Intraoperative detection of sentinel lymph nodes using Patent Blue V in non-small cell lung cancer.

AIM: The aim of this article was to determine sentinel lymph node (SLN) identification rate (IR) using Patent Blue V in patients with non-small cell lung cancer (NSCLC) and to evaluate the accuracy of SLN for the presence of mediastinal metastasis. METHODS: Between 2004 and 2006 the data from 32 patients with clinical stage IA to IIB, who underwent lung resection for NSCLC, were prospectively analyzed. Patent blue V dye was injected in the peritumoral tissue, and the first lymph node to stain was identified as a sentinel node. RESULTS: SLN was identified in fifteen patients (IR=46.9%). SLN with metastatic involvement was observed in four patients. Accuracy, sensitivity and specificity of the sentinel lymph node in predicting the status of other mediastinal lymph node stations were respectively 86.7%, 100%, and 84.6%. In 63.1% patients, the SLNs corresponded to the lymph node stations 10 and 11. In seven patients (36.9%), the SLNs were located in the N2 stations. CONCLUSION: Although the use of Patent Blue V for SLN identification is feasible, this technique presents relatively low identification rate. The major difficulty on the detection of SLNs was the black coloration of the lymph node, which interfered with the visualization of the dye.

Is pro-matrix metalloproteinase-3 a marker for posttraumatic cartilage degradation?

OBJECTIVE: Since the development of posttraumatic osteoarthritis (OA) is a relatively slow process, estimation of OA risk would be of value with regard to chondroprotective measures and medication. In this study we investigated the significance of pro-matrixmetalloproteinase-3 (proMMP-3) for this purpose. DESIGN: Synovial fluid (SF) and serum samples were collected from 259 patients of our trauma clinic at the time of arthroscopy. The extent of cartilage damage was assessed according to the Outerbridge-score. ProMMP-3 levels in SF and serum were determined by enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody. Additionally we determined SF and serum levels of total MMP-3 and COMP levels as well as TIMP-1 and -2 concentrations in 40 randomly selected patients by ELISA. RESULTS: Serum proMMP-3 levels of the total cohort were markedly increased compared to healthy controls (P<0.007). The comparison of serum and SF lavage proMMP-3 concentrations showed a significant correlation (r(s)=0.41, P<0.0001), however, only 26% of the investigated samples were increased above normal ranges. The grade of cartilage damage did not correlate with enzyme concentration neither in patients' serum nor in SF samples. ProMMP-3 SF concentration was increased early after trauma. Furthermore, proMMP-3 correlated significantly with total MMP-3 serum and SF levels as well as COMP SF levels. CONCLUSIONS: The measurement of proMMP-3 in serum or SF did not reflect the present cartilage damage and thus appears to have only minor potential for clinical use, but it should be considered for longitudinal studies, since it may reflect a risk for cartilage degradation in a subset of patients.

Intrathoracic desmoid tumor with invasion of the great vessels.

A desmoid tumor of the mediastinum was diagnosed and treated in a 35-year-old white male who presented with a right supraclavicular mass. He was treated with resection, which involved several vascular structures, requiring multiple vascular reconstructions followed by post-operative radiotherapy. The authors concluded that, when located in the mediastinum, the invasive character of such tumors and its tendency to recur may pose a considerable surgical challenge, requiring careful pre-operative planning and long term post-operative follow -up. The role of radiation therapy is limited to the control of local recurrences.

[Results after rebuilding the ossicular chain using the autogenous incus, ionomer-cement-and titanium implants (tympanoplasty type III)]. / Ergebnisse der Tympanoplastik Typ III mit autogenem Amboss sowie Ionomerzement- und Titanimplantaten.

BACKGROUND: A defective ossicular chain can reliably be reconstructed with standardized techniques using e. g. modern alloplastic materials. The comparison of clinical and functional results have proved its worth. Prospective clinical trial as well as collecting and evaluating relevant intraoperative and postoperative findings may be helpful to find the appropriate bone substitute in each case when rebuilding middle ear structures. METHOD: In 354 middle ears (332 patients) the defective or destroyed ossicular chain was rebuilt with the carefully trimmed autogenous incus (n = 83), with ionomer-cement implants (n = 100) and with titanium prostheses (n = 171). The follow-up of the earmicroscopic findings and middle ear function extended over a period of 1.5 years postoperatively on an average (min. 3 months, max. 6 years). The modified otologic record form named "Würzburger Ohrbogen" was used for preoperative and operative data, the "Ohrnachsorgebuch" for the postoperative follow-up. RESULTS: Using incus the air bone gap was improved up to 15 dB in the main speech area. Thus the average remaining conduction deficit was less than 10 dB. The "taking" of ionomer based cement prostheses and titanium prostheses was equally good. The cement implants showed a tendency to protrusion (n = 3), 2 titanium implants were extruded. The air bone gap decreased about 10 to 35 dB using titanium total prosthesis and about 15 to 20 dB using ionomer-cement total prosthesis. The remaining air bone gap with titanium implants was slightly less than with the ionomer-cement PORP (10-15 dB). The air bone gap using the titanium TORP was diminished in a reach of 10 to 35 dB, with the ionomer cement prosthesis between 15 to 20 dB. The remaining gap in the main speech area was slightly favorable to titanium (less than 15 dB) compared with the ionomer-cement TORP. Comparing higher frequencies the air bone gap of titanium was recognizable due to its light weight, but less impressive than expected. Revision surgery (n = 50) has to be performed by reason of cholesteatoma (n = 9), adhesive process (n = 8), dislocation of alloplastic prostheses (n = 8) and because of proposed "second look" (n = 14). CONCLUSIONS: Compared with other materials autogenous implants used for reconstruction of the incus have proved their value, however a deterioration of the sound transmission may develop in the long run. The middle ear compatibility of ionomer-cement implants is similar to titanium implants. The functional results of the titanium implants seem to be slightly superior.

Differential effects of growth hormone therapy in malnourished hemodialysis patients.

BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.

[Toxicity of glass ionomer cement]. / Untersuchungen zur Toxizität von Glasionomerzement.

BACKGROUND: The hybrid bone substitute ionomeric cement achieves a stable and durable space-free bond to adjacent bone during hardening. Clinical studies have evaluated the material differently: Fully hardened ionomeric cement showed in middle ear surgery, e.g. as an ossicular prosthesis, good biocompatibility with outstanding functional results. In a few cases, freshly mixed ionomeric cement led to severe complications after contact with CSF in skull base surgery. Therefore we intended to evaluate the influence of early fluid contact on the quality of cement and to define the interval for a safe application of the material, using a cell culture model. Further we intended to investigate whether combining cement with homologous and alloplastic materials influenced its quality. METHODS: 1) Ionomeric cement (Ionocem) test bodies were placed in Ringer's solution at different times after the mixing phase. 2) Ionomeric cement (Ionocem) test bodies were coated with different clinically used homologous and alloplastic materials during the setting and hardening phase. The concentrations of released cement-forming ions and the toxic effects on mouse fibroblasts within cell cultures were measured. RESULTS: Cytotoxic effects were observed when ionomeric cement was not carefully protected from fluid contact for the first two hours after mixing. This was due to forced fast elution of large amounts of cement-constituting fluoride ions and aluminium ions and to the development of acid valences and their interactions. A total hardening time of less than 25 min had an especially unfavourable influence on cell behaviour. Cell impairments could be reduced significantly by coating the 30-minute cured cement with PDS sheeting and significantly by covering it with viscous collagene. On the other hand, cement toxicity was intensified in part by combinations with some other coating materials. CONCLUSIONS: Ionomeric cement should be kept dry and protected from any fluid contact for at least 30 minutes after mixing. Contact with soft tissue should also be avoided for this time. With a hardening time of 30 minutes, the quality and biocompatibility of glass ionomeric cement could be substantially optimized by coating it with PDS sheeting. These results should be verified in animal experiments and clinical trials.

CT findings in post-operative subphrenic abscess with teratomatous inclusions.

A 39-year-old woman presented with abdominal pain after tubal sterilization. CT showed a subphrenic abscess with fatty inclusions owing to laceration or rupture of a mature ovarian teratoma. Although subphrenic abscess is a well recognized post-operative complication, and ovarian teratomas are frequent, a teratomatous inclusion within a subphrenic abscess is a unique finding.

[Materials for reconstruction of the middle ear]. / Materialien zur Rekonstruktion des Schalleitungsapparats.

To rehabilitate most cases of conductive hearing loss closure of ear drum perforations and rebuilding of the ossicular chain can be performed. Due to the great number of biocompatible bone substitute materials available it is occasionally difficult for the surgeon to choose the most favorable substitute. Autogenous structures (ossicles, cortical bone, cartilage) and allogenous tissues (ossicles, cortical bone, cartilage, dentin) are possible bone replacement materials. Xenogenic tissue is currently not used in middle ear surgery. Ionomer cement is a hybrid material for replacement of bone but does not fit direct classification of the various classes of alloplastic materials in current use: that is, metals (gold, steel wire, platinum, titanium), plastics (polyethylene, polytetrafluorethylene) and ceramics (ceramic oxide, carbon, calcium-phosphate ceramic, vitreous ceramic). For restoration of the sound conductive apparatus preference is given to autogenous ossicles because cortical bone is resorbed and cartilage weakens over time. Most surgeons do not use allogenous tissue, because of the possible transmission of such infectious disease as immunodeficiency syndrome or Creutzfeldt-Jakob disease. Only dentin deserves special attention as a possible bone substitute in the middle ear because its form can be preserved during sterilization. Based on the observations available to date, it becomes apparent that titanium implants hold greater promise than gold. Form-stable synthetic materials are not generally recommended due to foreign body reactions which have been confirmed by many investigators. Ceramic materials (e.g. ceramic oxide, carbon, calcium-phosphate ceramic, glass ceramic) are well tolerated in the middle ear and have also proved to be useful over time. Hybrid bone substitute ionomer cement is easily workable and well integrated, showing a good functional outcome. For many years good results in otosclerosis surgery have been achieved with a prosthesis made of platinum-wire and Teflon. Short-term follow-up periods hold great promise with pistons made of gold. Autogenous ossicles, ionomer cement and recently titanium protheses--as far as usable--are employed by the author for reconstructing the middle ear. For the time being platinum-Teflon prostheses and gold are used in otosclerosis surgery.

[Modification of bacterial growth by alloplastic bone substitutes]. / Zur Beeinflussung des Bakterienwachstums durch alloplastische Knochenersatzmaterialien.

BACKGROUND: To determine the applicability of alloplastic materials as bone substitutes it is now standard procedure to test materials for possible toxic effects and to study their behavior in animal models and cell cultures. This is especially important with respect to middle ear implants that can be put at risk by recurrent infections and require additional testing in a bacterially contaminated environment. MATERIALS AND METHODS: In the present study ionomeric cement (V-O CEM), bioactive glass ceramic and hydroxyapatite were subjected to contamination with S. aureus, E. coli, Pr. mirabilis, Ps. aeruginosa and Enterococci using agar diffusion and microbial suspension tests and examined for their antibacterial activity. A special feature of V-O CEM that had to be considered was that it could be implanted in two physical states (as a viscous substance and a fully hardened material). RESULTS: The agar diffusion test showed that an antibacterial effect of freshly mixed V-O CEM was demonstrable for up to 60 min. In the microbial suspension test growth of E. coli was found to be promoted after 48-h incubation by V-O CEM set for 1 h. S. aureus exhibited a depressed growth, while Pseudomonas cultures demonstrated cell death after 48 h. V-O CEM set for 24 h and 7 days, respectively, exerted a similar though less pronounced effect. Using the microbial suspension test, a comparison was also made of the antibacterial activities of 24-h V-O CEM, bioactive glass ceramic and hydroxyapatite against cultures of S. aureus, Pseudomonas and E. coli. The inhibitory effect of hydroxyapatite on the growth of S. aureus was found to persist beyond the 48-h incubation period. There was slight growth of E. coli in the presence of bioactive glass ceramic after 48 h, whereas hydroxyapatite produced inhibition of microbial growth. V-O CEM inhibited the growth of Pseudomonas, unlike bioactive glass ceramic and hydroxyapatite, which transiently promoted bacterial growth. DISCUSSION AND CONCLUSIONS: Our findings showed that V-O CEM, bioactive glass ceramic and hydroxyapatite exhibited material-dependent bacterial colonization and thus resembled polymeric bone substitutes (susceptible to invasion by S. epidermidis) and metals (sensitive to S. aureus). In general, users of bone substitutes should conduct preclinical tests in order to obtain advance information on the properties of possible replacement material. Since there can be varying interactions between the materials studied and bacterial growth, material-specific effects on bacterial growth should be investigated. While it is recognized that in vitro studies are an inadequate simulation of the clinical situation, they still provide some insight into the likely behavior of a bone substitutes in human sites.

Ionomeric cement implants in the middle ear of the baboon (Papio ursinus) as a primate model.

Faced with an inadequate supply of autogenous materials, the otologic surgeon may have to utilize various alloplastic materials to reconstruct bony middle ear structures. Allogenic materials have fallen into disfavor clinically because of the possible spread of infections. Implantation of the hybrid bone substitute ionomeric cement in viscous or hardened physical states into the middle ears of a primate animal model was undertaken in order to be able to approximate as closely as possible conditions found clinically. The posterior meatal wall was replaced by freshly mixed ionomeric cement in nine baboons (Papio ursinus). After repositioning the meatal flap, the residual skin defect was left to secondary epithelialization. After removal of the stapes superstructure, incus and malleus head, a columella of hardened ionomeric cement was trimmed to the appropriate size and inserted between the footplate and the malleus handle. In three cases the prosthesis shaft was fixed in position with freshly mixed cement near the footplate. The time of follow-up ranged from 47 to 277 days. Gross sections were obtained without decalcification (using a Zeiss saw microtome) and stained with Giemsa solution. In no instance was there any spontaneous epithelialization of the external meatus, although occasional granulation was seen to develop at the free edge of the flap and subepithelially. Epithelialization of the alloplastic columellae occurred as early as 42 days post-implantation. Over the middle ears reconstructed with the viscous cement, there was growth of a thickened epithelium that partially tended to granulate. On light microscopy, the bony footplate area was found to be unaffected by the cement that had been applied when still fluid. Our findings indicate that reconstruction of the posterior meatal wall with the viscous ionomeric cement can be useful clinically. The material does not become dislocated but, as with all other alloplastic materials, spontaneous overgrowth of the adjacent meatal skin is unlikely to occur. The early epithelialization of the columellae and their middle ear compatibility and biostability give support to the excellent tolerability of the ionomeric cement. At present, complications occurring during otoneurological application of the material necessitated its commercial withdrawal from the market in May 1995.

[Long-term outcome after reconstruction of the cranial base with ionomer cement]. / Langzeitergebnisse nach Rekonstruktion der Schädelbasis mit lonomerzement.

BACKGROUND: Congenital, posttraumatic, inflammatory or tumours skull base lesions with CSF leakage require reconstruction to mechanically stabilize the CNS and to securely seal the CSF space. PATIENTS AND METHODS: Ionomeric cement was used from 1988 until 1994 in 44 patients for skull base reconstruction at the Department of Otolaryngology-Head and Neck Surgery, University of Würzburg. Thirty-five patients were reexamined. The longest follow-up time was 8 years. The program for the present follow-up study comprised a general ENT and neurological examination as well as CT scans of the skull base, MRI tomography of the CNS, and the determination of the aluminium plasma concentration. RESULTS: None of the patients reexamined presented with complaints. Neurological examinations and MRI tomography in all patients did not reveal any pathological finding related to ionomeric cement application. Aluminium plasma concentrations in patients who received ionomeric cement implantations were not significantly elevated when compared to controls. General ENT examinations and CT scans in thirty-two patients demonstrated regular postoperative findings. The cement at the anterior skull base was not covered completely by mucosa in three patients. In one these cases, CT scans revealed dislocation of the ionomeric cement so that revision surgery was performed for removal. None of the patients to date presented with a CSF leak. CONCLUSION: Long-term results of the present study show that ionomeric cement is a suitable material for closure of osseous skull base lesions to permanently seal the CSF space. These results, however, can only be obtained when handling and application of the material is adequate. Unfortunately, the production of ionomeric cement has been stopped since 1995 following four cases of aluminium encephalopathy reported in the literature.

Titanium and glass-ionomer cement as ossicular replacement materials: biocompatibility results after implantation in the rabbit.

The middle ear poses unique challenges when finding suitable materials for ossicular reconstruction, primarily because of its link to the external environment via the eustachian tube, which leads to a greater potential for exposure to infectious agents. In this animal study, the biocompatibilities of titanium and glass-ionomer cement were assessed in the middle ear of the rabbit after being implanted as total ossicular replacement prostheses (TORPs) or as free pins. Animals were sacrificed after 28, 84, 168, 336, or 504 days or 2 years, and a cutting saw technique was used to prepare slides for light microscopy. Slides were examined for mucosal coverage and any sign of foreign body reaction. Both materials showed good acceptance in the middle ear. After 28 days, the TORPs were covered by middle ear mucosa. As expected, it took a longer time (up to 504 days) to cover the free implants. An interesting finding was the growth of new bone on both the surface of the titanium implants and the glass-ionomer prostheses. The results of this animal study indicate that both titanium and glass-ionomer cement are favorable materials for ossicular replacement prostheses.

Epidural application of ionomeric cement implants. Experimental and clinical results.

During setting and hardening, the hybrid bone substitute ionomeric cement (Ionocem) achieves a stable and durable bond with the apatite of the adjacent bone without interpository soft tissue. Fluid contact during setting results in the release of aluminium ions which may reach critical levels as high as 3000 micrograms/l. On epidural application it is, therefore, essential to prevent cement constituents from gaining access to the intradural space. After the cement has hardened, the presence of aluminium is demonstrable in the adjacent bone to a maximum depth of 20 microns (EDX microanalysis). In rabbits, epidural placement of freshly mixed cement causes slight thickening of the dura. There is reason to believe that human dura, with a thickness 10 times greater, is impermeable to components of the cement. After epidural application of the freshly mixed cement in the frontobasal and laterobasal regions and at the skull cap and petrous apex, 76 patients in all have been followed for up to 6.5 years. During this period no complications have arisen and functional (and cosmetic) results are promising. The availability of preformed implants (Ionoroc, Ionocast) permitted the peridural placement of minimal quantities of freshly mixed cement. These implants were fixed to localized sites on the adjacent calvarial bone by use of Ionocem. Notwithstanding the stringent manufacturer guidelines, there have been reports in the literature that during the vulnerable stage of setting neurotoxic aluminium ions were released into the dural space with a fatal outcome in two cases. In view of potential intradural complications, such as may occur in case of dural leaks, it was considered that further application of the material adjacent to the dura was no longer warranted. The production of Ionocem was discontinued in May 1995.

Fungal infection in single and bilateral lung transplantation: report of 17 cases in 42 consecutive recipients

We reviewed the frequency and type of fungal infections in patients undergoing lung transplantation at Pavilhäo Pereira Filho Hospital between may 1989 and january 1995. Among the 42 lung transplant recipients studies, 17 ( 40 por cento ) had histologic diagnosis of fungal infection: aspergillosis 8 casos, candidosis 6 cases, and aspergillosis combined with candidosis 3 cases. Among all fungal infections, 47 por cento ( 8 of 17 cases ) occurred in the first month after transplantation, and 82 por cento occurred within the first six months after the transplant. The diagnosis was done during life in candidosis in 77 por cento of patients by transbronchial biopsy. However, aspergillosis was revealed in autopsy material in 82 por cento of cases. Most of the patients with candidosis had a local infection in the transplanted lung. On the contrary, in aspergillosis patients 88 por cento had the mycosis in the native lung