[Surgical Management of Peritoneal Surface Malignancy with Respect to Tumour Type, Tumour Stage and Individual Tumour Biology]. / Chirurgische Therapie der peritonealen Metastasierung in Abhängigkeit von Tumorentität, -stadium und -charakteristik(a).

Peritoneal tumour dissemination is still considered as a terminal disease. For the last two decades, cytoreductive surgery (CRS) combined with intraoperative hyperthermic chemotherapy (HIPEC) has been popularised by Paul Sugarbaker almost doubling survival in selected patients compared with systemic chemotherapy alone. Nowadays, this particular treatment protocol is available in comprehensive cancer centres with reasonable mortality and morbidity. However, patient selection is still challenging. In general, CRS and HIPEC is indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei as well as in peritoneal metastases derived from gastrointestinal malignancies and ovarian cancers. Since systemic tumour spread is uncommon in patients with peritoneal metastases, peritoneal tumour dissemination was defined as localised disease within the "compartment abdomen". However, CRS and HIPEC are only beneficial as long as complete cytoreduction is achieved (CC-0 or CC-1). Histopathological parameters, the Sugarbaker peritoneal carcinomatosis index (PCI) and general condition of the patient have been established as patient selection criteria. In primary peritoneal cancers, individual tumour biology is the predominant criterium for patient selection as opposed to intraabdominal tumour load in peritoneal metastases derived from gastrointestinal cancers. In gastric cancer, CRS and HIPEC should be restricted to synchronous limited disease because of its biological aggressiveness. In patients with free floating cancer cells without macroscopic signs of peritoneal spread, however, CRS and HIPEC following preoperative "neoadjuvant" chemotherapy preserves chances for cure. So far, there is no general recommendation for CRS and HIPEC by clinical practice guidelines. In the recent S3 guideline for treatment of colorectal cancer, however, CRS and HIPEC have been included as possible treatment options.

[Recurrent Peritoneal Metastases after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer]. / Rezidive nach zytoreduktiver Chirurgie und hyperthermer intraperitonealer Chemotherapie (HIPEC) beim kolorektalen Karzinom.

BACKGROUND: Peritoneal recurrences after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer are challenges in conservative and surgical oncology. METHODS: Surgical concepts are discussed in this review on the basis of the current literature. RESULTS: The majority of patients suffer from recurrent disease after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer. In most cases, a palliative chemotherapy is performed. Repeated surgery with the aim of complete cytoreduction may be done in selected cases. CONCLUSIONS: New concepts are necessary to treat patients with recurrent disease as early as possible.

Impact of perioperative immunosuppressive medication on surgical outcome in Crohn's Disease (CD).

INTRODUCTION: Patients with Crohn's disease [CD] carry an 80 - 90 % lifetime risk of undergoing surgery. Many of these patients are on immunosuppressive medication at the time of surgery. The aim of this study was to evaluate the effect of immunosuppression on the surgical outcome in CD patients. METHODS: We retrospectively analyzed 484 consecutive abdominal operations for CD from 1995 to 2008 for surgical complications. RESULTS: A total of 241 operations (= 49.8 %) were performed under perioperative immunosuppression (corticoids and thiopurine). The overall complication rate was 18.6 %, the major complication rate was 8.7 % and the anastomotic leakage rate was 3.3 %. No differences were observed between patients without immunosuppression compared to those with immunosuppression. Patients with colo-rectal resections showed a higher complication rate than patients with small bowel resection independently of immunosuppression. CONCLUSION: Nearly 50 % of the patients undergoing abdominal surgery for CD are receiving immunosuppressive medication during surgery. However, perioperative immunosuppression with corticoids, thiopurine or the combination of both does not significantly alter the surgical complication rate. Therefore the decision of a required surgery should not be delayed due to the fact that the patient is under immunosuppressive medication.

Gene expression analysis in chronic postradiation proctopathy.

PURPOSE: Radiotherapy is one of the important treatment modalities for tumors of pelvic organs. The fixed location of the rectum and its anatomic relationship with other pelvic organs makes it prone to radiation injury resulting in chronic radiation proctopathy in 5% to 20% of patients. Endothelial dysfunction has been associated with a number of pathophysiological processes. Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability. METHODS: Rectum tissue samples from 20 patients with established chronic radiation proctopathy were analysed for the expression of genes related to oxidative stress, tissue hypoxia, angiogenesis, and inflammation [endoglin (ENG), activin receptor-like kinase 1 (ALK1), platelet endothelial cell adhesion molecule 1 (PECAM), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), hypoxia-inducible factor 1 (HIF-1), and interleukin-1 beta (IL-1ß)]. RESULTS: Overexpression of HIF-1, VEGF, FGF2, and IL-1ß was detected in affected tissue. For the first time, a significant suppression of activin receptor-like kinase 1 and ENG could be revealed. CONCLUSION: The data provided here allow further insight into the pathogenesis of radiation-induced rectum injury. Radiation-induced damage is not confined to a single event but involves complex signaling between different pathways, enhancing and maintaining the processes that lead to mucosal damage. The results indicate that postradiation tissue hypoxia is critical for fibrosis, which involves changes in the expression of profibrotic and angiogenic factors in rectal tissue.

[Peritoneal carcinomatosis of colorectal cancer: cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. / Peritoneal Metastasiertes Kolorektales Karzinom: Zytoreduktive Chirurgie und Hypertherme Intraperitoneale Chemotherapie.

Peritoneal carcinomatosis caused by colorectal carcinoma is still considered as the end-stage of disease. A multi-modal therapeutic concept including maximal cytoreduction followed by intraperitoneal hyperthermic chemotherapy (HIPEC) has the potential to cure selected patients. In case of peritoneal carcinomatosis palliative systemic treatment is no longer the state of the art. This article addresses aspects of the disease, the rationale behind peritonectomy with HIPEC, and the surgical management of peritoneal carcinomatosis.

Rapamycin-induced impaired wound healing is associated with compromised tissue lactate accumulation and extracellular matrix remodeling.

INTRODUCTION: Extracellular matrix (ECM) remodeling involving matrix metalloproteinases (MMPs) and wound lactate accumulation are essential elements of tissue repair. The aim of this study was to investigate whether rapamycin-induced impaired healing is associated with compromised wound fluid lactate accumulation and altered ECM remodeling. METHODS: Polyvinyl alcohol sponges were subcutaneously implanted in male C57/BL6 mice. Animals were randomized to daily intraperitoneal treatment with either vehicle or 1.5 mg/kg rapamycin. After 7 or 14 days, sponges were harvested to collect wound fluid for subsequent analyses. Wounds were excised for assessment of tensile strength. RESULTS: After 7 days, wound hydroxyproline content was significantly decreased due to rapamycin therapy, whereas the observed difference in tensile strength marginally failed to show statistical significance. In addition, rapamycin reduced wound lactate accumulation and enhanced MMP-2 protein expression, and both MMP-2 and MMP-9 activity. At day 14, wound tensile strength and hydroxyproline content were significantly lower along with an increase in MMP-2 and MMP-9 activity in rapamycin-treated mice. Similarly, wound fluid lactate concentration and MMP-2 protein expression were found to be persistently decreased and increased, respectively. CONCLUSIONS: Rapamycin affects tissue repair by interfering with fundamental mechanisms involved in healing, namely lactate accumulation and ECM remodeling.

Wound fluid lactate concentration: a helpful marker for diagnosing soft-tissue infection in diabetic foot ulcers? Preliminary findings.

AIMS: To investigate the impact of wound fluid lactate concentration on diagnosing soft-tissue infection in diabetic foot ulcers. METHODS: Lactate concentration in wound fluid obtained from diabetic foot ulcers was determined using a lactate analyser and compared with clinical examination findings. RESULTS: Overall median wound fluid lactate concentration was 21.03 mm (5.58-80.40 mm). Wound lactate levels were significantly higher in infected compared with non-infected diabetic foot ulcers (P=0.001). Non-infected diabetic foot ulcers that healed within 6 months of treatment showed a significantly lower wound fluid lactate concentration at baseline as opposed to those that did not heal (P=0.007). CONCLUSIONS: Non-healing diabetic foot ulcers are characterized by high wound fluid lactate levels. Assessment of wound fluid lactate concentration might be helpful for confirming the suspicion of soft tissue infection, particularly when clinical signs are atypical.

[Selection criteria for peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) in peritoneal carcinomatosis]. / Selektion zur Peritonektomie mit hyperthermer intraoperativer Chemotherapie (HIPEC) bei Peritonealkarzinose.

BACKGROUND: Cytoreductive peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) is an established therapy for patients with gastrointestinal, gynaecological metastasised peritoneal carcinomatosis as well as primary peritoneal carcinomatous tumours. METHODS: On the basis of a literature review and our personal experience, selection criteria for peritonectomy are discussed. RESULTS: Computed tomography (CT) scans and diagnostic laparoscopy are not sufficient for the diagnosis of peritoneal carcinomatosis. The combination of fluorodeoxyglucose positron emission tomography (FDG-PET) and CT seems to be the most reliable diagnostic imaging method. In our institution, all patients undergo PET / CT prior to peritonectomy. CONCLUSION: The PET / CT scan may play an important role in forecasting the operability of patients with peritoneal carcinomatosis.

Microarray technology--the future analyses tool in exercise physiology?

Microarray analysis offers a set of analytical platforms that provide rapid, affordable and substantial information at the DNA, RNA or protein level. It enables the analysis of thousands of genes simultaneously in a parallel manner across samples derived from various biological sources and treatment regimens. This development became possible as a result of the combination of three technological advances achieved at the beginning of the 1990's, namely parallelism, miniaturization and automation. In regular physical checkups the microarray technology could be used to supplement the current spectrum of tests and therefore enhance the quality of the data obtained. Arrays for analyses of RNA expression will allow gene expression profiling also in exercise physiology. DNA chips may also be used for genetic screening and diagnostics to analyze polymorphisms and mutations which may underlie genetic diseases or interindividual variations between subjects. Using microarrays in exercise physiology will provide new insights into the complex molecular mechanisms of the exercise-induced stress response, adaptation to training and modulation of immune function. Gene expression profiling and genetic screening will probably help to characterize and predict the individually variable response to and efficiency of training.