.

[Intraductal papillary mucinous neoplasia: which findings support observation?]. / Intraduktal papillär muzinöse Neoplasie: Welche Befunde sprechen für Beobachtung?

On abdominal CT scans asymptomatic cystic lesions of the pancreas are accidentally detected in 1-2% of patients. Congenital cysts and pancreatic pseudocysts account for two thirds of these lesions. Pancreatic pseudocysts are a frequent complication of acute and chronic pancreatitis. Among resected cystic neoplasms serous cystic adenoma accounts for 30%, mucinous cystic neoplasms for 45% and intraductal papillary mucinous neoplasms for 25%. The diagnosis of a cystic pancreatic lesion is usually made by diagnostic imaging. Symptomatic lesions require definitive therapeutic treatment after appropriate diagnostic work-up. In the diagnosis of asymptomatic cystic lesions several factors are important, among them whether the cyst is connected to the pancreatic duct (as in IPMN and pseudocysts), the size of lesion (for treatment indications) and whether nodules form in the wall of the cyst (a sign of potential malignancy). EUS-guided fine needle aspiration of the cyst fluid adds to the discrimination between benign, premalignant and malignant cystic lesions. Measuring lipase activity, CEA, viscosity and mucin as well as cytology can help in differentiating cystic lesions. An algorithm is discussed for the differential diagnosis and for selection of the appropriate treatment for pancreatic cystic lesions, most of which never require surgery.

A syngeneic orthotopic murine model of pancreatic adenocarcinoma in the C57/BL6 mouse using the Panc02 and 6606PDA cell lines.

BACKGROUND/AIMS: To develop a clinically relevant immunocompetent murine model to study pancreatic cancer using two different syngeneic pancreatic cancer cell lines and to assess MRI for its applicability in this model. METHODS: Two cell lines, 6606PDA and Panc02, were employed for the experiments. Cell proliferation and migration were monitored in vitro. Matrigel™ was tested for its role in tumor induction. Tumor cell growth was assessed after orthotopic injection of tumor cells into the pancreatic head of C57/BL6 mice by MRI and histology. RESULTS: Proliferation and migration of Panc02 were significantly faster than those of 6606PDA. Matrigel did not affect tumor growth/migration but prevented tumor cell spread after injection thus avoiding undesired peritoneal tumor growth. MRI could reliably monitor longitudinal tumor growth in both cell lines: Panc02 had a more irregular finger-like growth, and 6606PDA grew more spherically. Both tumors showed local invasiveness. Histologically, Panc02 showed a sarcoma-like undifferentiated growth pattern, whereas 6606PDA displayed a moderately differentiated glandular tumor growth. Panc02 mice had a significantly shorter (28 days) survival than 6606PDA mice (50 days). CONCLUSION: This model closely mimics human pancreatic cancer. MRI was invaluable for longitudinal monitoring of tumor growth thus reducing the number of mice required. Employing two different cell lines, this model can be used for various treatment and imaging studies.

Determination of antiseptic efficacy of rubs on the forearm and consequences for surgical hand disinfection.

While hands are acknowledged to be the most important source of pathogens from the skin of the surgical team, the transmission of pathogens from the forearms may also be relevant. Preoperative hand disinfection is recommended, but evidence-based standards for the forearms are lacking. As neither the European standard EN 12791 nor the American guidelines ASTM 1115 are applicable to the forearms, a new test method based on the European standard EN 12791 and the German Society for Hygiene and Microbiology (DGHM) method for testing for the efficacy of skin antiseptics was developed to address the forearms. The antiseptic efficacy of a commercially available alcohol-based hand rub [76.7% (w/w) ethanol] was assessed on the upper arm after 15s, 2.5 min, and 30 min, and on the lower arm after 2.5 min, 30 min, and 3 h. On the upper arm, application of the product followed the DGHM standard procedure. On the forearm, the product was applied by the participants themselves with the right hand over the left forearm and vice versa as performed during preoperative hand disinfection. Sampling and culture were performed according to the DGHM method for skin antisepsis on the upper arm. Twenty-two volunteers were investigated. The efficacy of the antiseptic treatment on the forearm was not significantly lower than on the upper arm for any of the areas tested (P > 0.05). Reduction factors for all tested areas and times were quite similar, with confidence intervals ranging between 1.43 and 2.31 log10. We suggest that an application time of 10s may be sufficient for the treatment of the forearm as part of preoperative hand disinfection, provided that an appropriate product is used.

[Atypical vascular supply from the coeliac trunk. Recurrent bleeding from a duodenal ulcer]. / Atypische Gefässversorgung aus dem Truncus coeliacus. Rezidivblutung aus einem Ulcus duodeni.

Hemorrhagic duodenal ulcers should primarily be controlled by endoscopy. In cases of recurrent bleeding or if bleeding cannot be controlled endoscopically, open surgery is the gold standard. Rarely, atypical origin of arteries or additional atypical arteries may lead to further unexpected hemorrhagic recurrences and angiography with surgical intervention is the treatment of choice. In this article a rare case of an atypical visceral artery connecting the coeliac trunk and the gastroduodenal artery leading to recurrent bleeding from a duodenal ulcer is presented.

Acute upper gastrointestinal hemorrhage: is a radiological interventional approach an alternative to emergency surgery?

The aim of our study was to discuss the option of endovascular treatment compared to surgery for patients with endoscopically unmanageable nonvariceal hemorrhage of the upper gastrointestinal tract. From 2000 to 2006, 23 patients (male, 15 male; female, 8; mean age, 69 years) who failed endoscopic therapy for upper gastrointestinal hemorrhage were retrospectively evaluated. Twelve patients were operated on (SG), whereas 11 patients had an endovascular intervention (IG). Technical and primary clinical success rates and complications rates were calculated. Clinical parameters and comorbidities were related to outcome. The surgical group suffered less frequently from pre-existing pulmonary diseases (SG, 17%; IG, 55%; p = 0.05) and had a higher incidence of shock requiring catecholamines (p < 0.01) or plasma expander therapy (p < 0.01). There was no significant difference in the incidence of recurrent bleeding episodes (SG, 17%; IG, 27%; p = 0.35) and mortality rates (SG, 17%; IG, 27%, p = 0.35). Deaths in the IG were due to recurrent bleeding. In patients with unsuccessful endoscopic control of nonvariceal bleeding of the upper GI tract, surgery remains a very effective treatment. However, in patients with a high surgical risk due to unknown bleeding sources and/or severe pre-existing diseases/comorbidities, endovascular therapy offers an excellent treatment option. These patients should then be operated on as early as possible to minimize the risk of recurrent bleeding episodes, which are associated with high morbidity and mortality.