Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC)

Purpose

Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor.

Methods

Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n?=?44; age 60.64?±?13.78, mean?±?SD) and carcinoma patients (n?=?11; age 58.91?±?12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1–3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR).

Results

M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2?>?M3 and M3?>?M2) were observed, which differed in associated purinergic and histamine receptor expression.

Conclusions

M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.     

Reduction of ischemia/reperfusion injury by antithrombin III after experimental pancreas transplantation

BACKGROUND: Graft pancreatitis is a major complication after pancreas transplantation. Antithrombin III (AT III) is an anticoagulatory and anti-inflammatory substance. The aim of our study was to evaluate a prophylactic application of AT III in experimental pancreas transplantation. METHODS: Pancreas transplantation was performed in rats. Cold ischemia time (University of Wisconsin solution at 4 degrees C) was 12 hours. After 4 hours of reperfusion, pancreatic enzymes were assessed and the pancreas was evaluated by intravital microscopy and histologic and immunohistochemical examination. Recipients were allocated randomly to 2 groups: 1 control group (n = 6) and 1 group in which recipients received 125 IU AT III/kg 30 minutes before reperfusion (n = 6). Six animals that did not undergo transplantation served as healthy controls. RESULTS: Enzyme levels showed no differences between the 2 transplantation groups but were significantly (P <.05) higher than in the control group. Histologic damage was significantly less evident in animals that received AT III compared with transplantation animals that did not receive AT III. During intravital microscopy, animals receiving AT III showed significantly higher capillary and venular erythrocyte velocities compared with untreated transplantation animals. The leukocyte-endothelium interaction in postcapillary venules was decreased significantly in animals with AT III treatment. CONCLUSIONS: AT III pretreatment decreases tissue damage by attenuating microcirculatory disturbances and leukocyte adherence in experimental graft pancreatitis by its anti-inflammatory and anticoagulatory properties.     

Use of single‐representative reverse‐engineered surface‐models for RSA does not affect measurement accuracy and precision

Implant migration can be accurately quantified by model‐based Roentgen stereophotogrammetric analysis (RSA), using an implant surface model to locate the implant relative to the bone. In a clinical situation, a single reverse engineering (RE) model for each implant type and size is used. It is unclear to what extent the accuracy and precision of migration measurement is affected by implant manufacturing variability unaccounted for by a single representative model. Individual RE models were generated for five short‐stem hip implants of the same type and size. Two phantom analyses and one clinical analysis were performed: “Accuracy‐matched models”: one stem was assessed, and the results from the original RE model were compared with randomly selected models. “Accuracy‐random model”: each of the five stems was assessed and analyzed using one randomly selected RE model. “Precision‐clinical setting”: implant migration was calculated for eight patients, and all five available RE models were applied to each case. For the two phantom experiments, the 95%CI of the bias ranged from ?0.28 mm to 0.30 mm for translation and ?2.3° to 2.5° for rotation. In the clinical setting, precision is less than 0.5 mm and 1.2° for translation and rotation, respectively, except for rotations about the proximodistal axis (<4.1°). High accuracy and precision of model‐based RSA can be achieved and are not biased by using a single representative RE model. At least for implants similar in shape to the investigated short‐stem, individual models are not necessary. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:903–910, 2016.

     

Transplantation of a severely lacerated liver – a case report with review of the literature

Abstract:  Using lacerated livers for liver transplantation (LTx) can add an option to the extended donor criteria. We present an LTx case using a severely lacerated liver and review of the literature for reported cases. We used a high-grade lacerated liver from a 19-yr-old brain-dead patient caused by traffic accident. The liver had grade IV and II lacerations in the right and left lobe, respectively. Lacerations were managed by sealants, stitching and perihepatic packing. The liver was transplanted to a 49-yr-old man suffering from hepatocellular carcinoma on hepatitis C-induced liver cirrhosis. The two-yr follow-up was uneventful. All published LTx cases using traumatized livers (n = 18) were analyzed. The liver injury ranged from subcapsular hematoma to deep ruptures. Most reported lacerations were in the right lobe, which were managed by digital compression, suturing, electrocautery, and perihepatic packing. The reported complications were primary non- (18%), or poor function, liver abscess, bilioma, and subhepatic hematoma each in one case (5.5%). Six-month graft and patient survival were 71% and 88%, respectively. With meticulous management lacerated livers can be transplanted successfully. Because of complexity of the management, procurement and transplantation should be done by experienced liver surgeons. These organs are marginal grafts and should be offered to selected patients.     

Vascular Resection in Pancreatic Cancer Surgery: Survival Determinants

Introduction

Pancreaticoduodenectomy (PD) is the standard operation for cancer of the pancreatic head. To achieve complete tumor resection and, thus, improve long-term survival, venous resection of the portal or superior mesenteric vein with reconstruction has become routine for advanced pancreatic adenocarcinoma (PDAC). However, its clinical benefit still remains controversial. The aim of this study was to investigate morbidity, mortality, and survival of patients with advanced PDAC following PD with venous resection and to identify significant survival determinants.

Material and Methods

From October 2001 to December 2007, 488 patients with PDAC of the pancreatic head underwent PD at our department. Venous resection was performed in 110 patients (22.5%). Clinical data, surgical techniques, perioperative parameters, and histopathologic data were analyzed on a prospective database.

Results

Major venous reconstruction was accomplished through primary lateral venorrhaphy in 18 patients (16.3%), polytetrafluoroethylene grafting (n?=?14, 12.7%), primary end-to-end anastomosis (n?=?72, 65.5%), an autologous saphenous venous graft patch (n?=?4, 4.6%) or a Goretex® patch (n?=?2, 2.3%). In 78.1% histopathologic examination revealed cancer invasion of the vein, whereas the remainder had peritumoral inflammation extending to the vessel wall. Perioperative morbidity rate was 41.8%; and the mortality rate 3.6%. The 1-, 2-, and 3-year survival rates were 55.2%, 23.1%, and 14.4%, respectively. Operating time (>420 min) and advanced age (>70 years) were the only prognostic variables, which significantly diminished survival on multivariate analysis.

Conclusion

Resection of the superior mesenteric or portal vein to achieve macroscopic tumor clearance can be performed safely with acceptable operative morbidity and mortality. However, improved local clearance in these patients cannot achieve a favorable long-term survival for all patients because distant metastases or local recurrence is frequent.     

Histological osseointegration of Tutobone<Superscript>®</Superscript>: first results in human

The aim of this study was to evaluate the histological and radiological osseointegration characteristics of implanted solvent-preserved cancellous bovine bone substitution material Tutobone after opening-wedge osteotomy and hip arthroplasty in human. The baseline hypothesis connected to the usage of bovine bone substitute materials is the assumption of temporary structural support, integration in the surrounding bone, bioresorption and replacement with vital bone. This hypothesis is based on numerous studies evaluating sintered bovine grafts showing good osseointegration and stability. Studies analyzing cancellous bovine grafts such as Tutobone hardly exist. The only rabbit defect model showed 100% remodeling of Tutobone after 26 weeks. However, no histological data are available on application of this xenograft in patients. In this study, nine patients biopsies were collected about 11 months after application of Tutobone. Unlike animal studies, the results showed incorporated avital graft remnants (47%) as well as new bone formation (53%) of the total mineralized area. Radiological evaluation confirmed increasing signs of osseointegration and an incomplete resorption. In conclusion, degradation and replacement of bovine graft seems to be less accelerated in patients than the animal study indicated. Nevertheless, Tutobone shows an excellent biocompatibility, good osteoconductive characteristics and may represent a useful alternative to autogenous graft.     

Osteitis Unterschenkel

Osteomyelitis patients feel their social and professional existence is threatened. Health insurances are faced with total treatment costs for each patient with osteomyelitis, which can reach 500.000,00 EUR. We must therefore make every effort, from the first onset of infection, to prevent the condition from becoming chronic and thus keep the potential problems to patients and insurance companies to a minimum: once the condition has become chronic there is absolutely no guarantee that treatment will be successful. Treatment must start with the removal of absolutely all necrotic tissue – soft tissue and bone – and of all implants. As in tumor surgery, en bloc resection is best. Up to now there is still no means of determining the exact limits of the infection. The surgeons's personal experience with osteomyelitis is the most important factor both in the treatment of these cases and therefore in the containment of treatment costs. Bone reconstruction is attempted after the soft tissue defects have been treated, either by bone grafting (defect < 3 cm) or by segment transfer. Modern techniques of reconstruction surgery can yield quite good results even in chronic oxteomyelitis, providing management has been optimum throughout. Patients with osteomyelitis should therefore be treated in specialist hospitals.     

Fixateur externe und Weichteilschaden

External fixation is an apparently simple and therefore highly fascinating method for the stabilization of fractures.Minimally invasive incisions guarantee that regional soft tissue perfusion is conserved after trauma,which makes it the best procedure for stabilization of fractures combined with severe soft tissue damage.However, modern trauma surgery is subject to cyclical trends in the same way as fashion is; noninternal devices are currently barely tolerated.The literature suggests that specialists are virtually competing to see who can stabilize fractures with the most severe soft tissue damage by internal procedures – with the best results, of course. It seems, then, that times are hard for external fixation, but we still believe that for fractures with severe soft tissue damage external fixation still brings a lot of benefit to the patient.     

Klinische Erfahrungen mit der Knorpel-Knochen-Transplantation

The treatment of deep cartilage defects in load-bearing joints is a problem that still has no satisfactory solution. Full-thickness defects of the articular cartilage rarely heal spontaneously, usually leaving damage that can lead to early arthrosis. Techniques currently available for the treatment of chondral defects include abrasion, drilling, micro-fracturing, transplantation of tissue autografts and allografts, and cell transplantation. Osteochondral autograft transplantation is currently the only surgical cartilage repair technique known to lead to the formation of genuine hyaline articular cartilage and its retention at least in the medium term. The Draenert method, in which a water-cooled diamond bone-cutting system is used, is an effective procedure for resurfacing the joints affected by localised cartilaginous defects, even when there is also severe bone loss. Donor-side morbidity can be kept to a minimum by filling the defect caused by harvesting with a press-fit cylinder of cancellous bone covered with periosteum for protection.