Volumetric analysis of bone substitute material performance within the human sinus cavity of former head and neck cancer patients: A prospective, randomized clinical trial.

BACKGROUND: In numerous animal and human studies, it could be detected that in bone augmentation procedures, material's physicochemical characteristics can influence the cellular inflammatory pattern and therefore the integration in the host tissue. Histological, histomorphometrical, and clinical analyses of the integration of the biomaterial in the surrounding tissue are well established methodologies; however, they do not make a statement on volume and density changes of the augmented biomaterial. AIMS: The aim of the present study was to assess the volume and density of a xenogeneic (Bio-Oss®, BO) and a synthetic (NanoBone®, NB) bone substitute material in split-mouth sinus augmentations in former tumor patients to complete histological and histomorphometrical assessment. METHODS: Immediately and 6 months after sinus augmentation computed tomography scans were recorded, bone grafts were marked, and the volume was calculated with radiologic RIS-PACS software (General Electric Healthcare, Chalfont St. Giles, Great Britain) to determine the integration and degradation behavior of both biomaterials. RESULTS: Radiographic analysis revealed a volume reduction of the initial augmented bone substitute material (i.e. 100%) to 77.36 (±11.68) % in the BO-group, respectively, 75.82 (±22.28) % in the NB-group six months after augmentation. In both materials, the volume reduction was not significant. Bone density significantly increased in both groups. CONCLUSION: The presented radiological investigation presents a favorable method to obtain clinically relevant information concerning the integration and degradation behavior of bone substitute materials.

Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation.

BACKGROUND: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. AIMS: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. SETTING AND DESIGN: Cross-sectional study, tertiary care center. PATIENTS AND METHODS: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3-16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. STATISTICAL ANALYSIS: One-sample t-test, Mann-Whitney-test, Kruskal-Wallis analysis. RESULTS: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. CONCLUSION: Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio.

Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results.

BACKGROUND: The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. MATERIALS AND METHODS: Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. RESULTS: Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. CONCLUSIONS: Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.

Periimplant changes in different transplanted soft tissues around loaded endosseous implants in patients after oral tumor surgery.

PURPOSE: To examine periimplant reaction of transplanted soft tissues foreign to oral cavity when compared with local gingiva. METHODS: In 58 oral cancer patients, 210 dental implants were inserted mainly in the mandible after radical surgery and reconstruction. Ninety-six implants penetrated transplants (split skin, mucosal, platysma, pectoralis major, and intestinal) and were compared with 114 implants penetrating local gingiva. Prosthetic treatment consisted of telescopic or bar-retained overdentures or (in case of intestinal grafts) implant-supported fixed prostheses. Follow-up lasted between 30 and 60 months. Plaque index, sulcus bleeding index, pocket probing depth, and width of vestibular-/oral attached mucosa were measured. RESULTS: Plaque index (before second year; P < 0.01) and pocket probing depth (after first year; P < 0.02-0.04) displayed significant differences with disadvantage for split skin grafts. Sulcus bleeding did not exceed index 1. Attached mucosa had no significant effect on periimplant health. CONCLUSION: Transplanted extraoral tissues behaved similarly when compared with local gingiva, showing no detrimental effect on periimplant health in oral cancer patients. Split skin and mucosal grafts had worst performance.

Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial.

BACKGROUND: Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes the long-term follow-up of a large European multicenter trial evaluating the accuracy of the technique. METHODS: A total of 227 SNB procedures were carried out across 6 centers, of which 134 were performed in clinically T1/2 N0 patients. All patients underwent SNB with preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel nodes were evaluated with hematoxylin and eosin (H&E) staining, step-serial sectioning (SSS), and immunohistochemistry (IHC). There were 79 patients who underwent SNB as the sole staging tool, while 55 patients underwent SNB-assisted elective neck dissection. RESULTS: Sentinel nodes were successfully identified in 125 of 134 patients (93%), with a lower success rate observed for floor-of-mouth tumors (FoM; 88% vs. 96%, P = 0.138). Also, 42 patients were upstaged (34%); of these, 10 patients harbored only micrometastatic disease. At a minimum follow-up of 5 years, the overall sensitivity of SNB was 91%. The sensitivity and negative predictive values (NPV) were lower for patients with FoM tumors compared with other sites (80% vs. 97% and 88% vs. 98%, respectively, P = 0.034). CONCLUSIONS: Sentinel node biopsy is a reliable and reproducible means of staging the clinically N0 neck for patients with cT1/T2 HNSCC. It can be used as the sole staging tool for the majority of these patients, but cannot currently be recommended for patients with tumors in the floor of the mouth.

Free fibula osteocutaneous flap for primary reconstruction of T3-T4 gingival carcinoma.

Lower gingival squamous cell carcinoma (SCC) frequently invades the mandibular bone and buccal or lingual oral mucosa. In the concept of en bloc surgery of malignant tumors, it is advisable to prefer segmental mandibulectomy for T3-T4 lower gingival carcinoma that had radiologic bone involvement and resection of soft tissue on the buccal or lingual side with negative border of margin. Consequential defects of oral mucosa and mandible need immediate reconstruction to provide the maximum probability of cure and quality of life with minimal donor site morbidity. The aim of this study was to evaluate the fibula osteocutaneous flap with skin island as a means to meet both hard and soft tissue reconstructions needed in a one-stage procedure of gingival SCC. Data of 17 patients, with gingival SCC pathologically and who underwent en bloc operations including segmental mandibulectomy and reconstruction of mandible and intraoral mucosa with fibular flap, were retrospectively analyzed. The segmental mandibular defects ranged from 8 to 17 cm, and intraoral soft tissue defects ranged from 4 degrees at 2.5 cm to 8.5 degrees at 4 cm. The flaps survived in all 17 patients including 9 patients who received postoperative radiotherapy with good final function of the lower leg. Of 17 patients, 11 had with no evidence of disease with a mean follow-up period of 25 months. Our study results, together with literature findings, revealed that the fibula that had a long length of good-quality bone and sufficient blood supply were suitable for stable osteosynthesis, with the overlying skin suitable in thickness and without limitation of skin flap size for intraoral reconstruction especially after ablative surgery. This method provides oral and maxillofacial surgeons with a means to meet both hard and soft tissue needs in a one-stage procedure for extensive resection of gingival SCC.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

Six years clinical experience with the dorsally pedicled buccal musculomucosal flap.

A dorsal pedicled buccal musculomucosal flap was developed to reconstruct medium-sized intraoral defects, too large for primary closure if major functional and esthetic impairment is to be avoided. Although free flaps, axial, or perforator flaps are excellent in large defects, they may not provide mucosal sensitivity, motility, volume, and texture to replace lost structures with similar tissue. Twenty-five flaps were performed in 24 patients, 1(bilateral) up to a flap-size of 60 x 35 mm, in average 45 x 34 mm. Reconstructed became the lateral mouth floor, lateral oral vestibule, lateral tongue margin, the oropharynx, hard and soft palate. Partial necrosis occurred in 1 flap, 22 (92%) patients recovered with good objective as subjective speech and swallowing, esthetics, and if necessary prosthetic rehabilitation. The donor site was closed primarily, mimics and mouth opening resolved after less than 3 months. The parotid duct had to be marsupialized in large flap preparations, never provoking stasis or infection. The 2-point sensitivity of the flaps was in average equal to the nonoperated mucosa in intraindividual correlation and the flaps lost in average 10% of their original size; 5 (21%) had weakness inflating their cheeks postoperatively. The results indicate dorsal pedicled buccal musculomucosal flap to be reliable and technically easy for reconstructing lateral intraoral, medium-sized defect that yields sensitivity, merely risking occasional buccal muscle weakness but facilitating the rehabilitation of oral function.

Organ preservation treatment using TPF-a pilot study in patients with advanced primary and recurrent cancer of the oral cavity and the maxillary sinus.

PURPOSE: Induction chemotherapy with Taxotere, cisplatin, and 5-fluororacil (TPF) was mainly used in hypopharyngeal and laryngeal cancer patients for larynx preservation. This study aimed to assess feasibility and toxicity in oral cavity and maxillary sinus cancer patients. PATIENTS AND METHODS: Between 2003 and 2008, 21 patients (18 male, three female; mean age 58 years; 15 patients Eastern Cooperative Oncology Group > or =1) suffering from advanced squamous cell cancers of the oral cavity (seven primaries, eight locoregional recurrences) and the maxillary sinus (six patients) were prospectively treated with three cycles of TPF (q3w) and were scheduled to undergo definitive chemoradiation. RESULTS: Of 21 patients, 15 (71%) could be treated with all three cycles, one patient with two cycles, and five patients with one cycle. Reasons for incomplete treatment were tumor progression, edema, seizure, bad general condition, sepsis, pneumonia (each once). The infections led to two treatment-related deaths (9.5%). Acute grade III/IV side effects were noted maximally in 11 patients (52%). Main toxicities were afebrile leukopenias and neutropenias and stomatitis. Of 15 patients, six and four patients had a clinical complete or partial remission following three cycles (67%); five patients with recurrences had no response. Ten patients underwent a definitive chemoradiation or radiation (47.6%). After a mean observation time of 17 months, nine patients are alive; one of them developed a local recurrence. CONCLUSIONS: Chemotherapy with TPF is a highly effective treatment with considerable toxicity that needs special expertise which is best assured in a multidisciplinary setting. Pretreated recurrent cancers demonstrated bad response. A target for organ preservation could be the maxillary sinus; due to tumor regression in advanced oral tongue cancer, consecutively, a reduced function has to be encountered.

Inducible NO synthase confers chemoresistance in head and neck cancer by modulating survivin.

The dual role of the inducible NO synthase (iNOS) and NO signaling in head and neck squamous cell carcinoma (HNSCC) is a complex and can both promote or inhibit tumor progression. However, the underlying molecular mechanisms are not yet resolved in detail. We show for the first time that conditions, favoring low NO levels conferred resistance against cisplatin/taxol-induced apoptosis in HNSCC cell lines. Cytoprotection was mediated by survivin, because we observed its upregulation subsequent to low doses of the NO donors S-nitroso-N-acetyl-penicillamine (SNAP) and sodium nitroprusside (SNP) or ectopic expression of physiologic amounts of iNOS. Also, RNAi-mediated depletion of survivin blocked NOs anti-apoptotic effects. Induction of survivin involves activation of the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway, which was antagonized by the PI3K-inhibitor LY294002. Importantly, application of the iNOS-specific inhibitor 1400W combined with RNAi-mediated downregulation of survivin cooperatively enhanced drug-induced cell death. The iNOS/survivin-axis appears to be also of clinical relevance since immunohistochemistry revealed that iNOS expression correlated with enhanced survivin levels in HNSCC specimens. In contrast, high NO concentrations suppressed survivin levels in HNSCC but also in non-malignant cells resulting in apoptosis. Cell death induced by high amounts of SNAP/SNP or by strong overexpression of iNOS involved activation of p38MAP-kinase, which was counteracted by the p38MAP-kinase inhibitor SB202190. Here, we provide evidence for a novel molecular mechanism how NO signaling may contribute to therapy resistance in HNSCC by modulating survivin expression. Our data further suggest pursuing pharmacogenetic iNOS/survivin-targeting approaches as potential therapeutic strategies in head and neck cancer.

Positive sentinel lymph nodes are a negative prognostic factor for survival in T1-2 oral/oropharyngeal cancer-a long-term study on 103 patients.

BACKGROUND: To evaluate prognostic value of sentinel node biopsy (SNB) in oral/oropharyngeal squamous cell cancer (OOSCC) concerning overall/disease-free survival. METHODS: One hundred three consecutive patients with T1-2N0 OOSCC were consecutively recruited for SNB as single invasive staging method for the neck. Two hundred seventy-three sentinel nodes (SNs) were removed (mean, 2.65 per patient). Nine patients had 10 positive SNs (upstaging rate, 8.7%) found in levels I to III, leading to a therapeutic neck dissection. RESULTS: Mean observation time of all patients was 6.7 years; mean survival time of patients with negative or positive SNs was 6.9 and 3.7 years, respectively. There has been no false-negative result of SNB to date becoming manifest in ipsilateral node metastasis during follow-up. Five-year overall/disease-free survival of all patients was 82%/72%, respectively. The same parameters for the patients with negative SNs were 85%/74%, for those with positive SNs 38%/47%, respectively (statistically significant). There has been a higher statistical risk for locoregional recurrence for patients with positive SNs. Rates of metachronous second primary tumors developing during follow-up were 10.6% (negative SNs) and 44.4% (positive SNs). CONCLUSION: SNB was a valuable diagnostic method in patients with T1-2N0 OOSCC avoiding elective neck dissections. Patients with positive SNs had statistically significantly higher rates of locoregional recurrences, second primary tumors, tumor-related deaths, and a worse overall/disease-free survival. To date, no therapeutic consequences in case of a positive SN beyond execution of modified radical neck dissection (to remove other positive nodes) and closer attention during follow-up can be concluded from this study.

Growth of the orbit after frontoorbital advancement using nonrigid suture vs rigid plate fixation technique.

PURPOSE: To demonstrate whether a measurable difference occurs on the growth of the orbit when using 2 forms of stabilization of the supra-orbital rim after upper orbital osteotomy in children with craniosynostosis. The 2 methods of fixation include sutures providing nonrigid fixation and titanium or resorbable osteosynthesis plates. PATIENTS AND METHODS: In this prospective randomized study, the influence of the mentioned fixation materials was analyzed in a tertiary care center (university hospital). Sixteen consecutive children with craniosynostoses (trigonocephaly, brachycephaly, plagiocephaly) were included. All patients underwent bilateral frontoorbital advancement surgery. In 8 patients each, the fixation of the mobilized and reshaped supraorbital rim was carried out using either miniplates or sutures, resulting in a rigid or nonrigid fixation. By means of computed tomography scans taken preoperatively (mean age, 8months) and postoperatively (mean age, 6.5years), the development of the orbit was measured using the anterior interorbital distance, lateral orbital distance, medial orbital-wall length, lateral orbital-wall length, and medial orbital-wall protrusion. The results were compared to norm values and statistically evaluated. RESULT: In all patients, a long-term improvement of the orbit was achieved with absolute distances staying below norm values. The choice of the fixation material was of minor importance. CONCLUSION: Sutures providing nonrigid fixation of bone flaps seem to be feasible in reaching the aims of surgery in craniosynostotic children.

Prospective evaluation of closed treatment of nondisplaced and nondislocated mandibular condyle fractures versus open reposition and rigid fixation of displaced and dislocated fractures in children.

PURPOSE: The purpose of the study was to evaluate open reposition and internal fixation of displaced or dislocated child mandibular condyle fractures, and closed treatment of nondisplaced, nondislocated fractures of the condyle with long-term follow-up outcomes. PATIENTS AND METHODS: Twenty-four patients less than 14 years of age were included from 2000 to 2005. Classes II to V after Spiessl and Schroll, eg, displaced or dislocated fractures were surgically treated; Class I and VI nondisplaced, nondislocated fractures were treated closed. At yearly intervals, facial symmetry, pain, nerve function, bone repositioning, scarring, and reossification were evaluated. Incisal opening, protrusion, laterotrusion and sonographic condylar translation were measured in mm. RESULTS: Nineteen (79%) patients presented for follow-up: Class I, 8; Class II, 3; Class III, 0; Class IV, 2; Class V, 5; and Class VI, 1. After 1 year, 11 patients (58%) presented for follow-up; after 2 years, 4 (21%) patients, and after 5 years, 4 (21%) patients presented for follow-up. The reasons for not presenting for follow-up given by the parents upon telephone interview were no symptoms and absent motivation. All patients exhibited sufficient opening; 1 Class IV patient had insufficient translation; 3 patients had opening deflection; 2 patients' partial facial nerve paresis subsided after 1 year; in 2 cases broken osteosyntheses were removed. Vertical and horizontal condyle support was successfully reconstructed; considerable bone resorption occurred in Class V; failure rate was 4 (17%). Of 5 Class V, 3 were failures (60%). CONCLUSIONS: The evaluated treatment rationale attained 83% treatment success; Class V should be repositioned with careful mobilization to not risk impaired perfusion and considerable remodeling. Patient number is limited; a negative bias for follow-up can be supposed, eg, symptom-free patients avoided a follow-up interview. Prospectively small, rigid, mainly intraosseous and hopefully resorbable osteofixation should be assessed.

Does tumor depth affect nodal upstaging in squamous cell carcinoma of the head and neck?

PURPOSE: The aim of this study was to determine whether tumor depth affects upstaging of the clinically node-negative neck, as determined by sentinel lymph node biopsy with full pathologic evaluation of harvested nodes including step-serial sectioning (SSS) and immunohistochemistry (IHC). PATIENTS AND METHODS: One hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the oral cavity/oropharynx undergoing primary resection and either sentinel node biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck. Harvested nodes were examined with hematoxylin-eosin staining, SSS, and IHC. Patients upstaged by SSS/IHC were denoted pN1mi. RESULTS: One hundred one of 172 patients were staged pN0, with 71 (41%) patients upstaged. Increasing tumor depth was associated with higher likelihood of upstaging (P < .001). Tumor depth showed a positive correlation with nodal stage according to TNM classification (P < .001). Tumor depth greater than 4 mm appears to be the most appropriate cutoff for risk stratification, although tumors in the oropharynx may require a lower value. CONCLUSION: Tumor depth is an important prognostic factor for patients with SCC of the oral cavity or oropharynx. Tumors greater than 4 mm are associated with greater risk of upstaging; however, this optimum cutoff value may vary between primary tumor sites.

[Survival improvement of a unicentric overall population in 20 years: 1038 patients with oral and oropharyngeal squamous cell cancer 1983-2004]. / Uberlebensverbesserung eines unizentrischen Gesamtkollektivs aus 20 Jahren: 1038 Patienten mit oralen und oropharyngealen Plattenepithelkarzinomen 1983-2004.

PURPOSE: The development of overall survival of a DOSAK (German-Austrian-Swiss Cooperative Group on tumours of the maxillofacial region) clinic's overall population comprising a time period of more than 20 years (1983-2004) should be assessed. At a cutoff date (January 1st, 1997), a change from a primarily surgically based to a consequent multi-modality treatment regimen was implemented. The periods of time before and after that change should be compared. METHODS AND PATIENTS: The data of the DOSAK registry entries on 1038 patients suffering from primary untreated oral and oropharyngeal carcinomas were updated with respect to follow-up and mortality data to achieve a 100% quality of follow-up. The end point (death) was reached in 67% of the overall population. Statistical analysis was carried out by the Trium Analysis Online corporation, Munich. RESULTS: The portion of female and older tumor patients increased, more than half of all tumor patients were clearly in stage IV of the disease at first referral. The portion of patients operated on persisted approximately (80%), the portion of additional treatment modalities could be increased considerably. The fact of a bony infiltration by the tumor and the operability remained highly significantly relevant for survival in multivariate analysis, despite of multi-modality treatment. The survival rate of the patients remained significantly dependent on the clinical stage of the disease in multivariate analysis but could be improved by 10% in the clinical stages II and III and in the patients who could not be operated on. All in all, the cutoff date was statistically relevant for survival in multivariate analysis, i.[Symbol: see text]e. the change in the treatment regimen had a verifiable positive effect on the survival of a unicentric overall population. CONCLUSION: Survival improvement in an overall population via change in treatment strategy is possible in relatively short time; the clinical stages II and III and the non-operable patients have the greatest benefit from a multi-modality treatment.

Interdisciplinary rehabilitation of a patient with Opitz C-syndrome and extensive craniofacial malformation.

A 24-year-old patient with C-syndrome and multiple congenital deformities was followed-up for his complete lifetime. The patient received extensive interdisciplinary rehabilitation of his complex somatic and craniofacial malformation. This article intends to show from the clinical point of view, how such patients can have profit from broad arrangements in specific periods of life, how far the rehabilitation can go in cases of good patients and parental compliance and how important an interdisciplinary cooperation is.

Head and neck squamous cell carcinoma: sentinel node or selective neck dissection.

Improved knowledge about the metastatic behavior of mucosal squamous cell cancer of the head and neck made it possible to reduce the extension of elective and even therapeutic neck dissections by sparing selected levels, thereby reducing morbidity. The diagnostic question of when to treat a clinically negative neck to avoid unnecessary overtreatment, even through selective neck dissections, might be answered with sentinel lymph node biopsy. A thorough and sophisticated evaluation of this technique is necessary when defining suited patients.

Nuclear export is essential for the tumor-promoting activity of survivin.

Survivin appears to function as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Here we report the molecular characterization of the nucleocytoplasmic transport of survivin and its potential implications for tumorigenesis. We identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. In dividing cells, the NES is essential for tethering survivin and the survivin/Aurora-B kinase complex to the mitotic machinery, which in turn appears to be essential for proper cell division. In addition, export seems to be required for the cytoprotective activity of survivin, as export-deficient survivin fails to protect tumor cells against chemo- and radiotherapy-induced apoptosis. These findings appear to be clinically relevant since preferential nuclear localization of survivin correlated with enhanced survival in colorectal cancer patients. Targeting survivin's nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We demonstrate that nuclear export is essential for the biological activity of survivin and promote the identification of molecular decoys to specifically interfere with survivin's nuclear export as potential anticancer therapeutics.

CT-based evaluation of tumor volume after intra-arterial chemotherapy of locally advanced carcinoma of the oral cavity: comparison with clinical remission rates.

PURPOSE: To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. METHODS: Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. RESULTS: Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. CONCLUSION: Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

The diagnostic role of radioactivity in sentinel nodes in oral and oropharyngeal cancer.

Sentinel lymph node biopsy (SNB), using radioactive tracers, is a novel, interesting tool in the staging of patients with oral and oropharyngeal squamous-cell carcinoma (OOSCC), which could lead to a reduced rate of elective neck dissections. The aim of the study was to evaluate the ranking of measured radioactivity in the sentinel lymph nodes (SLNs) and to correlate these findings with histopathological results to assess the number of SLN being sufficient for exact staging of the neck. In 77 consecutive patients with T1-4 OOSCC clinically and positron emission tomography-staged N0, between 15 and 55 MBq of Tc- 99m-labeled albumin-microcolloids were injected peritumorally and 213 SLNs were excised by small skin incisions using a gamma probe 2-3 hours later. The counts per second (cps) were measured ex vivo and excised SLNs were ranked according to their cps defining the LN with the highest activity as primary SLN, followed by a 2nd, 3rd, and so forth, SLN. Elective neck dissections were not performed. Median activity was 213 cps. All levels harbored SLNs with a maximum (43%) in level II and a minimum in level V (1%). SLNs in level II had significantly higher tracer accumulation (median, 289 cps) than those in levels I (144 cps) and IV (149 cps), but distant levels did not have significantly lower counts, compared to proximal. Eight (8) pathologically positive SLNs in 7 patients (7/77 = 9%; median activity, 157 cps) were detected. The median counts of the positive SLNs were not significantly different from those of the 205 negative SLNs (235 cps). The positive SLN was the one with the highest tracer accumulation in 4 cases, with the second highest in 1 case, and with the third highest tracer accumulation in 2 cases. Three (3) positive SLN were in level IB, 4 in level IIA, and 1 in level III. One (1) patient had 2 positive SLNs: a SLN with the third highest activity in level IIB and a SLN with the fifth highest activity in level III. In OOSCC, excision of only 1 SLN is not feasible. The positive SLNs were not necessarily the hottest nodes. Utilizing radiotracer lymphatic mapping, the 3 SLNs with the highest activity should be excised for exact staging of the neck in patients with T1-3 tumors. Excision of all radioactive nodes is recommended until further studies will prove this result. Large T4a tumors should not be staged using SNB.