Gerhard F. Huber

Dysphagia in head and neck cancer patients following intensity modulated radiotherapy (IMRT)

BackgroundTo evaluate the objective and subjective long term swallowing function, and to relate dysphagia to the radiation dose delivered to the critical anatomical structures in head and neck cancer patients treated with intensity modulated radiation therapy (IMRT, +/- chemotherapy), using a midline protection contour (below hyoid, ~level of vertebra 2/3).Methods82 patients with stage III/IV squamous cell carcinoma of the larynx, oropharynx, or hypopharynx, who underwent successful definitive (n = 63, mean dose 68.9Gy) or postoperative (n = 19, mean dose 64.2Gy) simultaneous integrated boost (SIB) -IMRT either alone or in combination with chemotherapy (85%) with curative intent between January 2002 and November 2005, were evaluated retrospectively. 13/63 definitively irradiated patients (21%) presented with a total gross tumor volume (tGTV) >70cc (82-173cc; mean 106cc). In all patients, a laryngo-pharyngeal midline sparing contour outside of the PTV was drawn. Dysphagia was graded according subjective patient-reported and objective observer-assessed instruments. All patients were re-assessed 12 months later. Dose distribution to the swallowing structures was calculated.ResultsAt the re-assessment, 32-month mean post treatment follow-up (range 16-60), grade 3/4 objective toxicity was assessed in 10%. At the 32-month evaluation as well as at the last follow up assessment mean 50 months (16-85) post-treatment, persisting swallowing dysfunction grade 3 was subjectively and objectively observed in 1 patient (1%). The 5-year local control rate of the cohort was 75%; no medial marginal failures were observed.ConclusionsOur results show that sparing the swallowing structures by IMRT seems effective and relatively safe in terms of avoidance of persistent grade 3/4 late dysphagia and local disease control.

Oral prion infection requires normal numbers of Peyer's patches but not of enteric lymphocytes

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphatic tissue, which includes Peyers patches (PPs) and M cells. Recruitment of activated B lymphocytes to PPs requires alpha(4)beta(7) integrin; PPs of beta 7(-/-) mice are normal in number but are atrophic and almost entirely devoid of B cells. Here we report that minimal infectious dose and disease incubation after oral exposure to logarithmic dilutions of prion inoculum were similar in beta 7(-/-) and wild-type mice, and PPs of both beta 7(-/-) and wild-type mice contained 3-4 log LD(50)/g prion infectivity > or =125 days after challenge. Despite marked reduction of B cells, M cells were present in beta 7(-/-) mice. In contrast, mice deficient in both tumor necrosis factor and lymphotoxin-alpha (TNF alpha(-/-) x LT alpha(-/-)) or in lymphocytes (RAG-1(-/-), mu MT), in which numbers of PPs are reduced in number, were highly resistant to oral challenge, and their intestines were virtually devoid of prion infectivity at all times after challenge. Therefore, lymphoreticular requirements for enteric and for intraperitoneal uptake of prions differ from each other. Although susceptibility to prion infection following oral challenge correlates with the number of PPs, it is remarkably independent of the number of PP-associated lymphocytes.

Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the n0 neck in patients with oral squamous cell carcinoma.

Sentinel node biopsy (SNB) has been proposed for staging of the cN0 neck in early oral/oropharyngeal squamous cell carcinomas (SCC). Because SNB is a minimally invasive procedure, it is thought to be associated with less morbidity than elective neck dissection.

Contrast-Enhanced PET/MR Imaging Versus Contrast-Enhanced PET/CT in Head and Neck Cancer: How Much MR Information Is Needed?

Considering PET/MR imaging as a whole-body staging tool, scan time restrictions in a single body area are mandatory for the cost-effective clinical operation of an integrated multimodality scanner setting. It has to be considered that 18F-FDG already acts as a contrast agent and that under certain circumstances MR contrast may not yield additional clinically relevant information. The concept of the present study was to understand which portions of the imaging information enhance the sensitivity and specificity of the hybrid examination and which portions are redundant. Methods: One hundred fifty consecutive patients referred for primary staging or restaging of head and neck cancer underwent sequential whole-body 18F-FDG PET with CT-based attenuation correction, contrast-enhanced (ce) CT, and conventional diagnostic MR imaging of the head and neck in a trimodality PET/CT–MR system. Assessed were image quality, lesion conspicuity, diagnostic confidence, and the benefit of additional coronal and sagittal imaging planes in cePET/CT, PET/MR imaging with only T2-weighted fat-suppressed images (T2w PET/MR imaging), and cePET/MR imaging. Results: In 85 patients with at least 1 PET-positive lesion, 162 lesions were evaluated. Similar robustness was found for CT and MR image quality. T2w PET/MR imaging performed similarly to (metastatic lymph nodes) or better than (primary tumors) cePET/CT in the morphologic characterization of PET-positive lesions and permitted the diagnosis of necrotic or cystic lymph node metastasis without application of intravenous contrast medium. CePET/MR imaging yielded a higher diagnostic confidence for accurate lesion conspicuity (especially in the nasopharynx and in the larynx), infiltration of adjacent structures, and perineural spread. Conclusion: The results of the present study provide evidence that PET/MR imaging can serve as a legitimate alternative to PET/CT in the clinical workup of patients with head and neck cancers. Intravenous MR contrast medium may be applied only if the exact tumor extent or infiltration of crucial structures is of concern (i.e., preoperatively) or if perineural spread is anticipated. In early assessment of the response to therapy, in follow-up examinations, or in a whole-body protocol for non–head and neck tumors, T2w PET/MR imaging may be sufficient for coverage of the head and neck. The additional MR scanning time may instead be used for advanced MR techniques to increase the specificity of the hybrid imaging examination.

Human prion diseases: epidemiology and integrated risk assessment.

Human prion diseases are devastating and incurable, but are very rare. Fears that the bovine spongiform encephalopathy epizootic would lead to a large epidemic of its presumed human counterpart, variant Creutzfeldt-Jakob disease (vCJD), have not been realised. Yet a feeling of uncertainty prevails in the general public and in the biomedical world. The lack of data on the prevalence of asymptomatic carriers of vCJD compounds this uncertainty. In addition to this problem, Switzerland is currently faced with another issue of major public concern: a recent rise in the incidence of CJD. Here we examine the plausibility of several scenarios that may account for the increase in CJD incidence, including ascertainment bias due to improved reporting of CJD, iatrogenic transmission, and transmission of a prion zoonosis. In addition, we present the design and current status of a Swiss population-wide study of subclinical vCJD prevalence.

Occult metastases detected by sentinel node biopsy in patients with early oral and oropharyngeal squamous cell carcinomas: Impact on survival†

Analysis of the lymphatic drainage pattern, the reliability of a negative sentinel lymph node biopsy (SLNB), as well as the impact of sentinel lymph node (SLN) metastases on regional control and survival in patients with early stage oral and oropharyngeal squamous cell carcinoma (SCC).

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer

PURPOSE Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

Outcome of sinonasal melanoma: Clinical experience and review of the literature

Primary sinonasal malignant melanoma (SNMM) is a rare clinical entity. There is neither a classification nor a staging system nor an evidence‐based treatment concept established. Our objective was to find potential risk factors predicting the outcome.

Quality of Life of Oropharyngeal Cancer Patients With Respect to Treatment Strategy and p16-Positivity

To assess the quality of life in long‐term survivors with oropharyngeal cancer (OPSCC), compare the results with our historic cohort in relation to the radiation technique, and explore the influence of treatment strategy and p16 expression on quality of life (QoL).

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesis in vitro. The value of cancer cell‐expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell‐expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty‐nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p = 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p = 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodes in vivo. Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck.