Malignancy grading is no better than conventional histopathological grading in small squamous cell carcinoma of tongue and floor of mouth: retrospective study in 128 patients.

There is an ongoing debate about the predictive value of histopathological parameters in oral cancer. In the past decades, the emphasis was on the possible added value of the so-called malignancy grading system. In a retrospective study on 128 previously untreated patients with a T1 or T2 squamous cell carcinoma of the tongue and the floor of the mouth, the value of the classical Broders' grading system and the malignancy grading system were compared with regard to various outcome measures such as regional metastasis, local recurrence and 5-year survival. The results show that neither of the histological grading systems has a strong predictive value and that none is superior to the other.

The status of the deep surgical margins in tongue and floor of mouth squamous cell carcinoma and risk of local recurrence; an analysis of 68 patients.

The objective of this study is to retrospectively assess the clinical relevance, i.c. the event of a local recurrence, in patients surgically treated for tongue and floor of mouth squamous cell carcinoma when tumour cell are observed histopathologically at a distance of less than 0.5 cm. Furthermore, the pattern of invasion and the presence or absence of perineural spread were recorded. A total of 68 patients, surgically treated because of a tongue or floor of mouth squamous cell carcinoma, were examined. Patients in whom any degree of epithelial dysplasia was observed in the mucosal surgical margins had been excluded beforehand. Local recurrence occurred in 2 out of 30 patients with a free surgical margins >0.5 cm and in 3 out of 38 patients with a free surgical margin <0.5 cm, the difference being not statistically significant. Apparently, the presence of tumour cells within a distance of less than 0.5 cm, but not into the deep surgical margin, does not necessarily seem to require additional treatment. The pattern of invasion and the presence or absence of perineural spread were not significantly related with local recurrence either.

Radioimmunodiagnosis of lymph node metastases in head and neck cancer.

INTRODUCTION: Reliable staging of the neck remains a diagnostic challenge in head and neck squamous cell carcinoma (HNSCC) patients. Monoclonal antibodies (MAbs) directed against tumour-associated antigens can be used for selective tumour targeting. When labelled with a gamma-emitting radionuclide like 99mTechnetium, such MAbs can be used for tumour detection by radioimmunoscintigraphy (RIS). OBJECTIVE: The aim of this study was to assess the potential of RIS for the detection of lymph node metastases in HNSCC patients. PATIENTS AND METHODS: In 49 patients with HNSCC, who were scheduled to undergo surgery including neck dissection, RIS using 99mTc-labelled squamous cell specific MAb E48 or U36 administered intravenously was compared with clinical palpation, computed tomography (CT), magnetic resonance imaging (MRI) and histopathological outcome. RESULTS: RIS detected lymph node metastases in 35 of 51 positive sides (sensitivity 69%). Interpretation of RIS was correct in 47 of 65 sides (accuracy 72%). Accuracy of palpation, CT and MRI were comparable. Immunohistochemical staining of lymph node metastases missed by RIS showed that the injected MAb had targeted these small tumour deposits but these were not visualized. CONCLUSIONS: RIS at its current stage of development is not superior to CT or MRI for the detection of lymph node metastases. As small tumour deposits were probably not visualized because of the limited sensitivity and/or spatial resolution of the gamma camera, positron emission tomography (PET) using MAbs labelled with positron emitters may improve the detection. As MAb-PET studies in an animal model showed promising results we will soon start a clinical MAb-PET study.

Ultra-sonic nebulizers as a potential source of methicillin-resistant Staphylococcus aureus causing an outbreak in a university tertiary care hospital.

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred on a head and neck surgical (HNS) ward of a university hospital in Amsterdam. The outbreak lasted from May 2000 until November 2000, and MRSA spread to two intensive care units. Amplified fragment length polymorphism analysis indicated that a single clone was responsible for the outbreak. Phage-typing indicated that this clone was of a type that was uncommon in The Netherlands. Strict isolation of patients, according to the Dutch national guidelines, was instituted. During the outbreak, surveillance culture specimens, from patients, healthcare workers, and the environment, were obtained at regular intervals. MRSA was found in the dust filters of nebulizers through which air from the room was filtered and subsequently humidified. These nebulizers were used to humidify tracheostomies. The dust filters were not maintained according to the guidelines. Restricted use and cleaning and disinfection of all ultra-sonic nebulizers led to termination of the outbreak. The outbreak illustrates that to terminate transmission of outbreak strains of MRSA, meticulous measures are necessary, which not only include strict isolation precautions, but also decontamination of the environment. In addition, it demonstrates the necessity of adhering to cleaning and disinfection guidelines for all medical and nursing equipment used in the hospital.

Lymphoscintigraphic details of sentinel lymph node detection in 82 patients with squamous cell carcinoma of the oral cavity and oropharynx.

Lymphoscintigraphy for sentinel node (SN) detection has been studied extensively in melanoma and breast cancer. In head and neck squamous cell carcinoma (HNSCC), however, experience in this field is relatively meagre. The purpose of this study was to document and evaluate lymphoscintigraphic findings in HNSCC patients. Eighty-two patients with clinical T1-T4 N0 SCC of the oral cavity or oropharynx received peritumoral injections of 25-75 MBq 99mTc-colloidal albumin (CA). Dynamic lymphoscintigraphy was performed in lateral projection for 20 min, followed by 2 min static imaging in anterior projection. In 26 patients, additional static images were obtained 2-6 h after injection of the tracer. In four of 82 patients, both early and late imaging revealed no tracer transport. In 78 of 82 patients, one (60), two (14) or three (4) SNs could be visualized, either by dynamic scintigraphy (73) or delayed static imaging (5). In 48 of 78 (62%) patients, the SN was visualized within the first minute of dynamic imaging. In particular, SNs of tumours of the mobile tongue were visualized within the first minute. No effect of T-stage or 99mTc-CA dose on the transport time of the tracer towards the SN was seen. The distribution of the SNs in the various levels of the neck relative to the primary tumour sites within the oral cavity was in concordance with the patterns of lymph node metastases reported traditionally for patients with SCC in the oral cavity. This study demonstrates the different variables affecting SN identification with lymphoscintigraphy using 99mTc-CA in HNSCC patients.

The clinical relevance of epithelial dysplasia in the surgical margins of tongue and floor of mouth squamous cell carcinoma: an analysis of 37 patients.

BACKGROUND: The clinical relevance of the presence of epithelial dysplasia in the margins of surgically removed oral squamous cell carcinoma is still unclear. METHOD: In a retrospective study, the presence of mild or moderate epithelial dysplasia in the surgical margins of tongue and floor of mouth squamous cell carcinoma was examined histologically. Patients with tumor cells within 0.5 cm of the surgical margins were excluded. Also patients with severe dysplasia were excluded, as this is usually regarded as carcinoma in situ. Patients that received postoperative irradiation were also excluded. Only patients who completed a follow-up period of five years were included. All together, a total number of 37 patients fulfilled the inclusion criteria. RESULTS: Epithelial dysplasia was observed in 7 out of the 37 patients. Five of these patients, and two of the 30 patients with no dysplasia, had a local recurrence (P < 0.01). CONCLUSION: The presence of mild or moderate epithelial dysplasia in the margins of surgically removed oral squamous cell carcinoma carries a significant risk for the development of local recurrence. However, it should be noted that this study was of a retrospective nature and that the group of patients with epithelial dysplasia in the surgical margins was rather small. On the other hand, the inclusion criteria were somewhat strict, by limiting the oral subsite to tongue/floor of mouth, by excluding patients in whom tumors cell were found within 0.5 cm of the surgical margins and by excluding patients who received postoperative radiotherapy, amongst others.

Botulinum toxin A in the treatment of patients with Frey syndrome.

BACKGROUND: This was a prospective study of the treatment of Frey syndrome, also known as gustatory sweating, with botulinum toxin A. METHODS: Thirteen patients with a mean involved skin area of 53 (range 36-80) cm2, as assessed with the Minor starch-iodine test, were treated with 0.1 ml toxin (75 units/ml) injected intracutaneously into every 4 cm2 of involved skin. The mean total dose was 100 (range 67.5-150) units. Treatment results were assessed every 3 months with the Minor test. The Frey Questionnaire Card (FQC) was used for subjective assessment. The mean follow-up after primary treatment was 20 (range 9-24) months. Treatment was repeated if the symptoms recurred. RESULTS: After 3 months 11 of the 13 patients showed a decrease of gustatory sweating of more than 90 per cent. All but one patient with a follow-up of 2 years suffered recurrent gustatory sweating. The mean recurrence-free period after primary treatment was 11 months and that after secondary treatment was 15 months. FQC score and objective assessment correlated well. Treatments were well tolerated, although two patients developed a temporary perioral muscle paresis. CONCLUSION: Botulinum toxin A produces good results in the treatment of Frey syndrome. Repeated treatment improves on the results of primary treatment.

The costs of head and neck oncology: primary tumours, recurrent tumours and long-term follow-up.

We retrospectively calculated the costs of head and neck oncology for reimbursement purposes. This analysis was based on 854 head and neck cancer patients treated between 1994 and 1996 in two major Dutch university hospitals. To anticipate future care costs, costs of required improvements in the quality of care were added. Costs of diagnosis, treatment and 2 years of follow-up of patients with a primary tumour were (euro) 21 858. For patients with a recurrent tumour, this amount was (euro) 27 629. The costs of 10 years of follow-up were (euro) 423 after discounting and correction for survival. In total, average costs per new patient were (euro) 31 829, which covered discounted costs of treating the primary tumour, costs of treating recurrent tumours in 40% of all patients and the costs of 10 years of follow-up. Costs of improving the quality of care were estimated to be (euro) 1598 per new patient.

Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36 radioimmunotherapy.

UNLABELLED: 186Re-labeled chimeric monoclonal antibody U36 (cMAb U36) was recently evaluated in a phase I dose escalation study in head and neck cancer patients. All 13 patients received 99mTc-labeled cMAb U36 before 186Re-cMAb U36 radioimmunotherapy. The aim of this study was to evaluate the suitability of multiple or limited blood sampling to predict clearance, red marrow absorbed dose, and myelotoxicity of 186Re-cMAb U36. METHODS: Population pharmacokinetics of 186Re-cMAb U36 were analyzed with a nonparametric expectation algorithm (NPEM 2) and used for Bayesian analysis of individual patient data to predict cMAb U36 clearance. RESULTS: 186Re-cMAb U36 clearance was most accurately predicted (r = 0.91, P < 0.001) with limited sampling for sample points 4 and 72 h after administration of 186Re-cMAb U36. These predictions were less accurate with 99mTc-cMAb U36 (r = 0.51, P = 0.078 for multiple sampling; r = 0.47, P = 0.104 for sampling at 4 and 21 h after administration). Thrombocytopenia was found to be correlated with the red marrow absorbed dose and was equally well predicted by limited blood sampling after administration of 99mTc-cMAb U36 (r = 0.81, P < 0.01) or 186Re-cMAb U36 (r = 0.79, P < 0.01). CONCLUSION: Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.

Metabolism and growth inhibition of four retinoids in head and neck squamous normal and malignant cells.

Isotretinoin (13-cis-retinoic acid, 13cRA) has proven to be active in chemoprevention of head and neck squamous cell carcinoma (HNSCC). Moreover, both all-trans-retinoic acid (ATRA) and 13cRA induce objective responses in oral premalignant lesions. After binding of retinoids to retinoic acid receptors (RARs and RXRs) dimers are formed that are able to regulate the expression of genes involved in growth and differentiation. We compared the metabolism and level of growth inhibition of 13cRA with that of ATRA, 9cRA and retinol in four HNSCC cell lines and normal oral keratinocyte cultures (OKC). These retinoid compounds are known to bind with different affinities to the retinoic acid receptors. We observed that all retinoids were similar with respect to their capacity to induce growth inhibition. One HNSCC line could be ranked as sensitive, one as moderately sensitive and the remaining two were totally insensitive; OKC were moderately sensitive. The rate at which the cells were able to catabolize the retinoid was similar for all compounds. Retinoid metabolism in HNSCC cells resulted in a profile of metabolites that was unique for each retinoid. These metabolic profiles were different in OKC. Our findings indicate that differences in retinoid receptor selectivity of these retinoids do not influence the level of growth inhibition and rate of metabolism.

Radioimmunotherapy in patients with head and neck squamous cell carcinoma: initial experience.

BACKGROUND: Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells. METHODS: The suitability of 186Re-labeled chimeric MAb U36 (186Re-cMAb U36) for radioimmunotherapy was evaluated in a phase I study, with radiation dose escalating steps of 11, 27, and 41 mCi/m2. Tumor targeting was monitored with a gamma camera, and the maximum tolerated dose was established in 13 patients with recurrent or metastatic disease. RESULTS: Administrations were well tolerated, and excellent targeting of tumor lesions was seen. Myelotoxicity was the only toxicity observed, resulting in dose-limiting toxicity in two patients treated with 41 mCi/m2. The MTD was established at 27 mCi/m2. A marked reduction in tumor size was observed in two patients, another showed stable disease for 6 months. CONCLUSIONS: Radioimmunotherapy with 186Re-cMAb U36 seems to be well tolerated, with bone marrow being the dose-limiting organ. The observation of antitumor effects is encouraging for further development of radioimmunotherapy for HNSCC.

Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications.

In 1953, Slaughter et al. [D. P. Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck (HNSCC) and discussed its clinical significance for the development of second primary tumors and local recurrences. To define the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management.

Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas.

High-risk human papillomaviruses (HPVs) have been proposed to be associated with a subset of head and neck cancers (HNSCCs). However, clear biological evidence linking HPV-mediated oncogenesis to the development of HNSCC is hardly available. An important biological mechanism underlying HPV-mediated carcinogenesis is the inactivation of p53 by the HPV E6 oncoprotein. In the present study we investigated this biological relationship between HPV and HNSCC. In total 84 HNSCC tumors were analyzed for the presence of high-risk HPV nucleic acids by DNA polymerase chain reaction-enzyme immunoassay (PCR-EIA) and E6 reverse transcriptase (RT)-PCR as well as for the presence of mutations in the p53 gene. We found 20/84 HPV16 DNA-positive cases with one or more DNA assays, 10 of which were consistently positive with all assays. Only 9/20 cases showed E6 mRNA expression, indicative for viral activity. Only these nine E6 mRNA-positive cases all lacked a p53 mutation, whereas both the other HPV DNA-positive and HPV-DNA negative tumors showed p53 mutations in 36% and 63% of the cases, respectively. Moreover, only in lymph node metastases of HPV E6 mRNA-positive tumors both viral DNA and E6 mRNA were present. Our study provides strong biological evidence for a plausible etiological role of high-risk HPV in a subgroup of HNSCC. Analysis of E6 mRNA expression by RT-PCR or alternatively, semiquantitative analyses of the viral load, seem more reliable assays to assess HPV involvement in HNSCC than the very sensitive DNA PCR analyses used routinely.

Expression of retinoic acid receptor gamma correlates with retinoic acid sensitivity and metabolism in head and neck squamous cell carcinoma cell lines.

Retinoids, analogues of vitamin A, can reverse premalignant lesions and prevent second primary tumors in patients with head and neck squamous cell carcinoma (HNSCC). The effects of retinoids are mediated by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act as ligand-activated transcription factors. The regulation of cell growth, differentiation and retinoid metabolism in normal, premalignant and malignant cells by retinoids is thought to be a result of their effects on gene expression. We investigated mRNA expression of RARs (alpha, beta, and gamma) and RXR-beta by means of RNase protection and related this to retinoic acid (RA)-induced growth inhibition and RA turnover in four HNSCC cell lines (UM-SCC-14C, UM-SCC-22A, UM-SCC-35 and VU-SCC-OE). An RA-resistant subline of UM-SCC-35 was generated by exposure to increasing concentrations of RA for 8 months (designated UM-SCC-35R). RA turnover was determined on the basis of decreasing RA levels in the cells and culture medium after exposure to 1 microM RA. We found that RAR-gamma mRNA expression was strongly correlated with RA-induced growth inhibition (p = 0.016, R = 0.92) and RA turnover (p = 0.041, R = 0.86). RAR-beta transcript levels were reduced in three of five cell lines compared with normal mucosa, and these did not correlate with RA-induced growth inhibition and RA turnover. Expression of RAR-alpha and RXR-beta was not substantially altered in any of the cell lines. These findings suggest that in HNSCC cell lines RAR-gamma is the most important retinoid receptor for regulation of RA turnover rate and RA-induced growth inhibition.

Enhanced turnover of all-trans-retinoic acid and increased formation of polar metabolites in head and neck squamous cell carcinoma lines compared with normal oral keratinocytes.

Retinoids show promise in the treatment of various (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). Previous studies have shown that the metabolic pathways of retinoids are important in the anticancer effect of retinoids, and that these pathways may change during carcinogenesis. In the present study, we analyzed HNSCC cell lines (n = 11) and normal oral keratinocyte cultures (n = 11) by reverse-phase high-performance liquid chromatography and conducted growth inhibition assays. We demonstrate here that in contrast to normal oral keratinocytes, HNSCC cell lines: (a) had averaged a 17-fold greater turnover rate of all-trans-retinoic acid (RA); (b) had a 1.9-fold less RA-induced growth inhibition; (c) were able to form polar metabolites; and (d) were able to catabolize 4-oxo-RA. Furthermore, the mRNA expression of the RA-specific 4-hydroxylase, CYP26A1, was dramatically increased after RA-induction in the two HNSCC cell lines with the highest metabolism, was undetectable in normal keratinocytes, and was not inducible by RA. Next, introduction of CYP26A1 cDNA in a low-metabolizing HNSCC cell line resulted in an 11-fold higher turnover rate of RA and a 12-fold increase in the amount of polar metabolites, but it did not change sensitivity to RA. These observations point to fundamental changes in RA metabolism pathways during HNSCC carcinogenesis and may provide clues to a more rational approach for RA-mediated intervention.

Targeting of aluminum (III) phthalocyanine tetrasulfonate by use of internalizing monoclonal antibodies: improved efficacy in photodynamic therapy.

The use of monoclonal antibodies (MAbs) directed against tumor-associated antigens for targeting of photosensitizers is an interesting option to improve the selectivity of photodynamic therapy (PDT). Hydrophilic photosensitizers are most suitable for conjugation to MAbs because of their water solubility. The photosensitizer aluminum (III) phthalocyanine tetrasulfonate [AlPc(SO3H)4] has many ideal photochemical properties; however, because of its hydrophilicity, the free form of this sensitizer does not readily reach the critical intracellular target and, therefore, is ineffective in PDT. On the basis of our previous studies, we hypothesized that AlPc(SO3H)4 might be suitable for PDT when coupled to internalizing tumor-selective MAbs. In this study, a reproducible procedure is presented for coupling of AlPc(SO3H)4 to MAbs via the tetra-glycine derivative AlPc(SO2Ngly)4. Conjugation was performed to chimeric MAb (cMAb) U36 and murine MAbs (mMAb) E48 and 425 using a labile ester. Conjugates showed preservation of integrity and immunoreactivity and full stability in serum in vitro. At molar ratios >4, the solubility of the conjugates decreased. Data on the in vitro efficacy of PDT showed that in the chosen experimental setup the internalizing AlPc(SO2Ngly)4-mMAb 425 conjugate was about 7500 times more toxic to A431 cells than the free sensitizer (IC50s, 0.12 nM versus 900 nM). The AlPc(SO2Ngly)4-mMAb 425 conjugate was also more toxic than meta-tetrahydroxyphenylchlorin-mMAb 425 conjugates and free meta-tetrahydroxyphenylchlorin that had been tested previously (M. B. Vrouenraets et al., Cancer Res., 59: 1505-1513, 1999) in the same system (IC50s, 7.3 nm and 2.0 nM, respectively). Biodistribution analysis of AlPc(SO2Ngly)4-125I-labeled cMAb U36 conjugates with different sensitizer:MAb ratios in squamous cell carcinoma-bearing nude mice revealed selective accumulation in the tumor, although to a lesser extent than for the unconjugated 125I-labeled cMAb U36, whereas tumor:blood ratios were similar. These findings indicate that AlPc(SO3H)4 has high potential for use in PDT when coupled to internalizing tumor-selective MAbs.

Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients.

BACKGROUND: Malnourished head and neck cancer patients are at increased risk of postoperative complications. OBJECTIVE: We studied the effect of perioperative, arginine-supplemented nutritional support on nutritional status, immune status, postoperative outcome, and survival in severely malnourished (weight loss >10% of body weight) head and neck cancer patients undergoing major surgery. DESIGN: Forty-nine patients were randomly assigned to receive 1) no preoperative and standard postoperative tube feeding, 2) standard preoperative and postoperative tube feeding, or 3) arginine-supplemented preoperative and postoperative tube feeding. RESULTS: Patients in both prefed groups received approximately 9 d of preoperative tube feeding, resulting in energy intakes of 110% and 113% of calculated needs (compared with 79% in the control group; P = 0.007). Compared with no preoperative feeding, preoperative enteral nutrition did not significantly improve nutritional status or any of the studied biochemical or immunologic indexes. Major postoperative complications occurred in 53%, 47%, and 59% of patients in study groups 1, 2, and 3 (NS). A trend was seen toward better survival in the arginine-supplemented group (P = 0.15). Secondary analysis showed that survivors had better human leukocyte antigen-DR expression on monocytes (P = 0.05) and higher endotoxin-induced cytokine production (P = 0.010 for tumor necrosis factor alpha and P = 0.042 for interleukin 6) at the start of the study than did patients who died. CONCLUSIONS: Nine days of preoperative tube feeding, with or without arginine, did not significantly improve nutritional status, reduce the surgery-induced immune suppression, or affect clinical outcome in severely malnourished head and neck cancer patients. Patients supplemented with arginine-enriched nutrition tended to live longer. Some markers of immune function may distinguish patients with good or bad prognoses.

Intracranial metastases in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Intracranial metastases are rarely clinically diagnosed in patients with head and neck squamous cell carcinoma. Only 7 patients with metastases to the cavernous sinus from head and neck squamous cell carcinomas have been reported. METHODS: A retrospective study revealed 13 patients with intracranial metastases of head and neck squamous cell carcinoma. In a 53-year-old woman a cavernous sinus metastasis of a laryngeal carcinoma was histologically diagnosed by using a CT-guided surgical navigation system and was treated with stereotactic radiotherapy. RESULTS: The mean survival was 4.3 months. Predictive factors for longer survival were absence of extracranial disease, age younger than 60 years, and treatment with radiotherapy. CONCLUSIONS: The prognosis for patients with intracranial disease is poor. The current development of computer-assisted stereotactic navigation and stereotactic radiotherapy may facilitate surgical diagnostic exploration and improve treatment, especially in patients without extracranial disease.

Head and neck squamous cell carcinoma: US-guided fine-needle aspiration of sentinel lymph nodes for improved staging--initial experience.

Ultrasonography (US)-guided fine-needle aspiration with cytologic examination was combined with lymphoscintigraphy for the identification of sentinel lymph nodes (SLNs) in 12 patients with a squamous cell carcinoma of the oral cavity or oropharynx. Dynamic lymphoscintigraphy and a hand-held gamma probe were used to depict the SLNs to be aspirated. Cytologic examination of the aspirated SLNs revealed neck lymph node status in patients who underwent neck dissection (n = 6). In patients who underwent only transoral excision, one false-negative cytologic result was observed. This combined approach is expected to improve the detection of occult neck lymph node metastases.

Survival of malnourished head and neck cancer patients can be predicted by human leukocyte antigen-DR expression and interleukin-6/tumor necrosis factor-alpha response of the monocyte.

BACKGROUND: Patients with advanced stages of head and neck cancer are often characterized by malnutrition and by an impaired immune system. Because some of the suppressed immune parameters were shown to be of prognostic importance in trauma and sepsis, we investigated whether these would also correlate with survival in head and neck cancer. METHODS: Severely malnourished head and neck cancer patients undergoing ablative and reconstructive surgery were followed prospectively and their perioperative immune parameters were related to long-term survival. RESULTS: Forty-nine patients with a preoperative weight loss of more than 10% were followed up for a period of at least 16 months after surgery. Analyses of variance revealed that preoperative human leukocyte antigen-DR (HLA-DR) expression on monocytes and endotoxin-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were different between patients who survived and patients who died. Proportional hazards identified a weight loss of more than 12%, the presence of coexistent disease, and an HLA-DR expression on monocytes below the cutoff points (mean fluorescence index < 15, peak channel index < 9) to be of significant influence on survival. CONCLUSIONS: In addition to known prognostic parameters such as tumor stage, coexistent disease, and weight loss, the immune parameters HLA-DR expression on monocytes and endotoxin-induced cytokine production may carry prognostic value in cancer patients. Immunomodulating therapies leading to improvement of these parameters might in the future lead to increased options for treatment.