Search

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cmDie Arbeitsgemeinschaft „Klinische Geweberegeneration“ hat bereits in den Jahren 2004, 2013 und 2016 Empfehlungen in Bezug auf die Indikation für verschiedene knorpelregenerative Verfahren zur Behandlung von Knorpelschäden am Kniegelenk publiziert. Auf Basis neuer wissenschaftlicher Erkenntnisse sollen in der vorliegenden Arbeit diese Empfehlungen auch unter Einbeziehung neuer Behandlungsverfahren aktualisiert werden. Die Einschätzung folgt damit dem Prinzip der besten verfügbaren Evidenz und berücksichtigt über prospektiv randomisierte Studien hinaus auch Studien mit niedrigerem Evidenzniveau. An Stellen fehlender publizierter Evidenz basiert die Entscheidung hier auf einem Konsensusprozess innerhalb der Mitglieder der AG Klinische Geweberegeneration.Das Prinzip der bereits vorausgehend publizierten Arbeiten bleibt auch in den neuen Empfehlungen erhalten. Kleine Knorpelschäden sind nach Ansicht der Arbeitsgruppe für eine Knochenmarkstimulation zugänglich, die matrixassoziierte autologe Chondrozytentransplantation (mACT) ist für größere Knorpelschäden die Methode der Wahl. Auf Basis neuerer Daten wird jedoch die Indikationsgrenze für die mACT auf 2,0 cm

Surgical principles for treatment of full-thickness cartilage defects of the knee include bone marrow stimulation techniques (i.e. arthroscopic microfracturing) and transplantation techniques (i.e. autologous chondrocyte implantation and osteochondral transplantation). On the basis of increasing scientific evidence, indications for these established therapeutical concepts have been specified and clear recommendations for practical use have been given. Within recent years, matrix-augmented bone marrow stimulation has been established as a new treatment concept for chondral lesions. To date, scientific evidence is limited and specific indications are still unclear. The present paper gives an overview of available products as well as preclinical and clinical scientific evidence. On the basis of the present evidence and an expert consensus from the "Working Group on Tissue Regeneration" of the German Orthopaedic and Trauma Society (DGOU), indications are specified and recommendations for the use of matrix-augmented bone marrow stimulation are given. In principle, it can be stated that the various products offered in this field differ considerably in terms of the number and quality of related studies (evidence level). Against the background of the current data situation, their application is currently seen in the border area between cell transplantation and bone marrow stimulation techniques, but also as an improvement on traditional bone marrow stimulation within the indication range of microfracturing. The recommendations of the Working Group have preliminary character and require re-evaluation after improvement of the study situation.Für die operative Sanierung lokalisiert vollschichtiger Knorpelschäden der großen Gelenke stehen mit den Transplantationstechniken (autologe Knorpelzelltransplantation, autologe osteochondrale Transplantation) und knochenmarkstimulierenden Techniken unterschiedliche Therapieoptionen zur Verfügung. Vor allem für das Kniegelenk konnte aufgrund der verbesserten Studienlage das jeweils geeignete Anwendungsspektrum dieser Verfahren in letzter Zeit weiter präzisiert werden. Für die matrixaugmentierte Mikrofrakturierung als einzeitige Methode besteht jedoch noch keine genauere Indikationsabgrenzung, insbesondere auch nicht gegenüber den bereits etablierten Verfahren. In der vorliegenden Arbeit werden die derzeit für diese Methode zur Verfügung stehenden Biomaterialien und Anwendungsvarianten beschrieben und ihre präklinische und klinische Evidenz zusammengefasst. Grundsätzlich kann dabei festgestellt werden, dass sich die verschiedenen in diesem Bereich angebotenen Produkte hinsichtlich der Zahl und Qualität zugehöriger Studien (Evidenzlevel) noch erheblich voneinander unterscheiden. Um die matrixaugmentierte Mikrofrakturierung im Sinne einer ersten Indikationsempfehlung als Methode in den therapeutischen Algorithmus der knorpelrekonstruktiven Verfahren im Knie einzuordnen, wurde durch die Mitglieder der Arbeitsgemeinschaft (AG) Klinische Geweberegeneration der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) im Rahmen eines Konsensusprozesses eine Bewertung der verfügbaren Evidenz vorgenommen. Vor dem Hintergrund der aktuellen Datenlage wird ihre Anwendung derzeit im Grenzbereich zwischen Zelltransplantations- und knochenmarkstimulierenden Techniken sowie als Verbesserung der klassischen Mikrofrakturierung und überwiegend im Indikationsbereich der Mikrofrakturierung gesehen. Die Empfehlungen der AG haben vorläufigen und orientierenden Charakter und bedürfen einer erneuten Überprüfung nach Verbesserung der Studienlage.

Background: Systemic complications including pancreatitis-associated lung injury (PALI) are critical factors that determine the outcome of severe necrotizing pancreatitis (SNP). The aim of the present study was to evaluate the role of chronic alcohol exposure on the development of PALI. Methods: 48 rats were fed either a Lieber deCarli control or alcohol diet for 6 weeks. After completion, SNP was induced by intraductal infusion of bile salt followed by intravenous infusion of cerulein over 6 h. Control animals received i.v. Ringer’s solution. Intravital microscopy of the liver was performed 6 h after induction of SNP to evaluate hepatic perfusion and leukocyte adhesion. Serum parameters, edema, inflammation, and histological changes were evaluated at 12 h. IL-6 levels were evaluated in portal venous and systemic blood as well as in pancreatic tissue homogenates. Results: Alcohol pretreatment did not affect pancreatic injury in SNP. PALI was aggravated after alcohol ingestion. These animals showed increased hepatic microcirculatory disturbances, compared to SNP alone. IL-6 showed peak levels in SNP with alcohol pretreatment, although they were also elevated in SNP alone. Systemic levels of IL-6 were higher than in the portal vein. Conclusion: In SNP, alcoholic pretreatment increases pulmonary damage, while pancreatic injury is identical. The liver seems to participate in this effect by increased hepatic cytokine release.

Background Despite improvement in the management of severe necrotizting pancreatitis, mortality remains high. Today, no specific treatment exists. Inflammatory cascades and microcirculatory disturbances play a key role in the pathogenesis of acute pancreatitis. The aim of the present study was to evaluate the effects of inosine, an immunomodulatory substance, on the severity of experimental necrotizing pancreatitis. Methods Severe necrotizing pancreatitis was induced in rats. Treatment groups received inosine either prophylactically or therapeutically. Pancreatic injury was evaluated by microcirculatory assessment and histology. Results Prophylactic inosine significantly attenuated pancreatic microcirculatory disturbances and morphologic injury in necrotizing pancreatitis. However, inosine treatment did not have any beneficial effects when applied therapeutically several hours after onset of the disease. Conclusions Prophylactic inosine reduces microcirculatory and pancreatic injury in acute necrotizing pancreatitis. These effects should be assessed in the clinical setting of ERCP and pancreas transplantation.

Accurate staging is essential to plan therapeutic strategies and appropriate surgical treatment in patients with advanced gastrointestinal malignancies. Tremendous efforts have been undertaken to develop more sensitive techniques for the detection of premalignant, early-stage lesions and micrometastases. Despite the improvements in preoperative radiologic imaging, precise assessment of the local, regional, or distant extent of the primary tumor can be a major problem. Even with computed tomography, magnetic resonance tomography, or ultrasound, minimal tumor spread remains undetected. 1 Laparoscopy has emerged as a highly sensitive and specific method of comprehensive abdominal exploration, 2–4 but even with this staging tool an unknown amount of lesions still remain occult. Fluorescence diagnosis, also known as photodynamic diagnosis, is being increasingly used to distinguish healthy from diseased tissue in various medical disciplines. Especially in urology, fluorescence diagnosis has been used to visualize even small, plane tumors of the bladder. The principle of fluorescence diagnosis is based on the accumulation of administered agents, called photosensitizers, in malignant cells. After intravenous, oral, or topical application, the agent concentrates in tumors and remains inactive until exposed to light of a specific wavelength. When light is delivered to the cancer site, either directly or indirectly through a fiberoptic device, it causes fluorescence of the photosensitizers. Whereas earlier generations of photosensitizers, such as Photofrin, were fluorescent at the time of application (exogenous photosensitizers), the photosensitizer aminolevulinic acid (ALA) requires endogenous metabolism before it becomes fluorescent (endogenous photosensitizer). ALA is the natural precursor of the heme pathway. Administration of ALA, either systemically or locally, overloads the last step in the heme biosynthesis pathway of tumor cells because of missing negative feedback mechanisms and reduced enzymatic activities. This results in increased accumulation of ALA’s metabolite protoporphyrin IX. Protoporphyrin IX is a fluorescent agent when stimulated by a defined wavelength within its absorption spectrum. One main emission wavelength is within the visible light spectrum at 635 nm (red light) 5 (Fig. 1). The positive, red fluorescence of protoporphyrin IX is even detectable in macroscopically invisible tumor foci and can indicate lesions that would have been missed under conventional white-light illumination. Detection of fluorescence may be achieved by two distinct technical principles. In an imaging system, a two-dimensional picture of the fluorescence intensity distribution of the examined tissue is captured with a charge-coupled device (CCD) camera and displayed on a monitor. In a point system, the fluorescence signal is measured in a restricted area and spectrometrically evaluated with an optical multichannel analyzer. Figure 1. Typical protoporphyrin IX fluorescence emission spectra of tumor tissue (CC531 colon carcinoma) and surrounding healthy tissue (peritoneal muscle) with its typical peak at 635 nm and a lower secondary emission peak in the far red around 700 ... Fluorescence diagnosis for surgical staging laparoscopy was adopted to achieve better assessment of disseminated intraabdominal tumor spread. 6 This allowed early detection of dysplastic and malignant peritoneal changes caused by metastatic growth of gastrointestinal tumors. The feasibility of this modality in the detection of lesions occult to conventional white-light laparoscopy has been evaluated and confirmed as practicable in an experimental setting. The use of fluorescence laparoscopy increased the visualization of tumors by 17.5% compared with white-light laparoscopy. 6 In the pilot study, photosensitization parameters, such as an ALA concentration of 3.0% and a photosensitization time of 4 hours, were chosen according to data gained in urology. The following experimental study evaluated the variation of these two parameters to achieve optimal diagnostic results in the detection of peritoneal tumors. Both fluorescence detection techniques, the imaging and point system, were applied. Serum samples were investigated for ALA and protoporphyrin IX.

Administration of delta-aminolevulinic acid (ALA) either systemically or locally results in tumor-specific accumulation of protoporphyrin IX (PpIX). When excited with light at a defined wavelength and viewed with the appropriate filter cells containing PpIX, have a characteristic red fluorescence. We evaluated both locally (intraperitoneally [i.p.]) and systemically (intravenously [i.v.]) administered ALA to compare its effectiveness for laparoscopic fluorescent visualization of intraperitoneal tumors.Peritoneal carcinosis was induced in rats using colon carcinoma cells (CC531). Photosensitization was achieved either by intravenous (i.v. group) or intraperitoneal (i.p. group) application of ALA solution. Staging laparoscopy was performed in both groups, first using conventional white light and subsequently using blue light (380-440 nm) to excite PpIX-induced fluorescence.Conventional white light laparoscopy showed 142 visible intraperitoneal tumor foci in the i.p. group and 116 such foci in the i.v. group. In the i.p. group, all tumors (100%) also were fluorescence positive, whereas in the i.v. group only 32 of the tumors (28%) showed the typical red fluorescence. In the i.p. group, 30 additional tumors were detected by fluorescence excitation (21%), as compared with eight additional tumors in the i.v. group (7%).Fluorescence laparoscopy after local (i.p.) photosensitization with ALA is a more reliable and effective method than systemic (i.v.) photosensitization for the detection of small or occult i.p. tumors.

Conventional staging laparoscopy in combination with fluorescence diagnosis has proven to be an effective modality in the detection of macroscopically occult intraperitoneal tumours and metastases. Rats with induced peritoneal carcinosis are photosensibilized by intraperitoneal aminolaevulinic acid (ALA) lavage. After visualization of the tumour foci, the emission from the lesions is measured spectrometrically and the fluorescence analysed quantitatively ('optical biopsy'). There is a considerable accordance between imaging by fluorescence diagnosis laparoscopy and point spectrometry in the detection of peritoneal malignancies. Compared with surrounding healthy peritoneum, tumour-positive areas show significantly higher fluorescence intensities in spectrometry.

Background: Lymph node metastases and peritoneal carcinosis, occurring as a result of gastrointestinal cancer, reduce the likelihood that conventional therapy will be adequate to remove the cancer. Although diagnostic techniques have greatly improved, it is not always possible to diagnose the entire extent of the metastases. Often, peritoneal micrometastases are not visible and may be missed during laparoscopic or open surgery. Methods: Peritoneal carcinosis was induced in WAG-Rij rats (n = 6), by laparoscopically implanting 1,2-dimethylhydrazine–induced colon carcinoma tumor cells (CC531, 5 × 10 5 ) at multiple sites within the peritoneal cavity. After 12 days of tumor growth, the animals were given δ-aminolevulinic acid (ALA) (5 mL, 3% solution in 0.17 mol/L NaHCO 3 ) by peritoneal lavage. The tumors were visualized laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany). Fluorescence was detected by using a modified CCD camera and a special observation filter incorporated into the laparoscope. Results: Peritoneal carcinoma foci ranging in size from 0.05 to 2.0 cm were clearly visible laparoscopically with conventional white light (n = 142). After blue light excitation, all 142 tumors identified with white light were also identified by fluorescence. There were an additional 30 tumors that could only be identified by blue light–induced fluorescence and were histologically confirmed to be derived from colon carcinoma tumor cells. Conclusions: Peritoneal colonic carcinoma foci were detected laparoscopically after intraperitoneal lavage with δ-aminolevulinic acid (ALA) and excitation with blue light. These experiments demonstrate that fluorescence laparoscopy is an important technique for the staging of gastrointestinal cancer, including colorectal cancer, because of the enhanced ability to detect small cancerous foci. (Surgery 1999;126:469-73)

Background: In severe necrotizing pancreatitis (SNP) systemic complications as pancreat it is associated lung injury (PALI) are crucial for morbidity and mortality. In the presented study we evaluated the role of chronic alcohol ingestion on the development of PALI. Methods: Wistar rats were fed for 6 weeks with either alcohol or control diet. This was followed by induction of SNP by intraductal bile salt followed by intravenous caerulein infusion for 6 hours. Control animals received Ringer’s solution. Hepatic microcirculation was assessed after 6 hours. Analyses of tissue and serum samples were performed after 12 hours in additional animals of each group. Results: SNP-related pancreatic tissue damage was not affected by preceeding alcohol exposure. In contrast, SNP was associated with increased pulmonary MPO-levels in alcohol fed animals indicating an increased pulmonary inflammatory damage. Furthermore, alcohol pretreatment revealed increased hepatic microcirculatory disturbances with an impairment of microperfusion and increased sticking leukocytes to control animals with SNP. Serum IL-6 levels were increased after both, alcohol pretreatment and induction of SNP. Highest levels were observed in alcohol fed SNP animals. Portal venous IL-6 levels were higher compared to systemic venous levels. Conclusion: Chronic alcohol exposure increases pulmonary inflammatory damage in experimental SNP. This may be explained by alcohol-related liver damage with a consecutive hepatic IL-6 release and does not seem to reflect a local pancreatic phenomenon.

Contains fulltext : 50765.pdf (Publisher’s version ) (Closed access) Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Accurate staging can be a major problem in therapeutic planning of advanced abdominal malignancies. We experimentally combined conventional staging laparoscopy with aminolevulinic acid (ALA) induced fluorescence diagnosis (FD) to improve the detection of disseminated peritoneal tumors. Using different photosensitization times and ALA concentrations we evaluated the optimal fluorescence parameters for laparoscopic fluorescence diagnosis of intra abdominal tumor spread. In a rat tumor model we performed conventional and fluorescence laparoscopy to determine the increase of sensitivity gained by FD in terms of additionally detected lesions. After laparoscopic examination, the fluorescence emission from the tumors was spectrometically analyzed. Serum levels of ALA and PpIX were measured by HPLC to determine their systemic metabolism. Fluorescence staging laparoscopy was able to visualize even macroscopically occult neoplasms. Using 1.5 percent ALA solution and a photosensitization time of 4 hours as favorable parameters the diagnostic value of conventional staging laparoscopy was significantly improved: 35 percent of all malignant lesions were detected only by FD. Therefore, fluorescence laparoscopy suggest to be a highly promising preoperative staging tool requiring minimal technical and clinical expenditure. It provides the laparoscopist with a rapid and accurate technique to assess more thoroughly the full extent of malignant tumor growth in the abdominal cavity.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Das Vorhandensein einer Peritonealkarzinose hat auf die adaquate Therapie gastrointestinaler Karzinome entscheidenen Einflus [1,2]. Die Diagnose ist jedoch an die makroskopische Erkennung mit anschliesender histologischer Verifizierung der Probeentnahme gebunden. Bei der Fluoreszenzdiagnostik konnen makroskopisch nicht sichtbare Tumore durch tumorspezifische Anreicherung sogenannter Fluoreszenzmarker (FM) and geeigneter Lichtanregung visualisiert werden [3, 4]. Bei der endogenen Photosensibilisierung des Tumors wird dazu das exogen zugefuhrte Substrat δ-Aminolavulinsaure (ALA) im Tumor vermehrt zu Protoporphyrin IX (PpIX) umgewandelt. PpIX selbst ist der letzte Schritt in der Hambiosynthese und kann mit Licht einer definierten Wellenlange zur Fluoreszenz angeregt werden. Die optimale Anregungswellenlange richtet sich nach dem jeweiligen Absorptionsspektrum des verwendeten FM. Die zu beobachtende Fluoreszenz bei PpIX liegt im sichtbaren roten and fur Porphyrine typischen Spektralbereich (635 nm) [4, 5]. Ziel dieser Untersuchung war es, die exakte Ausdehnung einer Peritoneallcarzinose laparoskopisch and fluoreszenzoptisch moglichst einfach zu visualisieren und zu verbessern, indem im Vergleich zur konventionellen Laparoskopie mehr intraabdominelle Tumore diagnostiziert werden konnen. Eine mogliche systemische Photosensibilisierung sollte abgeschatzt werden.