GSH attenuates organ injury and improves function after transplantation of fatty livers.

Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS, diminishing IRI. The aim of this study was to evaluate whether GSH also protects steatotic allografts from IRI following transplantation. Fatty or lean livers were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4 h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver transplantation was then performed in lean syngeneic Zucker rats. Recipients of fatty livers were treated with GSH (200 µmol/h/kg) or saline during reperfusion (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured. Transplantation of steatotic livers enhanced early reperfusion injury compared to lean organs as measured by increased aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also reduced in steatotic grafts. Intravenous administration of GSH effectively decreased liver damage in fatty allografts and resulted in improved bile flow. Intravenous application of GSH effectively reduces early IRI in steatotic allografts and improves recovery of these marginal donor organs following transplantation.

Long-term results after surgical treatment of nonparasitic hepatic cysts.

BACKGROUND: Studies evaluating surgical success in patients with benign liver cysts focus on cyst recurrence. The aim of this study was to evaluate the efficacy of surgical treatment with regard to clinical complaints. MATERIALS AND METHODS: Between 1995 and 2007, 99 patients (M:F 1:7.25) with symptomatic, benign, nonparasitic liver cysts (77 simple liver cysts [SLCs], 22 polycystic liver disease [PCLD]) underwent surgical treatment (77% laparoscopic surgery, 23% open surgery). Perioperative parameters (including morbidity) were evaluated. Moreover, a questionnaire was completed by 65 patients monitoring subjective complaints focusing on abdominal pain, vegetative symptoms, and dyspnea pre- and postoperatively (mean follow-up 76 months). RESULTS: Severe complications occurred in 7 patients. Abdominal pain, vegetative symptoms, and dyspnea were significantly improved in SLC patients. In PCLD patients abdominal pain and dyspnea were significantly decreased, whereas vegetative symptoms were unaffected by surgery. The symptom recurrence rate for SLC patients was significantly lower compared with PCLD patients (41% vs 66.6%). CONCLUSION: Indications for surgical treatment of PCLD should be well considered and limited to a selected group of patients.

Islets of Langerhans are protected from inflammatory cell recruitment during reperfusion of rat pancreas grafts.

BACKGROUND: Ischemia/reperfusion (I/R) injury plays a pivotal role in the development of graft pancreatitis, with ischemia time representing one of its crucial factors. However, it is unclear, whether exocrine and endocrine tissue experience similar inflammatory responses during pancreas transplantation (PTx). This study evaluated inflammatory susceptibilities of islets of Langerhans (ILH) and exocrine tissue after different preservation periods during early reperfusion. METHODS: PTx was performed in rats following 2 h (2h-I) or 18 h (18h-I) preservation. Leukocyte-endothelial cell interactions (LEI) were analyzed in venules of acinar tissue and ILH in vivo over 2 h reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry. RESULTS: In exocrine venules leukocyte rolling predominated in the 2h-I group. In the 18h-I group, additionally, high numbers of adherent leukocytes were found. Histology revealed significant edema formation and leukocyte extravasation in the 18h-I group. Notably, LEI in postcapillary venules of ILH were significantly lower. Leukocyte rolling was only moderately enhanced and few leukocytes were found adherent. Histology revealed minor leukocyte extravasation. CONCLUSION: Ischemia time contributes decisively to the extent of the I/R-injury in PTx. However, ILH have a significantly lower susceptibility towards I/R, even when inflammatory reactions in adjacent exocrine tissue are evident.

[Usage of marginal organs for liver transplantation: a way around the critical organ shortage?]. / Die Transplantation marginaler Lebern: Ein Ausweg aus dem Organmangeldilemma?

The transplantation of marginal organs or those meeting the so-called extended donor criteria (EDC) is today a significant option to alleviate the low availability or organs and to increase the number of transplantation which in turn is -accompanied by a lower mortality among wait-ing-list patients. However such an extension of the spender pool carries the risks of an increased incidence of organ dysfuntions and a higher recipient mortality. This situation presents an ethical problem when marginal organs are accepted for transplantation because the anticipated mortality for the individual recipient cannot be determined. The transplantation of marginal organs from -donors with a high MELD score seems to be linked to a higher mortality. In particular, the combina-tions of high donor age and long ischaemic time or advanced donor age and hepatitis C infection in the recipient are definitively associated with a significantly poorer organ survival rate. In view of the serious lack of organs, efforts should be made, for example, by shortening of the is-chae-mic time and the development of therapeutic strategies, to improve the function and increase the number of usable marginal organs and thus to increase pool of donor organs. The refusal of marginal organs on the basis of individual EDC without consideration of the status of recipient does not seem to be adequate.

Surgical management of splenic echinococcal disease.

BACKGROUND: Infection of the spleen with echinococcus is a rare clinical entity. Because the diagnosis of a splenic infestation with echinococcus is sometimes delayed, large hydatid cysts or pseudotumors may develop, demanding a differential surgical approach to cure the disease. METHODS: In a retrospective study 10 patients out of 250 with abdominal echinococcosis (4%) were identified to have splenic infestation, either limited to the spleen (n=4) or with synchronous involvement of the liver (n=4), major omentum (n=1), or the liver and lung (n=1). Only one patient had alveolar echinococcosis whereas the others showed hydatid cysts of the spleen. Surgical therapy included splenectomy in 7 patients or partial cyst excision combined with omentoplasty in 3 patients. In case of liver involvement, pericystectomy was carried out simultaneously. RESULTS: There was no mortality. Postoperative complications were observed in 4 patients. Hospital stay and morbidity were not influenced when splenic procedures were combined with pericystectomies of the liver. Mean follow-up was 8.8 years and all of the patients are free of recurrence at this time. CONCLUSIONS: Splenectomy should be the preferred treatment of hydatid cysts but partial cystectomy is suitable when the cysts are located at the margins of the spleen. Due to low morbidity rates, simultaneous treatment of splenic and liver hydatid cysts is recommended.

Ischemic preconditioning improves postoperative outcome after liver resections: a randomized controlled study.

BACKGROUND: Clamping of the portal triad (Pringle maneuver) prevents blood loss during liver resection, but leads to liver injury upon reperfusion. Ischemic preconditioning (IP) has been shown to protect the liver against prolonged ischemic injury in animal models. However, the clinical value of this procedure has not yet been established. METHODS: 61 Patients undergoing hepatic resection under inflow occlusion were randomized to either to receive (Group-A n = 30) or not to receive (Group-B n = 31) an IP (10 minutes of ischemia followed 10 minutes of reperfusion). RESULTS: Mean (+/- SD)/ Group-A vs. Group-B. Pringle time of 34 +/- 14 and 33 +/- 12 minutes and the extent of resected liver tissue (2.7 +/- 1.3 vs. 2.7 +/- 1.1 segments) were comparable in both groups. Complications, including death, severe liver dysfunction and biliary leakage occurred in 6 patients of Group-A vs. 14 patients of Group-B (p<0.05). Intraoperative blood loss was significantly lower in Group-A (1.28 +/- 0.91 l vs. 1.94 +/- 0.76 l; p<0.001) with 5 vs. 15 patients requiring transfusions (p<0.01). In a multivariate analysis the duration of the Pringle maneuver (p<0.05) and the absence of preconditioning (p<0.05) were independent predictors for the occurrence of postoperative complications. CONCLUSIONS: IP protects against reperfusion injury, reduces the incidence of complications after hepatic resection under inflow occlusion and is simple to use in clinical practice.

Influence of surgical trauma on the mRNA expression of sex hormone receptors in PBMCs in male and female patients.

INTRODUCTION: Gender-specific immune responses have been found after trauma-hemorrhage. Male and female sex hormones seem to be responsible for this gender dimorphism. Alterations in sex hormone receptor expression in mice appear to contribute to the immunomodulatory effect of sex hormones after blood loss. The effect of surgical trauma on the expression of sex hormone receptors in peripheral blood mononuclear cells (PBMCs) from patients, however, remains unknown. MATERIALS AND METHODS: PBMCs were obtained from 14 patients (7 men and 7 women) undergoing major abdominal surgery preoperatively and 2 h postoperatively. The expression of the androgen and the estrogen alpha- and beta- receptors were determined by reverse transcriptase polymerase chain reaction (RT-PCR). beta-Actin was used as housekeeping gene. RESULTS: The results indicate that surgical trauma has no influence on the expression of the androgen receptor and the estrogen receptors alpha and beta in male and female patients. DISCUSSION: The data demonstrate that, in contrast to mice, no alterations in the expression of androgen and estrogen hormone receptors were evident after surgery in patients. Thus, differences in the expression of sex hormone receptors do not appear to be responsible for the gender-specific immune response after surgery.

Depressed T cell-derived IFN-gamma following trauma-hemorrhage: a potential mechanism for diminished APC responses.

INTRODUCTION: Prolonged immunosuppression has been demonstrated after trauma-hemorrhage resulting in an increased susceptibility to sepsis. The contribution of antigen-presenting cells (APC) vs T cells to this diminished immune response, however, remains unknown. MATERIALS AND METHODS: To study this, male mice were trauma-hemorrhaged (35 +/- 5 mmHg for 90 min and resuscitation) or sham operated. At 24 h thereafter, spleens were harvested and T cells (via Microbeads) and APC (via adherence) were isolated. Cocultures of combined T cells and APC were established for 48 h, stimulated with ConA and LPS. The T cell-derived cytokine IFN-gamma and IL-12 for APC responses were measured in the supernatants by the multiplex assay. RESULTS: The release of IFN-gamma was suppressed by T cells after trauma-hemorrhage irrespective of whether sham or trauma-hemorrhage APC were added. Trauma-hemorrhaged APC did not affect T cells-derived IFN-gamma release by sham T cells. In contrast, trauma-hemorrhaged T cells depressed the release of IL-12 by APC. The release of IL-12 by trauma-hemorrhaged APC was not altered when sham T cells were cocultured. CONCLUSION: Prolonged immunosuppression after trauma-hemorrhage appears to be predominantly due to diminished T cell function. Thus, attempts to prevent immunodysfunction should be directed towards T cells.

[Titanium-coated silicone is not effective for preventing graft infection]. / Die Beschichtung von Silikonimplantaten mit Titan ist nicht effektiv zur Vermeidung von Infektionen.

AIM: Titanium-coated grafts for breast augmentation are available since 2001 and are used clinically. The titan surface is supposed to improve the tissue compatibility and to lower the infection rate. It was the aim of the present study to validate the antibacterial efficiency of titanium-coated silicone. MATERIAL AND METHODS: C3H/HcN mice were assigned to four different groups (n=6/group). Silicone without (group I and III) or with (group II and IV) titanium were implanted subcutaneously. Following this in groups III and IV a local contamination was induced with 2 x 10 (7) CFU/0.1 ml Staphylococcus aureus ATCC 25923. Groups I and II were not infected. 14 days after primary operation all animals were euthanized and the grafts harvested. Specimens were examined for signs of infections by macroscopy, histology and microbiology. RESULTS: In group I none of the grafts were infected (0/5). In group II (silicone, + titanium, no contamination) one infection was evident due to biting of the animal (1/6). In group III (silicone, no titanium, contamination) an infection was detected in all mice (6/6). The use of titanium, however, did not significantly reduce the infection rate in contaminated animals (group IV, 5/6). Interestingly, tissue integration of titanium-coated grafts was macroscopically reduced compared to non- titanium-coated grafts (group II vs. I). CONCLUSION: The titanium-coated silicone grafts were not effective in protecting infection in vivo. The decreased tissue integration of titanium-coated grafts, however, might reduce the rate of capsular contracture. This potential advantage of titanium needs to be validated in controlled clinical trials.

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage.

Several studies indicate that cell-mediated immune responses, i.e., macrophage (MPhi) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after trauma-hemorrhage in male mice. Testosterone has been shown to be responsible for the depression of MPhi cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic MPhi was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in MPhi from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss.

Immunomodulation during sepsis in organ transplanted children.

Newer immunosuppressive agents have dramatically reduced the rates of acute graft rejection over the last decade but may have exacerbated the problem of post-transplant infections. Causes of early mortality include graft dysfunction and sepsis. Late mortality occurs mainly due to sepsis. An excessive inflammatory response followed with a dramatic paralysis of cell-mediated immunity has been documented in septic patients. In transplanted individuals the pathophysiological changes of the immune response are further complicated by immunosuppressive agents. This article will focus on the effect of immunosuppressive agents and sepsis on cell-mediated immune responses. Moreover, potentially promising immunomodulatory approaches, i.e. human activated protein C, immunomodulatory diets containing L-arginine and fish oil, selective cytokine blockade, platelet-activating factor receptor antagonist, LPS receptor CD14 blockade and G-CSF, for the treatment of immunodysfunction in septic patients will be outlined in this review article. Most of them, however, have not been tested in the clinical arena in transplanted patients. Thus, the main part of the article, immunomodulation during sepsis in organ transplanted children is quite speculative and based on immunomodulatory strategies in other non-transplanted septic patients.

Value of systematic mediastinal lymph node dissection during pulmonary metastasectomy.

BACKGROUND: Systematic mediastinal lymph node dissection is the accepted standard when curative resection of bronchial carcinoma is performed. However, mediastinal lymph node dissection is not routinely performed with pulmonary metastasectomy, in which only enlarged or suspicious lymph nodes are removed. The incidence of malignant infiltration of mediastinal lymph nodes in patients with pulmonary metastases is not known. METHODS: Sixty-three patients who underwent 71 resections through a thoracotomy for pulmonary metastases of different primary tumors were studied prospectively. Selected patients showed no evidence of tumor progression or extrathoracic metastases and pulmonary metastasectomy was planned with curative intent. All patients underwent preoperative helical computed tomography (CT) scanning. Only patients with no evidence of suspicious mediastinal lymph nodes on the CT scan (less than 1 cm in the short axis) were included in this study. A mediastinal lymph node dissection was performed routinely with metastasectomy. RESULTS: In 9 patients (14.3%) at least one mediastinal lymph node revealed malignant cells in accordance with the resected metastases. When compared with the preoperative CT scan, additional pulmonary metastases were detected in 16.9% of performed operations. There was a trend toward an improved survival rate in patients without involvement of the mediastinal lymph nodes. The number of pulmonary metastases had no influence on survival. CONCLUSIONS: On a patient-by-patient basis, the frequency of misdiagnosed mediastinal lymph node metastases is about the same as compared with non-small cell bronchial carcinomas. Systematic mediastinal lymph node dissection reveals a significant number of patients, who otherwise are assumed free of residual tumor. The knowledge of metastases to mediastinal lymph nodes after complete resection of pulmonary metastases could influence the decision for adjuvant therapy in selected cases.

Influence of long-term preservation with endobronchially administered perfluorodecalin on pulmonary graft function.

BACKGROUND: Experimental studies demonstrated a suppression of oxygen-derived free radicals, reduced adhesion of activated neutrophils on the endothelium and an increase of de novo synthesis of surfactant during liquid ventilation with perflurocarbon. The purpose of this study was to assess the pulmonary graft function after preservation with endobronchially administered perfluorocarbon as an alternative to flush perfusion. METHODS: Native bred pigs underwent orthotopic left lung transplantation. Donor lungs were flushed in situ with either a low-potassium dextran solution (LPD, n=6) or a perfluorochemical was administered endobronchially (PFC, n=6) and were then stored after removal for 18 hr at 4 degrees C. Pulmonary graft function was assessed after reperfusion for 5 hr by measuring pulmonary gas exchange and hemodynamics during isolated ventilation and perfusion. Tissue specimens were taken for analysis of morphology and wet/dry ratio. All values were compared to a sham-operated group (n=6). RESULTS: Pulmonary gas exchange of the graft revealed reduced paO2 values and elevated paCO2 values in the PFC group throughout the observation period as compared with the LPD group and sham group. Endothelial alterations and fibrin exudate in the PFC group were significantly more pronounced. Lungs in the LPD group showed functional and morphological recovery close to sham group. CONCLUSIONS: Long-term preservation with endobronchially administered perfuorocarbon is possible. Impaired pulmonary graft function and pronounced morphological alterations indicate an aggravation of the ischemic reperfusion injury after lung transplantation compared to LPD preserved lungs.

Long-term results after video-assisted thoracoscopic surgery for first-time and recurrent spontaneous pneumothorax.

BACKGROUND: Few investigators have reported on results after video-assisted thoracoscopic surgery (VATS) for spontaneous pneumothorax (SP) with follow-up periods longer than 24 months. The aim of this study was to evaluate VATS for first-time and recurrent SP and to follow patients long-term. METHODS: One hundred nine patients were followed long-term after treatment of SP by VATS. Ninety-five patients had primary SP and 14 had secondary SP. Sixty-two patients had a first episode and 47 had a recurrence. In 72 patients leaks or ruptured blebs were identified and excised without subsequent pleurodesis. In 37 patients showing no ruptured bullae or leaks only pleurodesis was applied. RESULTS: Median follow-up was 53.2 months. Postoperative complications were rare. Three patients (2.7%) had a prolonged air leak. The long-term recurrence rate was 4.6%. Only those patients who had not received pleurodesis at the time of first treatment by VATS experienced recurrence. CONCLUSIONS: Immediate postoperative results show VATS to be a safe and reliable method in first-time and recurrent SP to obtain quick reexpansion of the lung. Long-term recurrence rates are acceptable and compare with results after open thoracotomy. Pleurodesis should be included in each procedure for adequate recurrence prevention.

Pulmonary graft function after long-term preservation of non-heart-beating donor lungs.

BACKGROUND: Critical organ shortage in lung transplantation could be attenuated by the use of non-heart-beating donor (NHBD) lungs. In addition, prolonged ischemic tolerance of the organs would contribute to the alleviation of organ shortage. The aim of this study was to investigate pulmonary graft function of NHBD lungs after long-term hypothermic storage. METHODS: Twelve native-bred pigs (bodyweight 20 to 30 kg) underwent left lung allotransplantation. In the heart-beating donor (HBD) group, lungs were harvested immediately after cardiac arrest. In the NHBD group, lungs were subjected to a warm ischemic period of 90 minutes before harvesting. After a total ischemic time of 19 hours, pulmonary grafts in both groups were reperfused and pulmonary graft function was assessed. All values were compared with a sham-operated control group. RESULTS: Pulmonary graft function in the HBD group was excellent. In the NHBD group, pulmonary gas exchange was impaired, but still provided good graft function compared with the excellent graft function in the HBD group. Pulmonary vascular resistance was even lower in the NHBD group. In the NHBD group, calculated intrapulmonary shunt fraction (Qs/Qt) was significantly increased compared with the sham-group. Histologic alteration and wet-to-dry ratio did not differ significantly between the HBD and NHBD group. CONCLUSIONS: We conclude that NHBD lungs (90 minutes of warm ischemic time) have the potential to alleviate organ shortage in lung transplantation even after an extended total ischemic time.

Quantitative analysis of incongruity, contact areas and cartilage thickness in the human hip joint.

Joint incongruity and cartilage thickness have been shown to determine the contact stresses and the load partitioning between the solid and fluid phases of articular cartilage. Matrix stresses, which are relevant in the development of osteoarthrosis, can, however, not be determined experimentally but must be calculated using numerical methods. The aim of the present study was to quantify the incongruity and cartilage thickness of the human hip, in order to allow for the construction of morphologically accurate finite element models. Twelve cadaveric specimens (34-86 years), two fresh and ten fixed, were investigated. The loading configuration was based on in vivo measurements of hip joint forces during midstance. The incongruity and contact areas were determined using a polyether casting technique, in the minimally and the fully loaded state. The cartilage thickness was measured at identical coordinate points with an A-mode ultrasonic system. Generally, the contact started at lower loads at the edge of the lunate surface, and the joint space increased towards its central aspects. In some specimens the contact started in the acetabular roof, leaving a joint space of up to 2 mm in the horns of the lunate surface. In others, the initial contact was observed in the anterior and posterior horns of the lunate surface with a joint space width of up to 0.75 mm in the acetabular roof. The size of the contact areas increased from about 20% of the lunate surface to 98% at higher loads. The articular cartilage thickness ranged from 0.7 to 3.6 mm, the maxima being located in the ventral aspects of the femoral head and acetabulum. These quantitative data on joint space width, contact, and cartilage thickness in the human hip joint may be used to construct and validate finite element models which are required to elucidate the mechanical factors involved in osteoarthrosis.