Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities.

PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation.

In the present study we prospectively evaluated the safety and efficacy of temporary fully covered, self-expandable metal stents (fcSEMS) to treat biliary strictures (n = 9), leaks (n = 9), and combined lesions (n = 1) occurring after liver transplantation, when standard endoscopic attempts had failed. Placement of fcSEMS and their removal in scheduled patients were successful and without complications. Resolution of the biliary lesion was confirmed in 15 of 19 patients (79 %). Treatment was not successful in two patients and not evaluable in 2 other patients. Complications occurred in 9 /19 patients (47 %): stent migration in 6, stent occlusion in 1, and de novo stricture after successful treatment of a biliary leak in 2. After a median follow-up of 12 months, one recurrent anastomotic stricture was noted. Temporary placement of fcSEMS in biliary strictures and leaks after liver transplantation provides satisfactory results even in patients who have undergone multiple previous conventional endoscopic attempts, and offers an alternative approach to surgical intervention.

Human pseudoterranovosis, an emerging infection in Chile.

Fifteen cases of human pseudoterranovosis are reported for Chile, representing an emerging parasitic infection in this country caused by larvae of the nematode Pseudoterranova sp. Our observations also included an outbreak of pseudoterranovosis in 3 of 4 individuals who shared the same raw fish dish (cebiche). Most of the cases occurred in adult patients. The main source of infection was from consumption raw or fried marine fish, including hakes (Merluccius australis or Merlucciuts gayi), pomfret (Brama australis), Inca scad (Trachurus murphvi), and corvina (Cilus gilberti). Seasonal distribution showed most of the cases to occur in fall and spring. Parasite larvae were isolated from the mouths of most of the patients after they reported a pharyngeal tickling sensation, coughing, vomiting, or a foreign body in the mouth or throat.

Can the inferior alveolar nerve be used as a marker in frozen section for free margin control after segmental mandibulectomy in tumour ablation?

This study critically assessed the possibility of tumour spread along the inferior alveolar nerve (IAN) and its sensitivity as an intraoperative marker for clear bony margin control in frozen section during segmental mandibulectomy. Fifteen patients with oral squamous cell carcinoma (OSCC) involving the mandible and requiring a segmental mandibulectomy were included in this prospective trial. The ends of the IAN were analyzed using quick section analysis and the results compared with those of the definite pathological report. Nerve tissue could be identified in 25 of the 27 specimens collected. No specimen revealed tumour invasion. All histological diagnoses were finally confirmed. Three positive bony margins with microscopic carcinoma infiltrates were found, whereas corresponding nerve tissue did not confirm tumour invasion. This study supports the assumption that the pattern of tumour invasion is rarely primarily along the IAN in OSCC involving the mandible. Quick section analysis of the nerve tissue alone is therefore not a valid marker for intraoperative bony margin control. However, it can be used as an additional intraoperative diagnostic tool combined with other methods in rare cases of primary tumour spread along the IAN. A review of current knowledge regarding bony margin control published in the literature is provided.

Accuracy of mandibular reconstruction by three-dimensional guided vascularised fibular free flap after segmental mandibulectomy.

Mandibular reconstruction with a fibular free flap has become standard in specialised centres for head and neck reconstruction, particularly for defects with more than one osteotomy that are challenging even for experienced surgeons. Virtual surgical planning is a potential tool to facilitate harvesting of the fibula and the osteostomy. The purpose of this study was to compare the two methods of mandibular reconstruction - conventionally planned (conventional group) and "virtually" planned (virtual group) - with regard to accuracy, bony consolidation, complications, and operating time. Fifty patients who required mandibular reconstruction after segmental mandibulectomy were evaluated retrospectively, 24 virtually planned and 26 conventionally planned. The overall survival of flaps was 92% (46/50). The bony consolidation rate in the virtual group was significantly better than that in the conventional group (p=0.002). The difference between the angle of the mandible before and after was highly significant with a median of 11.5° (range 2°-75°) in the conventional group and 4.5° (range 0-18°) in the virtual group (p=0.0001). Operations were mean (SD) of 34 (21.2) minutes shorter in virtually-planned cases (p=0.12). The overall morbidity did not differ significantly between the groups. The use of virtual surgical planning in mandibular reconstruction by fibular free flap is beneficial for optimising accuracy, consolidation of bony segments, and operating time, while increasing the predictability of results for the surgeon. However, additional costs have to be carefully weighed against the benefits.

Medical device-induced thrombosis: what causes it and how can we prevent it?

Blood-contacting medical devices, such as vascular grafts, stents, heart valves, and catheters, are often used to treat cardiovascular diseases. Thrombus formation is a common cause of failure of these devices. This study (i) examines the interface between devices and blood, (ii) reviews the pathogenesis of clotting on blood-contacting medical devices, (iii) describes contemporary methods to prevent thrombosis on blood-contacting medical devices, (iv) explains why some anticoagulants are better than others for prevention of thrombosis on medical devices, and (v) identifies future directions in biomaterial research for prevention of thrombosis on blood-contacting medical devices.

Sandwich flaps as a feasible solution for the management of huge mandibular composite tissue defects.

In the current therapy of head and neck defects, surgical reconstruction with the aid of pedicle or free flaps is common practice. Suitable single flaps are available to solve most reconstructive challenges. However, reconstruction can become a problem in extensive mandibular defects, as they are often caused by large primary tumors or osteoradionecrosis. These composite defects often lead to large intraoral or extraoral fistulas due to the involvement of mucosa, skin, mandible and soft tissue. These issues call for a double flap approach in order to achieve adequate reconstruction. Therefore, we developed a surgical sandwich technique as presented in this study. The procedure features the acquisition and use of two vascular flaps which can be freely combined according to their desired features (for example being of high tissue volume or osteomyocutaneous). In our study we included 11 patients (ten male, one female) with a mean age of 57 years. Seven of the patients had defects due to osteoradionecrosis and four due to tumor resection. A sandwich technique was performed in a single operation in eight patients, whereas for three patients several operations were necessary. The flaps used included: fibula free flap (FFF); anterolateral thigh (ALT); radial forearm flap (RFF); deltopectoral flap (DPF) and tensor fascia lata (TFL). The following combinations were used: FFF and ALT (three cases), FFF and RFF (two), FFF and DPF (three), ALT and TFL (two), and two ALT flaps (one). The sandwich technique proved suitable for complex reconstructions and led to desirable esthetic and functional results. The flexibility in combining different free or pedicle flaps made it possible to address various defect situations and consequently offer satisfactory surgical reconstruction for complex cases.

The effect of antithrombin III-independent thrombin inhibitors and heparin on fibrin accretion onto fibrin-coated polyethylene.

Prosthetic vascular grafts become coated with a layer of fibrin that contributes to graft thrombosis and occlusion. We compared the effect of antithrombin III-independent inhibitors of thrombin with heparin for their ability to prevent fibrin accretion onto a model of a vascular graft formed in vitro by coating polyethylene tubing with thrombin bound to a layer of polymerized fibrin. Equivalent antithrombin concentrations of heparin, D-Phe-Pro-Arg CH2Cl (PPACK), recombinant hirudin (r-hirudin), and Hirulog-1 were added to barium chloride-absorbed plasma containing radiolabelled fibrinogen. Whereas, PPACK and r-hirudin persistently inhibited fibrin accretion, the inhibition by heparin was transient. Hirulog-1 had no effect on early fibrin accretion and was actually associated with enhanced accretion at 30 min (control 11.7 +/- 2.0 micrograms fibrin/cm2; Hirulog-1, 18.4 +/- 3.5 micrograms fibrin/cm2, p < 0.001). Both Hirulog-1 and r-hirudin displaced radiolabelled thrombin from the fibrin surface. Whereas hirudin-thrombin complexes are stable, Hirulog-1 produces only transient inhibition of the displaced thrombin thereby accounting for the enhanced fibrin accretion with this anticoagulant. These studies show that the antithrombin III-independent inhibitors, r-hirudin and PPACK, are more effective inhibitors of fibrin accretion onto fibrin-coated polyethylene than heparin or Hirulog-1. In addition, they emphasize the importance of determining the ability of anticoagulants to displace thrombin from fibrin and to form stable thrombin-inhibitor complexes; lack of stability of thrombin-inhibitor complexes must be countered by levels of anticoagulant that are adequate to maintain its effectiveness.

Oral congenital cystic choristomas: a case report.

Solitary choristomas containing gastrointestinal mucosa occur rarely in the tongue and the oral mucosa and usually present as an asymptomatic mass. This report documents the occurrence of two congenital intraoral cystic choristomas in a 5-month-old male infant. The cysts were located on the dorsum of the base of the tongue and left floor of mouth anterior to the lingual cyst. Both cysts were lined by nonkeratinizing squamous epithelium and gastric, intestinal, and respiratory epithelium. The cysts were excised by an oral approach.

Interactions of thermally denatured fibrinogen on polyethylene with plasma proteins and platelets.

During the investigation of fibrin deposition onto hydrophobic polymers in contact with human blood, a model was developed in which fibrinogen was denatured and irreversibly coated onto a polyethylene surface by heating to 70 degrees C for 10 min. The denatured fibrinogen-polyethylene surface is resistant to fluid wall shear rates of up to 550 s-1 and the fibrinogen does not desorb in the presence of plasma proteins. Compared to uncoated polyethylene, little albumin or fibrinogen adsorbs to heat-denatured fibrinogen. Thrombin binds to the denatured fibrinogen-coated polyethylene with low affinity and also acts on the surface-bound denatured fibrinogen and cleaves fibrinopeptide A (FPA) quantitatively. Washed, 51Cr-labeled platelets do not adhere to the thermally denatured fibrinogen at either low or high shear rates compared to surfaces coated with undenatured fibrinogen (p < 0.01). These observations support the role of the D domain of fibrinogen in platelet adhesion because this is the region that is denatured by heating. In contrast, the E domain of fibrinogen is not altered by heating to 70 degrees C and hence remains susceptible to thrombin and/or plasmin cleavage. The characteristics of this surface are such that it can be used to develop fibrin-coated surfaces for use in studies of thrombus formation on artificial surfaces.

Investigation of the anticoagulant mechanisms of a covalent antithrombin-heparin complex.

Recently, we developed a covalent antithrombin-heparin complex (ATH) as a possible treatment for respiratory distress syndrome. ATH reacted rapidly with thrombin and efficiently catalyzed the inhibition of either thrombin or factor Xa by exogenous antithrombin. In order to investigate mechanisms for the conjugate's unusual anticoagulant properties, changes in fluorescence due to covalent linkage or addition of exogenous antithrombin were studied in relation to reaction with thrombin derivatives or factor Xa. The emission spectrum of ATH was similar to that of antithrombin plus heparin mixtures. ATH quickly inhibited thrombin or factor Xa activities, as measured by a fluorogenic substrate. Fluorescein-labeled heparin was displaced from either thrombin or active site blocked thrombin by ATH, indicating that thrombin must bind to the conjugate's heparin moiety. Interaction of thrombin with ATH's heparin component was confirmed by a slow reaction rate of conjugate with a thrombin mutant that has weak heparin binding. Total intrinsic fluorescence increased when exogenous antithrombin was added to ATH, indicating that the catalytic mechanism may occur through a second inhibitor binding site. Thus, ATH reacts directly with thrombin through a bridge mechanism and probably catalyzes the reaction of thrombin with antithrombin by a second binding sequence on its heparin chain.