Levels of potential oral cancer salivary mRNA biomarkers in oral cancer patients in remission and oral lichen planus patients.

OBJECTIVES: To gather preliminary data concerning the feasibility of using seven salivary mRNAs-IL-8; IL-1ß; dual specificity phosphatase 1 (DUSP1); H3 histone family 3A (H3F3A); ornithin decarboxylase antizyme 1 (OAZ1); S100 calcium-binding protein P (S100P); and spermidine/spermine N1-acetyltransferase 1 (SAT1)-for detecting development of oral squamous cell carcinoma (OSCC) in oral lichen planus (OLP) patients and OSCC patients whose disease was in remission. MATERIALS AND METHODS: Saliva samples were collected from five study groups (25 subjects/group): newly diagnosed OSCC, OSCC-in-remission, disease-active OLP, disease-inactive OLP, and normal controls. The salivary mRNA levels were determined by a pre-amplification RT-qPCR approach with nested gene-specific primers. Mean fold changes between each pair of study groups were analyzed by the Mann-Whitney U test. RESULTS: Salivary levels of OAZ1, S100P, and DUSP1 mRNAs were significantly higher in newly diagnosed OSCC patients, compared to: (1) normal controls (p = 0.003; p = 0.003; and p < 0.001, respectively); (2) OSCC-in-remission (p < 0.001; p = 0.001; and p < 0.001, respectively); (3) disease-active OLP (p < 0.001; p = 0.016; and p < 0.001, respectively); and (4) disease-inactive OLP (p = 0.043; p < 0.001; and p < 0.001, respectively). No significant differences were found in the levels of salivary IL-8, IL-1ß, H3F3A, and SAT1 mRNAs between newly diagnosed OSCC patients and the normal controls (p = 0.093, 0.327, 0.764, and 0.560, respectively). CONCLUSION: Salivary OAZ1, S100P, and DUSP1 mRNAs are candidate biomarkers for detecting OSCC development in OSCC patients in remission and in OLP patients. CLINICAL RELEVANCE: The results of this study serve as the basis for a further large-scale study which may lead to a non-invasive screening method for early detection of OSCC.

Transcervical elective superior mediastinal dissection for thyroid carcinoma.

OBJECTIVES: To review our results with elective superior mediastinal dissections for thyroid carcinomas. STUDY DESIGN: Retrospective review. METHODS: We searched operative case logs for all patients with thyroid carcinoma treated with an elective superior mediastinal dissection by the senior author (Y.D.) during a 6-year period. Charts were reviewed for demographic information and pathologic results. Elective superior mediastinal dissections were performed when the frozen section was consistent with anaplastic or medullary carcinoma or with a well-differentiated carcinoma when there was fixation of the primary tumor to the laryngotracheal complex, there was overt clinically evident paratracheal and/or cervical adenopathy, or the primary tumor measured greater than 2.0 cm in dimension. RESULTS: Thirty-one patients meeting the above criteria were reviewed, and superior mediastinal disease was present in 19 patients (61.3%). Superior mediastinal nodes were positive in 13 (65%) of 20 patients with papillary carcinoma, 0 of 4 with follicular thyroid carcinoma, 4 of 5 patients with medullary thyroid carcinoma, and 2 of 2 patients with anaplastic thyroid carcinoma. Patients with follicular carcinoma had a lower incidence of mediastinal disease (0%) compared with nonfollicular thyroid carcinoma (70.4%), P = .02. Patients with cervical metastasis had an increased incidence of superior mediastinal disease (100% vs 53.3%). CONCLUSIONS: Elective transcervical superior mediastinal dissection was commonly positive in patients with papillary, medullary, and anaplastic thyroid carcinomas. A transcervical approach may be safely performed without sternotomy to the level of the brachiocephalic vein. Further studies are required to determine if performing elective superior mediastinal lymph node dissections will have an impact on survival.

Intraoperative evaluation of cortical bony margins with frozen-section analysis.

OBJECTIVE: To describe and evaluate the efficacy of frozen-section analysis of cortical bone margins in surgery of the craniofacial skeleton. STUDY DESIGN: Retrospective analysis of a consecutive series of patients undergoing oncologic resection of various head and neck neoplasms with osseous involvement by the senior author (Y.D.) from 1998 to 2003. RESULTS: Frozen-section analysis of cortical bone was performed in 38 patients. Adequate specimens for histological analysis were obtained in all patients. Frozen sections were positive in 21 of 22 patients with bone invasion on decalcified specimens. After validating our technique for frozen analysis of cortical bone in 13 patients, the method had a sensitivity of 89% and a specificity of 100% in 25 patients. Malignancies diagnosed on frozen cortical bone specimens included squamous cell carcinoma (15), mucoepidermoid carcinoma (3), and sarcoma (3). Frozen cortical margins altered the extent of bony resection in 8 patients. CONCLUSION: A simple technique for analysis of cortical bone involvement by neoplasm is presented and reviewed. It allows for frozen-section analysis with standard equipment and appears to be a reliable method to evaluate bony margins intra-operatively. EBM RATING: C-4.

Transoral approach to the superomedial parapharyngeal space.

OBJECTIVES: To present our early experience with the transoral approach to the superomedial parapharyngeal space (PPS) and describe our technique for removal of these neoplasms. STUDY DESIGN: Consecutive case series by one author (Y.D.). METHODS: Eight patients with various neoplasms of the superomedial PPS were retrospectively reviewed for type of neoplasm, size, success with the transoral approach, need for conversion to another approach, length of hospitalization, and complications. RESULTS: The transoral approach described herein safely allowed for en bloc resection of benign neoplasms with intraoperative control and exposure of the internal carotid artery. The most common pathology encountered was that of schwannoma. All patients were started on liquid diet on postoperative day 1. Average length of stay was 3.2 days (range, 2 to 5). Mean tumor size was 3.3 cm (range, 1.5 to 7 cm). No significant complications were felt to be related to the approach itself and visualization was felt to be excellent in each case without the need for conversion to a more extensive approach. CONCLUSIONS: The transoral approach safely provides access to superomedial PPS lesions with decreased morbidity compared with traditional approaches. This technique is indicated for neoplasms with benign appearance on preoperative imaging or fine needle aspiration. This approach alone may not provide adequate access for resection of malignant lesions especially those with extension intracranially or to more inferior or laterally placed lesions of the parapharyngeal space. EBM RATING: C-4.

Medical and surgical management of subperiosteal orbital abscess secondary to acute sinusitis in children.

OBJECTIVE: To evaluate the presentations and outcomes of pediatric subperiosteal orbital abscesses (SPOA) secondary to acute sinusitis. STUDY DESIGN: Case series SETTING: Tertiary children's hospital. PATIENTS: Forty-three admissions diagnosed with SPOA by clinical presentation and contrast enhanced computed tomography (CECT) were retrospectively reviewed. MAIN OUTCOME MEASURES: Clinical presentations, CECT dimensions, treatment, outcomes, and microbiology. RESULTS: Eighteen/43 (42%) patients resolved their infection with medical management only, including five children older than nine. Twenty-five/43 (58%) children underwent surgical drainage. Purulence was identified in 22 of 25 surgical patients, and the most common organism was Streptococcus milleri (7 patients). Compared to 22 patients with drained purulence, the 18 patients with abscesses managed medically had significant differences for: chemosis in 2/18 (11.1%) versus 14/22 (63.6%, p=0.001), proptosis in 10/18 (55.6%) versus 20/22 (90.9%, p=0.025), elevated intraocular pressure (IOP) in 0/18 (0%) versus 11/22 (50%, p<0.001), severe restriction of extraocular movements in 1/18 (5.6%) versus 12/22 (54.5%, p=0.002), and length of stay (4.3 versus 5.8 days, p=0.038). The dimensions of medial SPOA managed medically were significantly smaller on CECT compared to surgically drained purulent SPOA: width (0.25 versus 1.46cm, p<0.001), height (0.73 versus 1.35cm, p=0.002), and length (1.1 versus 1.86cm, p=0.004). Persistent morbidities occurred in no patients managed medically and in 2/25 (8%) managed surgically. CONCLUSIONS: Children with small medial SPOA without significant ocular signs may be managed medically with favorable outcomes. Proposed criteria for medical management of medial SPOA include: (1) normal vision, pupil, and retina; (2) no ophthalmoplegia; (3) IOP<20mmHg; (4) proptosis of 5mm or less; and (5) abscess width of 4mm or less. In contrast to prior series, older children with SPOA were managed successfully with medical therapy.

Therapeutic HPV Cancer Vaccine Targeted to CD40 Elicits Effective CD8+ T-cell Immunity.

Human papillomavirus (HPV), particularly HPV16 and HPV18, can cause cancers in diverse anatomical sites, including the anogenital and oropharyngeal (throat) regions. Therefore, development of safe and clinically effective therapeutic vaccines is an important goal. Herein, we show that a recombinant fusion protein of a humanized antibody to CD40 fused to HPV16.E6/7 (αCD40-HPV16.E6/7) can evoke HPV16.E6/7-specific CD8+ and CD4+ T-cell responses in head-and-neck cancer patients in vitro and in human CD40 transgenic (hCD40Tg) mice in vivo The combination of αCD40-HPV16.E6/7 and poly(I:C) efficiently primed HPV16.E6/7-specific T cells, particularly CD8+ T cells, in hCD40Tg mice. Inclusion of montanide enhanced HPV16.E6/7-specific CD4+, but not CD8+, T-cell responses. Poly(I:C) plus αCD40-HPV16.E6/7 was sufficient to mount both preventative and therapeutic immunity against TC-1 tumors in hCD40Tg mice, significantly increasing the frequency of HPV16-specific CD8+ CTLs in the tumors, but not in peripheral blood. In line with this, tumor volume inversely correlated with the frequency of HPV16.E6/7-specific CD8+ T cells in tumors, but not in blood. These data suggest that CD40-targeting vaccines for HPV-associated malignancies can provide a highly immunogenic platform with a strong likelihood of clinical benefit. Data from this study offer strong support for the development of CD40-targeting vaccines for other cancers in the future. Cancer Immunol Res; 4(10); 823-34. ©2016 AACR.

Elective transcervical superior mediastinal lymph node dissection for advanced laryngeal and level 4 N3 squamous cell carcinoma.

OBJECTIVES: To review our results with elective superior mediastinal lymph node dissections in patients with advanced laryngeal squamous cell carcinoma (SCCA) and overt level 4 adenopathy. STUDY DESIGN: Retrospective review. METHODS: We searched operative case logs for all patients treated with an elective superior mediastinal dissection by the senior author (Y.D.) during a 7-year period. Charts were reviewed for demographic information, prior treatment with chemotherapy or radiotherapy, and pathologic results. RESULTS: Fifty-six patients who underwent elective superior mediastinal lymph node dissection for advanced laryngeal SCCA and overt level 4 adenopathy were reviewed, and superior mediastinal disease was present in 15 of 56 (26.8%) patients. Superior mediastinal nodes were positive in 11 of 42 (26.2%) patients with advanced laryngeal SCCA and 4 of 14 (28.6%) patients with N3 SCCA involving level 4. Patients with SCCA receiving prior chemotherapy and radiotherapy had a significantly higher rate of positive superior mediastinal nodes (10/21 patients, 47.6%) compared with patients without prior therapy (5/35 patients, 14.3%, P = .01, Fisher's exact test). There were no stomal recurrences in 42 patients treated for advanced laryngeal cancer. CONCLUSIONS: Elective transcervical superior mediastinal dissection was positive in 26.8% of patients with advanced laryngeal cancer or N3 disease in level 4. A transcervical superior mediastinal dissection may be safely performed without a sternotomy.

Complications of acute sinusitis in children.

OBJECTIVE: To review the demographic, microbiologic, and outcome data for children with complications of acute sinusitis. STUDY DESIGN AND SETTING: Retrospective review of children admitted with complications of acute sinusitis from January 1995 to July 2002 to a tertiary care children's hospital. RESULTS: One hundred four patients were reviewed with the following complications: orbital cellulitis (51), orbital abscesses (44), epidural empyemas (7), subdural empyemas (6), intracerebral abscesses (2), meningitis (2), cavernous sinus thrombosis (1), and Pott's puffy tumors (3). Sixty-six percent were males (P < 0.001), and 64.4% presented from November to March (P < 0.001). Patients with isolated orbital complications were younger than patients with intracranial complications (mean, 6.5 versus 12.3 years), had a shorter stay (mean, 4.2 versus 16.6 days), and had shorter duration of symptoms (mean, 5.4 versus 14.3 days; all P < 0.0001). Complete resolution was documented for 54/55 patients with restricted ocular motility, 7/8 with visual loss, 3/3 patients with a nonreactive pupil, 7/7 with neurological deficits, and 2/4 with seizures. The most common organism isolated was Streptococcus milleri (11/36 patients with surgical cultures). No mortalities occurred, and persistent morbidity occurred in 4 patients (3.8%). CONCLUSIONS: Despite significant deficits on presentation, permanent morbidity was low. Streptococcus milleri is a common pathogen with complications of sinusitis in children.

Hydroxyapatite cement in craniofacial reconstruction.

OBJECTIVES: To evaluate the long-term efficacy of hydroxyapatite cement in craniofacial reconstruction, specifically examining the role (if any) of radiation, implant location, and cement type. STUDY DESIGN: A retrospective chart review was conducted of all patients presenting to the senior surgeon (Y.D.) for craniofacial reconstruction from September 1997 to April 2004. METHODS: Data were collected including type of cement used, size of defect, complications, need for removal of cement, reason for defect, and pathologic results of examination of removed cements. RESULTS: One hundred two patients were identified who underwent craniofacial reconstruction with hydroxyapatite cements, 7 of whom required complete implant removal (6 Norian and 1 Mimix), and 4 (2 Norian and 2 Bone source) of whom required partial implant removal for foreign body reaction. Five of the removals were in patients who underwent postoperative radiation. CONCLUSIONS: Hydroxyapatite cements are safe in craniofacial reconstruction. The highest risk of implant infection comes from reconstruction in the area of the frontal sinus, immediately beneath coronal incisions, and in patients who receive postoperative radiation treatment. Based on our results, there does appear to be a statistically significant difference in rates of infection and foreign body reaction between the different types of hydroxyapatite cement. We would not recommend implantation of this material in contact with the frontal sinus. Caution should be exercised when it is placed directly beneath an incision or in patients receiving postoperative radiation, particularly if a boost dose is given.

Use of fibula-free tissue transfer with preoperative 2-vessel runoff to the lower extremity.

OBJECTIVE: To present our experience with fibula-free tissue transfer in patients with documented 2-vessel runoff to the lower extremity on preoperative angiography. METHODS: A case series of 16 patients with segmental mandibular defects reconstructed with a fibula-free flap by the senior author with 100% stenosis of the anterior or posterior tibial arteries were retrospectively reviewed for radiographic data and complications. RESULTS: All flaps performed were successful, and there were no donor site complications. Angiography documented flow of contrast to the foot by a patent anterior or posterior tibial artery in all patients. Occlusive arteriosclerotic disease was identified in the anterior tibial artery in 10 patients and in the posterior tibial artery in 6 patients. CONCLUSIONS: Using our specific criteria, we experienced no complications with the use of a fibula-free flap in extremities with 100% obstructive vascular disease in the anterior or posterior tibial artery. Preoperative angiography is indicated to select appropriate candidates for fibula-free tissue transfer with 2-vessel lower extremity runoff to avoid potential donor site ischemic complications.

Use of precontoured positioning plates and pericranial flaps in midfacial reconstruction to optimize aesthetic and functional outcomes.

OBJECTIVES: To present our experience with reconstruction of midfacial defects using "precontoured positioning plates" with or without pericranial flaps and to describe our technique in detail. METHODS: Thirty-two consecutive patients with midfacial defects subsequent to oncologic resection that were reconstructed primarily with cranial bone grafts and precontoured positioning plates were reviewed for type of defect, functional outcome, complications, and postoperative appearance. RESULTS: Primary reconstruction of all defects in this series was performed. Defects involved the orbital rim, orbital floor, or both in 28 patients (88%), the body of the zygoma in 24 patients (75%), and extended to the skull base in 16 patients (50%). Pericranial flaps were used to cover the bone grafts in 22 patients (69%). Postoperative radiotherapy was performed in 22 patients (69%), preoperative radiotherapy in 5 (16%), and the other 5 (16%) had no radiotherapy. There were no intraoperative complications, and postoperative complications included plate exposure (n = 2), ectropion (n = 3), and partial bone graft loss or resorption subsequent to completion of radiotherapy (n = 2). Postoperatively, appearance was excellent in 24 patients, fair in 6 patients, and poor in 2 patients. Secondary reconstructive procedures were performed in 4 patients (12%). Follow-up ranged from 12 months to 6 years (median, 4.2 years). CONCLUSIONS: Precontoured positioning plates with or without pericranial flaps enable precise reconstruction of midfacial defects with precise incorporation of cranial bone grafts. In our series we routinely covered the bone grafts with well-vascularized tissues, leading to a low incidence of complications and excellent aesthetic results.

Congenital tracheocutaneous fistulas.

OBJECTIVE: To outline two cases of congenital tracheocutaneous fistula and discuss the potential pathogenesis of this previously unreported developmental abnormality. METHODS: Two cases of tracheocutaneous fistula evaluated at John Peter Smith Hospital (Fort Worth, TX) from May to October 2001 were reviewed. The surgical treatment of one infant is described. RESULTS: Two infants were evaluated with a congenital fistula extending from the suprasternal region of the neck dorsally to the trachea in the midline. The infants were otherwise developmentally normal with unremarkable prenatal histories. Primary surgical closure of a fistula was accomplished without complication. CONCLUSIONS: Congenital tracheocutaneous fistula appears to be an isolated developmental abnormality not associated with the same degree of morbidity as acquired tracheocutaneous fistula. The development of a congenital tracheocutaneous fistula may be the result of abnormal epidermal migration secondary to a localized midline mesodermal defect. Congenital tracheocutaneous fistula may be successfully treated with primary closure. Observation and close follow-up of asymptomatic fistulas may be reasonable.

Differential diagnosis and treatment options in paranasal sinus cancers.

Paranasal sinus malignancies are challenging to treat. Most patients present with advanced lesions, often with intracranial or intraorbital extension, and have a poor overall prognosis. Given the low incidence and diverse pathologies of paranasal sinus cancers, it is extremely difficult to perform prospective, randomized clinical trials to compare different treatment approaches. Improving the prognosis of these cancers continues to be a difficult task, even in light of advances in surgical techniques,radiation delivery techniques, and new chemotherapeutic agents. Cranio-facial resection techniques developed in the past few decades have cured many patients with skull base invasion, who would have been considered unresectable in the past. Furthermore, improvements in radiation therapy can allow more accurate administration to the desired region, with decreased damage to surrounding structures such as the orbit and brain. Aggressive and oncologically sound surgical resection combined with radiation therapy remains the treatment of choice for most patients.Finally, advances in the diagnosis and staging by use of molecular or DNA markers of tumor behavior may allow for more directed therapy.

Proximal peroneal perforator in dual-skin paddle configuration of fibula free flap for composite oral reconstruction.

BACKGROUND: Composite defects of the oral cavity are often the result of trauma or advanced-stage tumor extirpation. The resultant deformity frequently requires a three-dimensional reconstruction of bone and soft-tissue. The fibula free flap is the preferred method of reconstruction, with various modifications focused on providing supplemental soft-tissue coverage. The objective of this study was to ascertain both anatomic and clinical data regarding the proximal peroneal perforator and its contribution to the evolution of the fibula free flap. METHODS: Ten cadaver lower extremities were dissected to isolate the most proximal perforator supplying skin over the proximal lateral lower leg. Data were recorded regarding perforator presence, location, and course. Furthermore, review of clinical cases in which the proximal perforator was used in fibula free flap design was performed for operative data collection. RESULTS: Cadaveric dissections revealed the proximal perforator to be present in 90 percent of specimens. Most commonly, the perforator, originating from the peroneal artery, traveled a short intramuscular course through the soleus muscle prior to supplying the overlying skin. In all clinical cases, the perforator was easily located with Doppler prior to incision, and there were no cases of flap failure or skin paddle loss. Flap inset was found to be optimal in all cases, with no tethering or undue tension. CONCLUSIONS: The proximal peroneal perforator was found to be anatomically reliable and clinically useful in composite oral cavity reconstruction following tumor removal. The gained separation between skin paddles allows for greater versatility in flap design and inset. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Salivary endothelin-1 potential for detecting oral cancer in patients with oral lichen planus or oral cancer in remission.

Endothelin-1 (ET-1) is a potent vasoconstrictor involved not only in vascular biology but also in carcinogenesis. Results of a study in 2007 suggested salivary ET-1 as a potential biomarker for oral squamous cell carcinoma (OSCC), but a later study showed conflicting results. The purpose of our pilot study was to investigate feasibility of using salivary ET-1 as a biomarker for OSCC in two groups: oral lichen planus (OLP) patients and patients with OSCC in remission. Saliva samples were collected from five groups of subjects: patients with newly diagnosed, active OSCC (Group A); patients with OSCC in remission (Group B); patients with active OLP lesions (Group C); patients with OLP in remission (Group D); and normal controls (Group E). Salivary ET-1 levels were determined by enzyme-linked immunosorbent assay, and the results were analyzed by the Mann-Whitney U test. The mean salivary ET-1 level in Group A was significantly higher than that found in Group C (p=0.001), Group D (p=0.015) or Group E (p=0.004). There were no significant differences (p>0.05) in the mean salivary ET-1 levels between Groups A and B; Groups B and C; Groups B and D; Groups B and E; Groups C and D; Groups C and E; or Groups D and E. Salivary ET-1 could be a good biomarker for OSCC development in OLP patients regardless of the degree of OLP disease activity. However, it appeared not to be a good biomarker for detecting recurrence of OSCC in patients in remission.

Advanced squamous cell carcinoma of the oropharynx: efficacy of positron emission tomography and computed tomography for determining primary tumor response during induction chemotherapy.

BACKGROUND: To evaluate the efficacy of fluorine-18-fluorodeoxyglucose emission tomography (FDG-PET) and CT versus endoscopy with biopsy under general anesthesia for estimating tumor volume reduction among patients treated with induction chemotherapy for advanced squamous cell carcinoma (SCC) of the oropharynx. METHODS: Twelve patients with oropharyngeal SCC nested in a phase II, induction chemoradiation, organ preservation trial (University of Michigan Cancer Center 9921) underwent tumor volume reduction estimation as assessed by FDG-PET, CT, and endoscopy with biopsy. RESULTS: In 9 of 12 patients, FDG-PET, CT, and endoscopy demonstrated agreement in estimation of tumor reduction. Two patients had discordant results, whereas 1 patient was inadequately evaluated with FDG-PET. The kappa value for PET versus endoscopy was 0.62, which is categorized as substantial agreement. The kappa value for CT versus endoscopy was 0.40, which is categorized as fair agreement. CONCLUSION: FDG-PET may be as efficacious as endoscopy with biopsy under general anesthesia for estimating tumor volume reduction with induction chemotherapy.

Retrograde balloon dilation of complete cervical esophageal and hypopharyngeal strictures.

OBJECTIVES: To evaluate and describe retrograde endoscopic dilation of 100% strictures of the cervical esophagus and hypopharynx. METHODS AND MATERIALS: All patients who presented to the senior author (Y.D.) from September 1997 to September 2003 with strictures of the cervical esophagus and hypopharynx were retrospectively reviewed. RESULTS: Six patients with 100% strictures of the cervical esophagus and hypopharynx were available for review. Eighty-three percent of these patients were successfully treated endoscopically with the outlined technique. All were able to handle their secretions successfully, and four were no longer dependent on a gastrostomy tube. CONCLUSIONS: Retrograde dilation of complete strictures of the hypopharynx and cervical esophagus appears to be safe, reliable, and associated with a high rate of ultimate success. It should be considered a first-line treatment prior to open approaches, which may be reserved for failures.