A Novel Morbidity Prediction Model for Head and Neck Oncosurgery

The purpose of the study was to construct and validate a risk model to predict morbidity in head and neck oncosurgeries. Potential risk factors of 300 surgically treated head and neck cancer patients like age, sex, tumor site, TNM stage, duration of surgery, adjunctive treatment, comorbidities and alcohol and tobacco usage were analyzed. Postoperative complications were noted. We developed a logistic model to predict the probability of patients developing morbidity based on the statistically significant variables-duration of surgery, preoperative radiation and hypertension. The validity of the test was assessed by the c-index which were 0.79 (95% C.I 0.71–0.87) for the study set (250 patients) and 0.86(95% C.I 0.73–0.90) for the test set (50 patients). The correlation of observed to expected morbidity was 0.709 (P < 0.0001). We validated a risk model and constructed a simple chart that provides us an assessment of the risk of a patient of developing morbidity.     

Prognostic Factors and Survival in Adenoid Cystic Carcinoma of the Head and Neck: A Retrospective Clinical and Histopathological Analysis of Patients Seen at a Cancer Center

Adenoid cystic carcinoma (AdCC) is a rare malignancy that accounts for approximately 1% of all head and neck cancers. This neoplasm is characterized by slow but often relentless growth and dissemination. Our aim was to retrospectively evaluate the clinical-pathological features of patients diagnosed with head and neck AdCC and to identify possible prognostic factors. This retrospective observational study analyzed 87 cases of AdCC of the head and neck. Clinical parameters (tumor size, lymph node and distant metastasis, clinical stage, and survival) were obtained from the records. Survival curves were constructed using the Kaplan–Meier method. A p value ≤ 0.05 was considered significant. There was a slight predominance of cases diagnosed in female patients (54%). The mean age at diagnosis was 51.5 years. Analysis using Cox’s proportional hazards model considering 10-year disease-specific survival identified histologic pattern and presence of perineural invasion as independent prognostic variables. Primary tumor size and distant metastasis were prognostic predictors of 5- and 10-year disease-free survival. Detailed analysis of the association between clinical-pathological parameters and prognosis can assist professionals with cancer treatment planning and adequate patient management. Considering the long-term aggressive behavior of AdCC, rigorous patient follow-up is important to identify possible locoregional or distant recurrences.     

Metastases to the Head and Neck: An Overview

This paper provides a review of the more common tumors to metastasize to 12 anatomic subsites of the head and neck, exclusive of cervical lymph nodes. Emphasis is placed on clinical rather than subclinical metastases discovered at autopsy.     

Acetylated Tubulin (AT) as a Prognostic Marker in Squamous Cell Carcinoma of the Head and Neck

Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens. We also examined AT expression on pre-therapy tissues of patients with SCCHN receiving induction chemotherapy with docetaxel, cisplatin and 5FU (TPF IC). AT expression was assessed on archival cases of SCCHN with (N = 63) and without (N = 82) locoregional lymph node metastases (LNM). The predominant tumor site was oral cavity (52 %). Immunohistochemistry staining was based on staining intensity and percentage of tumor cells stained to create a weighted index (WI). A total of nine patients who received TPF IC were evaluable for response by RECIST and also had pre-therapy tissues available. A significant independent correlation between AT and tumor grade (p = 0.001) and primary location (p = 0.008) was noted. There was a trend of higher AT in patients with presence of LNM (p = 0.052) and a trend in improved OS for patients with an AT WI below the median compared to those above the median for patients with no LNM (p = 0.054). For patients treated with induction TPF, we observed an inverse correlation between AT expression and response to TPF IC (p = 0.0071). AT expression is correlated with tumor grade and primary site. There was an observed trend correlating AT with presence nodal metastases. The observed inverse correlation with response to taxane based chemotherapy needs validation in a larger sample size.     

Dermatofibrosarcoma Protuberans of the Head and Neck

Background: Dermatofibrosarcoma protuberans (DFSP) of the head and neck is a rare, locally infiltrative, low-grade sarcoma. This study defines the clinical behavior of DFSP, evaluates the role of frozen section analysis, and identifies factors that predict local control.Methods: Hospital records and pathological slides were reviewed for 33 patients with pathologically confirmed head and neck DFSP treated at Memorial Sloan-Kettering Cancer Center between 1964 and 1999. Factors were analyzed by using Fishers exact or (² tests.Results: For 21 primary and 12 recurrent patients, median age and tumor size at presentation was 39 years and 2.0cm, respectively. Thirty-two (97%) patients were alive at a median follow-up of 82 months. Three patients recurred locally, all with smaller than 2-cm resection margins. Deep tumors were more likely to have a margin-positive resection than superficial lesions (P = .03). Gross margin 2cm or more was a significant predictor of a negative histological margin (P < .001). There was a trend toward improved recurrence-free survival for tumors treated with wide (2 cm) margin resection (P = .059). Accuracy, sensitivity, specificity, and false negative rates of frozen section were 80%, 43%, 100%, and 57%, respectively.Conclusions: Wide margin resection of head and neck DFSP predicts negative histological margins and impacts favorably on local recurrence-free survival. Frozen section analysis does not assess resection margins accurately.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16–19, 2000.     

Sentinel Node Biopsy in Head and Neck Cancer: Preliminary Results of a Multicenter Trial

Background: The aim was to determine the reliability and reproducibility of sentinel node biopsy (SNB) as a staging tool in head and neck squamous cell carcinoma (HNSCC) for T1/2 clinically N0 patients by means of a standardized technique.Methods: Between June 1998 and June 2002, 227 SNB procedures have been performed in HNSCC cases at six centers. One hundred thirty-four T1/2 tumors of the oral cavity/oropharynx in clinically N0 patients were investigated with preoperative lymphoscintigraphy (LSG), intraoperative use of blue dye/gamma probe, and pathological evaluation with step serial sectioning and immunohistochemistry, with a follow-up of at least 12 months. In 79 cases SNB alone was used to stage the neck carcinoma, and in 55 cases SNB was used in combination with an elective neck dissection (END).Results: In 125/134 cases (93%) a sentinel node was identified. Of 59 positive nodes, 57 were identified with the intraoperative gamma probe and 44 with blue dye. Upstaging of disease occurred in 42/125 cases (34%): with hematoxylin-eosin in 32/125 (26%) and with additional pathological staging in 10/93 (11%). The sensitivity of the technique with a mean follow-up of 24 months was 42/45 (93%). The identification of SNB for floor of mouth (FOM) tumors was 37/43 (86%), compared with 88/91 (97%) for other tumors. The sensitivity for FOM tumors was 12/15 (80%), compared with 30/30 (100%) for other tumor groups.Conclusion: SNB can be successfully applied to early T1/2 tumors of the oral cavity/oropharynx in a standardized fashion by centers worldwide. For the majority of these tumors the SNB technique can be used alone as a staging tool.     

Improved Staging of Cervical Metastases in Clinically Node-Negative Patients With Head and Neck Squamous Cell Carcinoma

Background: The management of the N0 neck in oral and oropharyngeal cancer is often determined by the risk of metastases related to features of the primary tumor. Where the risk of metastases is >20%, elective neck dissection (END) has been advocated. This study reviewed clinical staging, surgical staging, pathologic staging, and histopathologic parameters to determine the prediction of nodal metastases and micrometastases in patients with head and neck squamous cell carcinoma.Methods: A prospective series of 61 clinically neck node–negative patients undergoing surgical resection of a T1/2 intraoral or oropharyngeal invasive squamous cell carcinoma and surgical staging of the neck, with sentinel node biopsy (SNB) alone or SNB-assisted END, between June 1998 and March 2002 were included in this study.Results: Pathologic upstaging of the clinically N0 neck occurred in 27 (44%) of 61 patients. Routine pathology with hematoxylin and eosin upstaged disease in 22 of 27 patients (sensitivity of 81%). Five patients with micrometastasis were staged pN1mi after stepped serial sectioning and immunohistochemistry. Tumor thickness, a noncohesive invasive front, and perineural and bone invasion were all histological predictors for cervical metastases. Five patients with micrometastases were staged pN1mi.Conclusions: Both clinical staging and routine pathologic staging underestimate the presence of nodal metastases. Staging with either SNB alone or SNB-assisted END shows promise in the management of the N0 neck by identifying patients with micrometastases (pN1mi).     

Microsurgical Tissue Transfers for Head and Neck Reconstruction in Patients with Alcohol-Induced Mental Disorder

Background Free tissue transfer in patients with organic mental disorder has always been known to be risky. Herein, the outcomes of free tissue transfers for head and neck reconstruction in those with alcohol-induced mental disorder were analyzed. Materials and methods We retrospectively reviewed and analyzed data from the past 10 years of 1,364 patients who had undergone microsurgical tissue transfers after head and neck cancer ablation. Among them, 54 patients had been diagnosed with alcohol-induced mental disorders post-operatively. Age ranged from 33 to 71 years. Alcohol-drinking history averaged 17.5 years. Reconstructive procedures included 25 forearm flaps, 13 anterolateral thigh (ALT) flaps, 10 fibula osteocutaneous flaps, and 6 double flaps (fibula+ALT). The outcomes and complications were analyzed. Results Onset periods ranged from the first to fourth days post-operatively. Duration of alcohol withdrawal or delirium tremens was 3–10 days. All patients gradually stabilized after immediate psychiatric consultation and intensive medical treatment. The flap survival rate in patients with alcohol withdrawal was significantly decreased in comparison with patients not suffering alcohol withdrawal (83% versus 96.4%, P < 0.001). During this critical post-operative period, 28 (52%) patients with alcohol withdrawal syndrome experienced complications; 26 (48%) suffered flap-related complications, and 19 (35.2%) required additional surgery. The analytical parameters revealed that secondary operative procedures and duration of hospitalization differed significantly between the complication and non-complication groups (P < 0.001). Conclusion Higher rates of complications and level of critical care were needed in patients with alcohol-induced mental disorder after head and neck microsurgical reconstructions. Treatment requires a multidisciplinary approach, rapid diagnosis, and intensive medical care. Presented at the 21st Annual Meeting of American Society for Reconstructive Microsurgery, 14–17 January, 2006, Tucson, AZ, USA     

Osteoprotegerin and Bone Mass in Squamous Cell Head and Neck Cancer Patients

Osteoprotegerin (OPG) is considered one of the main regulators of bone remodeling. Various patterns of serum OPG levels have been described in different types of tumors. We undertook this study to determine serum OPG levels in patients with squamous cell head and neck cancer (SCHNC), analyzing their relationship with other metabolic bone parameters and bone mineral density (BMD), as well as the possible influence of chemotherapy. Forty male patients with localized SCHNC were studied, and their results were compared with those of 40 healthy male controls. The type of treatment followed by each patient was noted. Age, weight, height, and lifestyle habits were recorded; and OPG, Ca²⁺, intact parathyroid hormone (iPTH), 25-Hydroxyvitamin D (25OHD) and 1,25-Dihydroxyvitamin D (1,25(OH)₂D), bone alkaline phosphatase, osteocalcin, and serum C-terminal cross-links telopeptide of type I collagen (ICTP) were determined. Dual-energy X-ray absorptiometry BMD at the lumbar spine, femoral neck, and hip was also measured. Serum OPG was higher in patients than in controls (91.7 ± 25.8 vs. 77.2 ± 26.3, P = 0.02). ICTP (a bone resorption marker) was 37% higher in patients (P = 0.007). Bone mass was lower in patients at the lumbar spine, femoral neck, and total hip. Lumbar spine Z-score showed a significant progressive decrease in controls, stage I-III patients, and stage IV patients. Logistic regression analysis showed a significant association between the disease and serum OPG levels, the odds ratio per standard deviation increase of this being 1.9 (95% confidence interval 1.1–3.8, P = 0.04) after adjusting for bone mass and ICTP serum levels, as well as for alcohol and smoking history. Adjustment for alcohol intake and tobacco use did not cancel out BMD differences between patients and controls. Patients with SCHNC show increased OPG serum levels, increased bone resorption, and decreased bone mass. The OPG rise appears to be unrelated to the BMD decrease, and the BMD decrease seems to be, at least in part, independent of smoking and drinking habits. No differences in either OPG or BMD were seen between patients with and without chemotherapy. Further studies are needed to clarify the mechanisms responsible for OPG and BMD changes in SCHNC.     

Audit of Clinical Coding of Major Head and Neck Operations

INTRODUCTION

Within the NHS, operations are coded using the Office of Population Censuses and Surveys (OPCS) classification system. These codes, together with diagnostic codes, are used to generate Healthcare Resource Group (HRG) codes, which correlate to a payment bracket. The aim of this study was to determine whether allocated procedure codes for major head and neck operations were correct and reflective of the work undertaken. HRG codes generated were assessed to determine accuracy of remuneration.

PATIENTS AND METHODS

The coding of consecutive major head and neck operations undertaken in a tertiary referral centre over a retrospective 3-month period were assessed. Procedure codes were initially ascribed by professional hospital coders. Operations were then recoded by the surgical trainee in liaison with the head of clinical coding. The initial and revised procedure codes were compared and used to generate HRG codes, to determine whether the payment banding had altered.

RESULTS

A total of 34 cases were reviewed. The number of procedure codes generated initially by the clinical coders was 99, whereas the revised codes generated 146. Of the original codes, 47 of 99 (47.4%) were incorrect. In 19 of the 34 cases reviewed (55.9%), the HRG code remained unchanged, thus resulting in the correct payment. Six cases were never coded, equating to £15,300 loss of payment.

CONCLUSIONS

These results highlight the inadequacy of this system to reward hospitals for the work carried out within the NHS in a fair and consistent manner. The current coding system was found to be complicated, ambiguous and inaccurate, resulting in loss of remuneration.     

Application of the Roche Cobas® HPV 4800 in Formalin-Fixed,Paraffin-Embedded Samples for Head and Neck Squamous Cell Carcinomas

Testing for high risk human papillomavirus (HR-HPV) status is standard of care in squamous cell carcinomas of the oropharynx as well as cervical lymph node squamous cell carcinomas of unknown primary origin. DNA or RNA in-situ hybridization (ISH) and p16 immunohistochemistry, widely used currently for HPV detection are operator-dependent. In addition, DNA ISH has a relatively low sensitivity, and p16 is not entirely specific for HR-HPV infection. In this study, we examined the performance of the cobas® HPV genotyping assay in formalin-fixed, paraffin-embedded (FFPE) samples of head and neck squamous cell carcinoma. FFPE samples from head neck and other anatomic sites tested by ISH and p16 for HR-HPV at ARUP Laboratories were selected for this study. Samples were deparaffinized, stained and micro-dissected for tumor contents followed by tissue lysis, then tested with cobas® for HR-HPV. All the samples were also tested by HPV Linear Array for confirmation. All (N = 18) high risk HPV positive specimens tested by cobas® were confirmed as positive by the Linear Array test. All the specimens tested as negative by cobas® were tested as negative (N = 5) or positive only for low risk HPV (N = 3) by Linear Array, as cobas® only detects HR HPV. Limits of detection for HPV16 and 18 were established at 160–320 and 320–1600 copies, respectively. Our data suggest that cobas® HR-HPV genotyping is a viable option for detection of HR-HPV in formalin-fixed, paraffin-embedded samples from head and neck and other anatomic sites and has been validated for clinical use.     

Integration of Biomarkers Including Molecular Targeted Therapies in Head and Neck Cancer

Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. The search for biomarkers includes evaluation of tumor tissues and surrogate materials by molecular, genomic and phenotypic means. Ideal biomarkers should be accurate and easy to perform, highly specific, objective, quantitative, and cost effective. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. For targeted therapy, however, a single key molecule must be identified. Key molecules and pathways for targeted therapy include growth factor receptors, MAPk/ERk pathway, angiogenesis, and epithelial to mesenchymal transition. Over-expression and mutations of genes in these pathways including EGFR, VEGF, HER2, BRAF and RET, contribute to tumorigenesis in head and neck cancers from squamous carcinomas, to salivary adenocarcinomas and thyroid carcinomas, both follicular and c-cell derived. Monoclonal antibodies to the EGFR receptor and oral tyrosine kinase inhibitors are currently being studied in multiple phase II and III clinical trials to determine their efficacy in head and neck cancers and correlative studies for biomarkers are on-going.     

Sentinel Lymph Node Biopsy for Head and Neck Melanomas

Background: Sentinel lymph node (SLN) biopsy for head and neck (H&&N) melanomas may be more technically challenging compared with other locations because of complex lymphatic drainage patterns. This analysis was performed to compare the results of SLN biopsy for H&&N, truncal, and extremity melanomas.Methods: The Sunbelt Melanoma Trial includes patients aged 18 to 70 with melanomas 1.0 mm thick. Statistical comparison was performed by ² or analysis of variance test.Results: A total of 2610 patients were evaluated with a median follow-up of 18 months. The mean number of SLN per nodal basin was 2.8, 2.7, and 2.1 for H&&N, truncal, and extremity melanomas, respectively. Median Clark level, Breslow thickness, and percentage of ulceration were similar between the groups. Peri-parotid SLN was identified in 25% of cases; there were no facial nerve injuries. SLN biopsy for H&&N melanoma had higher false-negative rates at 1.5% (vs. 0.5% for trunk or extremity) but less histologically positive SLN at 15% (vs. 23.4%, and 19.5%; P &< .001) compared with truncal and extremity melanoma. Blue dye was visualized less frequently in SLN of H&&N melanoma patients compared with those with trunk or extremity melanomas.Conclusions: Preoperative lymphoscintigraphy and meticulous intraoperative search for blue/radioactive nodes may improve results in H&&N melanomas.Presented at the Society of Surgical Oncology Annual Meeting, Denver, CO, March 14–17, 2002.     

Neuroendocrine Neoplasms of the Head and Neck: Some Suggestions for the New WHO Classification of Head and Neck Tumors

As knowledge and understanding in pathology evolve, classifications and nomenclature also change to reflect those advances. The 2005 World Health Organization Classification of Head and Neck Tumours was a significant step towards diagnostic standardization of head and neck neuroendocrine carcinomas; however, in the last 10 years there have been new data supporting the recognition of “large cell neuroendocrine carcinoma” as a distinctive high grade carcinoma in the head and neck, a lesion not included in the 2005 Classification. In addition, the terms “middle ear adenoma” and “carcinoid tumor of middle ear” are still widely used to describe a neoplasm that is neither a pure adenoma nor a carcinoid tumor but a lesion with variable mixed exocrine and endocrine differentiation. Largely using the diagnostic criteria of the WHO classification of neuroendocrine carcinomas of the lung, we propose the terms “neuroendocrine carcinoma, grade 1”; “neuroendocrine carcinoma, grade 2”; “neuroendocrine carcinoma, grade 3, large cell type”; and “neuroendocrine carcinoma, grade 3, small cell type” for the classification of neuroendocrine carcinomas of the head and neck in a future WHO classification. In addition, we also proposed the term “mixed epithelial neuroendocrine tumor” of the middle ear as an alternative for “middle ear adenoma” and “carcinoid tumor of the middle ear”.     

~(125)I粒子组织间植入治疗头颈部复发和转移恶性肿瘤

目的探讨125I植入治疗复发和转移头颈部恶性肿瘤的可行性。方法2003年1月~2007年7月,对29例头颈部癌术后或放化疗后复发或转移,在局部浸润麻醉下,CT、B超或腔内镜引导125I粒子植入术,粒子间距0.5~1.0cm。肿瘤周边匹配剂量(matched peripheral dose,MPD)90~160Gy,粒子活度29.6MBq。结果29例均顺利完成手术,每例植入粒子12~67颗,中位数23颗。术后未发生出血、感染、粒子移位等严重并发症。29例随访3~24个月,平均16个月,局部控制率术后3个月为55%(16/29),6个月71%(20/28),12个月45%(10/22),2年36%(5/14)。结论放射性125I粒子植入治疗复发和转移头颈部肿瘤可行,近期疗效可靠。