Global WaterPack - The development of global surface water over the past 20 years at daily temporal resolution.

Open surface water across the globe is essential for many life forms and is an important source for human settlements, agriculture, and industry. The presence and variation in time and space is influenced by different natural conditions (e.g. climate, topography, geology) and human use (e.g. irrigation, flood protection). The information on the spatial and temporal distribution of open surface water is fundamental for many disciplines and is also required as an essential parameter for hydrological and climatological modelling. Here, we present a dataset derived from satellite earth observation, which is based on more than 6.3 million single MODIS products with a volume of approx. 300 TB. The resulting dataset reflects the situation of open surface water on a global scale for each day over the time period from 2003 to 2022 at a spatial resolution of 250 m. The dataset enables the analysis of the development of lake and reservoir surface areas, freezing cycles, and inundation areas.

Iatrogenic extracellular matrix disruption as a local trigger for postoperative ileus.

BACKGROUND: Active matrix metallopeptidase 9 (MMP-9) disruption of the extracellular matrix (ECM) plays an important role in inflammatory disorders. In this study, we investigated the inflammatory role of MMP-9 and the ECM breakdown product hyaluronan as a trigger for the postoperative intestinal inflammatory response of postoperative ileus. METHODS: We performed a standardized intestinal surgical manipulation on rats to produce ileus assessed by the oral non-digestible fluorescein isothiocyanate-dextran transit assay. We studied isolated intestinal muscularis extracts for mRNA expressions of interleukin 6 (IL-6), MMP-9 and CD44. We quantified peritoneal MMP-9 activity using zymography, and quantified peritoneal fluid and serum for hyaluronan and tissue inhibitor of metalloproteinase 1 levels by enzyme-linked immunosorbent assay (ELISA). We cultured peritoneal macrophages and exposed them to peritoneal fluid or synthetic hyaluronan for ELISA analysis of IL-6 and macrophage inflammatory protein-1α. RESULTS: Transit was significantly delayed after surgical manipulation, and extracts of the isolated jejunal and colonic muscularis demonstrated a significant induction of IL-6, MMP-9, and CD44 mRNAs compared with controls. Zymography confirmed significant MMP-9 activity in peritoneal fluid compared with controls. Enzyme-linked immunosorbent assay measurements showed a significant up-regulation in hyaluronan and tissue inhibitor of metalloproteinase 1 in the peritoneal fluid and serum. In addition, ELISA and reverse transcriptase-polymerase chain reaction measurements of peritoneal macrophages stimulated with postsurgical peritoneal fluid and synthetic hyaluronan resulted in higher expressions of IL-6 and macrophage inflammatory protein-1α in the macrophage supernatant. CONCLUSIONS: Our results confirm that MMP-9 disruption in the ECM with hyaluronan release and muscularis CD44 receptor induction has the potential to trigger muscularis proinflammatory cascades that cause postoperative ileus. Matrix metallopeptidase 9 inhibition may be a novel therapeutic approach to limit postoperative ileus.

Association of socio-economic status and stage of pancreatic cancer at time of surgery in a German setting.

BACKGROUND/AIMS: Curative resection has been proven to be one of the most important factors determining outcome in pancreatic cancer patients. Advanced stage of pancreatic cancer at diagnosis is strongly associated with a low socioeconomic status (SES), and patients from affluent areas have better cancer survival than patients from deprived areas. We tested, in our population of pancreatic cancer patients, the hypothesis that surrogates representing a lower SES or demographic factors (DGF) linked to rural areas are associated with a more advanced disease stage at presentation. METHODOLOGY: Between 1989 and 2008, patients with pancreatic adenocarcinoma and pancreaticoduodenectomy were identified from our pancreatic resection database. DGF, SES surrogates and tumor stage were obtained from patients' files together with pathology reports, a residents' registration office questionnaire and telephone interviews with patients and family members. RESULTS: Follow-up was completed in 117 patients. There were no significant differences regarding tumor stage (local size and lymph node metastases), or the likelihood of negative resection margins in relation to the patients' DGF or any surrogate parameters for SES. Furthermore, comparison of two different treatment periods showed no significant advances regarding secondary cancer prevention within 20 years. CONCLUSIONS: Longer waiting times for appointments combined with less sensitive imaging techniques and consecutive later referral to a cancer specialist are likely to be associated with inferior quality of medical results. Therefore, a lively debate is currently underway in Germany concerning the harmonization of reimbursement modes for statutory and private health insurance. Our data with no negative correlation of low SES or unfavorable DGF and disease stage at time of presentation or the likelihood for a curative resection, do not promote the universal accusation of health care disparities solely based on economic issues in Germany.

Efficiency and safety of bipolar vessel and tissue sealing in visceral surgery.

BACKGROUND: The aim of this study was to analyze the efficiency and safety of the bipolar tissue/vessel sealing and cutting device EnSeal(™) in comparison to the conventional clamp and ligation technique in visceral surgery. MATERIAL AND METHODS: In an acute animal model, a part of the small bowel, a part of the colon and the kidneys were resected either with the conventional clamp and ligation technique or with EnSeal(™). Operation time, blood loss and blood parameters as well as the lateral thermal spread were evaluated. RESULTS: Small bowel, colon and kidney resection time with the EnSeal(™) device was shorter compared to the conventional clamp and ligation technique (small bowel: EnSeal(™): 4.7 ± 1.0 min vs. con: 35.1 ± 2.3 min; colon: EnSeal(™): 7.0 ± 1.4 min vs. con: 16.3 ± 1.5 min, kidney: EnSeal(™): 5.7 ± 1.3 min vs. con: 16.7 ± 3.7 min, p < 0.05) and blood loss was significantly lower. Blood analysis demonstrated no differences in both groups. The lateral thermal spread was not more than 1 mm with EnSeal(™). CONCLUSION: The bipolar sealing in visceral surgery with EnSeal(™) can be performed more efficiently in a shorter time, with significantly less blood loss, minimal thermal damage and without changes of blood parameters, indicating biological safety and integrity.

Mechanical strain and TLR4 synergistically induce cell-specific inflammatory gene expression in intestinal smooth muscle cells and peritoneal macrophages.

Mechanical trauma of the gut is an unavoidable event in abdominal surgery. Former studies demonstrated that intestinal manipulation induces a strong inflammation within the tunica muscularis. We hypothesized that mechanical strain initiates or aggravates proinflammatory responses in intestinal smooth muscle cells (iSMC) or macrophages. First, an appropriate isolation and culture method for neonatal rat iSMC was established. Purified iSMC and primary peritoneal macrophages (pMacs) were subjected to static or cyclic strain, and gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6, and IL-1ß was analyzed by quantitative PCR. Supernatants from stretched iSMC were transferred to untreated pMacs or contrariwise, and medium transfer-triggered inflammatory gene expression was measured in unstretched cells. Finally, we investigated the synergistic effect of static strain on LPS-induced proinflammatory gene expression. Although cyclic strain failed, static strain significantly induced iNOS, COX-2, and IL-1ß mRNA in iSMC. pMacs showed an increase in all inflammatory genes investigated as well as macrophage inflammatory protein (MIP)-1α and MIP-2 mRNA after static strain. Both cell entities liberated unknown mediators in response to stretch that mutually stimulated iNOS gene expression. Finally, mechanostimulation amplified LPS-induced iNOS and IL-1ß gene expression in iSMC as well as COX-2 and IL-6 mRNA in pMacs. In conclusion, static strain initiates proinflammatory gene expression in iSMC and pMacs and triggers a bidirectional paracrine communication between both cultured cell entities via the liberation of unknown mediators. Furthermore, static strain synergistically operates with Toll-like receptor 4 ligation in a cell-specific manner. Hence, this study demonstrates that mechanical strain functions as an immunomodulatory stimulus in abdominal cells.

Inhibition of p38 mitogen-activated protein kinase pathway as prophylaxis of postoperative ileus in mice.

BACKGROUND & AIMS: Postoperative ileus, an iatrogenic complication of abdominal surgery, is mediated by severe inflammation of the tunica muscularis. Macrophages that reside in the muscularis have important roles in initiating the inflammation. We investigated whether activation of the p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase is involved in the genesis of postoperative ileus, and whether p38-MAPK inhibition by the macrophage-specific inhibitor semapimod prevents intestinal dysmotility. METHODS: Postoperative ileus was induced by intestinal manipulation of the small bowel in mice. Protein kinase phosphorylation was assessed by immunoblotting of muscularis externa preparations. Proinflammatory gene expression was quantified by real-time polymerase chain reaction. Myeloperoxidase histochemistry for neutrophils was performed in jejunal segments. Nitric oxide production was measured by Griess reaction in smooth-muscle organ culture supernatants. Jejunal contractility was assessed within an organ bath setup. Intestinal motility was analyzed by gastrointestinal and colonic transit measurements. RESULTS: High levels of p38-MAPK and stress-activated protein kinase phosphorylation were observed immediately after intestinal manipulation. Semapimod treatment led to a significant decrease of p38-MAPK phosphorylation in macrophages; proinflammatory gene expression of macrophage inflammatory protein-1alpha, interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1; and neutrophil infiltration. Furthermore, semapimod completely abrogated nitric oxide production within the tunica muscularis. Subsequently, semapimod prevented the suppression of smooth muscle contractility and small intestinal and colonic motility after intestinal manipulation. CONCLUSION: A single preoperative semapimod administration prevents intestinal macrophage activation and subsequent gastrointestinal dysmotility induced by abdominal surgery. Semapimod inhibits p38-MAPK and nitric oxide production in macrophages, making it a promising strategy for prophylaxis of postoperative ileus.

Use of a new modified HTK solution for machine preservation of marginal liver grafts.

BACKGROUND: The present study was undertaken to investigate the putative benefit of a new, modified HTK solution for hypothermic machine perfusion using a model of rat livers from non-heart beating donors. METHODS: Livers were retrieved 30 min after cardiac arrest of male Wistar rats and put on a recirculating machine perfusion device. Hypothermic machine perfusion (HMP) was performed for 18 h at 4 degrees C and a rate of 0.5 mL/g(-1) min(-1) while the preservation solution was oxygenated with 100% O(2). Each liver was randomly assigned to the use of one of the following preservation solutions: HTK (histidine-tryptophan-ketoglutarate solution); Custodiol-N base solution (modified HTK-solution) without additives or with the addition of 25 microM deferoxamine + 2.5 microM (Custodiol-N, 2.5) or 7.5 microM (Custodiol-N) of the permeable iron chelator LK 614. Viability of livers was evaluated upon reperfusion in vitro with Krebs-Henseleit buffer according to previously validated techniques for 120 min at 37 degrees C. RESULTS: The use of Custodiol-N base solution led to a significantly decreased release of ALT or LDH during HMP and after reperfusion, which was further reduced by Custodiol-N and minimal use of Custodiol-N, 2.5. Only the use of Custodiol-N, 2.5 resulted in an improvement of metabolic activity upon reperfusion, as evaluated by hepatic production of C0(2), significantly reduced cleavage of caspase 9, and abrogated positive signs of cellular of apoptosis [terminal deoxynucleotide transferase-mediated deoxy-UTP nick-end labeling (TUNEL)-test)]. CONCLUSION: The data presented provide first experimental evidence for enhanced organ protective potential of the new Custodiol-N solution compared with HTK upon hypothemic machine preservation of marginal liver grafts. Moreover, for continuous perfusion preservation the dosage of the lipophilic chelator LK 614 should probably be lower than for static cold storage.

Impaired autophagic clearance after cold preservation of fatty livers correlates with tissue necrosis upon reperfusion and is reversed by hypothermic reconditioning.

Fatty livers are particularly susceptible to mitochondrial alterations after cold preservation. We thus aimed to improve graft integrity by brief hypothermic oxygenation prior to warm reperfusion. Macrovesicular steatosis was induced in rat livers by fasting and subsequent feeding of a fat-free diet enriched with carbohydrates. Fatty livers were retrieved and stored ischemically at 4 degrees C for 20 hours in histidine-tryptophan-ketoglutarate solution. Hypothermic reconditioning (HR) was performed in some livers by insufflation of gaseous oxygen via the caval vein during the last 90 minutes of preservation. Viability was assessed upon isolated reperfusion. HR resulted in a significant (approximately 5-fold) reduction of parenchymal (alanine aminotransferase and lactate dehydrogenase) and mitochondrial (glutamate dehydrogenase) enzyme release. Functional recovery (bile production, oxygen consumption, and tissue levels of adenosine triphosphate) was significantly improved by HR. In untreated grafts, cellular autophagy (cleavage of LC3B and protein expression of beclin-1) was significantly impaired (<50% of baseline) after preservation/reperfusion but was restored to normal values by HR. HR also increased cleavage of caspase 9 (P < 0.5) and caspase 3 enzyme activity (by a factor of 1.5). In contrast, histological signs of tissue necrosis were abundant after reperfusion in untreated livers and largely abrogated in reconditioned livers. In conclusion, HR limits mitochondrial defects and restores basal rates of cellular autophagy. This may represent a rescue mechanism for maintaining cellular homeostasis and tissue survival.

Endoscopic management of anastomotic hemorrhage from pancreatogastrostomy.

BACKGROUND: Hemorrhage from pancreatic-enteric anastomosis after pancreaticoduodenectomy (PD) is a critical condition due to its difficult accessibility and delicate condition, and therefore remains a major challenge for the surgeon in charge. OBJECTIVE: This study analyzed presentation and management of pancreatogastrostomy hemorrhage (PGH) after PD to determine the respective roles of endoscopy and surgery. PATIENTS AND METHODS: Patients who underwent PD with pancreatogastrostomy between 1989 and January 2008 were identified from a pancreatic resection database and analyzed with regards to PGH, treatment strategy and outcome, and incidence of postoperative complications. RESULTS: Out of 265 consecutive patients with PD, 10 patients (3.7%) experienced an episode of PGH, detected on average on postoperative day 5. No patient with PGH died during hospital stay as opposed to a mortality rate of 2.7% in patients without PGH. Morbidity rates were 50% versus 48% and length of hospital stay was 23 versus 21 days for patients with and without PGH, respectively, with no statistical differences between the groups. Endoscopic approach to control PGH was successful in nine patients. Pancreatogastrostomies were not compromised regarding procedure or air insufflations and no concomitant development of pancreatic fistula was observed. Open surgery was inevitable in one patient with recurrent PGH in order to achieve hemostasis, but resulted in pancreatic fistula and protracted hospital stay. CONCLUSIONS: The present study demonstrates a feasible endoscopic approach for the management of PGH with high success rate and no concomitant procedure-related morbidity.

Gaseous oxygen persufflation or oxygenated machine perfusion with Custodiol-N for long-term preservation of ischemic rat livers?

The aim of the present study was to evaluate the potential benefit of two different techniques for the provision of tissue aerobiosis upon cold preservation of marginal livers from non-heart beating donors using a recently developed improved preservation solution. Rat livers were harvested 30 min after cardiac arrest, flushed via the portal vein and cold-stored in HTK or modified HTK-solution (Custodiol-N) for 18 h at 4 degrees C. Other organs were flushed with Custodiol-N and subjected to aerobic conditions by either vascular systemic oxygen persufflation (VSOP) of the cold stored organ or hypothermic machine perfusion (HMP) with oxygenated Custodiol-N. Viability of the livers was assessed after 18 h of preservation by warm reperfusion in vitro for 120 min. Free radical mediated lipid peroxidation was significantly abrogated by the use of Custodiol-N in all groups compared with HTK. Custodiol-N improved enzyme leakage upon reperfusion and histological integrity, but had no impact on functional recovery (bile production, energetic status). However, VSOP further minimized enzyme release during the whole reperfusion period, led to a rise in hepatic bile production and enhanced recovery of energy charge (p<0.05, resp. vs Custodiol-N). Histological appearance was concordantly improved in VSOP. During the first 45min of reperfusion, leakage of ALT and LDH was also reduced by MP but deteriorated thereafter and became significantly higher compared to Custodiol-N at the end of the experiment. In conclusion, the results of the present study recommend the use of gaseous oxygen persufflation to improve tissue integrity and functional recovery of predamaged livers.

Extended liver resection after preoperative chemotherapy: influence on regeneration and endoplasmic reticulum stress response.

BACKGROUND: The increasing interest in preoperative chemotherapy (CH) of liver metastasis after colorectal carcinoma has focused surgical concerns on the influence of CH on hepatic tolerance during intraoperative ischemia. In this context, CH was described to lead to massive parenchyma harm but also to induce protective cascades initiated by stressed endoplasmic reticulum (ER). The aim of this study was to investigate whether ischemic resection after systemic CH affects liver regeneration and induces antiapoptotic mechanisms on the ER. METHODS: Rats were randomized into two groups and treated either by intraperitoneally injected CH (n = 12) or saline (PL, n = 12); 24 h later, 2/3 of the liver was resected paired +/- Pringle's maneuver (PM) under general anesthesia. Tissue samples were taken from resected left-lateral lobe immediately and 24 h/7 days after the operation from the remaining proliferated right lobe. PCNA (Western blotting) and Ki67 (immunohistochemistry) were analyzed as proliferating markers. ER stress (elF2alpha, GRP78, cleaved caspase 3) was analyzed by Western blotting after 24 h. RESULTS: Only the PL group without PM showed an increase in protein reactivity for PCNA and Ki67. During 7 days of observation, the livers regained weight steadily in both groups. An upregulation of cleaved caspase 3 as indicator for cellular apoptosis was detected in PL animals with PM compared to CH with PM; by contrast, elF2alpha and GRP78, as markers of ER stress-inducing protective mechanisms, were significantly augmented in CH with PM. CONCLUSION: It is concluded that CH leads to a delay in liver regeneration but is no contraindication for ischemia. On the contrary, CH seems to cause a preconditioning of livers leading to the induction of antiapoptotic chaperones in our short-term model.

Parkinson's disease influences the perioperative risk profile in surgery.

BACKGROUND AND AIMS: Aim of this study was to define the perioperative risk profile in surgery of patients suffering from Parkinson's disease (PD) in order to improve treatment options in these patients. MATERIALS AND METHODS: Over a period of 13 years, 51 patients suffering from Parkinson's disease treated in the departments of general, visceral, thoracic, vascular, and trauma surgery were retrospectively compared using matched-pair analysis with 51 controls not affected by PD. Both groups of patients were assessed regarding morbidity and mortality, length of treatment, and rehabilitation. RESULTS: Surgical patients suffering from Parkinson's disease showed an increase in risk of morbidity. Postoperative falls occurred more commonly (entire cohort, p < 0.03). In PD patients treated in the trauma surgery department, postoperative falls (p < 0.04), postoperative stay (p < 0.03), and overall duration of treatment (p < 0.02) were significantly longer than in patients without PD. PD patients of the trauma unit could be discharged home less often for ambulantory rehabilitation after in-patient treatment (p < 0.03). CONCLUSIONS: Concomitant Parkinson's disease is a significant factor of perioperative morbidity in surgical patients, especially of patients treated in the trauma unit. Perioperative morbidity in PD patients may be influenced by early diagnostic and therapeutic measures.

Lymph node dissection in primary intrahepatic malignant mesothelioma: case report and implications for diagnosis and therapy.

INTRODUCTION: In this rare case of intrahepatic malignant mesothelioma with subsequent lymph node metastases, hepatic segmentectomy in combination with repeated lymphadenectomy resulted in prolonged survival, currently 37 months after initial diagnosis. DISCUSSION: Immunohistochemically, vascular endothelial growth factor receptor-1 expressing tumor cells were surrounded by a dense D 2-40-positive lymphangiovascular network, suggesting tumor induced lymphangiogenesis correlating to 2-deoxy-2[(18)F]fluoro-d-glucose-positron emission tomography/computed tomography-positive recurrent intraabdominal and intrathoracic lymphatic tumor spread. Therefore, extended lymphadenectomy during primary tumor resection and combined adjuvant chemotherapy with promising anticancer agents possessing antilymphangiogenic and antimetabolite properties should be considered to prolong survival in cases of extrathoracic malignant mesothelioma. Additionally, as shown in our case, individual operative concepts and (sometimes) multiple operations can be beneficial for highly selected patients. Importantly, a case-by-case optimized antitumor regimen requires interdisciplinary expertise and consensus of all involved faculties.

The use of a colon cancer associated nuclear antigen CCSA-2 for the blood based detection of colon cancer.

The early diagnosis of colorectal cancer (CRC) is central for effective treatment, as prognosis is directly related to the stage of the disease. Development of tumor markers found in the blood from patients, which can detect CRC at an early stage, should have a major impact in morbidity and mortality of this disease. The nuclear matrix is the structural scaffolding of the nucleus and specific nuclear matrix proteins (NMPs) have been identified as an "fingerprint" for various cancer types. Previous studies from our laboratory have identified four colon cancer associated NMPs termed colon cancer-specific antigen (CCSA)-2 to (CCSA)-5. The objective of the present study was to analyze the expression of one of these proteins, CCSA-2 in serum from various patient populations and to determine whether CCSA-2 antibodies could be used in a clinically applicable serum-based immunoassay specifically to detect colon cancer. Using an indirect ELISA, which detects CCSA-2, the protein was measured in the serum from 174 individuals, including healthy individuals, patients with colon cancer, patients with diverticulosis, colon polyps, inflammatory bowel disease (IBD) as well as other cancer types. With a predetermined cutoff absorbance of 0.6 OD we have successfully utilized this approach to develop an immunoassay that detected colon cancer. The immunoassay showed a sensitivity of 88.8% (24/27) and an overall specificity of 84.2% (106/127). This initial study showed the potential of CCSA-2 to serve as a highly specific blood based marker for colon cancer. Although potentially promising, the results of this study must be confirmed in larger independent validation studies.

Perioperative glycine treatment attenuates ischemia/reperfusion injury and ameliorates smooth muscle dysfunction in intestinal transplantation.

BACKGROUND: Ischemia/reperfusion evokes a functionally relevant inflammatory response within the muscularis propria of small bowel grafts by activation of resident macrophages and leukocyte recruitment. We hypothesized that immunomodulatory perioperative treatment with glycine attenuates the proinflammatory cascade and improves smooth muscle dysfunction of small bowel grafts. METHODS: Orthotopic SBTx was performed in Lewis rats. Glycine (1 mg/g body weight) was infused (0.1 mL/g/hr) for 2 hr before harvest as preconditioning in the donor, and for 2 hr from the onset of reperfusion in the recipient. Transplanted vehicle (isotonic saline)-treated animals and naive animals served as controls. Rats were sacrificed after 3 hr and 24 hr. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by real-time-PCR. Jejunal circular smooth muscle contractility was assessed in a standard organ bath. RESULTS: Compared with vehicle controls, glycine-treated graft muscularis expressed a significant alleviation in mRNA peak expression for IL-6, IL-1beta, ICAM-1, MCP-1, TNFalpha, COX-2, and iNOS. Also glycine-treated grafts exhibited significantly less infiltration with ED-1-positive macrophages and MPO-positive neutrophils as well as reduced apoptosis. Concurrent to these results, vehicle controls showed an 80% decrease in smooth muscle contractility, whereas glycine-treated animals exhibited only a 40% decrease in contractile activity compared with controls. CONCLUSIONS: The data indicate that perioperative glycine treatment reduces the molecular and cellular inflammatory response within the grafts and improves smooth muscle dysfunction after transplantation. Therefore, the glycine-activated chloride channel on resident and infiltrating leukocytes could be a promising pharmacologic target to attenuate ischemia/reperfusion injury after ITx.

Acute rejection and the muscularis propria after intestinal transplantation: the alloresponse, inflammation, and smooth muscle function.

BACKGROUND: It has been shown that in transplantation the intestinal muscularis may act as an immunologically active layer via the activation of resident macrophages and the recruitment of leukocytes. Thus we hypothesized that inflammation within the intestinal muscularis is involved in the promotion of acute rejection in intestinal allografts and that this causes smooth muscle dysfunction. METHODS: Orthotopic allogenic and small bowel transplantation (Brown-Norway rats-Lewis rats) was performed without immunosuppression. Animals were sacrificed 1, 4, and 7 days after small bowel transplantation. Isogenic transplanted grafts (Brown-Norway rats-Brown-Norway rats) as well as nontransplanted bowel served as controls. Mediator mRNA expression was determined by real-time reverse-transcriptase polymerase chain reaction. Leukocyte infiltration was evaluated in muscularis whole mounts by immunohistochemistry. Apoptosis was evaluated by TdT-mediated dUTP-X nick end labeling assay. Contractility was assessed in a standard organ bath under bethanechol stimulation. Statistical analysis was performed using a Student's t test and one-way analysis of variance. RESULTS: Transplanted animals showed a significant early inflammatory response within the graft muscularis because of reperfusion injury. Only allogenic transplanted animals exhibited a significant second molecular inflammatory peak in the muscularis during rejection (mRNA induction for interleukin (IL)-6, intercellular adhesion molecule-1, monocyte chemoattractant protein (MCP)-1, interferon-gamma, IL-2, tumor necrosis factor-alpha, IL-10, inducible nitric oxide synthase). These findings were associated with significant leukocyte infiltration within the muscularis, increasing apoptotic cells and massive impairment of smooth muscle contractile activity by 78%. CONCLUSIONS: The data shows that transplantation results in an early and temporary inflammatory response within the intestinal graft muscularis, that is reactivated and intensified during acute allograft rejection. The immunoreaction within the intestinal muscularis leads to intestinal allograft smooth muscle dysfunction.

Inducible nitric oxide synthase expression in the intestinal muscularis mediates severe smooth muscle dysfunction during acute rejection in allogenic rodent small bowel transplantation.

BACKGROUND: Acute rejection in small bowel transplantation is associated with dysmotility. Therefore, host and organ not only face the threat of destructive immunological processes but also the risk of bacterial translocation, endotoxemia, and systemic inflammatory response syndrome. We hypothesized that dysmotility during acute rejection is based on an alloreactive leukocyte infiltrate and coexpression of the kinetically active mediator inducible nitric oxide synthase (iNOS) in the muscularis propria. MATERIALS AND METHODS: Allogenic and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis and BN to BN) was performed without immunosuppression. Animals were sacrificed 4 and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by immunohistochemistry and immunohistology. Real-time reverse transcription polymer chain reaction was used to detect iNOS expression. Griess reaction was used to evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N(6)-(1-iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in a standard organ bath in vitro. RESULTS: On d 7 after SBTx, allogenic transplanted animals showed significant infiltration with ED-1- and ED-2-positive monocytes and macrophages within the muscularis parallel to the manifestation of acute rejection. Additionally, immunohistochemistry localized iNOS protein in leukocytes within the muscularis. Reverse transcription polymer chain reaction showed a significant increase in iNOS mRNA expression (460-fold) in allogenic transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold). Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle contractility, while isogenic grafts showed only an 8% decrease of contractility on d 7. L-N(6)-(1-iminoethyl)-L-Lysin application in vitro significantly improved muscle contractility and decreased NO production. CONCLUSION: The data show that inflammation associated iNOS expression in the intestinal graft muscularis is involved in motoric graft dysfunction during acute rejection.

Optimising post-conditioning time of marginal donor livers.

BACKGROUND: Due to the discrepancy between organ donors and receptors, the use of marginal livers (e.g., non-heart-beating-donor grafts) for transplantation purpose increased. The potential of a short-term aerobic machine perfusion (post-conditioning) for "less than optimal" grafts after cold storage (CS) was recently demonstrated. In our study, the optimal time course of post-conditioning (PC) is to be evaluated. MATERIALS AND METHODS: Livers from male Wistar rats were withdrawn 30 min after cardiac arrest and flushed with histidine tryptophan ketoglutarate (HTK) solution. Then they were stored in HTK at 4 degrees C for 18 h. After 16 h, some livers were put on PC by cold perfusion with HTK for 0.5, 1, 2 or 3 h. Afterwards, the viability of the organs was estimated by warm reperfusion (2 h) in vitro. RESULTS: After 1 h of PC, a significant increase in bile production and a decrease in enzyme release could be detected in comparison to CS. The adenosine triphosphate content of the PC livers after 1 h of treatment was significant higher than in CS organs. No markers for apoptosis could be detected after 1 h PC. CONCLUSION: It can be concluded that a PC of 1 h after cold storage can ameliorate the organ viability of marginal livers. The extension or abbreviation of PC time seems to have no further beneficial effects.

Liver integrity after warm ischemia in situ and brief preservation ex vivo: the value of aerobic post-conditioning.

We evaluated the respective effects of warm ischemic injury in non-heart-beating donor (NHBD) grafts and/or cold ischemia time on liver viability. Eventually, the restorative potential of oxygenated hypothermic perfusion after cold storage should be investigated. Livers were retrieved from male Wistar rats and preserved with HTK-solution for 6h or 18 h by cold storage (CS). Organ retrieval took place either prior to (ctrl.) or 30 min after cardiac arrest (NHBD). Compared to 6h CS of ctrl. livers, enzyme leakage and functional recovery (oxygen consumption, ammonia clearance, bile production) upon warm reperfusion were massively deteriorated after 18 h CS in NHBD-livers. By contrast, 6h CS of NHBD resulted in an only limited impairment of all parameters, which was found quite similar to the results in ctrl. after 18 h CS. Induction of cellular apoptosis (cleavage PARP) was found equally influenced by preceding warm ischemia (NHBD) or extended times of CS, but significantly triggered only by the combination of both events. After 6h of CS, 1h of oxygenated hypothermic machine perfusion ('post-conditioning') was able to bring the performance of NHBD-liver into line with the controls. Based on this work, we concluded that a limited time of warm ischemia in the donor only multiplied graft injury after long-term CS, but does not need to preclude acceptable results if reperfusion is initiated after short periods of CS. Moreover, conditioning of those grafts is effective even 1h prior to implantation and may help to judge liver viability according to adequate parameters after hypothermic machine perfusion has been established.

Thrombosis of a large portal vein aneurysm: treatment by thrombectomy, aneurysmorrhaphy, and portocaval shunt.

An otherwise healthy 32-year-old woman had unspecific upper abdominal complaints. Diagnostic work-up, including a helical computed tomography (CT) scan and indirect splenoportography, revealed a giant extrahepatic portal vein aneurysm (PVA) extending to the central part of the splenic vein. On laparotomy, a thrombectomy and creation of a portocaval side-to-side shunt were performed. Thirteen days later, she was readmitted for re-thrombosis of the aneurysm. She underwent another laparotomy with thrombectomy and tapering of the portal venous wall (aneurysmorrhaphy) by vascular staplers. On follow-up 25 months after the operation, full relief of symptoms was noted. She was on warfarin therapy. Her portal venous system was patent.