Is there a change in the mandibular cortical shape index in panoramic radiographs over time? A longitudinal retrospective study.

BACKGROUND: A longitudinal study design was conducted to assess the mandibular cortical shape index (CI) in panoramic radiographs retrospectively. An association between age and a deterioration of different radiological parameters on panoramic radiographs was stated in cross-sectional studies. As longitudinal studies are rare, this one is designed to assess radiological changes over time. MATERIALS AND METHODS: In this longitudinal study, The archive of the dentomaxillofacial radiology department was searched for panoramic radiographs of patients who have two radiographs with a time lapse of at least 15 years between both. The radiographs were then examined and the CI was categorized into three categories: normal, mild, and severely eroded. The following factors were examined to determine if they had an effect on possible changes of the CI using the Chi-square test: The time period between both radiographs, the gender and the age of the subjects when both radiographs were made also compared using the Kolmogorov-Smirnov test. RESULTS: Ninety radiographs met the inclusion criteria. The mean age, when the 1st radiograph and the 2nd radiograph were made, was 48.7 and 66.9 years, respectively. A deterioration of the CI over time was observed and only 31.1% of the radiographs remained in the same CI category while 57.8% dropped down by one category and 11.1% dropped down by two. The change of CI was significant (P < 0.001 using the McNemar's test). CONCLUSION: In this longitudinally designed study, a deterioration of the CI over time when assessing the nonstandardized panoramic radiographs could be confirmed. This study shows that 68.9% of the patients had CI deterioration of at least one category over the average time of 17.96 years. This is the first study to quantify the CI deterioration over time to our knowledge.

Evaluation of a novel elastic registration algorithm for spinal imaging data: A pilot clinical study.

BACKGROUND: Rigid image coregistration is an established technique that allows spatial aligning. However, rigid fusion is prone to deformation of the imaged anatomies. In this work, a novel fully automated elastic image registration method is evaluated. METHODS: Cervical CT and MRI data of 10 patients were evaluated. The MRI was acquired with the patient in neutral, flexed, and rotated head position. Vertebrawise rigid fusions were performed to transfer bony landmarks for each vertebra from the CT to the MRI space serving as a reference. RESULTS: Elastic fusion of 3D MRI data showed the highest image registration accuracy (target registration error of 3.26 mm with 95% confidence). Further, an elastic fusion of 2D axial MRI data (<4.75 mm with 95% c.) was more reliable than for 2D sagittal sequences (<6.02 mm with 95% c.). CONCLUSIONS: The novel method enables elastic MRI-to-CT image coregistration for cervical indications with changes of the head position.

Sensitivity and specificity of sentinel lymph node biopsy in patients with oral squamous cell carcinomas using indocyanine green fluorescence imaging.

PURPOSE: The purpose of this clinical study was to evaluate the sensitivity and specificity of cervical sentinel lymph node biopsy after mapping with indocyanine green fluorescence (ICG) for imaging early-stage oral cancer. PATIENTS AND METHODS: A sentinel lymph node biopsy (SLNB) was performed during a selective neck dissection (SND) in 20 patients with oral squamous cell carcinoma (OSCC, cT1 or cT2, N0 status). The sentinel lymph nodes (SLN) were identified using an infrared video camera after ICG injection. Lymph nodes were examined histologically. The endpoint of this study was to investigate the rate of false-negative results in SLNB. RESULTS: Sentinel lymph nodes could be detected after 8.1 min (range 1-22 min). In eight out of 20 cases, lymph node metastases were found during histopathological evaluation of the neck dissection specimen. In four cases a metastasis could be found in the detected SLN (sensitivity 50%). In the other four cases metastases were found in different lymph nodes. Specificity was 100%, positive predictive value 100%, and negative predictive value 75%. CONCLUSION: In this study, reliability of sentinel lymph node biopsy after ICG imaging could not be verified, as there were false-negative results in 50% of the cases. Therefore, SND can still be recommended as for patients with cT1 or cT2 OSCC, and a N0 neck status.

Effect of Systemic Antioxidant Allopurinol Therapy on Skin Flap Survival.

BACKGROUND: It has been reported that systemic administration of allopurinol improves cell survival. This study was aimed to evaluate effects of allopurinol on skin flaps in dogs. METHODS: Twenty dogs underwent one skin flap surgery with a 2-week interval. The first procedure was performed according to the standard protocols. The second phase was started by a 1-week pretreatment with allopurinol. Length of the necrotic zone was measured and recorded daily. At each phase, flaps were removed and sent for histopathological study after 1 week observation. RESULTS: Mean length of the necrotic zone in allopurinol treated skin flaps has been significantly less than normal flaps over all 7 days of observation (p<0.0001). Histopathology study showed less inflammation and more normal tissue structure in the allopurinol treated skin flaps. CONCLUSION: It was demonstrated that systemic administration of allopurinol significantly improved skin flap survival.

Postoperative bleeding risk for oral surgery under continued rivaroxaban anticoagulant therapy.

OBJECTIVES: The purpose of this study was to assess the risk of postoperative bleeding complications after oral procedures performed under continued mono or dual anticoagulation therapy with rivaroxaban (and aspirin). METHODS: This retrospective single-center observational study included 52 oral procedures performed under continued oral anticoagulant therapy with rivaroxaban (20 mg/day). Among them, two procedures were performed under continued dual therapy with aspirin (100 mg/day) added to the regimen. Postoperative bleeding events were compared with 285 oral procedures in patients without any anticoagulation/antiplatelet therapy. RESULTS: Postoperative bleeding complications after oral surgery occurred significantly more often in patients under continued rivaroxaban therapy (11.5 %) than in the control cases without anticoagulation/antiplatelet medication (0.7 %). All of the bleeding events were manageable: Two of them were treated with local compression, three by applying new fibrin glue with (one case) or without (two cases) secondary sutures, one occurred during a weekend and was therefore treated under inpatient conditions with suture replacement. All postoperative bleeding episodes occurred during the first postoperative week. CONCLUSIONS: According to our data, continued anticoagulation therapy with rivaroxaban significantly increases postoperative bleeding risk for oral surgical procedures, although the bleeding events were manageable. CLINICAL RELEVANCE: Oral surgeons, cardiologists, general physicians, and patients should be aware of the increased bleeding risk after oral surgical procedures. Close observation up to 1 week postoperatively is advisable to prevent excessive bleeding.

Surgically Assisted Rapid Palatomaxillary Expansion With or Without Pterygomaxillary Disjunction: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this review was to evaluate the outcome measurements of anterior expansion, posterior expansion, and complications after surgically assisted rapid palatal expansion (SARPE) with or without pterygomaxillary disjunction (PMD). MATERIALS AND METHODS: A computerized database search was performed using PubMed, CINAHL, Cochrane, Scopus, and Web of Science. Then, a computerized search was conducted in Google Scholar and ProQuest to overcome publication bias. RESULTS: From the original 125 combined results, 3 met the inclusion criteria. The Quality Assessment Tool for Quantitative Studies of the Effective Public Health Practice Project assessed 2 articles as weak and 1 as moderate. The systematic review included a total of 48 patients (11 male and 37 female). For 25 patients, SARPE was performed with PMD and for 23 patients SARPE was performed without PMD. A tooth-borne fixed hyrax-type palatal expansion screw appliance was used for all cases, activated 1 to 2 mm intraoperatively, and, after a latency period of 3 to 7 days, activated 0.5 to 0.6 mm per day for 38 patients and 0.25 mm for the other 10 until adequate expansion. Postexpansion retention was performed using ligature wired hyrax in 18 patients for 4 months. Comparisons were based on cone-beam computed tomographic projections, study models only, or a combination of study models, anteroposterior cephalometric radiographs, and occlusal radiographs. The time to measure the changes ranged from before fixed orthodontic retention to 6 months after the completion of active expansion. A meta-analysis was possible only for anterior (intercanine) and posterior (inter-molar) dental expansions. CONCLUSION: The literature is inconclusive regarding the effect of PMD on the outcomes of SARPE. Further controlled trials are needed.

Is immediate bony microsurgical reconstruction after head and neck tumor ablation associated with a higher rate of local recurrence?

The purpose of this retrospective study was to examine the possible effect of immediate bony microvascular free flap reconstruction of mandibular defects after radical tumor resection of oral squamous cell carcinoma (OSCC) on the rate of local relapse. Our own data regarding recurrence rates for 1-step immediate reconstruction were compared to the published recurrence rates of 2-step reconstructions. A total of 21 patients (aged 45-77 years) with OSCC who underwent a primary surgical therapy with subsequent immediate bony microvascular free flap reconstruction of mandibular defects were followed up for 18-38 months. Four local relapses (19%) were recorded, all in patients with initial tumor stage of T4. Although intraoperative histological findings were R0 in all 21 cases, definitive histology later detected R1 status in the resected bone in 2 cases (10%). Immediate bony free flap reconstruction of mandibular defects after radical surgical resection of OSCC does not seem to increase the risk of local recurrence nor affect patient survival when compared with the 2-step surgical approach.

Postoperative bleeding risk for oral surgery under continued clopidogrel antiplatelet therapy.

OBJECT: To determine the incidence of postoperative bleeding for oral osteotomy carried out under continued monoantiplatelet therapy with clopidogrel and dual therapy with clopidogrel/aspirin. Design. Retrospective single center observatory study of two study groups and a control group. METHODS: A total of 64 and 60 oral osteotomy procedures carried out under continued monoclopidogrel therapy and dual clopidogrel/aspirin therapy, respectively, were followed for two weeks for postoperative bleeding. Another 281 similar procedures were also followed as a control group. All oral osteotomy procedures were carried out on an outpatient basis. RESULTS: We observed postoperative bleeding in 2/281 (0.7%) cases in the control group, in 1/64 (1.6%) cases in the clopidogrel group, and in 2/60 (3.3%) cases in the dual clopidogrel/aspirin group. The corresponding 95% confidence intervals are 0-1.7%, 0-4.7%, and 0-7.8%, respectively, and the incidences did not differ significantly among the three groups (P > 0.09). Postoperative hemorrhage was treated successfully in all cases with local measures. No changes of antiplatelet medication, transfusion, nor hospitalisation were necessary. No major cardiovascular events were recorded. CONCLUSIONS: Our results indicate that minor oral surgery can be performed safely under continued monoantiplatelet medication with clopidogrel or dual antiplatelet medication with clopidogrel/aspirin.

Virtual planning of complex head and neck reconstruction results in satisfactory match between real outcomes and virtual models.

OBJECTIVES: The reconstruction of large facial bony defects using microvascular transplants requires extensive surgery to achieve full rehabilitation of form and function. The purpose of this study is to measure the agreement between virtual plans and the actual results of maxillofacial reconstruction. MATERIALS AND METHODS: This retrospective cohort study included 30 subjects receiving maxillofacial reconstruction with a preoperative virtual planning. Parameters including defect size, position, angle and volume of the transplanted segments were compared between the virtual plan and the real outcome using paired t test. RESULTS: A total of 63 bone segments were transplanted. The mean differences between the virtual planning and the postoperative situation were for the defect sizes 1.17 mm (95 % confidence interval (CI) (-.21 to 2.56 mm); p = 0.094), for the resection planes 1.69 mm (95 % CI (1.26-2.11); p = 0.033) and 10.16° (95 % CI (8.36°-11.96°); p < 0.001) and for the planes of the donor segments 10.81° (95 % CI (9.44°-12.17°); p < 0.001) The orientation of the segments differed by 6.68° (95 % CI (5.7°-7.66°); p < 0.001) from the virtual plan; the length of the segments differed by -0.12 mm (95 % CI (0.89-0.65 mm); not significant (n.s.)), respectively, while the volume differed by 73.3 % (95 % CI (69.4-77.6 %); p < 0.001). The distance between the transplanted segments and the remaining bone was 1.49 mm (95 % CI (1.24-1.74); p < 0.001) and between the segments 1.49 mm (95 % CI (1.16-1.81); p < 0.001). CONCLUSIONS: Virtual plans for mandibular and maxillofacial reconstruction can be realised with excellent match. CLINICAL RELEVANCE: These highly satisfactory postoperative results are the basis for an optimal functional and aesthetic reconstruction in a single surgical procedure. The technique should be further investigated in larger study populations and should be further improved.

Osteogenic differentiation of mesenchymal stem cells in fibrin-hydroxyapatite matrix in a 3-dimensional mesh scaffold.

AIM: To explore the feasibility of culturing mesenchymal stem cells in an hydroxyapatite-fibrin matrix held by a mesh scaffold and inducing osteogenic differentiation of these cells. The aim was to obtain bone-material in vitro in a desired form. MATERIALS AND METHODS: Rat mesenchymal stem cells were mixed with fibrin and nanocrystalline hydroxyapatite in tubular scaffolds constructed from a poly(L-lactic acid) mesh, and cultured under standard and osteogenic differentiating conditions. Cell viability, cytotoxicity and alkaline phosphatase activity were followed for 3 weeks. Living cells and the expression of bone markers were visualized by fluorescence staining and immunofluorescence staining, respectively. Attachment of cells to the scaffold mesh surface was examined by scanning electron microscopy. RESULTS: Cell viability decreased and cytotoxicity increased rapidly during the first day of culture but stabilized gradually afterwards, indicating fast adaptation of the cells in the matrix-scaffold environment. From day 17, cytotoxicity started to decrease, paralleled by an increase in alkaline phosphatase activity, indicating osteogenic differentiation. A large number of living cells were visible in the matrix and on the mesh scaffold. Expression of collagen type I, osteoponin, osteocalcin and core binding factor 1 were evident under osteogenic differentiation conditions. CONCLUSION: The three-dimensional construction of a fibrin-hydroxyapatite matrix in a biocompatible poly(L-lactic acid) as mesh-scaffold provides a promising carrier for producing bone-material in vitro in a desired form for applications in regenerative medicine.

Face transplantation: on the verge of becoming clinical routine?

UNLABELLED: INTRODUCTION; Face transplantation (FT) is an innovative achievement of modern reconstructive surgery and is on the verge of becoming a common surgical opportunity. This review article was compiled to provide an update on this surgical field, especially regarding clinical outcomes, benefits, and complications implied. METHODS: We performed an extensive research on all English-language Medline articles, case reports, and reviews published online until September 15, 2013. Used search terms were "face transplantation," "face transplant," "facial transplantation," "facial transplant," "face allograft," and "facial allograft." RESULTS: To date 27 FTs have been performed worldwide. 19 of these cases have been published in the Medline database. Long-term follow-up reports of FT cases are rare. Three deaths associated with the procedure have occurred to date. The clinical outcomes of FT are satisfying. Reinnervation of sensation has been faster than motor recovery. Extensive functional improvements have been observed. Due to strict immunosuppression protocols, no case of hyperacute or chronic rejection and no graft-versus-host disease have occurred to date. CONCLUSIONS: As studies on long-term outcomes are missing, particularly regarding immunosuppression-related complications, FT will stay experimental for the next years. Nevertheless, for a small group of patients, FT already is a feasible reconstructive option.

Outcome of microvascular free flaps in a high-volume training centre.

PURPOSE: Microvascular free tissue transfer allows major ablative defects following oncologic surgical and traumatic reasons to be reliably reconstructed in the head and neck region. A retrospective analysis of the microvascular flap procedures which were performed within one year in a high volume training centre was performed. PATIENTS AND METHODS: The microvascular free flap procedures of the year 2011 were reviewed and followed up until the 31st December 2012. The type and indication of the reconstructive procedure, operation time, operating team, experience and level of training of the surgeons involved, postoperative IMC (intermediate care unit) and/or ICU (intensive care unit) time, inpatient time, flap revisions, further postoperative complications, preoperative and postoperative radiation of the patients, the placement of dental implants were studied. RESULTS: From 1st of January 2011 to 31st of December, 2011, the data of 101 patients with 103 microvascular free flap procedures were analysed of which 72% (84 flaps) were harvested by residents. The patients ranged in age from 14 to 89 years (mean age 59 years, 71 males and 40 females). The mean operation time was 591 min with the longest operation times for scapular flaps (744 min) and the shortest operation times for ALT flaps (455 min). Mean inpatient time was 34.2 days with a minimal time for the fibular flaps of 27.2 days and a maximum of 45.7 days for the latissimus dorsi flaps. 24 flaps (23.3%) in total had to be revised with bleeding being the main cause of immediate revisions (41.7% of all revisions). 5 flaps (4.85% of all flaps) were lost despite a revision procedure meaning a successful revision rate in 79.2% of all revisions. CONCLUSION: Microvascular reconstruction procedures are safe and should be considered as standard procedures for reconstruction of large defects especially in high volume training centres. Intensive flap monitoring and early revisions maximize the flap outcome.

Postoperative bleeding risk for cutaneous surgery in the head and neck region with continued phenprocoumon therapy.

In a total of 171 surgical procedures for lesions in the head and neck region in patients in whom phenprocoumon therapy was not stopped, 16 (9%) postoperative bleeding events were observed over a follow-up period of two weeks. Local measures were sufficient in all cases except one severe case where blood transfusion was needed and anticoagulant treatment was stopped for 7 days. The bleeding risk was significantly higher for the surgical procedures of the nose than those in other areas (21% versus 6%, P = 0.014), but was not influenced by the international normalized ratio (INR) of blood coagulation, size, site and type of the lesion, surgical procedure, and sex and age of the patients. The bleeding rate in patients not on any anticoagulation therapy was significantly lower (6/211 = 3%). Across both groups, just over 80% of the bleeding episodes were within the first two days (55% on the same day and 32% on the next day) of the surgery. No bleeding was recorded after 5 days. Our data suggest that cutaneous surgery in the head and neck region can be safely performed with continued phenprocoumon therapy in most cases in an INR range of 1.3-3.4, but rarely severe bleeding does occur and can be managed with a close-contact follow-up and with 24-h on call services during the first two days postoperatively.

P53 immunohistochemical expression does not correlate with clinical features in 207 carcinomas of the oral cavity and in the head and neck region.

OBJECTIVES: The present study aims to investigate the relevance of immunohistochemical p53 expression in carcinomas of the oral cavity and of the head and neck region. Long-term clinical and histopathological follow-up findings as well as HPV status are correlated with the results of this examination. MATERIALS AND METHODS: Sections made from two tissue arrays composed of 222 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, were examined for p53 expression and Ki-67 index by means of immunohistochemistry. Correlation of long-term clinical findings of the patients and pathological features of tumours with laboratory results were examined statistically. RESULTS: No significant correlation was found between the p53 immunohistochemical expression in the 207 oral carcinomas and features of the tumours and patient outcomes. There was no significant association between the Ki-67 labelling index and the p53 expression. DISCUSSION: Our failure in detecting any association of the p53 immunohistochemical expression regardless of HPV status with clinical features of these tumours suggests it lacks a prognostic value for squamous cell carcinomas of the oral cavity. CLINICAL RELEVANCE: The prognostic value of p53 immunostaining in oral squamous carcinoma is not clarified yet. In the present study, there is no impact on any prognostical item nor even a correlation with cell proliferation (Ki-67) regardless of HPV status.

Amplification of the PPFIA1 gene region on 11q13 in oral squamous cell carcinomas (OSCC).

INTRODUCTION: Analyzing chromosomal amplifications delivers valuable information for identification of oncogenes. For carcinomas of the oral cavity only few genes have been identified in amplified regions. The aim of this study was to search genes in amplified regions as possible biomarkers and targets for novel therapies. MATERIAL AND METHODS: DNA from 10 carcinomas of the floor of the oral cavity was examined using a 500K Array GeneChip (Affymetrix 6.0) to detect chromosomal losses, gains or amplifications. Suspicious alterations were validated on tissue microarrays using fluorescence in situ hybridization (FISH) with respective probes. RESULTS: FISH-validation on tissue arrays confirmed PPFIA1 amplifications as one of the most frequent events (32.6%). High (10-20 signals) and low (<10 signals) amplification of PPFIA1 was found in 10.9% (5/46) and 21.7% (10/46) tumours, respectively. Fine mapping with overlapping FISH probes showed co-amplification of PPFIA1 and the Cyclin D1 gene which are approximately 600 kb apart from each other, likely in the same amplicon. DISCUSSION: PPFIA1 was frequently co-amplified with the Cyclin D1 gene in oral carcinomas and could present a biomarker as well as a novel target for specific gene therapy. Further studies are necessary to investigate the role of PPFIA1 in development and pathogenesis of oral carcinomas.

Mandibular cortical shape index in non-standardised panoramic radiographs for identifying patients with osteoporosis as defined by the German Osteology Organization.

The aim of this prospective controlled study was to determine the validity of the mandibular cortical shape index (CI) on panoramic radiographs in distinguishing patients with osteoporosis as defined by the German Osteology Organization (Dachverbands der Deutschsprachigen Osteologischen Fachgesellschaften, DVO). The study group contained 50 patients (33 female, 17 male, mean age: 74.9 years), who had a high risk of osteoporosis. 50 young patients (33 female, 17 male, mean age: 37.9 years) with no anamnestic evidence of osteoporosis served as control. Three blinded observers evaluated panoramic views of the study and the control group in a mixed manner regarding the mandibular cortical shape index. The study group underwent bone mineral density measurement using dual energy X-ray absorptiometry and received a diagnosis according to the Organization's guidelines (normal, osteopenia, osteoporosis). The CI showed a high sensitivity of 72.2% and a high specificity of 93.9% with a highly significant predictive value (Chi-square = 22.96, p < 0.001), while the observer's agreement was moderate (kappa = 0.47). We concluded that patients with a cortical shape index of the category assessed as "severe" on non-standardised panoramic radiographs have a higher risk of suffering systemic osteoporosis. The CI in panoramic radiographs is a good screening tool, which could be implemented in the routine assessment of panoramic radiographs in elder patients.

An odontogenic keratocystic tumor in the buccal space: an unusual site of origin and a review of the literature.

AIM: Keratocystic odontogenic tumors (KCOTs) arise from remnants of epithelial structures associated with the development of teeth and occur predominantly intraosseously. In rare occasions they can appear extraosseously in the gingiva as peripheral counterparts; only 15 cases have been reported to date. Evenmore rare are cases of KCOTs of the buccal soft tissues. The aim of this report is to present a rare case of KCOT affecting the buccal soft tissue as an original site and a review of the literature regarding diagnostic and therapeutic options.

Extensive sublingual epidermoid cyst--diagnosis by immunohistological analysis and proof by podoplanin.

AIM: We present the case of a surgically treated 39-year-old man with diagnosis of a giant sublingual internal epidermoid cyst. Usually, such dermoid or epidermoid cysts are caused by aberrant ectodermal tissues or by acquired aberrant epithelial tissues arising from the foetal period, or from trauma or surgery. The incidence of oral dermoid or epidermoid cysts is about 1.6%; most occur at the mouth floor but they nevertheless are very rare. CASE REPORT: The patient presented with a history of progressive swelling of the sublingual region with dysphagia, progressive snoring during sleep and occasional shortness of breath. The suspected clinical diagnosis of a giant sublingual dermoid or epidermoid cyst was supported by the radiological finding after performing magnetic resonance imaging. The cyst was surgically removed under general anaesthesia through an intraoral approach. The immunohistological analysis of the specimen with a monoclonal antibody against podoplanin (D2-40) showed a positive reaction in the basal epithelial layer, exclusively in areas with secondary inflammation, but not in the remaining cyst wall. CONCLUSION: Sublingually situated extensive epidermoid cysts are rare findings in the oral cavity. In such cases, surgical excision remains the only treatment. We demonstrated that cystic epithelia were normally not immunoreactive for D2-40 but strong immunoreactivity was observed in the basal epithelial cell layer, in areas of ruptured cyst wall associated with secondary inflammatory changes.

Cisplatin tumor concentrations after intra-arterial cisplatin infusion or embolization in patients with oral cancer.

BACKGROUND: One neoadjuvant course of intra-arterial high-dose cisplatin (cis-diamminedichloroplatinum [CDDP]) tumor perfusion combined with intravenous sodium thiosulfate (STS) (cisplatin neutralizer) infusion is part of a multimodality concept for treatment of oral cancer. Recently, crystalline cisplatin embolization has been described as a novel treatment variant with increased tumor response rates. METHODS: We have compared tumor and plasma concentrations of cisplatin and STS by means of microdialysis in 10 patients with oral cancer treated with intra-arterial cisplatin perfusion (150 mg/m(2) in 500 mL of 0.9% sodium chloride) and 6 patients with oral cancer treated with crystalline cisplatin embolization (150 mg/m(2) in 45-60 mL of 0.9% sodium chloride), respectively. The microdialysis catheter was placed into the tumor, and the intra-arterial catheter into the tumor-feeding artery. Cisplatin was rapidly administered through the intra-arterial catheter and STS (9 g/m(2)) was infused intravenously to reduce the systemic toxicity of cisplatin. STS infusion was started 10 seconds after the cisplatin infusion was started. RESULTS: After embolization, cisplatin tumor maximum concentration (C(max)) and tumor area under the concentration-time curves (AUCs) were about 5 times higher than those achieved after intra-arterial perfusion (C(max), 180.3 +/- 62.3 micromol/L versus 37.6 +/- 8.9 micromol/L), whereas the opposite was true for plasma concentrations (C(max), 0.9 +/- 0.2 micromol/L versus 4.7 +/- 0.6 micromol/L). STS plasma levels were about 3 times higher than its tumor concentrations (C(max) tumor, 1685 +/- 151 micromol/L; C(max) plasma, 5051 +/- 381 micromol/L). After the standard intra-arterial perfusion, the average STS/CDDP AUC ratios for tumor and plasma were 211 +/- 75 and 984 +/- 139, respectively. After cisplatin embolization, the respective ratios were 48.5 +/- 29.5 and 42966 +/- 26728. CONCLUSION: Molar STS/CDDP ratios of greater than 500 are required outside the tumor to neutralize cisplatin, whereas tumor ratios should be lower than 100 to avoid a loss of tumor cell killing. The first goal is achieved with both treatment modalities and the second only with cisplatin embolization, suggesting that crystalline cisplatin embolization is superior to intra-arterial cisplatin perfusion in terms of tumor cisplatin concentrations. Whether this translates into higher tumor response rates needs to be investigated further.