Correlation of clinicopathological features with immunohistochemical expression of cell cycle regulatory proteins p16 and retinoblastoma: distinct association with keratinisation and differentiation in oral cavity squamous cell carcinoma.

BACKGROUND: The p16 and retinoblastoma (Rb) gene products are part of the retinoblastoma pathway controlling the G1-S transition of the cell cycle. Few studies on the expression of p16 and retinoblastoma proteins in oral cavity squamous carcinomas have been conducted. AIM: To correlate the expression of p16 and retinoblastoma proteins to clinicopathological characteristics in these tumours. METHODS: 45 patients with resected oral cavity squamous carcinoma were selected, for whom this was the initial treatment and who were followed up for 5 years or until death. Immunohistochemical stains with antibodies to the Rb and p16 gene products were carried out on paraffin wax-embedded tissue. Data on clinicopathological features such as tumour differentiation, nodal status, stage and survival outcome were collected. RESULTS: Retinoblastoma expression was seen in 39 of 45 (87%) patients and p16 expression in 6 of 45 (13%) patients. A significant inverse correlation was observed between retinoblastoma and p16 expression as nearly all retinoblastoma negative cases were p16 positive, and vice versa. When examined for clinicopathological correlates, it was found that all 39 tumours that expressed retinoblastoma displayed marked keratinisation and were of low-moderate histological grade. Conversely, five of the six tumours that expressed p16 were found to be poorly differentiated, with minimal keratin expression. CONCLUSIONS: Salient relationships were seen between expression of retinoblastoma and p16 and keratinisation. A marked loss of keratin production was evident in the tumours that expressed p16. Tumours expressing retinoblastoma were seen to exhibit more widespread keratinisation. In addition, an inverse staining pattern was found for retinoblastoma and p16 as retinoblastoma-expressing tumours were nearly universally p16 negative and vice versa. No correlation of expression of either p16 or retinoblastoma was found with survival or stage. A link between the histologically observable morphology and expression of cell cycle regulatory protein with the expression of p16 and retinoblastoma has been suggested with keratinisation and differentiation of status.

Frontal sinus fractures: evaluation of CT scans in 132 patients.

PURPOSE: To determine the frequency of detection of frontal sinus fractures on initial CT scans of patients with intracranial injuries, and to characterize associated injuries. METHODS: The initial head CT scans in 132 patients with clinical or radiographic evidence of a frontal sinus fracture were retrospectively reviewed to further characterize the fracture. Additional radiographic studies and medical records were reviewed to determine associated injuries, therapy, clinical outcome, and complications. RESULTS: In 90% (124) of the patients, the frontal sinus fractures were visualized on initial head CT scans that were obtained to evaluate suspected intracranial injury. Complex fractures involving both the anterior and posterior wall of the sinus accounted for 65% of cases (86 patients), whereas fractures of the anterior wall only or posterior wall only occurred in 24% (32) and 11% (14) of patients, respectively. Significant intracranial hemorrhage occurred in over 90% of patients with fractures involving the posterior wall. CONCLUSIONS: In general, fractures that involved the posterior wall had more complications and a worse clinical outcome than fractures that only involved the anterior wall; nearly all frontal sinus fractures can be detected on head CT studies in patients with intracranial injuries.

The effect of hemolyzed erythrocytes in the virulence of Escherichia coli and of normal human oral flora in a mouse model.

Hemoglobin enhances the virulence of E. coli in the peritoneum. This study investigates the effect of blood on the virulence of E. coli and human oral anaerobes in the mouse neck. E. coli neck infectivity is significantly enhanced by blood. Oral anaerobic infections are not affected.

The communicating vein and its use in the radial forearm free flap.

Thrombosis is the most frequent cause of failure in microvascular free-tissue transfer. The large communicating vein of the cubital fossa connects the deep and superficial venous drainage of the radial forearm free flap (RFFF). This vein allows the surgeon to simultaneously drain both systems by means of the large veins of the cubital fossa. We prospectively collected data on the venous anatomy of the cubital fossa in 40 consecutive RFFFs over a 3-year period. We then retrospectively reviewed available data from the 14 cases preceding the cases in the prospective series. At least 78% of our patients had a communicating vein that facilitated dual venous drainage; 87% of our RFFFs were drained by both the superficial and deep venous systems, and 90% of our RFFFs had two or more venous anastomoses. We had no RFFF failures in our series of 54 flaps. We present our venous anatomy findings in this series of forearms as well as the venous anastomoses of our 54 patients. The surgi- cal-flap harvest, including the communicating vein and its use, may provide an advantage in the dependability and quality of venous outflow.

Frontal sinus fractures in the pediatric population.

Full development of the frontal sinus is not achieved until approximately 19 years of age. An evaluation of frontal sinus injuries isolated to the subset of patients less than 20 years old has yet to be reported. In order to determine whether age was a factor in the clinical course of patients with frontal sinus fractures, 209 patients who sustained frontal sinus fractures from January 1985 to April 1990 were identified using the trauma registry from all six major trauma centers, one of which is a pediatric trauma center, in a county of 2.5 million people. Forty patients (19%) were between the ages of 6 and 19 years at the time of their injury. Computed tomography imaging of these pediatric patients identified associated head and neck fractures in 37 (93%) as well as significant central nervous system injury in 22 (55%). Seventeen pediatric patients were treated nonoperatively and 1 died prior to the planned surgery. A detailed analysis of extent of injury and treatment together with a comparison of the 169 adult and the 40 pediatric patients is presented.

Amyloid of the facial nerve.

Although facial nerve paralysis has been reported in association with amyloidosis, histologic confirmation of facial nerve involvement with amyloid has not been previously demonstrated. A case of localized primary amyloidosis of the facial nerve is presented, and a new magnetic resonance technique for imaging the facial nerve is described.

Increased stability of airflow following botulinum toxin injection.

OBJECTIVES: The purpose of this study was to determine whether stability of airflow, as well as mean airflow, increased following botulinum toxin injection to laryngeal and extralaryngeal muscles in persons with spasmodic dysphonia (SD), some with associated vocal tremor (VT). STUDY DESIGN: Aerodynamic data were collected from five subjects before and at 2, 4, and 8 weeks after they received treatment by each of two different arms in an injection protocol in a crossover study. One arm of the protocol involved treatment of the thyroarytenoid muscles only. The other arm involved treatment of both the thyroarytenoid muscles and the strap muscles. METHODS: Measures of mean airflow and coefficient of variation (COV) of airflow during phonation were obtained. A decrease in the COV of airflow would indicate increased stability of phonatory airflow. RESULTS: Before treatment, all subjects with SD/VT exhibited mean airflows that were similar to controls. The COV of airflow ranged from normal to substantially elevated. Following botulinum injection, mean airflow characteristically increased and COV of airflow decreased. CONCLUSIONS: This finding suggests there is a change in the type, as well as the level, of activity in the muscles of speech production following botulinum toxin injection. The increase in airflow stability identified could be due to increased stability of the laryngeal system and possibly of the respiratory system as well.

Evaluation of maxillary sinus aspiration in patients with fever of unknown origin.

The value of diagnostic maxillary sinus aspiration in patients with abnormal findings on sinus radiographs and fever of unknown origin is unclear. To better define indications for this procedure, the results of 51 sinus aspirations in 34 patients with fevers of unknown origin and abnormal findings on sinus radiographs were analyzed retrospectively. Results of aerobic and anaerobic cultures were evaluated in the context of clinical signs and symptoms at the time of the maxillary sinus puncture. Typical symptoms of paranasal sinus disease were found to be the best predictor of a positive culture. Of patients with sinusitis complaints, 86.4% had culture-positive aspirations, whereas only 8.3% of patients without clinical symptoms of sinusitis had culture-positive aspirations. This study indicates that symptoms of sinus disease play an important role in determining the benefit of sinus aspiration in this group of patients.

Elevated arginine vasopressin levels in squamous cell cancer of the head and neck.

The reported effectiveness of single tumor markers (TMs) associated with squamous cell cancer of the head and neck ranges from 15% to 71%, with most studies reporting sensitivity no higher than 50%. An increased incidence of the syndrome of inappropriate secretion of antidiuretic hormone or arginine vasopressin (SIADH) in patients with head and neck cancer has been reported. Serum arginine vasopressin (AVP) was studied as a possible TM in these patients. Sixty-three patients with squamous cell carcinoma of the head and neck determined as potentially curable were prospectively evaluated before treatment and compared to 17 patients with apparent cure of head and neck squamous cell cancer who served as controls. Serum AVP levels were obtained and determined by radioimmunoassay in the preoperative period and 1 week postoperatively in 15 patients. Thirty-four patients were staged as T4, 26 as T3, and 3 as T2. Twenty-one (33%) of the 63 patients had no neck involvement. Twenty-four (38%) of 63 patients had elevated serum AVP levels corrected for serum osmolarity. Of the 15 patients evaluated before and after surgery, 8 (53%) had elevated serum AVP levels preoperatively. Of these 8 patients, 3 had reduction in AVP levels and 5 had complete normalization after 1 week. The result obtained for serum AVP do not exceed results of other TMs reported. AVP may also not be as specific as other TMs for cancer of the head and neck. Our group with AVP sampled postoperatively is too small for us to draw conclusions, but reduction of its levels after treatment in all patients may be significant. These preliminary results indicate that further evaluation of AVP during the posttreatment course in a larger number of cases, and perhaps with other TMs as well, is warranted.

Resource utilization and patient morbidity in head and neck reconstruction.

Many papers have addressed the technical aspects of free tissue transfer in head and neck cancer patients. However, there has not been a critical assessment of the impact of free tissue transfer on resource utilization and patient morbidity compared with pedicle flap reconstructions. Two cohorts of patients derived from 245 consecutive reconstructions were tightly matched by age, site, stage, and histology, yielding 44 patient pairs differing in method of reconstruction. Patients undergoing free flap reconstruction spent more time in the operating room than those reconstructed with pedicled flaps (993 min vs. 777 min, P < 0.0001). The group with free flap reconstruction spent fewer days in the surgical intensive care unit and hospital (2 days vs. 2.5 days; 18.5 days vs. 22.6 days). This difference is attributed to the paucity of postoperative complications in the group with free flap reconstruction (fistula formation 4.5% vs. 21%, P < 0.04). These data indicate that the continued use of sophisticated reconstructive techniques in head and neck cancer patients is economically sound as assessed by patient morbidity and resource utilization.

Chondrosarcoma of the head and neck.

Chondrosarcoma is a malignancy rarely encountered in the head and neck. In an attempt to define this tumor's characteristics and response to therapy, all cases of chondrosarcoma treated at the University of Michigan over the past 25 years were retrospectively studied. Fourteen cases originating in the nose and paranasal sinuses, mandible, temporal bone, and larynx were reviewed. Aggressive surgical resection was the mainstay of treatment, and resulted in an overall survival of 70%, with an average follow-up of 3.5 years. Survival was highest in primary temporal bone lesions, and lowest in paranasal sinus lesions. Unresectable lesions were not cured by other modalities. This study, therefore, continued to support the crucial role of wide surgical resection in the treatment of head and neck chondrosarcoma, but conservative resection, when needed to preserve important structures, has resulted in long-term survival.

Arytenoid adduction combined with Gore-Tex medialization thyroplasty.

OBJECTIVE: To describe the technique of combined Gore-Tex medialization thyroplasty with arytenoid adduction and to determine the long-term vocal outcome of patients treated for unilateral vocal cord paralysis with this procedure. STUDY DESIGN: A retrospective chart review and patient reevaluation for patients treated at The University of Iowa Hospitals and Clinics between May 1995 and June 1999. METHODS: The review addressed patient demographics, perioperative and long-term complications, and voice outcomes. Details of the surgical technique are provided within the manuscript. RESULTS: Seventy-two Gore-Tex medialization procedures were completed. Arytenoid adduction was included in 22 of these procedures. This subset of patients was compared with the patients treated with Gore-Tex alone. No major postoperative complications occurred in either group. Preoperative and postoperative voice and videostroboscopy data were available for 19 arytenoid adduction patients and 25 Gore-Tex alone patients. On a seven-point scale (6 [severely abnormal] --> 0 [normal voice]), the average patient rating of voice dysfunction improved from 4.2 to 1.6 (arytenoid adduction) and 4.5 to 2.8 (Gore-Tex alone). Maximum phonation time improved from 6.9 seconds to 16.7 seconds in the arytenoid adduction group. Subjective voice assessment employing the four-point GRBAS scale (3 [severely abnormal] --> 0 [normal]) identified average improvement from an overall grade of 2.1 to 0.8 arytenoid adduction and 2.2 to 1.5 in the Gore-Tex alone group. Improvement was identified in the vocal quality of breathiness from 1.9 to 0.2 (arytenoid adduction) and 1.9 to 0.9 (Gore-Tex alone). CONCLUSIONS: The combined technique of Gore-Tex medialization thyroplasty and arytenoid adduction provide functional results that appear to exceed the improvement attained with medialization alone.

Esthesioneuroblastoma: the University of Iowa experience 1978-1998.

OBJECTIVE: Esthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution. METHODS: Between 1978 and 1998, 13 patients with esthesioneuroblastoma were identified using the University of Iowa Tumor Registry. All patients were staged according to Kadish criteria. Mean follow-up was 6.3 years. Six patients had 5 or more years of follow-up and four had follow-up exceeding 9.5 years. One patient was lost to follow-up at 36 months. RESULTS: No patients had Kadish stage A disease, five were stage B, and eight stage C. Overall actuarial 5- and 10-year survival rate was 61% and 24%, respectively. Disease-free survival rate at 5 and 10 years was 56% and 42%, respectively. Seven patients have died, three of intercurrent disease and three of disease progression, one with an unknown disease status. Six patients remain alive, three without evidence of disease and three have experienced a local or regional recurrence. Five patients who were initially controlled developed recurrence, three local only, one locoregional, and one regional and distant. Median time to failure was 96 months. All patients with follow-up exceeding 12 years have experienced either a local or regional recurrence. Survival after salvage therapy in these patients ranged from 3 to 12 years. CONCLUSION: Esthesioneuroblastoma has a long natural history characterized by frequent local or regional recurrence after conventional treatment. Successful retreatment can lead to prolonged survival.

Human papillomavirus and risk of oral cancer.

Although human papillomavirus (HPV), a sexually transmitted virus, is established as a necessary cause for more than 95% of cervical carcinomas, the association with oral squamous cell carcinoma is less well delineated. The purpose of this study was to determine the frequency and types of HPV in squamous cells of a group of patients with newly diagnosed oral or pharyngeal cancer (n = 93) compared with an age- and gender-frequency-matched control group of patients with no history of oral cancer (n = 205). HPV was evaluated from a mouth rinse collection of cells in the oral cavity and tested by 32P-labeled HPV generic probes and DNA sequencing for HPV types. HPV was identified in 15% of the oral cancer cases but in fewer than 5% of the controls (P < .05). The risk of cancer associated with HPV infection was independent of tobacco and alcohol use (adjusted odds ratio [OR] = 3.70; 95% confidence interval [CI]: 1.47-9.32; P < .05). HPV types included similar and other types not identified previously in the genital tract. There was no statistically significant increased risk of cancer among former tobacco users (former vs. never users: adjusted OR = 0.67, 95% CI: 0.31-1.44, P < .05), but the risk was significantly increased for current users (current vs. never: adjusted OR = 2.63; 95% CI: 1.22-5.71; P < .05). Likewise, former alcohol users were not at increased risk of disease (former vs. never: adjusted OR = 1.78; 95% CI: 0.87-3.67), whereas current alcohol users were (current vs. never: adjusted OR = 2.57; 95% CI: 1.22-5.42; P < .05). HPV-related genital lesions (14.3% vs. 10.6%), oral-genital sexual behavior (42.4% vs. 45.2%), and number (11 or more) of sexual partners (23% v. 17%) were not significantly different between cases and controls. These data suggest that in addition to tobacco and alcohol, HPV plays a role in the development of oral cancer.

A classification scheme for paradoxical vocal cord motion.

Paradoxical vocal cord motion (PVCM) is characterized by the inappropriate adduction of the true vocal cords during inspiration. Multiple causes have been proposed for this group of disorders, which share the common finding of mobile vocal cords that adduct inappropriately during inspiration and cause stridor by approximation. Management of this group of disorders has been complicated by the lack of a classification scheme to include all types of PVCM. We propose that PVCM be classified according to its underlying etiology and recognize the following causes of the disorder: 1. brainstem compression; 2. cortical or upper motor neuron injury; 3. nuclear or lower motor neuron injury; 4. movement disorder; 5. gastroesophageal reflux; 6. factitious or malingering disorder; 7. somatization/conversion disorder. Case reports are presented to illustrate the characteristic features and diagnostic evaluation used in assessing patients with PVCM. Management varies depending on the cause of PVCM and entails speech therapy, pharmacologic therapy, behavioral modification, and/or surgical intervention. Recognition of the multiple causes of PVCM allows otolaryngologists to formulate well-directed diagnostic evaluation and treatment.

Squamous carcinoma of the head and neck in organ transplant recipients: possible role of oncogenic viruses.

A consistently increased incidence of malignancies in renal transplant recipients has been attributed to the effect of chronic immunosuppression required to prevent transplant rejection. Tumors arising in such patients offer a unique opportunity to study the interactions of the immune system and tumor development. A series of three cases of head and neck squamous cell carcinoma arising in patients after renal, cardiac, or bone marrow transplantation are reported. Patient ages at tumor diagnosis were 18, 29, and 53 years, respectively. Time from transplant to diagnosis of tumor ranged from 7 months to 12 years. Only the youngest patient lacked a history of exposure to the traditional pre-disposing factors of tobacco and alcohol use. Histopathologic examination in all three tumors showed features of koilocytosis with hyperkeratosis and parakeratosis suggestive of papillomavirus infection. Squamous carcinoma cells from one of these patients have been successfully established in cell culture. Immune system impairments secondary to the use of antirejection drugs could allow the expression of oncogenic viruses. A recent report of human papillomavirus (HPV) DNA in a primary and metastatic perianal squamous cell carcinoma from a renal transplant recipient, as well as the reported presence of HPV in benign and malignant neoplasms of the upper aerodigestive tract suggests that HPV infection could play a role in the development of squamous carcinomas in transplant recipients. Further studies of HPV infection in cultured cell lines derived from head and neck tumors occurring in immunosuppressed patients are needed to define this relationship.

Functional magnetic resonance imaging using iron oxide particles in characterizing head and neck adenopathy.

OBJECTIVES: In lymph nodes harboring metastases the reticuloendothelial system is replaced by tumor cells and does not concentrate iron particles. This study assesses the value of contrast magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide particles (Combidex, Advanced Magnetics, Inc., Cambridge, MA) to characterize and stage neck nodes. STUDY DESIGN: Prospective analysis of neck imaging by Combidex MRI, with correlation from pathological assessment of resected lymph nodes. METHODS: Nine patients underwent MRI and subsequent bilateral neck dissections (three), unilateral neck dissections (five) or fine-needle aspiration (one). Each case was evaluated for the number, location, MRI characteristics, and pathological assessment of lymph nodes. RESULTS: Forty-nine separate nodal levels were evaluated with both Combidex MRI and pathological assessment. The presence of metastatic nodal involvement among 45 levels was correctly assessed by the Combidex MRI (three false-negative results, one false-positive result; sensitivity, 84%; specificity, 97%). Analysis was possible for 101 of the individual lymph nodes identified by MRI that could be correlated with individual nodes pathologically examined. Combidex MRI assessment was correct for 99 nodes (one-false positive result, one false-negative result; sensitivity, 95%, specificity, 99%). Standard MRI interpretation without Combidex identified that 12 of 18 nodes (67%) that were greater than or equal to 10 mm (greatest dimension) contained tumor, whereas 9 of 83 nodes (ll%) that were less than 10 mm contained tumor. CONCLUSIONS: Combidex MRI provides functional information to characterize lymph nodes in the clinical staging of squamous cell carcinoma of the head and neck. The inability of MRI to identify small lymph nodes restricts the usefulness of this technique.

Laryngeal cancer cost analysis: association of case-mix and treatment characteristics with medical charges.

OBJECTIVES: To examine the relationship of various pretreatment case-mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2-year follow-up for patients with laryngeal cancer. DESIGN: Retrospective chart review and billing record analysis. METHODS: The charts and billing records of patients diagnosed with laryngeal cancer at the University of Iowa Hospitals and Clinics (UIHC) between January 1, 1991 and December 31, 1994 were reviewed. The independent variables included various pretreatment patient-mix and tumor characteristics (age, AJCC TNM clinical stage, smoking history, ASA class, and comorbidity as defined by Kaplan-Feinstein grade) as well as type of treatment. The dependent variables included total physician, office, and university hospital-based charges incurred during the pretreatment evaluation and 0- to 3-, 3- to 12, and 12- to 24-month billing periods after the initiation of cancer-directed therapy. Total 1-year and 2-year charges were also evaluated. Univariate and multivariate analyses were used to investigate the relationships between dependent and independent variables and to develop models predictive of management charges during the individual and total billing periods. RESULTS: Pretreatment charges showed no significant associations (P < .05) with any of the independent variables. Multiple regression analyses indicated that comorbidity, stage, and initial treatment modality were significant variables in one or more of the models predicting charges incurred during the 0- to 3-month, 3- to 12-month, total 1-year, and total 2-year billing periods. The models yielded R2 values for the total 1- and 2-year billing periods of 0.5246 and 0.5055, respectively. CONCLUSIONS: This work supports continued study of measures that may result in earlier detection of laryngeal cancer as a potential means of reducing management charges. These results also indicate that a more accurate method of stratifying the disease severity of laryngeal cancer patients for reimbursement purposes would include measurements of the severity of the index disease as well as comorbid diseases.

Hypopharyngeal cancer patient care evaluation.

A survey was conducted to identify demographics and standards of care for treatment of hypopharyngeal squamous cell carcinoma in the United States. Data were accrued from voluntary submission of cancer registry and medical chart information from 769 hospitals representing 2939 cases diagnosed from 1980 to 1985 and 1990 to 1992. Clinical findings, diagnostic procedures employed, treatment practices, and outcome are presented. Overall, 5-year disease-specific survival was 33.4%, which segregated to 63.1% (stage I), 57.5% (stage II), 41.8% (stage III), and 22% (stage IV). Survival was best for patients treated with surgery only (50.4%), similar with combined surgery and irradiation (48%), and worse with irradiation only (25.8%). This analysis provides a standard to which current treatment practice and future clinical trials may be compared.

Tracheostoma diverticulum following tracheoesophageal puncture.

Although the initial reports of tracheoesophageal puncture after total laryngectomy reported little to no morbidity, subsequent studies with longer follow-up have reported a significant number of complications. We present the first reported case (to our knowledge) of prolapse of the posterior tracheal wall with diverticulum formation developing 6 years after continuous use of tracheoesophageal puncture speech. Preoperative assessment with a barium esophagogram and rigid esophagoscopy aided in the successful surgical treatment of this disorder. The pathogenesis of this complication and method of repair are discussed.