[Thoracic Surgery during Pregnancy and Breastfeeding - an Interdisciplinary Consensus Paper]. / Operieren in der Schwangerschaft und Stillzeit (OpidS) in der Thoraxchirurgie ­ ein interdisziplinäres Konsensuspapier.

If thoracic surgery is to remain an attractive career path for young physicians, it is essential to provide opportunities to balance work, residency, and family time. With an increasing proportion of women in thoracic surgery, it has become increasingly important to create a work environment that allows safe employment during pregnancy and breast feeding becomes an important concern.Based on the legal requirements of the German Maternity Protection Act (Mutterschutzgesetz), this interdisciplinary consensus paper was developed by representatives of thoracic surgery, anaesthesiology, and occupational medicine.The vast majority of thoracic operations can be performed by pregnant or breast-feeding surgeons. We established a risk-stratified list of operations with potentially acceptable risk, and a list of operations that pregnant or breast-feeding surgeons should not perform. A checklist aims to aid the individual implementation of thoracic surgery during pregnancy and breast feeding.Thoracic surgery can be performed by pregnant or breast-feeding surgeons when certain protective measures are observed. The prerequisite is the voluntary and independent decision of the surgeon, and the implementation of safety precautions by the employer.

Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-ß.

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-ß (TGF-ß) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-ß, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-ß signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-ß.

Procedural times in early non-intubated VATS program - a propensity score analysis.

BACKGROUND: Non-intubated video-assisted thoracic surgery (NiVATS) has been introduced to surgical medicine in order to reduce the invasiveness of anesthetic procedures and avoid adverse effects of intubation and one-lung ventilation (OLV). The aim of this study is to determine the time effectiveness of a NiVATS program compared to conventional OLV. METHODS: This retrospective analysis included all patients in Leipzig University Hospital that needed minor VATS surgery between November 2016 and October 2019 constituting a NiVATS (n = 67) and an OLV (n = 36) group. Perioperative data was matched via propensity score analysis, identifying two comparable groups with 23 patients. Matched pairs were compared via t-Test. RESULTS: Patients in NiVATS and OLV group show no significant differences other than the type of surgical procedure performed. Wedge resection was performed significantly more often under NiVATS conditions than with OLV (p = 0,043). Recovery time was significantly reduced by 7 min (p = 0,000) in the NiVATS group. There was no significant difference in the time for induction of anesthesia, duration of surgical procedure or overall procedural time. CONCLUSIONS: Recovery time was significantly shorter in NiVATS, but this effect disappeared when extrapolated to total procedural time. Even during the implementation phase of NiVATS programs, no extension of procedural times occurs.

Cerebrospinal fluid melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) in Alzheimer's disease.

Ancillary to decline in cognitive abilities, patients with Alzheimer's disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = -0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

Blood lactate and pyruvate levels in the perioperative period of liver resection with Pringle maneuver.

INTRODUCTION: Bleeding during liver surgery is often routinely controlled by the Pringle maneuver consisting in the temporary clamping of hepatic artery, portal vein, and bile duct. This study aimed at investigating a possible influence of the Pringle maneuver on tissue hypoxia during liver resection. METHODS: Twenty-five consecutive patients undergoing elective liver resection were prospectively randomized either to be treated with the Pringle maneuver (Pringle group, n = 14) or without clamping (Controls, n = 11). Blood lactate levels, pyruvate levels, and hepatic vein oxygen saturation were monitored perioperatively. RESULTS: Patients were comparable with respect to resection time, intraoperative blood loss, and duration of surgery. The Pringle maneuver induced a significant increase in arterial lactate levels during liver resection when compared to Controls (2.6 +/- 0.3 vs 1.8 +/- 0.2 mmol/l; p < 0.05). Further, the Pringle maneuver significantly increased hepatic venous lactate (3.3 +/- 0.3 vs 1.6 +/- 0.3 mmol/l; p < 0.05) and lactate/pyruvate ratio in hepatic venous blood (43 +/- 8 vs 21 +/- 5; p < 0.05) during surgery. This was paralleled by a temporal decrease in hepatic venous oxygen saturation in the Pringle group (61 +/- 4 vs 73 +/- 4%; p < 0.05). CONCLUSION: Our findings demonstrate that liver metabolism and tissue oxygenation were markedly affected by occlusion of the liver hilus. Restricting the use of the Pringle maneuver to cases with severe bleeding might therefore be beneficial in patients undergoing liver resection.

A new vagal anchor electrode for real-time monitoring of the recurrent laryngeal nerve.

BACKGROUND: Despite conventional neuromonitoring, the recurrent laryngeal nerve (RLN) is still at risk for damage during thyroid surgery. The feasibility of continuous RLN monitoring by vagal nerve (VN) stimulation with a new anchor electrode should be shown, and electromyographic signal alterations of stressed RLN were analyzed to be alerted to imminent nerve failure whereby the nerve damage becomes reversible. METHODS: VN stimulation was achieved in 23 pigs. Sensed signals were analyzed and stored as real-time audio/video feedback EMG system. RLN was stressed by mechanical and thermal injury; signal alterations were evaluated. RESULTS: VNs were successfully real-time stimulated by using the anchor electrode. No complications or side effects during stimulation were detected. RLN injury led to an alteration of signal amplitude and latency period but signal restitution after injury. CONCLUSIONS: Real-time monitoring of the RLN is technically feasible to perceive imminent nerve failure. The anchor electrode was safely and easy to handle. Its implementation is being tested in an ongoing clinical trial.

Percutaneous intragastric catheter (PIC) for administration of an unpalatable substance to large animals.

We studied an easy and reliable technique for administration of an unpalatable substance to large animals. There were three groups of pigs: group I (n = 6) received 1 g ethanol/kg body weight per day orally with water for 24 days, group II (n = 6) received 2 g ethanol/kg orally with water for 24 days and 4 g ethanol/kg via percutaneous intragastric catheter (PIC) for the next 24 days, group III (n = 6) received 6 g ethanol/kg via PIC for 72 days. The catheter was placed after insufflation of the stomach using an orogastric tube. PIC was successfully placed in each pig. No complications occurred during placement. The total amount of the administrated dose was assimilated each time. PIC is a safe, effective, well tolerated, and precise method of administering ethanol that is inexpensive and easy to perform. Ethanol administration via PIC is a convenient and effective mean of exposing animals to high levels of alcohol on a long-term basis.

Glial cell reactivity in a porcine model of retinal detachment.

PURPOSE: Detachment of the neural retina from the pigment epithelium causes, in addition to photoreceptor deconstruction and neuronal cell remodeling, an activation of glial cells. It has been suggested that gliosis contributes to the impaired recovery of vision after reattachment surgery that may involve both formerly detached and nondetached retinal areas. Müller and microglial cell reactivity was monitored in a porcine model of rhegmatogenous retinal detachment, to determine whether gliosis is present in detached and nondetached retinal areas. METHODS: Local detachment was created in the eyes of adult pigs by subretinal application of hyaluronate. Retinal slices were immunostained against glial intermediate filaments and K+ and water channel proteins (aquaporin-4, Kir4.1, Kir2.1), and P2Y receptor proteins. In retinal wholemounts, adenosine 5'-triphosphate (ATP)-induced intracellular Ca2+ responses of Müller cells were recorded, and microglial and immune cells were labeled with Griffonia simplicifolia agglutinin isolectin I-B4. K+ currents were recorded from isolated Müller cells. RESULTS: At 3 and 7 days after surgery, Müller cells in detached retinas showed a pronounced gliosis, as revealed by the increased expression of the intermediate filaments glial fibrillary acidic protein and vimentin, by the decrease of Kir4.1 immunoreactivity and of the whole-cell K+ currents, and by the increased incidence of cells that showed Ca2+ responses on stimulation of purinergic (P)2 receptors by ATP. By contrast, the immunohistochemical expression of Kir2.1 and aquaporin-4 were not altered after detachment. The increase in the expression of intermediate filaments, the decrease of the whole-cell K+ currents and of the Kir4.1 immunolabeling, and the increase in the Ca2+ responsiveness of Müller cells were also observed in attached retinal areas surrounding the focal detachment. The density of microglial-immune cells at the inner surface of the retinas increased in both detached and nondetached retinal areas. The immunoreactivities for P2Y1 and P2Y2 receptor proteins apparently increased only in detached areas. CONCLUSIONS: Reactive responses of Müller and microglial cells are not restricted to detached retinal areas but are also observed in nondetached regions of the porcine retina. The gliosis in the nondetached retina may reflect, or may contribute to, neuronal degeneration that may explain the impaired recovery of vision observed in human subjects after retinal reattachment surgery.

Attenuation of proinflammatory gene expression and microcirculatory disturbances by endothelin A receptor blockade after orthotopic liver transplantation in pigs.

BACKGROUND: Endothelin-1 (ET-1), a very potent mediator of vasoconstriction, leads to microcirculatory disturbances and release of proinflammatory cytokines under pathophysiologic conditions. Our aim was to evaluate the effect of a selective ET(A)-receptor antagonist (ET(A)-RA) on cold ischemia/reperfusion (I/R) injury in a pig model. METHODS: Twenty pigs revealed orthotopic liver transplantation. The animals were randomized into 2 groups: control pigs received isotonic saline; the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were re-laparotomized to obtain tissue specimens. Liver tissue samples were collected and quantitative mRNA expression for prepro-ET-1, ET(A) receptor, pro-IL-1beta, pro-IL-6, pro-TNF-alpha, and endothelial nitric oxide synthase was analyzed using the TaqMan system. Additionally, immunohistochemical analysis for ET-1 was performed. Hepatic microcirculation was evaluated by laser Doppler flow measurement and partial pressure of oxygen and carbon dioxide measurements with the Paratrend sensor. Postischemic liver damage was monitored by measurement of liver enzymes and by histologic analysis using a semiquantitative scoring classification. RESULTS: Treatment with the ET(A)-RA significantly reduced the severity of I/R injury evidenced by lower serum AST, ALT and GLDH. Analysis of partial pressure of oxygen and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with a relevant reduction of tissue injury. One hour after reperfusion, quantitative RT-PCR revealed significantly lower expression of prepro-ET-1, ET(A) receptor, endothelial nitric oxide synthase, pro-TNF-alpha, pro-IL-1beta and pro-IL-6 in the therapy group. Immunohistochemical analysis demonstrated significantly reduced ET-1 immunostaining after therapy. Histologic investigation suggested less tissue damage in treated animals. CONCLUSIONS: Treatment with the selective ET(A)-RA BSF 208075 has protective effects on microcirculation after liver transplantation. ET(A)-RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6.

Assessment of hepatic ischemia-reperfusion injury by simultaneous measurement of tissue pO2, pCO2, and pH.

INTRODUCTION: The objective of this study was to determine whether the simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple-parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A) receptor antagonist (ET(A)-RA) or isotonic saline. METHODS: Fourteen anesthetized swine were subjected to 2 h of hepatic vascular exclusion. The animals were randomized into two groups: control group (n = 7, saline solution iv) and therapy group (n = 7, ET(A)-RA). For evaluation of ischemia-reperfusion injury, the data of the multiple-parameter sensor (pO(2para), pCO(2para), and pH(para)) were compared with partial oxygen pressure in tissue (p(ti)O(2)), laser Doppler flow, and systemic hemodynamic, metabolic data, and time course of transaminases. RESULTS: In the control group 30 and 60 min after reperfusion, the following values were measured: p(ti)O(2): 34.0 +/- 8.6 / 36.3 +/- 7.0 mm Hg (P < 0.05 vs. preop.: 49.8 +/- 12.1 mm Hg), laser Doppler area: 133.3 +/- 23.2 / 156.4 +/- 15.4 (P < 0.05 vs. preop.: 215.9 +/- 14.8). Animals in the therapy group revealed significantly improved values (p(ti)O(2): 54.0 +/- 8.6 / 58.1 +/- 7.8 mm Hg, laser Doppler: 210.2 +/- 38.5 / 225.2 +/- 21.3; P < 0.05). Using the Paratrend, also an improvement in the therapy group was seen 30 and 60 min after reperfusion. The values showed a strong correlation with p(ti)O(2) (r = 0.895; P < 0.05) and laser Doppler flow (r = 0.807; P < 0.05). In the treatment group, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase (GLDH) were reduced 6 and 18 h after reperfusion, respectively, indicating hepatoprotection by the therapy (P < 0.05 vs. control). CONCLUSIONS: The Paratrend sensor offers the opportunity to study postischemic organ hemodynamics through the simultaneous measurement of interstitial pH, pCO(2), and pO(2) in a small tissue region. This method offers a prognostic tool for the study of the effects of experimental vasoactive therapy on liver microcirculation and perspectives for continuous monitoring of human liver microperfusion after liver surgery and trauma.

Changes of vasoregulatory gene expression following hepatic ischemia/reperfusion and treatment with endothelin-A receptor blockade.

The objective of this study was to investigate the effect of a specific endothelin-A receptor antagonist on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines following complete vascular exclusion of the porcine liver. Fourteen adult German Landrace pigs were subjected to 120 minutes of warm hepatic ischemia by total vascular exclusion. The animals were divided into two groups: the control group received saline solution and the therapy group was given the selective endothelin-A receptor antagonist BSF 208075. Liver tissue samples were collected 1 hour after reperfusion and mRNA expression for preproendothelin-1, prointerleukin-1beta, prointerleukin- 6, pro-tumor necrosis factor-alpha and endothelial nitric oxide synthase was analyzed quantitatively using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for endothelin-1 and endothelin-A receptor was performed. One hour after reperfusion, quantitative reverse transcriptase-polymerase chain reaction revealed significantly lower expression of preproendothelin-1, pro-tumor necrosis factor-alpha, and prointerleukin-6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced endothelin-1 immunostaining after therapy. Treatment with the selective endothelin-A receptor antagonist exerts a protective effect on the microcirculation after liver ischemia and reperfusion. We were able to show that the endothelin-A receptor antagonist not only has effects on the expression of vasoactive genes, it also decreases gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6.

Endothelin(A) receptor blockade reduces ischemia/reperfusion injury in pig pancreas transplantation.

OBJECTIVE: The effect of prophylactic administration of a selective endothelin(A) receptor antagonist (ET(A)-RA) on ischemia/reperfusion injury in an experimental model of graft pancreatitis after pancreas transplantation was evaluated. SUMMARY BACKGROUND DATA: It is well established that endothelin-1 (ET-1), a powerful vasoconstrictor, plays an important role in the development of pancreatitis. Recent studies have shown a beneficial effect of endothelin receptor antagonists in the therapy for experimental pancreatitis. METHODS: Relevant ischemia/reperfusion injury was induced in pig pancreas transplants after 6 hours hypothermic preservation in University of Wisconsin solution. The recipients were randomized into 2 groups: control pigs received isotonic saline and the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 2 and 5, animals were relaparotomized to obtain tissue specimens. Blood monitoring included lipase, amylase, C-reactive protein, trypsinogen-activation peptide, thiobarbituric acid-reacting substances, and ET-1. Partial oxygen tension (p(ti)O(2)) was measured by a Clarke-type electrode and blood flow by laser doppler. A semiquantitative score index was used for assessment of histologic injury and for immunohistochemical analysis of ET-1 and ET(A) receptor expression. Tissue mRNA levels of prepro ET-1, ET(A) receptor, pro-interleukin (IL)-6, and pro-IL-1beta were quantified using TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Prophylactic treatment with ET(A)-RA significantly reduced the severity of graft pancreatitis evidenced by C-reactive protein. The finding of transient capillary perfusion at the beginning of reperfusion supports the application of the ET(A)-RA during this period. The dramatic increase of plasma ET-1 in the therapy group is a clear evidence of effective receptor blockade. Mean trypsinogen-activation peptide levels from the portal venous effluent, but not mean systemic plasma TAP values were significantly lower in the treated group. Analysis of p(ti)O(2) and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with relevant reduction of tissue injury. Intrapancreatic ET-1 and IL-6 mRNA expression and ET-1 protein levels were significantly lower in the therapy group as compared with the control group. In contrast, ET(A) mRNA showed a marked up-regulation by ET(A) receptor blockade. CONCLUSION: Application of a ET(A)-RA reduces ischemia/reperfusion induced graft pancreatitis in a pig transplantation model by improving microcirculation and reducing tissue injury.

Endothelin A receptor blockade reduces hepatic ischemia/reperfusion injury after warm ischemia in a pig model.

It is well established that endothelin-1 (ET-1) is a very potent mediator of vasoconstriction that leads to microcirculatory disturbances. The aim of the study was to evaluate the effect of a selective endothelin A receptor antagonist on severe ischemia/reperfusion injury in a pig model. Fourteen pigs were subjected to 120 minutes of complete vascular exclusion of the liver with a passive bypass. The animals were randomized into two groups: a control group, which was given isotonic saline solution, and a therapy group, which received the selective endothelin A receptor antagonist BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were relaparotomized to obtain tissue specimens. Blood monitoring included aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), alkaline phosphatase, and ET-1. Partial oxygen tension (p(ti)O(2)) was measured by a Clarke-type electrode and blood flow by laser Doppler. A semiquantitative scoring index was used for assessment of histologic injury and for immunohistochemical analysis of ET-1. Treatment with the endothelin A receptor antagonist significantly reduced the severity of the ischemia/reperfusion injury, as evidenced by lower levels of AST, ALT, and GLDH. The dramatic increase in plasma ET-1 in the therapy group is clear evidence of effective receptor blockade. Analysis of p(ti)O(2) and blood flow revealed a significant improvement in capillary perfusion and blood flow in the treated group and was associated with relevant reduction of tissue injury. In summary, in the control group we observed serious microcirculatory disturbances and severe histologic damage in the liver after reperfusion. Treatment with a selective endothelin A receptor antagonist attenuated the ischemia/reperfusion injury in a porcine model of severe ischemia/reperfusion, as demonstrated by improved microcirculation, a reduction in histologic damage, and an decrease in liver enzymes.

Comparison of Celsior and UW solution in experimental pancreas preservation.

BACKGROUND: The University of Wisconsin solution (UW) is the gold standard for pancreas preservation. Celsior (CEL) was formulated specifically for heart preservation. Recently, experimental and clinical experience has been reported on the application of CEL to abdominal organs. In this animal study, pancreas preservation with CEL was compared with that in UW solution. PATIENTS AND MATERIALS: Heterotopic, allogeneic pancreaticoduodenal transplantation was performed in female Göttingen Minipigs (n = 12 donors, n = 12 recipients). The grafts were flushed and stored for 6 h at 4 degrees C in UW or CEL. The recipients were randomized into two groups receiving either UW (n = 6)- or CEL (n = 6)-preserved grafts with a follow-up of 5 days. Blood flow (laser Doppler), partial oxygen tension, histological changes, endothelin-1 (plasma, immunohistochemistry), lipase, amylase, trypsinogen activation peptide, and C-reactive protein (CRP) were measured. RESULTS: Partial oxygen tension was lower in the CEL group (P < 0.05). However, blood flow did not differ between UW- and CEL-preserved organs. The histomorphologic analysis of the pancreatic grafts revealed significantly less edema in the UW-preserved organs. Serum levels of amylase, lipase, CRP, and TAP taken from the central venous blood were comparable in the two groups, except for higher amylase values 36 h after reperfusion in the CEL group compared to the UW group (P < 0.05). Likewise, TAP taken from the portal venous effluent of the graft was found to be higher in the CEL group than in UW (P < 0.05). Endothelin-1 serum levels rose significantly during reperfusion without differences between the two groups. ET-1 immunohistochemistry revealed increased local ET-1 during reperfusion in all grafts. However, the ET-1 immunostaining in the CEL group was more pronounced than that in the UW group (P < 0.05). CONCLUSIONS: Our results suggest that CEL solution is not as effective in preventing pancreatic ischemia/reperfusion damage as the standard UW solution in experimental pancreas transplantation. Increased ET-1 immunostaining and reduced p(ti)O(2) in the CEL group indicate increased microcirculatory damage in the CEL group.