BACKGROUND: We aimed to determine predictors of morbidity in patients undergoing microvascular free flap reconstruction of the head and neck. METHODS: We prospectively evaluated 796 cases between 1999 and 2007 using univariate and multivariate analysis to determine predictors of morbidity and prolonged hospital stay. RESULTS: Two hundred thirty-nine patients (30%) developed major complications. Age, body mass index (BMI), American Society of Anesthesiology (ASA) score, Kaplan Feinstein comorbidity index (KFI) score, preoperative hemoglobin, and tracheostomy were independent predictors of major complication. Predictors of prolonged hospital stay included age, recent weight loss, alcohol excess, ASA, KFI, preoperative hemoglobin, mucosal surgery, anesthesia duration, and crystalloid replacement volume. CONCLUSION: Several variables are associated with an increased risk of development of major complications following free flap reconstruction of the head and neck. Although many of these variables are irreversible, they aid risk stratification of patients undergoing free flap reconstruction, and assist clinicians in making treatment decisions, consenting, and providing patients with realistic expectations regarding their perioperative course.(c) 2010 Wiley Periodicals, Inc. Head Neck, 2010.

The role of open surgery for management of laryngeal cancer has been greatly diminished during the past decade. The development of transoral endoscopic laser microsurgery (TLS), improvements in delivery of radiation therapy (RT) and the advent of multimodality protocols, particularly concomitant chemoradiotherapy (CCRT) have supplanted the previously standard techniques of open partial laryngectomy for early cancer and total laryngectomy followed by adjuvant RT for advanced cancer. A review of the recent literature revealed virtually no new reports of conventional conservation surgery as initial treatment for early stage glottic and supraglottic cancer. TLS and RT, with or without laser surgery or CCRT, have become the standard initial treatments for T1, T2 and selected T3 laryngeal cancer. Photodynamic therapy (PDT) may have an emerging role in the treatment of early laryngeal cancer. Anterior commissure involvement presents particular difficulties in application of TLS, although no definitive conclusions have been reached with regard to optimal treatment of these lesions. Results of TLS are equivalent to those obtained by conventional conservation surgery, with considerably less morbidity, less hospital time and better postoperative function. Oncologic results of TLS and RT are equivalent for glottic cancer, but with better voice results for RT in patients who require more extensive cordectomy. The preferred treatment for early supraglottic cancer, particularly for bulkier or T3 lesions is TLS, with or without postoperative RT. The Veterans Administration Study published in 1991 established the fact that the response to neoadjuvant CT predicts the response of a tumor to RT. Patients with advanced tumors that responded either partially or completely to CT were treated with RT, and total laryngectomy was reserved for non-responders. This resulted in the ability to preserve the larynx in a significant number of patients with locally advanced laryngeal cancer, while achieving local control and overall survival results equivalent to those achieved with initial total laryngectomy. Following this report, similar "organ preservation" protocols were employed in many centers. By 2003, results of the RTOG 93-11 trial, utilizing CCRT as initial treatment, were published, demonstrating a higher rate of laryngeal preservation with this protocol. Surgery was reserved for treatment failures. This concept changed the paradigm for management of advanced laryngeal cancer, greatly reducing the number of laryngectomies performed. While supracricoid laryngectomy has been employed for selected patients, total laryngectomy is the usual procedure for salvage of failure after non-surgical treatment.

OPINION STATEMENT: The incidence of cancer among older patients continues to rise. The use of combined modality therapy has improved survival in a variety of malignancies, including rectal, head and neck, and lung cancer; however, the addition of chemotherapy increases substantially the toxicities of treatment. Elderly patients have generally been excluded from prospective clinical trials and as such, there is a lack of evidence-based data with regards to the most appropriate treatment. Age itself should not be used as a criterion for foregoing combined modality therapy in elderly patients. Due to the increased toxicity of therapy, patients must be carefully selected. Any medical intervention should account for life expectancy, performance status, tolerance to therapy, and presence of medical or social conditions that may impact therapy. We encourage a comprehensive geriatric assessment to evaluate functional status, comorbidities, mental status, psychological state, social support, nutritional status, polypharmacy, and geriatric conditions in order to improve a patient's overall functional status during the course of therapy. Fit elderly patients should be considered candidates for combined modality therapy, however, because they are potentially more vulnerable to therapy, careful attention should be paid to hydration and nutritional status with early intervention when necessary. Investigators should be encouraged to expand eligibility to include elderly patients on non age-related clinical trials. Additionally, therapy-related clinical trials directed at the elderly should be developed.

Hospital stays constitute the main component of costs of cancer treatment. We conducted a prospective study to identify the determinants of the length of stay (LOS) after head and neck cancer surgery (HNCS). Patients who underwent major HNCS with opening of mucosa and with curative intent were enrolled. Data were collected for patient characteristics, type of tumour, surgical procedures and postoperative outcome. LOS defined as the interval between the day of admission for surgery until hospital discharge or death was determined by the Kaplan-Meier method. Independent determinants of LOS were identified using a Cox model. All 260 patients were included. Median LOS was 26 days (range, 3-178). In the multivariate model, four variables remained associated with increased LOS: American Society of Anaesthesiologist's score equal to 3 (hazard ratio 1.62 [1.23-1.99]), duration of surgical procedure >220min.,(HR=1.37 [1.22-1.56]), SSI (HR=2.09 [2.02-2.54]), occurrence of SSI caused by multi-resistant pathogen (HR=2.92 [2.78-3.77]) and occurrence of PP (HR=2.09 [1.78-2.81]). The present results highlighted the long duration of LOS after head and neck cancer surgery. Two variables (duration of surgical procedure and occurrence of nosocomial infections) were associated with LOS and might be improved by appropriate strategies.

Since the original data from the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated that nonsurgical therapy could achieve survival rates comparable to total laryngectomy in selected cases, there has been a progressive increase in employment of nonsurgical therapy for the management of advanced laryngeal cancer. Both neoadjuvant chemotherapy followed by conventionally fractionated or hyperfractioned radiotherapy for chemotherapy responders, or simultaneously administered chemoradiation has resulted in a significant number of patients who achieved cure while preserving their larynges. Nevertheless, combined chemotherapy and external beam radiation is associated with a variety of acute and chronic sequelae that can have a debilitating impact on function and quality of life. Although no therapeutic option is without risk, the decision regarding the modality of therapy for a patient with advanced laryngeal cancer should prompt a careful review of the current surgical techniques available for treatment. Data on quality of life and aging, as well as advances in minimally invasive surgical techniques, are available today that were not available at the time of the Veterans study. Selection of optimal therapy is often complex and raises the question whether the pendulum may have swung too far in the direction of nonsurgical therapy for advanced laryngeal cancer. This article reviews the current options available for a patient with advanced laryngeal cancer and discusses the impact of therapy.(c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

BACKGROUND.: Postoperative complications are relevant outcomes in patients with head and neck tumor who have undergone surgery. Few trials have assessed predictive factors in older patients. We assessed the predictive effect of preoperative clinical factors on postoperative complications. METHODS.: We conducted a cohort study with 242 patients older than 70 years with head and neck cancer who underwent surgery. Logistic regression identified predictive factors for postoperative complications. Significant variables were used to build a predictive index. RESULTS.: Comorbidities were present in 87.6% of patients, and 56.6% had some type of complication (44.6% local and 28.5% systemic). Male sex, bilateral neck dissection, presence of 2 or more comorbidities, reconstruction, and clinical stage IV were associated with postoperative complications. The predictive index showed a receiver operating characteristics curve (ROC) area of 0.69. CONCLUSION.: It is possible to predict postoperative complications in older patients with head and neck tumors who underwent oncologic surgery using clinical preoperative variables.(c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

BACKGROUND: Aggressive surgical treatment of oral and oropharyngeal cancers may be compromised by significant surgical complications. Early identification of patients at risk for postoperative complications may assist in clinical decision-making. The objective of this study was to assess the value of the Acute Physiology and Chronic Health Evaluation (APACHE II) score in predicting early postoperative surgical complications. METHODS: There were 510 cases of free tissue transfer surgery identified on the Liverpool Oncology Head and Neck Database for 1995 to 2002. APACHE II data were collected independently from critical care records and by case note retrieval. The authors' main a priori outcomes were total flap failure and any immediate complication requiring further surgery (including any from hemorrhage, hematoma, partial flap failure, airways, and anastomosis exploration). RESULTS: Overall total flap loss and immediate complication rates were 6.2 percent (30 of 485) and 13.6 percent (66 of 485), respectively. APACHE II data were known for 399 operations (82 percent) and, of these, 90 percent (360 of 399) were managed postoperatively in the critical care unit. There were clear correlations between APACHE II scores with total flap loss and with other immediate complications. CONCLUSIONS: The APACHE II score is associated with immediate postoperative surgical complications involving flap compromise and thus may be a useful tool in postoperative decision-making.

Little is known about long-term treatment outcome of elderly head and neck cancer patients and their quality of life (QOL). One hundred and eighteen older (>/=70 years) and 148 younger (45-60 years) patients with head and neck cancer were followed up for 3-6 years. In the long-term follow-up 33 younger and 24 older patients completed the EORTC QLQ-C30 and H&N35 and a questionnaire about depression. The survival rate after 3-6 years for younger patients was 36%, as compared to 31% in the older patient group. Higher tumour stages, more co-morbidity and non-standard treatment showed to be independent prognostic factors for mortality. No independent prognostic value of age could be found. The global QOL score remains roughly comparable. Even up to 6 years after treatment, we found no significant differences in survival or overall QOL between older and younger head and neck cancer patients.

BACKGROUND: Craniofacial resection (CFR) for patients over 70 years of age is uncommon. This study examines a cohort of 36 patients who had CFR at a single institution with the aim of reporting mortality, complications, and outcome. METHODS: Thirty-six patients 70 years of age and older were identified from a prospective database of 234 patients who had CFR at a single institution. The median age was 72 years (range, 70-87). Seventeen (47%) patients had had prior single-modality or combined treatment, which included surgery in 14 (40%), radiation in 13 (36%), and chemotherapy in 2 (6%). Thirty-five patients had a malignant tumor and 1 patient a benign tumor; 15 (42%) had high-grade, 17 (47%) intermediate-grade, and 4 (11%) low-grade pathology. The margins of resection were close or microscopically positive in 18 (50%). Adjuvant radiotherapy was given in 15 (42%) and chemotherapy in 1 (3%). Complications were classified into overall, local, central nervous system (CNS), systemic, and orbital. Overall survival (OS) and disease-specific survival (DSS) were determined using the Kaplan-Meier method. Outcomes were compared with patients less than 70 years of age. RESULTS: Postoperative mortality occurred in 6 (17%) patients and postoperative complications occurred in 23 (64%) patients. Local wound complications occurred in 11 (30%), CNS in 12 (33%), systemic in 6 (17%), and orbital in 1 (3%). Postoperative mortality and complications were significantly higher in patients 70 years of age and older compared with patients less than 70 years of age (17% versus 1.5%, p =.0005; 64% versus 36%, p =.003, respectively). With a median follow-up of 27 months (range, 1-237), the 3 year OS and DSS were significantly poorer than patients less than 70 years of age (OS: 53% versus 69%, p =.0004; DSS: 61% versus 70%, p =.01) due to increased medical comorbidity (53% versus 24%, p =.001) and poorer histology (high-, intermediate-, low-grade histology: 42%, 47%, 11% versus 26%, 47%, 27%, p =.05, respectively) in patients over 70 years of age. CONCLUSION: CFR in patients 70 years of age and older is associated with increased mortality, increased incidence of complications, and a poorer overall and disease-specific 3-year survival, compared with patients less than 70 years of age. The survival was likely due to increased medical comorbidity and adverse histology. These factors must be taken into account when considering an elderly patient for craniofacial resection.(c) 2006 Wiley Periodicals, Inc. Head Neck, 2006.

We performed microsatellite analysis at chromosomal regions frequently altered in head and neck squamous carcinoma on matched saliva and tumor samples from 37 patients who had oral squamous carcinoma. The results were correlated with the cytologic findings and traditional clinicopathologic factors to assess the diagnostic and biological potential of these markers. Our data showed that 18 (49%) of the saliva samples and 32 (86%) of the tumors had loss of heterozygosity (LOH) in at least one of the 25 markers studied. In saliva, the combination of markers D3S1234, D9S156, and D17S799 identified 13 (72.2%) of the 18 patients with LOH in saliva (P < 0.001). For tumors, markers D3S1234, D8S254, and D9S171 together identified 27 (84.3%) of the 32 tumors with LOH at any of the loci tested (P < 0.001). Eleven (55%) of the 20 saliva samples with cytologic atypia and seven (35%) of the 17 specimens without atypia had LOH. Significant correlation between LOH in tumor at certain markers and smoking and alcohol use was found. Our results indicate that: 1) epithelial cells in saliva from patients with head and neck squamous tumorigenesis provide suitable material for genetic analysis; 2) combined application of certain markers improves the detection of genetic alteration in these patients; 3) clonal heterogeneity between saliva and matching tumor supports genetic instability of the mucosal field in some of these patients; and 4) LOH at certain chromosomal loci appears to be associated with smoking and alcohol consumption.

Genomic imprinting is an inherited epigenetic phenomenon that results in parental-origin-specific gene expression in somatic cells. Relaxation or loss of this feature in certain genes has been demonstrated in several pediatric and adult neoplasms, suggesting an association with tumorigenesis. We analysed 64 primary untreated head and neck squamous carcinoma for the loss of imprinting in the IGF2 and H19 genes to determine the implications of this alteration in the development and progression of these tumors. Forty-nine (77%) of the 64 tumors were informative for imprinting analyses of these genes. IGF2 and H19 were imprinted in all normal squamous epithelium examined. Twelve (37.5%) of 32 tumors informative for H19 and 11 (40.7%) of 27 tumors informative for IGF2 manifested loss of imprinting. Ten tumors were informative for both genes, of which four maintained the constitutional imprinting and six showed loss of imprinting at either H19 or IGF2. These data suggest that loss of imprinting at the IGF2 and H19 loci play a role in the oncogenesis of head and neck carcinoma.

PURPOSE: Extrapolating from our experience delivering a "boost" field of radiation concurrently with fields treating both gross and subclinical disease at the end of a course of radiation therapy, we developed a regimen to deliver concurrent chemotherapy during the last 2 weeks of a conventionally fractionated course of radiation. PATIENTS AND METHODS: Patients had stage III or IV biopsy-proven squamous cell carcinoma originating from a head and neck mucosal site. The regimen was 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisplatin given daily with each radiation dose during the last 2 weeks. A phase I study was performed to determine the maximum-tolerated dose (MTD) before a phase II study was conducted. RESULTS: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day for cisplatin. Mucositis persisting more than 6 weeks after therapy was the dose-limiting toxicity. A total of 60 patients were treated on the two phases of the study. Eighteen patients (35%) treated at the MTD developed prolonged mucositis. There were two cases of neutropenic sepsis, including one fatality. The actuarial 2-year rates for overall survival, freedom from relapse, and local control were 62%, 59%, and 80%, respectively. CONCLUSION: Preliminary locoregional control rates seem to be higher than those reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliver an intense treatment schedule, which could be completed without significant interruptions, and to obtain high control rates above the clavicles. These end points were achieved.

Because reduced DNA repair capacity (phenotype) has been suggested as a risk factor for squamous cell carcinoma of the head and neck (SCCHN), newly-identified DNA repair gene polymorphisms (genotype) may also be implicated in risk. To test this hypothesis, we conducted a case-control study of 203 SCCHN patients and 424 control subjects (matched for age, sex and ethnicity) to investigate the role of two XRCC1 polymorphisms (XRCC1 26304 T and XRCC1 28152 A, respectively) in SCCHN. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (CI). A total of 180 cases (88.7%) and 363 controls (85.6%) lacked the XRCC1 26304 T allele [adjusted OR = 1.34 (CI, 0.80-2.25)]. Lack of this polymorphism was a significant risk factor specifically for cancers of the oral cavity and pharynx [adjusted OR = 2.46 (CI, 1.22-4.97)]. Thirty-two cases (15.8%) and 46 controls (10.8%) were homozygous for the XRCC1 28152 A allele [adjusted OR = 1.59 (CI, 0.97-2.61) for all cases, and 1.41 (CI, 0. 80-2.48) for oral and pharyngeal cancer only]. Furthermore, when the two genotypes were combined into a three-level model of risk, a polymorphism-polymorphism interaction of increasing risk (trend test, P = 0.049) was evident: OR = 1.0 for those with neither risk genotype (referent group), adjusted OR = 1.51 (CI, 0.87-2.61) for those with either risk genotype, and 2.02 (CI, 1.00-4.05) for those with both risk genotypes. For oral and pharyngeal cancer, this trend was even more pronounced with the adjusted OR = 2.68 (CI, 1.28-5.61) for those with either risk genotype, and 3.22 (CI, 1.33-7.81) for those with both risk genotypes. The findings support the hypothesis that a polymorphic XRCC1 DNA repair gene contributes to risk of developing SCCHN.

OBJECTIVES: To evaluate the efficacy and secondarily the toxic effects of biochemopreventive therapy (high-dose isotretinoin [13-cis-retinoic acid], alpha-tocopherol, and interferon alfa) in the reversal of advanced premalignant lesions of the upper aerodigestive tract and to correlate the therapeutic events with modulation of biomarkers. DESIGN: Prospective, nonrandomized chemoprevention trial. SETTING: Tertiary cancer care referral center and ambulatory care. PARTICIPANTS: Thirty-six patients with advanced premalignant lesions of the upper aerodigestive tract, without cancer during the 2 years before the intervention, with evaluable lesions, and without retinoid therapy for 3 months before the trial. INTERVENTION: Administration of oral isotretinoin (100 mg/m2 per day), oral alpha-tocopherol (1200 IU/d), and subcutaneous interferon alfa (3 megaunits per square meter twice weekly) for 12 months, with serial biopsies and clinical examination at 0, 6, 12, and 18 months from study start. MAIN OUTCOME MEASURES: Clinical and histologic responses to the intervention. RESULTS: Of the 36 patients, evaluation was possible in 30 for response at 6 months and in 21 at 12 months. At 6 months, there were 10 pathologic complete responses and 7 partial responses; at 12 months, 7 complete and 3 partial responses. A striking difference in response was observed in favor of laryngeal lesions (9/19 [47%] complete response rate at 6 months and 7/14 [50%] at 12 months vs 1/11 [9%] and 0/7 [0%], respectively, for oral lesions). Toxic effects were acceptable and did not exceed grade 3. CONCLUSION: Biochemoprevention is a promising biologic approach for laryngeal dysplasia and needs to be investigated further.

BACKGROUND: Surgeons have been using selective neck dissections in the treatment of squamous carcinoma of the upper aerodigestive tract for over 20 years. To date, no data is available that can answer the question "What are the patterns of failure in the neck following a selective neck dissection and is a selective neck dissection a reliable procedure for metastatic disease?" METHODS: To answer this question, the medical records of all patients with squamous carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx treated at The University of Texas M. D. Anderson Cancer Center from January 1, 1985-December 31, 1990, with a selective neck dissection were reviewed. Five hundred seventeen neck dissections were analyzed: suprahyoid (41), supraomohyoid (284), and anterolateral (192). The end point of the study was regional failure and survival. RESULTS: Regional recurrence in patients treated with a suprahyoid dissection was 43% with pathologically positive nodes. The regional recurrence in the patients treated with a supraomohyoid neck dissection was 1.9% with pathologically negative nodes, 35.7% with path N1 without postoperative radiation therapy, and 5.6% with postoperative radiation therapy. The neck staged pathologically N2B failed with and without postoperative radiation, 8.3% and 14%, respectively. Thirteen percent of the anterior/lateral neck dissections failed regionally. If multiple pathologically positive nodes (N2B) were present, the regional failure with postoperative radiation was 30% and 33.3% without postoperative radiation. CONCLUSION: The results of this retrospective study suggest that a selective neck dissection is a satisfactory staging procedure and is a definitive operation if all the nodes are pathologically negative. However, if a node is found to be invaded with cancer, the use of postoperative radiation is advisable.

A high incidence of locoregional failure contributes to the poor overall survival rate of around 50% for patients with squamous cell carcinoma of the head and neck (SCCHN). In vitro and in vivo preclinical work with adenovirus-mediated wild-type p53 gene transfer using the recombinant p53 adenovirus (Ad-p53) has shown its promise as a novel intervention strategy for SCCHN. These data have translated into Phase I and Phase II studies of Ad-p53 gene transfer in patients with advanced, locoregionally recurrent SCCHN. The safety and overall patient tolerance of Ad-p53 has been demonstrated. Of 15 resectable but historically noncurable patients in the surgical arm of a Phase I study, 4 patients (27%) remain free of disease, with a median follow-up time of 18.25 months. Surgical and gene transfer-related morbidities were minimal. These results provide preliminary support for the use of Ad-p53 gene transfer as a surgical adjuvant in patients with advanced SCCHN. The implications of our findings for the management of SCCHN in general are discussed.

E2F-1, a transcription factor by discovery, is thought to play a crucial role in regulating G1/S cell cycle progression. Its activity is modulated by complex formation with the retinoblastoma protein and related proteins. Overexpression of E2F-1 has been shown to induce apoptosis in quiescent fibroblasts. We constructed a recombinant E2F-1 adenovirus to test whether an overexpression of E2F-1 in head and neck squamous cell carcinoma cell lines would also induce apoptosis. Two cell lines, Tu-138 and Tu-167, were chosen for use in this study. Both cell lines harbor p53 mutations but express different levels of the retinoblastoma protein. Upon E2F-1 adenovirus infection, both cell lines expressed elevated levels of E2F-1 protein and then activated a pRb-chloramphenicol acetyltransferase reporter construct containing an E2F-1 binding motif. In vitro growth assay demonstrated that growth suppression by the E2F-1 protein was effective on both cell lines. Results from DNA fragmentation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analyses indicated apoptosis induction in cells infected with AdCMV-E2F-1. Moreover, ex vivo experiments in nude mice showed total suppression of tumor growth at sites that received cells infected AdCMV-E2F-1. An in vivo analysis of apoptosis using in situ end-labeling further demonstrated the induction of apoptosis by AdCMV-E2F-1 in tumor-bearing animals. These data indicate that overexpression of E2F-1 via an adenoviral vector suppresses in vitro and in vivo growth of head and neck squamous carcinoma cell lines through induction of apoptosis.

The organotypic (raft) culture system has been shown to be a useful model for examining the effects of biochemical manipulations on various epithelial cell types, using in vitro conditions that simulate the in vivo environment of the tissue of origin. To investigate this method as a model for topical gene therapy, we cultured the oral head and neck squamous cell carcinoma cell line TR146 on fibroblast-containing collagen gels at the air-medium interface and assessed the efficiency of transduction of a topically applied adenoviral vector containing beta-galactosidase cDNA. Diffuse expression of -galactosidase activity in multiple cell layers demonstrated effective penetration of the vector. Transduction efficiency and therapeutic activity of a replication-defective recombinant adenovirus containing wild-type p53 cDNA linked to a FLAG marker (AdCMV-p53-FLAG) were then assessed in TR146 organotypic cultures transduced by topical application. Twenty-four, 48, and 72 h after transduction, the cultures were harvested, and residual cell number and FLAG peptide expression were determined. The number of cells in p53 transduced cultures was significantly reduced in comparison to controls at all three time points (P < 0.001), which resulted from the induction of apoptosis as determined by in situ DNA end labeling. In addition, the FLAG peptide was expressed diffusely in the residual cells, further confirming effective transduction and expression of the exogenous gene products throughout multiple layers. We conclude that the organotypic culture is an effective in vitro model for assessing the efficacy of topically applied gene therapy on head and neck squamous carcinomas and premalignancies.

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

In order to evaluate the Dynasplint Trismus System (DTS) for the relief of trismus secondary to the treatment of head and neck cancer, we conducted a retrospective chart review of patients who had undergone DTS therapy during a 1-year period. Our inclusion criteria were cancer of the upper aerodigestive tract; treatment with radiation, chemotherapy, and/or surgery; and a maximal incisal opening (MIO) of less than 30 mm. MIO and the rate of improvement of trismus ("gain") were measured at selected intervals. Twenty-six patients met our study criteria; their pretherapy mean MIO was 19.3 mm. At the time of their most recent measurement, the mean MIO had increased to 25.5 mm-a measured gain of 32%. Although the initial rate of gain was 0.36 mm/day during the first 6 weeks, improvement leveled off over time, and the overall rate of gain was 0.16 mm/day. We conclude that the DTS is effective in increasing the mandibular range of motion at a rate of change that is maximized during initial treatment.

OBJECTIVES To determine conditional survival rates of 2-year survivors of head and neck cancer and to identify risk factors of increased mortality. DESIGN Prospective, observational study conducted from September 1, 2001, through September 31, 2008. SETTING Tertiary care institution. PATIENTS Two hundred seventy-six patients who survived 2 years after the diagnosis of their upper aerodigestive carcinoma. INTERVENTION Patients prospectively provided health-related information. MAIN OUTCOME MEASURES The primary outcomes were observed (death from all causes) and disease-specific (cancer-related) survival for 2-year survivors. RESULTS Five-year observed (90.8%) and disease-specific (94.8%) survival rates were 29.7 and 25.0 percentage points higher, respectively, than rates calculated for all patients at diagnosis. Older age and advanced stage were associated with poorer survival, whether death was due to the cancer or from all causes. Patients with pain or poor overall quality of life at 2 years were more likely to die from all causes, whereas those still smoking 2 years after diagnosis were more likely to die from their cancer. CONCLUSIONS In addition to older age and advanced stage, pain, poor overall quality of life, and tobacco use 2 years after diagnosis characterize patients who might need longer and more intense follow-up care to improve their observed and disease-specific survival. This information is useful in developing management plans for patients transitioning from a focus on cancer surveillance into survivorship.

Surgical approaches to the craniovertebral junction (CVJ) can result in dysfunction of the upper aerodigestive tract. However, few data are available regarding the incidence of complications after such surgery. Evaluation of a CVJ lesion for treatment must establish the biology, transverse and longitudinal extent of the lesion, and the preoperative and postoperative stability of the spine. Endoscopic approaches to the CVJ, which should reduce the expected morbidity of an open transoral approach, have been described recently. This article reviews common pathologies of the CVJ and surgical approaches, and provides an evidence-based analysis of whether endoscopic approaches reduce velopharyngeal insufficiency.

Patients with head and neck cancer have complex swallowing and nutritional concerns. Most patients are malnourished, and treatment modalities within the aerodigestive tract have profound effects on future swallowing and nutrition. The objective of this study is to investigate whether the introduction of fortified soft ice-cream to post-operative head and neck cancer patients would increase compliance with oral-feeding regimes. Using a questionnaire study, an ice-cream machine that produces fortified soft ice-cream was introduced onto our ward, and 30 patients were asked to fill out questionnaires based on their experience in addition to their oral-feeding regime. Results indicate that overall patient satisfaction and compliance with oral-feeding regimes increased: 77% felt that the taste was excellent and also felt that it was easy to eat; 60% felt that it eased the symptoms associated with their symptoms, in particular its cold temperature. We conclude from the results that the inability of patients undergoing multi-modal treatment for upper aerodigestive tract cancer to enjoy normal foods and its effects on their quality of life is underestimated. Providing a food to that is palatable, familiar and acceptable as it is safe and nutritionally sound can increase compliance with oral-feeding regimes. The ice-cream was safe to use in the early post-operative period, especially soothing in patients undergoing upper aerodigestive radiotherapy and high in protein and calorific content. Our practice may have wider benefits, including patients with oral and oropharyngeal infections, the elderly and patients with neurological dysphagia resulting from stroke.

BACKGROUND Elderly ovarian cancer patients often undergo non-optimal surgery due to their age despite of the high risk of recurrence. The aim of this study was to determine if more postoperative complications occurred in patients over 70 years and to compare extent of surgery with younger patients. MATERIALS AND METHODS Between 2001 and 2009, 172 patients with ovarian cancer were included. We compared patient characteristics, surgical course, postoperative complications and outcome for patients under and over 70 years. RESULTS 143 patients were under 70 years and 29 over. There were no difference between the two groups for tumors characteristics, time of surgery, FIGO stage, standard surgical procedures and rate of optimal resection. Patients over 70 years had less peritoneal surgery (p < 0.001) especially diaphragmatic surgery (p = 0.006), pelvic (p = 0.02) and para-aortic (p = 0.003) lymphadenectomy. There was no difference in the occurrence of per- or post-operative complications and patients over 70 years had shorter duration of hospitalization (p = 0.04). There was no difference between the two groups for disease-free survival (DFS)(p = 0.08) but overall survival (OS) was better in patients under 70 years (p = 0.002). CONCLUSION Elderly ovarian cancer patients undergo less extensive surgery and have lower OS despite similar postoperative morbidity, optimal resection and DFS. OS decrease could be explained by difference in the management of recurrences.

Advanced age is one of the variables more frequently considered to be associated with an adverse prognosis in Waldenström's macroglobulinemia (WM). In a series of 238 symptomatic and asymptomatic WM patients, we retrospectively identified an age cut-off distinguishing two groups of patients with different outcome in terms of overall survival (OS), disease-specific survival (DSS) and treatment-free survival (TFS). Although for the OS the best cut-off was identified at 65 years with shorter OS for elderly patients, no difference was detected in terms of DSS between the two groups. Furthermore, patients over 65 years showed a longer TFS compared with patients under 65 years. Clinical and laboratory disease characteristics did not significantly differ between the two groups of patients except for β2M level. Therefore, the poorer survival of patients over 65 years at diagnosis should probably be attributed to the higher number of no disease-related deaths and is independent from WM.

The aim of this study was to evaluate the long-term outcomes of the reversal of laryngotracheal separation (LTS) in patients who underwent extensive resection of tumors located in the upper aerodigestive tract. We performed a retrospective analysis of the medical records of eight patients who had LTS reversal. The operation was successful in six patients who were followed up for a period of 17-99 months (mean = 46.3 +/- 26.2). The mean interval between LTS and surgical reversal was 16.6 +/- 9.1 months. Four patients had postoperative complications: mild to moderate transient aspiration in two, tracheal stenosis in one, and severe aspiration followed by tracheal stenosis in one. In the last two cases, surgical reversal was not successful. The patients whose surgery was effective maintained oral feeding and comprehensible speech until the end of the follow-up period. We conclude that reversal of LTS is technically simple and, when successful, permits the return to oral feeding and comprehensible speech for an indefinite period of time. However, the frequency of complications and inefficacy of LTS reversal should not be overlooked.

The population in developed countries is growing older, with the number of people over 85 years of age increasing especially rapidly. The incidence of a head and neck cancer increases with age, only a few patients are under 40 years of age and the highest incidence in many sites occurs in patients over 70 years of age. The aging population has increasing amounts of comorbidities. The treatment protocols for head and neck cancer have over the last two decades become intensified as a consequence of larger surgical resections with reconstruction, high dose radiotherapy often in combination with chemotherapy or targeted therapeutic drugs. Should the elderly and old patients be treated similarly to the younger counterparts or should the treatment be altered based on chronologic age? During the EUFOS Congress in Oto-Rhino-Laryngology Head and Neck Surgery in Vienna, Austria 2007, a panel addressed this issue and this is a summary of the conclusions.

AIM: To evaluate the validity of surgical therapy for colorectal liver metastases in the elderly patients. PATIENTS AND METHODS: Between 1992 and 2004, 401 patients were diagnosed as having liver metastases from colorectal cancer. These comprised 64 patients aged 75 years or older and 337 patients aged less than 75 years. RESULTS: Two hundred and thirty-two patients (57.9%) underwent potentially curative hepatic resection. Postoperative complications occurred in 29.6% of the older patients and in 23.4% of the younger patients. Mortality was 0% in the older group and 0.5% in the younger group. The overall 5-year survival rates of the older and younger group were 33.2% and 47.9%, respectively (p < 0.01). The proportion of patients who died of other diseases was significantly higher in the older (11.1%) than the younger group (2.0%)(p = 0.04). CONCLUSION: Age cannot be regarded as a medical contraindication for hepatic resection of colorectal liver metastases.

OBJECTIVES:: Oropharyngeal cancers represent 10%-15% of all head and neck cancers. At presentation 60%-70% will have advanced-stage disease with a high incidence of neck metastases. Primary treatment employing radiotherapy, with or without chemotherapy, is widely prescribed. The aim of this study is to analyze the outcome of definitive surgical management of T1-T2 cancers of the oropharynx. METHODS:: We conducted a retrospective cohort study of patients treated at the Sydney Head and Neck Cancer Institute. Patients with previously untreated squamous cell carcinoma (SCC) of the oropharynx were included according to the TNM stage of the disease as follows: T1 or T2, any N-stage, and M0. All patients underwent definitive primary surgical management. Primary analysis endpoints were locoregional control rates and disease-specific survival. RESULTS:: Ninety-two patients were identified, of which 26 were T1 and 66 were T2. Forty-four patients had clinical neck disease, and 57 had postoperative radiotherapy. The results showed no significant difference between the T1 and T2 groups with respect to local control or treatment type; however, advanced-stage neck disease was associated with a worse prognosis. The 5-year disease-specific survival was 83% and local control rate was 87%. Ultimately, 25 of the 92 patients had treatment failure (27%). CONCLUSIONS:: Selected patients with early-stage primary cancers of the oropharynx may be effectively treated with definitive primary surgery. Laryngoscope, 119:307-311, 2009.