Acute myocardial infarction and arterial embolism in a patient with newly diagnosed renal mass: management dilemmas! A case report.

BACKGROUND: Cancer is often associated with a hypercoagulable state and new thrombosis is often the first clinical manifestation of cancer. Surgical treatment of the primary tumor is crucial since it provides the only curative approach in most cases, but management of patients is highly complex, especially in the presence of new antiplatelet drugs and/or anticoagulants. Paraneoplastic syndromes (PNS) represent a frequent complication of renal cell carcinomas (RCC) and include different hematological symptoms in patients, whilst occlusion of arterial blood vessels displays a rare form of PNS accompanying renal tumors. CASE PRESENTATION: We report the case of a 62-year old man who was initially hospitalized due to acute coronary syndrome. He subsequently underwent coronary angioplasty treatment including multiple stenting and treatment with ticagrelor and aspirin. Post-interventional, acute arterial thrombotic emboli of several limb arteries required thrombectomy. By computer tomography we identified a renal lesion suspicious for an RCC and suspected a PNS as underlying cause of the thrombotic complications. Triple anticoagulant therapy was maintained with therapeutic dose low molecular weight heparin (LMWH), aspirin, and clopidogrel, by which we replaced ticagrelor. Surgery was postponed for 4 weeks. We paused LMWH, aspirin and clopidogrel only at the day of surgery and perioperatively restored hemostasis by transfusion of two platelet concentrates. Laparoscopic nephrectomy was uneventful. Pathology confirmed a clear cell RCC. The patient fully recovered whilst slowly reducing anticoagulation dose. CONCLUSIONS: A multidisciplinary team approach of experts in urology, cardiology and hemostasis was key in managing this patient since a personalized thrombosis consult was needed to minimize the risk of reinfarction due to in-stent thrombosis. We report a therapeutic protocol that may be helpful for the management of similar cases. Furthermore, the finding of thrombotic arterial occlusions in larger blood vessels represents a novel complication of PNS in RCC and adds to the varied possible manifestations of this clinical chameleon.

Effects of copper-impregnated collagen implants on local pro- and anti-inflammatory and regenerative tissue reactions following implantation in rats.

Combining collagen, an established regenerative biomaterial, and copper (Cu) with its known antibacterial and angiogenic effects could improve wound healing. However, Cu is also cytotoxic. Thus, this study aimed at examining the tissue reactions after simultaneous intramuscular implantation of collagen discs either without Cu (controls) or impregnated in 2, 20, or 200 mmol/L Cu acetate in 24 rats. After 7, 14, and 56 days, implants with peri-implant tissue were retrieved from 8 rats/day for immunohistochemical detection of CD68+ monocytes/macrophages and CD163+ macrophages, MHC-II+ cells, T lymphocytes and nestin as tissue regeneration marker. CD68+ monocytes/macrophages around implants increased with Cu amount but decreased over time except for the highest Cu amount, while CD163+ macrophages increased over time around and within implants. MHC-II+ cells were similar to CD68+ monocytes/macrophages. T lymphocyte numbers around implants were higher for Cu-impregnated samples vs. controls on day 7 and highest on day 14, but declined afterwards. Nestin expression around and within implants was largely unaffected by Cu. In conclusion, pro-inflammatory reactions around implants were dose-dependently influenced by Cu but mostly decreased over time, while Cu did not negatively affect anti-inflammatory and regenerative reactions. These results suggest that Cu-impregnated collagen could be beneficial in wound treatment.

The in vivo inflammatory and foreign body giant cell response against different poly(l-lactide-co-d/l-lactide) implants is primarily determined by material morphology rather than surface chemistry.

Biomaterials can cause a chronic local inflammation called foreign body reaction, with formation of foreign body giant cells (FBGC) by monocyte/macrophage fusion. However, FBGC appearance and role for biomaterials with different physicochemical properties are not yet fully understood. This study aimed at examining FBGC and inflammatory cells after intramuscular implantation of poly(l-lactide-co-d/l-lactide) (PLA) as membranes and uncoated electro-spun fiber meshes or meshes with a positively charged plasma-polymer coating into rats. After 7, 14 and 56 days, CD68+ and CD163+ macrophages, T lymphocytes, MHC-II+ cells, FBGC, and nestin-stained tissue area as regeneration marker were morphometrically analyzed. FBGC occurrence was primarily determined by material morphology, as their numbers for meshes were 10-fold higher during acute and 50-fold higher during chronic inflammation than for membranes but comparable between uncoated and coated meshes. CD68+ macrophages decreased around and within meshes, while CD163+ macrophages and MHC-II+ cells increased within meshes. T lymphocytes within meshes were higher for coated meshes, suggesting that the peri-implant tissue immunological response is also influenced by surface chemistry. FBGC were predominantly CD68+ and CD163- , and nestin-stained tissue area was negatively correlated with CD68+ monocytes/macrophages numbers and positively correlated with CD163+ macrophages numbers, highlighting differing roles in FBGC formation and tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2726-2734, 2018.

Systemic IFNγ predicts local implant macrophage response.

Implantation of biomaterials can cause complications often associated with inflammatory reactions. However, repeated evaluation of the implant site would be burdening for patients. Alternatively, blood examinations with analysis of inflammatory serum markers could potentially be useful to reflect the local cellular response for detection and/or prediction of inflammation-related complications. Therefore, following intramuscular implantation of surface-modified Ti implants in rats, this study aimed at examining possible associations between the post-implantation time course of pro-inflammatory (INFγ, IL-2) and anti-inflammatory (IL-4, IL-10) cytokine serum concentrations and the local peri-implant tissue response after 56 days (pro-inflammatory CD68-positive monocytes/macrophages, anti-inflammatory CD163-positive macrophages, MHC class II-positive cells, activated natural killer cells and mast cells). Multivariate correlation analysis revealed a significant interaction between serum IFNγ and peri-implant tissue CD68-positive monocytes/macrophages (p = 0.001) while no interactions were found for other cytokines and cell types. Additional Pearson correlation analysis of IFNγ serum concentrations on each experimental day vs. the CD68-positive monocytes/macrophages response on day 56 demonstrated a consistently positive correlation that was strongest during the first three weeks. Thus, high early pro-inflammatory IFNγ serum concentration was associated with high late number of pro-inflammatory CD68-positive monocyte/macrophages and low early serum IFNγ with low late CD68-positive monocyte/macrophage numbers. Further studies aimed at examination of patient samples could establish the relevance of this association to predict clinical complications. After implantation of titanium samples, high early IFNγ serum concentrations were associated with a pronounced late pro-inflammatory CD68-positive monocyte/ macrophage (red circle) response, while no correlation was found for other investigated cytokines and inflammatory cells (green circle). In contrast, low early IFNγ serum concentrations were correlated with low late monocyte/ macrophage numbers.

Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.

Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX) were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells) were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like) macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like) macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material.

Evaluation of short-term and long-term results after laparoscopic antireflux surgery: esophageal manometry and 24-h pH monitoring versus quality of life index.

PURPOSE: The objective of this long-term study is to compare data on postoperative quality of life with objective functional measurements in patients with gastroesophageal reflux disease who have undergone laparoscopic antireflux surgery. METHODS: Between 1995 and 2005, 162 patients with gastroesophageal reflux disease underwent laparoscopic surgery. A minimum of 4 years after surgery, 60 patients were contacted at random, 29 of whom agreed to follow-up examination. The following examinations were performed preoperatively, 6 months postoperatively, and 4-12 years postoperatively: esophageal manometry, 24-h gastroesophageal pH-metry, and assessment of patient quality of life based on the gastrointestinal quality of life index (GIQLI). RESULTS: The number of postsurgical reflux episodes was reduced significantly, both at 6 months and at 4 or more years after surgery. The number of episodes dropped from 183 before surgery to 58 at 6 months after surgery and remained constant ≥ 4 years later. Surgery also produced a significant drop in reflux time, seen both 6 months and ≥ 4 years later. Six months after surgery, the median reflux time had fallen from 134 min (preoperatively) to 27 min, and at ≥ 4 years it was still significantly reduced at 35 min. Sphincter length (median preoperative length, 3 cm; median postoperative length (at 6 months and at ≥ 4 years), 4 cm) and sphincter pressure (median preoperative pressure, 3 mmHg; median at 6 months, 12 mmHg; median at ≥ 4 years, 10.9 mmHg) were significantly improved by surgery as well. Finally, surgery produced an improvement in quality of life. The median preoperative GIQLI was 102, while at 6 months after surgery it was 113 and at ≥ 4 years after surgery it was 124. CONCLUSION: Laparoscopic fundoplication guarantees long-term improvement in symptoms and quality of life for patients suffering from gastroesophageal reflux disease. The effectiveness of reflux surgery can thus be demonstrated by long-term quality of life assessments and postoperative functional measurements. No statistically significant correlation between total score (DeMeester) and GIQLI could be demonstrated.

In vivo evaluation of copper release and acute local tissue reactions after implantation of copper-coated titanium implants in rats.

Copper (Cu) based coatings can reduce infections for titanium (Ti) implants. However, Cu is also cytotoxic. To examine the balance of antibacterial versus adverse tissue effects, this study aimed at evaluating a Cu coating regarding in vivo Cu release and local inflammatory reactions for 72 h. TiAl6V4 plates received either plasma electrolytic oxidation only (Ti), or an additional galvanic Cu deposition (Ti-Cu). No Staphylococcus aureus were found in vitro on Ti-Cu after 24 h. Following simultaneous intramuscular implantation of two Ti and two Ti-Cu plates into nine rats, serum Cu was elevated until 48 h and residual Cu on explanted samples reduced accordingly after 48 h. Total and tissue macrophages around implants increased until 72 h for both series, and were increased for Ti-Cu. As numbers of total and tissue macrophages were comparable, macrophages were probably tissue-derived. MHC-class-II-positive cells increased for Ti-Cu only. T-lymphocytes had considerably lower numbers than macrophages, did not increase or differ between both series, and thus had minor importance. Tissue reactions increased beyond Cu release, indicating effects of either surface-bound Cu or more likely the implants themselves. Altogether, Ti-Cu samples possessed antibacterial effectiveness in vitro, released measurable Cu amounts in vivo and caused a moderately increased local inflammatory response, demonstrating anti-infective potential of Cu coatings.

Examination of the inflammatory response following implantation of titanium plates coated with phospholipids in rats.

Implantation of biomaterials like titanium (Ti) causes inflammatory reactions possibly affecting implant functionality. Surface modifications could improve biocompatibility and functionality of implants. Biomembrane-derived phospholipids might be useful as implant coating due to their biomimetic properties. In vitro studies demonstrated beneficial effects for 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphoethanolamin (POPE) as coating regarding interactions with cells and bacteria. Therefore, this in vivo study aimed at examining local inflammatory reactions after implantation of POPE-coated Ti plates. Ti implants with POPE attached non-covalently or covalent via octadecylphosphonic acid (OPA), with OPA alone and uncoated controls were simultaneously implanted intramuscularly in rats for 7, 14 and 56 days. The peri-implant tissue was quantitatively analyzed by immunohistochemistry for total macrophages, tissue macrophages, T cells, antigen-presenting cells and proliferating cells. Overall, both POPE-coated series were comparable to the controls. Furthermore, no differences were found between POPE coating on a covalently linked OPA monolayer and POPE coating dried from solution. Together with earlier in vitro results, this demonstrates the potential of phospholipids for implant surface modification.

Laparoscopic partial splenectomy using a detachable clamp with and without partial splenic embolisation.

BACKGROUND: In many centres, the laparoscopic total splenectomy is a well-established routine procedure. However, the crucial immunological role of the spleen in combating bacterial infections, in particular pneumonias, has led to a search for splenic-preserving techniques whenever possible. Yet, laparoscopic partial splenectomies are still rarely described possibly due to difficulties in controlling intra-operative parenchymal bleeding during splenic transection. METHODS: Here, we present a case series of laparoscopic partial splenectomies using a new technique. The main splenic artery and vein were temporarily clamped using a detachable clip. Transection of the spleen was possible working with the LigaSure™ instrument. After transection, the margin was sealed with a collagen fleece. In one case of a haemangioma, the patient underwent a radiological coil embolisation of the feeding arteries of the splenic pole in question. This was done 4 weeks prior to surgery and included embolisation of the tumour. RESULTS: Three patients (2 males, 1 female, mean age 58.3 years) have been successfully treated using a detachable clamp. The pre-surgical mean size of the spleen was 8.0 × 16.7 cm (range 6 × 14-11 × 22 cm). The removed specimens had a mean size of 4.2 × 5.5 cm (range 2.5 × 4.0-5.0 × 6.5 cm). The time of surgery averaged 144 min (range 110-187 min). Blood loss was minimal thereby avoiding the need for blood transfusions. The post-surgical course was uneventful; patients were discharged 5 days following surgery. Histopathology showed a benign splenic haemangioma, a benign splenic hamartoma and the presence of Hodgkin's disease stage III. CONCLUSIONS: The technique of laparoscopic partial splenectomy and, in certain patients, pre-surgical partial splenic embolisation is safe and effective for patients with localised diseases of the spleen. This approach combines the benefits of the minimal surgical access with saving a significant amount of splenic tissue, thereby preserving the immune function of the spleen.

Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs.

Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear. This study was aimed at investigating the time course of the fibronectin area fraction and neointima formation following the functional implantation of three different polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n = 5/group) was replaced by prosthesis segments with low, medium and high primary porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically examined. Overall, the fibronectin area fraction was inversely correlated with the neointima thickness, demonstrating high fibronectin levels in the early phase (days 7 and 14) and low levels in the later phase with almost complete neointima formation (days 21-116). Throughout the study, fibronectin levels were highest at the proximal anastomosis region. The low porosity prosthesis had the highest fibronectin area fraction and a delayed neointima formation in the middle phase (days 21 and 28) but the highest neointima lining on day 116. The results indicate a relationship between fibronectin and neointima formation with the prosthesis porosity, demonstrating the importance of the textile design for tissue reactions following implantation.

Morphometric immunohistochemical examination of the inflammatory tissue reaction after implantation of calcium phosphate-coated titanium plates in rats.

Calcium phosphate (CaP) preparations are established coatings for titanium-based medical implants used for bone reconstruction. However, biodegradation of the coating can result in microparticles that subsequently cause inflammatory reactions. The present study was therefore aimed at investigating the inflammatory response to two series of CaP-coated titanium plates: Ti-brushite (Ti-B) and Ti-hydroxyapatite (Ti-H) implants. Fifteen male LEW.1A rats received one plate of each series and a pellet (5 x 2 mm) of sol-gel derived silica/CaP (SCP implants) implanted into the back musculature. After 7, 14 and 28 days, five rats were killed and the implants were removed with the surrounding tissue. Quantitative immunohistochemistry was performed on frozen sections. Total monocytes/macrophages, tissue macrophages, T-cells, MHC-class-II-positive cells and proliferating cells were counted. For the Ti-B implants, the number of monocytes/macrophages remained constant while the other cell populations increased. In contrast, for the Ti-H implants the number of monocytes/macrophages decreased while the other cell populations remained constant. The SCP implants demonstrated degradation and scattering into smaller particles with an increase for all cell populations except the proliferating cells. Human mesenchymal stem cells demonstrated adherence and a flat morphology on Ti-B and Ti-H implants and no remarkable difference between both implants. Taken together, the in vivo data demonstrate that the short-term inflammatory response against a hydroxyapatite coating is lower in comparison to a brushite coating, and that the morphology of cells growing in vitro is similar on both layers.

Pathophysiological measurement and results after laparoscopic fundoplication for gastroesophageal reflux disease.

PURPOSE: Both surgical and conservative treatments for gastroesophageal reflux disorder (GERD) are controversial. The aim of this prosepective study was to examine outcomes after laparoscopic antireflux surgery. METHODS: The subjects were 143 patients who underwent laparoscopic antireflux surgery. Following diagnostic procedures 126 patients were allocated to a total fundoplication group (360 degrees C, Nissen-DeMeester) and 17, to a posterior semifundoplication group (250-270 degrees, Toupet). All complications were registered, and pathophysiological and outcome data were examined 3, 6, and 9 months after surgery. RESULTS: By 6 months after surgery the mean lower esophageal sphincter (LES) pressure had improved significantly, to 14.8 mmHg in the Nissen-DeMeester group, and to 12.1 mmHg in the Toupet group, corresponding to successful prevention of esophageal reflux in both groups. Dysphagia was more common in the early postoperative period after total fundic wrap (17% vs12%), but this difference disappeared in time. All patients reported complete relief of reflux symptoms, although two of those who underwent the Nissen-DeMeester fundoplication experienced relapse of GERD and required open reconstruction (1.4%). The laparoscopic procedure was converted to open surgery in three patients (2%). There were no associated deaths and the perioperative complication rate was 4.2%. CONCLUSION: Laparoscopic antireflux surgery is an effective treatment for GERD. More than 93% of the patients in this series rated their outcome as good to excellent following the operation.