Excessive Granulation Research Articles

Atemwegskomplikationen nach Lungentransplantation – Klinik, Diagnose und interventionelle Behandlung

Tracheobronchial complications following lung transplantation are defined as local structural or infectious alterations of the airways, which occur early or several months after lung transplantation (LTx). They preferentially develop in the region of the bronchial anastomosis. The most frequently reported complications are bronchial stenosis, bronchial dehiscence, exophytic excessive granulation tissue formation, tracheo-bronchomalacia, bronchial fistulas, and endobronchial infections. Airway complications are mainly attributed to ischaemia of the donor bronchus during the immediate post-transplant period. The most relevant risk factors for the development of airway complications include local infections, surgical techniques, and the immunosuppressive regimen. Thus, management of post-transplant bronchial complications requires early interventional bronchoscopic procedures including balloon bronchoplasty, cryotherapy, laser photoresection, endobronchial brachytherapy, and bronchial stents. In addition, antibiotic treatment, or non-invasive positive-pressure ventilation may be necessary. The procedures required depend on the time of occurrence, the type, and clinical relevance of the airway complication. This review summarises clinical presentation, risk factors, the diagnostic methods as well as management options for the most common LTx-associated airway complications.

Low-Level Laser Therapy (LLLT) at 830 nm Positively Modulates Healing of Tracheal Incisions in Rats: A Preliminary Histological Investigation

The aim of the present study was to evaluate whether LLLT at 830 nm is able to positively modulate trachea incisional wound healing in Sprague-Dawley rats. Tracheotomy may be associated with numerous complications. Development of excess granulation tissue represents a late complication that may lead to airway occlusion. Low-level laser therapy (LLLT) has been shown to have stimulatory effects on wound healing of different tissues. Therefore, it may be suggested that LLLT could be able to positively modulate trachea wound healing as well. Using general anesthesia, a median incision was performed from the second to the fifth tracheal cartilage ring in 24 rats. Animals were then randomly divided into sham-irradiated control and laser-treated groups. LLLT (power density: 450 mW/cm(2); total daily dose: 60 J/cm(2); irradiated area ∼1 cm(2)) treatment was performed daily during the first week after surgery. Samples for histological evaluation were removed 7 and 28 days after surgical procedure. Histological sections were stained with hematoxylin-eosin and van Gieson. Results from our investigation showed that LLLT was able to reduce granulation tissue formation and simultaneously increase new cartilage development at both evaluated time intervals. From this point of view, LLLT at 830 nm may be a valuable tool in trachea wound healing modulation. Nevertheless, further detailed research is needed to find optimal therapeutic parameters and to test these findings on other animal models.

The effects of Vaseline gauze strip, Merocel, and Nasopore on the formation of synechiae and excessive granulation tissue in the middle meatus and the incidence of major postoperative bleeding after endoscopic sinus surgery

Background Endoscopic sinus surgery (ESS) has become the widely accepted procedure for the treatment of medically refractory chronic rhinosinusitis and nasal polyps. Nasal packing is usually placed after ESS to prevent synechia formation and postoperative bleeding and to support wound healing. The aim of this study was to evaluate the effects of three different nasal packing materials [Vaseline gauze strip, Merocel (Metronic Xomed, Jacksonville, FL, USA), and Nasopore (Polyganics, Rozenburglaan, Groningen, The Netherlands)] on the formation of synechiae and excessive granulation tissue in the middle meatus and incidence of major postoperative bleeding in patients who had undergone ESS. Methods A total of 626 patients (1,018 sides) who had undergone ESS were studied retrospectively. Each patient chose one of the three different nasal packing materials according to his or her own preference. The outcome variable was the formation of synechiae and excessive granulation tissue in the middle meatus, which was identified from the medical records of endoscopic evaluations performed 3–4 weeks and 10–12 weeks after surgery. Major postoperative bleeding within 2 weeks after the operation was also documented for analysis. Finally, multiple logistic regression models were used to confirm the results of this study. Results We did not observe significant intergroup differences in the effect on the formation of synechiae in the middle meatus. Nasopore packing showed a trend toward causing the formation of excessive granulation tissue during the early stages of wound healing ( p = 0.004). Patients who had received packing with Nasopore had a greater chance of undergoing readmission or additional packing because of major nasal bleeding within the first 2 weeks after the operation ( p = 0.03). Multivariable logistic regression models showed that Nasopore was a significant factor for the formation of excessive granulation tissue at 3–4 weeks after the operation ( p = 0.022) and for major postoperative nasal bleeding within the first 2 weeks after the operation ( p = 0.023). Conclusion Among patients who had undergone ESS for rhinosinusitis with or without polyps, the incidence of synechiae and excessive granulation tissue in the middle meatus and major postoperative bleeding in the patients who received Vaseline gauze packing was equivalent to the incidence of these complications in the patients who received Merocel. Nasopore was not superior to the other two nonabsorbable packing materials.

Percutaneous Endoscopic Gastrostomy Placement in a Human Immunodeficiency Virus–Positive Pediatric Population Leads to an Increase in Minor Complications

The development of effective multiple drug regimens for treating human immunodeficiency virus (HIV) are associated with nonadherence in children. HIV-positive children also have a higher incidence of malnutrition. Placement of a percutaneous endoscopic gastrostomy (PEG) is a potential solution. Primary outcome was to determine the complications of PEG placement in a pediatric HIV-positive population. A 10 year retrospective data analysis was carried out on all HIV-positive children undergoing insertion of a PEG at two institutions. Parameters examined included infections, leakage, displacement, reasons for removal, total time in situ, HIV stage, CD4 count, and serological investigation. Data were compared against published data for PEG insertion in pediatric oncology patients and other comparable pediatric series using Fisher's exact test. Eighteen children were identified, with a median age 35 months and follow-up of 62 months. The majority of patients had advanced disease (Stage C; 65%). Fifty percent of PEGs were inserted for feeding supplementation and all were used for the administration of medications. Sixty-one percent experienced a minor complication; 5/18 (27.7%) experienced peristomal infection; 2/18 (11.1%) experienced either bleeding, leakage, or excessive granulation; and 1/18 (5.6%) experienced dislodgement. Stage of HIV did not affect the incidence of bleeding or infection: 5/11(Stage C) versus 2/7(Stage B) (P = .3). There was no significant difference for major complications when compared with any series though comparison with a large pediatric series revealed a significant difference for minor complications 11/18 versus 27/120 (P = .0003). There is a low rate of serious complications with PEG insertion in our patients, and the rate is comparable to that seen in pediatric oncology patients. The minor complication rate is, however, higher than a nonimmune compromised population; and careful follow-up for these patients is recommended so that the appropriate therapy can be promptly initiated.

The influence of macrophage depletion on ligament healing

Despite a complex cascade of cellular events to reconstruct damaged extracellular matrix (ECM), ligament healing results in a mechanically inferior, scar-like tissue. During normal healing, the number of macrophages significantly increases within the wound site. Then, granulation tissue expands into any residual, normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise, and an inefficient repair process. To study the effects of macrophages on the repair process, bilateral, surgical rupture of their medial collateral ligaments (MCLs) was done on rats. Treatment animals received liposome-encapsulated clodronate, 2 days before rupture to ablate phagocytosing macrophages. Ligaments were then collected at days 5, 11, and 28 for immunohistochemistry (IHC) and/or mechanical testing. Clodronate treatment reduced both the M1 and M2 macrophages at day 5 and altered early healing. However, the macrophages effectively returned to control levels after day 5 and reinitiated a wound-healing response. Our results suggest that an early macrophage response, which is necessary for debridement of damaged tissue in the wound, is also important for cytokine release to mediate normal repair processes. Additionally, nonspecific inhibition of macrophages (without regard to specific macrophage populations) can control excessive granulation tissue formation but is detrimental to early matrix formation and ligament strength.

Removal of metallic tracheobronchial stents in lung transplantation with flexible bronchoscopy

BackgroundAirway complications are among the most challenging problems after lung transplantation, and Self-Expandable Metallic Stents (SEMS) are used to treat airway complications such as stenosis or malacia at the bronchial anastomosis sites. Several transplantation centers are reluctant to use SEMS since their removal is sometimes needed and usually requires the use of rigid bronchoscopy under general anesthesia. The objective of the current report is to describe our experience in SEMS retrieval by flexible bronchoscopy under conscious sedation.MethodsA retrospective review was done of patients requiring tracheobronchial stent placement after lung transplantation in which the SEMS had to be removed. The retrieval procedure was done by flexible bronchoscopy on a day-care ambulatory basis.ResultsBetween January 2004 and January 2010, out of 305 lung transplantation patients, 24 (7.8%) underwent SEMS placement. Indications included bronchial stenosis in 20 and bronchomalacia in 4. In six patients (25%) the SEMS had to be removed due to excessive granulation tissue formation and stent obstruction. The average time from SEMS placement to retrieval was 30 months (range 16-48 months). The stent was completely removed in five patients and partially removed in one patient; no major complications were encountered, and all patients were discharged within 3 hours of the procedure. In all procedures, new SEMS was successfully re-inserted thereafter.ConclusionsThe retrieval of SEMS in patients that underwent lung transplantation can be effectively and safely done under conscious sedation using flexible bronchoscopy on a day-care basis, this observation should encourage increasing usage of SEMS in highly selected patients.

Aortic valve replacement and coronary artery bypass via left anterior thoracotomy after previous left pneumonectomy

stabilization of the long-segmental tracheobronchomalacia has been described. This report demonstrates that this concept is effective for carinal stabilization. A recent study of 40 children, 11 of whom had left PA sling, identified preoperative mechanical ventilatory support and duration of CPB to be significant risk factors for prolonged postoperative ventilatory support. Repair of PA sling complex and other cardiovascular anomalies increases the complexity of surgery and duration of CPB, thus exposing patients to a higher risk of prolonged postoperative ventilatory support. Excessive endotracheal granulation at the site of mechanical irritation by the endotracheal tube often develops in patients with PA sling complex and tracheomalacia, who require prolonged ventilatory support. External stabilization of the carina permitted an uneventful and early extubation in our patient despite prolonged CPB. Covering the trachea with the pericardial flap after tracheoplasty, as previously described, was helpful in our patient to reinforce the tracheal anastomotic seal, to prevent erosion of the polytetrafluoroethylene (GoreTex) rings into the blood vessels, and to enable safer subsequent bronchoscopic interventions. Potential long-term

Complete and partial hoof wall resection for keratoma removal: post operative complications and final outcome in 26 horses (1994-2004)

There are no data on the frequency of post operative complications following keratoma removal, such as recurrence, hoof wall instability and excessive granulation tissue formation, or their relation to the method of surgical removal. To identify important factors in the outcome for horses undergoing surgical removal of a keratoma and compare the post operative complications encountered following keratoma removal by complete hoof wall resection (CR) and partial hoof wall resection (PR). Horses undergoing PR would have fewer post operative complications and would return to work more quickly than those undergoing CR. A retrospective review of medical records from one equine hospital identified 26 horses that underwent removal of a keratoma by CR or PR. Clinical, radiological and surgical findings and outcome were analysed. Common clinical signs included lameness and the presence of a subsolar abscess. Fourteen horses underwent CR and 12 PR. The complication rate following CR (71%) was significantly lower than that following PR (25%) (P<0.01). Complications encountered included excess granulation tissue formation, hoof crack formation and keratoma recurrence at the surgical site. The time taken to return to full work post operatively was significantly shorter in horses undergoing PR compared to CR (P<0.01). All horses, except one, returned to their previous exercise level. PR resulted in fewer post operative complications and a more rapid return to athletic activity than CR. Although the overall complication rate for CR was higher than for PR, the overall prognosis for return to soundness and the previous performance level is very good.

Impaired cutaneous wound healing with excess granulation tissue formation in TNFα-null mice

We examined the effects of lacking tumor necrosis factor alpha (TNFalpha) on the healing process of a cutaneous wound in mice using TNFalpha-deficient mice. A full-thickness circular cutaneous wound 5.0 mm in diameter was produced in the dorsal skin of wild-type (WT) or TNFalpha-null (KO) mice. After specific intervals of healing, the healing pattern was evaluated by macroscopic observation, histology, immunohistochemistry, or real-time reverse transcription-polymerase chain reaction. Effect of Smad7 gene transfer on the healing phenotype of KO mice was also examined. The results showed that loss of TNFalpha promotes granulation tissue formation and retards reepithelialization in a circular wound in mouse dorsal skin. Immunohistochemistry showed that distribution of macrophages and myofibroblasts in newly generated granulation tissue seemed similar between WT and KO mice. However, lacking TNFalpha enhanced mRNA expression of TGFbeta1 and collagen Ialpha2 in such tissue. Smad7 gene transfer counteracted excess granulation tissue formation in KO mice. In conclusion, lacking TNFalpha potentiates Smad-mediated fibrogenic reaction in healing dermis and retards reepithelialization in a healing mouse cutaneous wound.

Effect of bandaging on second intention healing of wounds of the distal limb in horses

To evaluate the effect of a non-occlusive dressing incorporated in a 3-layer bandage on second intention healing of wounds of the distal portion of the limb. Untreated wounds in 33 adult horses used in four studies using the same wound-healing model conducted over 5 years. Standardised, full-thickness wounds were made in the skin overlying the dorsomedial aspect of the mid-metacarpus; 17 horses were bandaged with a non-occlusive dressing covered by gauze-coated cotton wool that was compressed with adhesive tape; 16 horses were left unbandaged. Wounds were photographed weekly for 9 weeks and the images were analysed electronically. There were significant effects associated with bandage (P < 0.0001), week (P < 0.001), and bandage by week interaction (P < 0.0001). There was no difference in wound area at the first time-point after wound creation (P = 0.38). After week 1, there was a difference between bandaged and unbandaged wounds in wound area at each measurement until the end of the study. Bandaged wounds showed greater and more prolonged retraction. Unbandaged wounds retracted for 2 weeks before beginning to contract, whereas bandaged wounds continued to retract for 3 weeks. In bandaged wounds excess granulation tissue required regular trimming, but not in unbandaged wounds. There was no difference between groups in the total days to healing or the overall rate of healing. These results should be treated with caution until validated with contemporaneous, controlled studies. Covering a wound with a non-occlusive dressing in a 3-layer bandage led to greater wound retraction, modulated the rate of wound contraction and promoted excessive granulation tissue. If excessive granulation tissue is excised regularly, bandaging has no effect on total time to healing.

Excessive granulation tissue at the harvest site following pterygium surgery with conjunctival autograft: a clinicopathological case report

A 31-year-old woman had an uneventful primary pterygium surgery with a conjunctival autograft. Four days following the surgery a red-violet-coloured lesion appeared at the bare autograft harvest site that was excised at postoperative 1 month leaving the autograft site bare again. The lesion recurred in a week. The excision was repeated but this time the sclera was closed by end-to-end suturation of conjunctiva. The lesion did not recur during the 3 months of follow up. Pathological examination revealed the lesion to be composed of granulation tissue composed of an overlying stratified epithelium and underlying marked vascularization, fibroblasts and lymphomonocyte cells. Excessive granulation tissue may form when there is a deviation in wound healing. Removal of the excessive granulation and restoration of the continuity of the surrounding epithelium should be curative.

Airway Complications and Management after Lung Transplantation: Ischemia, Dehiscence, and Stenosis

Overall survival rates of lung transplantation have improved since the first human lung transplantation was performed. A decline in the incidence of airway complications (AC) had been a key feature to achieve the current outcomes. Several proposed risk factors to the development of airway complications have been identified, ranging from the surgical technique to the immunosuppressive regimen. There are essentially six different airway complications post-lung transplantation. The most frequently reported complication is bronchial stenosis. Other complications include bronchial dehiscence, exophytic excessive granulation tissue formation, tracheo-bronchomalacia, bronchial fistulas, and endobronchial infections. The management of post-transplant bronchial complications needs a multispecialty team approach. Prevention of some complications may be possible by early and aggressive medical management as well as by using certain surgical techniques for transplantation. Interventional bronchoscopic procedures, including balloon bronchoplasty, cryotherapy, laser photoresection, electrocautery, high-dose endobronchial brachytherapy, and bronchial stents are among the armamentarium. Also, medical management, like antibiotic prophylaxis and therapy for endobronchial infections, or noninvasive positive-pressure ventilation in case of bronchomalacia, are used to treat an AC. In some cases, different surgical approaches are occasionally required. In this article we review the risk factors, the clinical presentation, the diagnostic methods, as well as the management options of the most common AC after lung transplantation.

Eosinophil-rich inflammatory response to FloSeal hemostatic matrix presenting as postoperative pelvic pain

FloSeal hemostatic matrix has been reported to be effective for the control of intraoperative bleeding in various surgeries. We report 3 patients who experienced a possible allergic response to FloSeal with the formation of excessive granulation tissue and fibrosis that were associated with early postoperative pelvic pain that led to additional surgical intervention.

Endotracheal Stent Granulation Stenosis Resolution after Colchicine Therapy in a Dog

Endotracheal Stent Granulation Stenosis Resolution after Colchicine Therapy in a Dog

Analysis of Calcium Ion homeostasis and mitochondrial function in cerebellar granule cells of adult Cav 2.1 Calcium Ion channel mutant mice

CaV 2.1 voltage-gated calcium channels (VGCC) are highly expressed by cerebellar neurons, and their dysfunction is linked to human disorders including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6. Altered calcium homeostasis, due to dysfunctional Ca(V 2.1 VGCC can severely affect mitochondrial function, eventually leading to neuronal cell death. We study leaner and tottering mice, which carry autosomal recessive mutations in the gene coding for the alpha 1A pore-forming subunit of CaV 2.1 VGCC. Both leaner and tottering mice exhibit cerebellar ataxia and epilepsy. Excessive leaner cerebellar granule cell (CGC) death starts soon after postnatal day 10, but it is not known whether the degree of CGC cell death observed in adult leaner mice is significantly different from wild type mice. We used Fluoro-Jade and TUNEL staining to quantify apoptotic cell death in leaner and wild type CGC. We investigated calcium homeostasis, mitochondrial function and generation of reactive oxygen species (ROS) in isolated CGC, using indicator dyes Fura-2AM, TMRM and CMH2DCFDA, respectively. We observed a small but significant increase in number of apoptotic adult leaner CGC. Calcium homeostasis and mitochondrial function also were altered in leaner CGC. However, no significant differences in ROS levels were observed. It is possible that CGC death in leaner mice may be related to mitochondrial dysfunction but may not be directly related to decreased basal intracellular calcium.

Results of treatment of displaced supracondylar humeral fractures in children by percutaneous lateral cross-wiring technique

Seventy children with displaced type II and III supracondylar fractures of the humerus were managed with percutaneous lateral cross-wiring technique from January 2006 to January 2007. There were 54 boys and 16 girls with a mean age of 6.1 +/- 3.07 years. All patients were operated within 24 h after trauma using the Dorgans percutaneous lateral cross-wiring technique. Patients were followed up for a mean period of 6.1 +/- 2.6 months and assessed both radiologically for union; and functionally and cosmetically according to Flynn's criteria. All patients achieved solid union. Functionally, all patients achieved satisfactory results, while cosmetically, 91.4% of patients had satisfactory results and 8.6% had unsatisfactory results. The most frequently occurring complications were minor pin tract infection in six patients, deep infection in two patients, and 32 patients suffered excessive granulation tissue formation mostly around the proximal pin. There was no iatrogenic neurological injury either for the ulnar or for the radial nerves. The obtained results and minor complications reported signify this technique as a viable treatment method for displaced type II and III supracondylar fractures in children.

Self-expanding nitinol stents for the treatment of tracheal collapse in dogs: 12 cases (2001–2004)

To evaluate long-term outcome following nitinol stent placement in dogs with tracheal collapse. Retrospective case series. 12 client-owned dogs with endoscopically diagnosed tracheal collapse refractory to medical management. Medical records were reviewed for 12 dogs in which 1 or more self-expanding nitinol stents were placed for the treatment of endoscopically diagnosed tracheal collapse. A total of 17 stents were placed. Survival times after stent placement ranged from 1 to 48 months. Three of 12 dogs died within 6 months after stent placement. Nine dogs survived > 1 year after stent placement, and 7 dogs survived > 2 years. Of the deceased dogs, 5 of 9 succumbed to tracheal disease. Other causes of death included congestive heart failure, cerebral neoplasia, cerebrovascular accident, and renal failure. Material failure (stent fracture) was a common complication (5/12 dogs). Other complications reported included excessive granulation tissue within the stent lumen, tracheitis, and pneumonia. Placement of an intraluminal stent with self-expanding nitinol stents was a successful palliative treatment for tracheal collapse in dogs that did not respond to medical management. Disease progression is inevitable, but substantial improvement in respiratory function may be achieved for a period of months to years.

Granulation tissue in palpebral conjunctivae associated with acitretin therapy

To the Editor: We would like to report the development of excess granulation tissue during treatment with acitretin on palpebral conjunctivae. This is a unique complication because this kind of reaction normally appears on nail sulcus or on acne lesions.

Laryngotracheal augmentation using titanium mesh

The management of laryngotracheal stenosis is still a serious surgical challenge. The fact that there are currently numerous reconstruction procedures indicates that there is at present no standard treatment. Titanium mesh was used instead of traditional homografts in reconstruction of the anterior laryngotracheal wall in 12 tracheostomised patients with benign chronic laryngotracheal stenosis. The anterior laryngotracheal wall was split, followed by excision of scar tissue and fixation of the titanium plate at the split end. A Silastic stent was inserted above the tracheostomy tube and fixed in place by running sutures fixed to the skin by buttons. The stent was removed endoscopically six weeks later and a trial of decannulation was undertaken. Endoscopically, good epithelisation was seen on the inner surface of the mesh in 10 cases and decannulation was possible. Four of these patients required endoscopic debulking of granulation tissue. Decannulation was impossible in two cases, one due to excessive granulation tissue and the other due to prolapse of the titanium mesh into the tracheal lumen (the mesh was removed endoscopically and a Montgomery T-tube inserted). Titanium mesh was found to be a good alternative for augmentation of the anterior laryngotracheal wall. It offered rigid support, with fewer of the complications reported with other grafts.

A child with laryngo-onychocutaneous syndrome partially responsive to treatment with thalidomide

Laryngo-onychocutaneous syndrome (LOCS) is a condition characterized by erosive or ulcerative skin lesions associated with excessive granulation tissue, at sites of trauma such as the digits, elbows and knees. Similar lesions can occur within the conjunctival mucosa, leading to corneal scarring and blindness. The main complications, however, occur in the respiratory tract, where a similar process of erosions and subsequent formation of granulation tissue causes airway obstruction which may lead to premature death. LOCS is now believed to be a nonblistering variant of junctional epidermolysis bullosa and to date there are no efficacious treatments available. We report a 16-year-old girl with LOCS who failed to respond to methylprednisolone and cyclophosphamide, but had a partial response to oral thalidomide with marked decrease in granulation tissue and tracheal secretions. Interruption of treatment resulted in prompt resurgence of the granulation tissue which was again controlled by reintroduction of thalidomide. We propose that in the absence of effective therapies for LOCS, a trial of thalidomide in these patients should be considered.