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1.
J Oral Maxillofac Surg ; 79(9): 1970-1976, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34023291

ABSTRACT

BACKGROUND: Recently, histologic grade was removed from salivary tumor nomenclature by the WHO to include disease of higher grade. One such entity, cribriform adenocarcinoma (CAC), is an aggressive group of polymorphous adenocarcinoma (PAC), with frequent nodal metastasis and locoregional recurrence. We aim to examine the biologic behavior of this disease as compared with the PAC general cohort inclusive of all subtypes. METHODS: A systematic review of the literature on polymorphous adenocarcinoma and cribriform adenocarcinoma was completed. A descriptive analysis was performed for the following predictor variables: nodal and distant metastasis, in addition to recurrence. The outcome variables, disease free recurrence, and disease specific survival, where plotted using Kaplan-Meier curves. RESULTS: PAC and CAC both show median age of diagnosis in the sixth decade of life and a female predominance. CAC occurs most frequently in the tongue and PAC in the palate. The 2 groups show a similar biologic behavior in regards to incidence of distant metastasis (4.1 vs 5.5%), recurrence (12.5 vs 17.8%), and death from disease (3 vs 2.7%). However, there was an increased incidence of nodal metastasis in CAC (53%) as compared with that in PAC of all subtypes (14%). CONCLUSIONS: CAC exhibits more aggressive biologic behavior as compared with the PAC cohort. Although CAC is not an officially recognized entity, these tumors likely comprise a significant portion of the cases of PAC with poor outcomes and are deserving of attention and consideration for escalation in oncologic treatment.


Subject(s)
Adenocarcinoma , Salivary Gland Neoplasms , Aggression , Female , Humans , Medical Oncology , Neoplasm Recurrence, Local , Transforming Growth Factor beta
2.
J Oral Maxillofac Surg ; 78(9): 1653.e1-1653.e6, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32428462

ABSTRACT

Regional flaps remain a cornerstone of head and neck reconstruction. Among their many functions, they serve a vital role in salvage surgery and for those in whom medical comorbidities preclude the use of microvascular free flaps. Recent research has also examined their potential benefit in value-based healthcare metrics such as operative time, cost, intensive care unit care, and length of stay as compared to free-flap reconstruction. The submental island flap is one such entity that is well described and validated to provide predictable, oncologically sound coverage for defects of the lower third of the face and oral cavity. Its application has also been documented for repair of defects of the midface, temporal region, oropharynx, and hypopharynx, albeit less frequently. Since its original description, there have been several modifications of this axial-based flap, though none of a vertically oriented long axis. We describe a case of a vertically based submental island flap for maxillary reconstruction that allowed for debulking and recontouring of prior pectoralis flap and correction of submental ptosis.


Subject(s)
Free Tissue Flaps , Plastic Surgery Procedures , Face/surgery , Humans , Neck/surgery , Pectoralis Muscles
3.
Ann Surg Oncol ; 23(Suppl 5): 850-857, 2016 12.
Article in English | MEDLINE | ID: mdl-27506662

ABSTRACT

BACKGROUND: Recurrent head and neck malignancies remain a therapeutic challenge. Tissue transfer, in addition to defect coverage and prevention of wound complications, may potentially decrease radiotoxicity. We evaluated radiation toxicity and survival outcomes of patients who underwent salvage surgery with reirradiation, comparing primary closure to flap reconstruction. METHODS: Retrospective outcomes analysis of recurrent head and neck squamous cell carcinoma (HNSCC) patients treated with curative intent by salvage surgery (± flap reconstruction) and reirradiation from 1996 to 2011. Recurrent stage, reirradiation modality, chemotherapy use, and toxicities were evaluated. RESULTS: Of 96 patients, 59 had primary closure, whereas 37 underwent flap reconstruction (26 free, 11 pedicled). Median radiation and reirradiation doses were 66 Gy and 60 Gy, respectively. Comparing nonflap and flap patients, there was no significant difference in acute mild toxicities (100 vs. 100 %, p = 1.0) or acute severe toxicities (33.9 vs. 37.8 %, p = 0.83). Nonflap patients experienced significantly greater incidence of both late mild toxicities (81.4 vs. 54.1 %, p = 0.006) and late severe toxicities (47.5 vs. 21.6 %, p = 0.02). Overall survival at 5 years was equivalent (33.1 vs. 34.7 %, p = 0.88). Free flap patients had greater delays to postoperative reirradiation and treatment package times compared with pedicled flap patients but no meaningful difference in survival outcomes. CONCLUSIONS: Vascularized tissue potentially helps offset late toxicities associated with a second radiation course in recurrent head and neck cancer patients. In these selected patients, flap coverage may confer functional benefits and improve the long-term radiotoxicity profile.


Subject(s)
Carcinoma, Squamous Cell/therapy , Fistula/etiology , Free Tissue Flaps , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Osteoradionecrosis/etiology , Plastic Surgery Procedures , Radiotherapy/adverse effects , Wound Closure Techniques , Female , Humans , Male , Middle Aged , Plastic Surgery Procedures/adverse effects , Retreatment , Retrospective Studies , Salvage Therapy/adverse effects , Surgical Wound Dehiscence/etiology , Survival Rate , Wound Closure Techniques/adverse effects
4.
Ann Surg Oncol ; 23(Suppl 5): 9001-9009, 2016 12.
Article | MEDLINE | ID: mdl-16715435

ABSTRACT

BACKGROUND: Sentinel lymph node biopsy (SLNB) for primary cutaneous head and neck melanoma (CHNM) has been shown to be successful and is the current standard of care for intermediate-thickness melanoma. We evaluated our experience with CHNM associated with SLNB mapping to the region of the parotid gland. METHODS: Retrospective review of a prospectively collected melanoma database identified 1014 CHNMs. Two-hundred twenty-three patients underwent SLNB, and 72 (32%) had mapping in the region of the parotid gland between May 1995 and June 2003. RESULTS: The mean number of SLNs per patient was 2.5. A sentinel lymph node (SLN) was successfully identified in 94% of patients, and in 12%, the SLN was positive for metastatic disease. Biopsy of intraparotid SLNs was performed in 51.4% and of periparotid SLNs in 26.4%, and a superficial parotidectomy was performed in 22.2%. Ten patients were found to have lymph nodes in the parotid region with metastatic disease (eight identified by SLNB), and two (20%) patients developed intraparotid lymph node recurrence in the setting of a negative SLNB. Same-basin recurrence in SLN-negative patients was 3.3% with a median follow-up of 26 months. Facial nerve dysfunction was identified in seven (10%) patients. Facial nerve function returned to preoperative status in all patients. CONCLUSIONS: SLNB for patients with primary CHNM mapping to the parotid gland can be performed with a high degree of accuracy and a low morbidity consisting of temporary facial nerve paresis.


Subject(s)
Ear Neoplasms/pathology , Facial Neoplasms/pathology , Lymph Node Excision , Melanoma/secondary , Neoplasm Recurrence, Local/pathology , Parotid Neoplasms/secondary , Sentinel Lymph Node Biopsy , Sentinel Lymph Node/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Cheek , Coloring Agents , Facial Nerve/physiopathology , Facial Nerve Injuries/etiology , Female , Forehead , Humans , Lymph Node Excision/adverse effects , Lymphatic Metastasis , Lymphoscintigraphy , Male , Middle Aged , Parotid Neoplasms/surgery , Parotid Region , Recovery of Function , Retrospective Studies , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node Biopsy/adverse effects , Tumor Burden , Young Adult
8.
Cancer ; 120(2): 214-21, 2014 Jan 15.
Article in English | MEDLINE | ID: mdl-24399417

ABSTRACT

BACKGROUND: This study sought to develop prognostic tools that will accurately predict overall and cancer-related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor-node-metastasis) staging system. METHODS: Demographic, host, and tumor characteristics of 1617 patients with cancer of the oral cavity, who were treated primarily with surgery at a single-institution tertiary care cancer center between 1985 and 2009, were reviewed from a preexisting database. Recurrent disease was recorded in 509 patients (456 locoregional and 116 distant); 328 patients died of cancer-related causes, and 542 died of other causes. The median follow-up was 42 months (range, 1-300 months). The following variables were analyzed as predictors of prognosis: age, sex, race, alcohol and tobacco use, oral cavity subsite, invasion of other structures, comorbidity, tumor size, and clinical nodal status. The stepdown method was used to select the statistically most influential predictors for inclusion in the final nomogram for each outcome of interest. RESULTS: The most influential predictors of both recurrence and cancer-specific mortality probability (CSMP) were tumor size, nodal status, subsite, and bone invasion. Nomograms were generated for prediction of overall survival (OS), CSMP, and locoregional recurrence-free probability (LRRFP). The nomograms were internally validated with an overfit-corrected predictive discrimination metric (concordance index) for OS of 67%, CSMP of 66%, and LRRFP of 60%. CONCLUSIONS: Nomograms have been developed that can reasonably estimate OS, CSMP, and LRRFP based on specific tumor and host characteristics in patients with oral cancer.


Subject(s)
Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Mouth Neoplasms/surgery , Nomograms , Aged , Bone Neoplasms/mortality , Bone Neoplasms/secondary , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Preoperative Period , Prognosis , Proportional Hazards Models , Reproducibility of Results
9.
Int J Cancer ; 133(5): 1214-21, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-23436584

ABSTRACT

Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with

Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Oropharyngeal Neoplasms/therapy , Adult , Aged , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Multimodal Imaging , Neck , Oropharyngeal Neoplasms/diagnostic imaging , Oropharyngeal Neoplasms/pathology , Papillomaviridae/isolation & purification , Positron-Emission Tomography , Tomography, X-Ray Computed
10.
Neuroradiol J ; : 19714009231173105, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37118651

ABSTRACT

AIM: Because the tongue is a midline structure, studies on the neural correlates of lateralized tongue function are challenging and remain limited. Patients with tongue cancer who undergo unilateral partial glossectomy may be a unique cohort to study tongue-associated cortical activation, particularly regarding brain hemispheric lateralization. This longitudinal functional magnetic resonance imaging (fMRI) study investigated cortical activation changes for three tongue tasks before and after left-sided partial glossectomy in patients with squamous cell carcinoma of the tongue. METHODS: Seven patients with squamous cell carcinoma involving the left tongue who underwent fMRI before and 6 months after unilateral partial glossectomy were studied. Post-surgical changes in laterality index (LI) values for tongue-associated precentral and postcentral gyri fMRI activation were calculated for the dry swallow, tongue press, and saliva sucking tasks. Group analysis fMRI activation maps were generated for each of the three tasks. RESULTS: There were significant differences in changes in LI values post-surgery between the tongue press (p < 0.005; median: +0.24), saliva sucking (-0.10), and dry swallow tasks (-0.16). Decreased contralateral activation (change in LI ≥+0.20) was observed post-surgery during tongue press in six of seven patients, but only in two patients during saliva sucking and one patient during dry swallow (p < 0.05). There was also increased activation in the supplementary motor area following surgery. CONCLUSION: Post-surgical fMRI changes following left-sided partial glossectomy may suggest task-specific sensitivities to cortical activation changes following unilateral tongue deficits that may reflect the impacts of surgery and adaptive responses to tongue impairment.

11.
Cancer ; 118(13): 3311-20, 2012 Jul 01.
Article in English | MEDLINE | ID: mdl-22072529

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm whose natural history is poorly understood. Here, the authors describe their experience with a large cohort of patients who were treated at a single institution to describe patterns of recurrence after curative therapy. METHODS: Review of a prospective database was performed. Patient-related, tumor-related, and treatment-related variables were recorded, and the site and timing of initial recurrence were recorded. Factors associated with receipt of adjuvant therapy and recurrence were determined. RESULTS: In total, 364 patients with stage I through III MCC who underwent complete resection were identified. Adjuvant local radiation therapy (RT), lymph node RT, and chemotherapy were received selectively by 23%, 23%, and 15% of patients, respectively. Factors associated with the receipt of adjuvant therapy included younger age, primary tumor features (larger size, lymphovascular invasion [LVI], positive margin excision), and increasing pathologic stage. With median follow-up of 3.6 years, 108 patients (30%) developed a recurrence, including 11 local recurrences (3%), 12 in-transit recurrences (3%), 43 lymph node recurrences (12%), and 42 distant recurrences (12%). Clinically involved lymph nodes, primary tumor LVI, and a history of leukemia/lymphoma were predictive of recurrence. The majority of recurrences (80%) occurred in patients who had clinically involved lymph nodes or patients who did not undergo pathologic lymph node evaluation. CONCLUSIONS: A low recurrence rate in patients with clinically lymph node-negative MCC was achieved with adequate surgery (including sentinel lymph node biopsy) and the selective use of adjuvant RT for high-risk tumors. In contrast, patients with clinically lymph node-positive MCC had significantly higher rates of recurrence, especially distant recurrence. The authors concluded that contemporary natural history studies are critical in designing treatment pathways and clinical trials for MCC.


Subject(s)
Carcinoma, Merkel Cell/therapy , Skin Neoplasms/therapy , Aged , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Humans , Lymphatic Irradiation , Male , Middle Aged , Radiotherapy, Adjuvant , Recurrence , Skin Neoplasms/pathology , Skin Neoplasms/surgery
12.
Ann Surg ; 254(3): 465-73; discussion 473-5, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21865945

ABSTRACT

OBJECTIVE: To identify factors associated with survival in Merkel cell carcinoma (MCC). BACKGROUND: Merkel cell carcinoma is a rare cutaneous neoplasm. Staging and treatment are based on studies, which incompletely characterize the disease. METHODS: Review of a prospective database was performed. Overall survival (OS) was estimated by the Kaplan-Meier method. Disease-specific death (DSD) was analyzed by the competing risks method. Factors associated with OS and DSD were determined by the log-rank test and Gray's test, respectively. RESULTS: A total of 500 patients with MCC treated at our institution from 1969 to 2010 were identified. Eighty-eight patients presented older than 6 months after diagnosis and were excluded from further analysis. Of the remaining 412 patients, the median age at diagnosis was 71 years. Median follow-up was 3 years. Fifty percent of patients died during follow-up: 25% died of disease, 24% died of other causes. Five-year OS and DSD were 56% and 30%, respectively. Pathologic stage and lymphovascular invasion were independent predictors of DSD. Patients with metastatic disease (stage 4) or clinically positive lymph nodes (stage 3b) had increased DSD compared with patients with microscopically positive (stage 3a) or negative lymph nodes (stage 1 and 2). There was no difference in DSD between stage 3a or 2 compared with stage 1. Importantly, only 1 of 132 patients without lymphovascular invasion died of MCC. CONCLUSIONS: OS is a poor measure of the influence of MCC on life expectancy. The presence of lymphovascular invasion and clinically, but not microscopically, positive lymph nodes were associated with increased DSD. These factors should be incorporated into MCC staging and treatment recommendations.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Merkel Cell/therapy , Skin Neoplasms/therapy , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Carboplatin/administration & dosage , Carcinoma, Merkel Cell/drug therapy , Carcinoma, Merkel Cell/mortality , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/radiotherapy , Carcinoma, Merkel Cell/surgery , Cisplatin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Infusion Pumps , Irinotecan , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Research Design , Skin Neoplasms/drug therapy , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/radiotherapy , Skin Neoplasms/surgery , Treatment Outcome
13.
Ann Surg Oncol ; 18(9): 2529-37, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21431988

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine neoplasm with propensity for lymphatic spread. The rarity of MCC has limited analysis of factors associated with a positive sentinel lymph node biopsy (SLNB) and survival. METHODS: Review of a prospective MCC database was performed. Factors associated with SLNB positivity were analyzed. Univariate and multivariate analyses of factors associated with recurrence and survival were performed using the cumulative incidence (CI) function, treating death from other causes as a competing risk. RESULTS: From 1996 to 2010, a total of 153 patients with localized MCC underwent SLNB, of whom 45 (29%) were positive. Factors associated with SLNB positivity were primary tumor size (25% ≤2 cm vs. 45% >2 cm; P = 0.02) and presence of lymphovascular invasion (LVI) (55% LVI positive vs. 4% LVI negative; P < 0.01). SLNB-positive patients were more likely to receive radiation or chemotherapy (60% vs. 7%, P < 0.01). With median follow-up of 41 months, there were 16 nodal/distant recurrences (10%), 11 deaths from MCC (7%), and 27 death from other causes (18%). The 2-year CIs of recurrence or death from MCC were 12% and 6%, respectively. There was no difference in recurrence or death from MCC between SLNB-positive and -negative patients. The 2-year CIs of recurrence or death from MCC for LVI-positive patients were 30% and 15%, respectively. No LVI-negative patient experienced recurrence of disease or died of MCC. DISCUSSION: SLNB identifies occult nodal metastases in 29% of patients with localized MCC. Predictors of SLNB positivity are tumor size and presence of lymphovascular invasion (LVI). Patients with SLNB-positive disease are more likely to receive further treatment; however, sentinel lymph node (SLN) status is not associated with recurrence or survival. In contrast, LVI is strongly associated with both recurrence and survival.


Subject(s)
Carcinoma, Merkel Cell/mortality , Neoplasm Recurrence, Local/mortality , Skin Neoplasms/mortality , Aged , Carcinoma, Merkel Cell/secondary , Carcinoma, Merkel Cell/surgery , Cohort Studies , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Prospective Studies , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Survival Rate
14.
Neuroimage ; 44(1): 175-81, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-18824236

ABSTRACT

Voice production involves precise, coordinated movements of the intrinsic and extrinsic laryngeal musculature. A component of normal voice production is the modification of pitch. The underlying neural networks associated with these complex processes remains poorly characterized. However, several investigators are currently utilizing neuroimaging techniques to more clearly delineate these networks associated with phonation. The current study sought to identify the central cortical mechanism(s) associated with pitch variation during voice production using event-related functional MRI (fMRI). A single-trial design was employed consisting of three voice production tasks (low, comfortable, and high pitch) to contrast brain activity during the generation of varying frequencies. For whole brain analysis, volumes of activation within regions activated during each task were measured. Bilateral activations were shown in the cerebellum, superior temporal gyrus, insula, precentral gyrus, postcentral gyrus, inferior parietal lobe, and post-cingulate gyrus. In the left hemisphere, activations in the medial and middle frontal gyri were also observed. Regions active during high pitch production when compared to comfortable pitch were evident in the bilateral cerebellum, left inferior frontal gyrus, left cingulate gyrus, and left posterior cingulate. During low pitch generation, activations were present in the inferior frontal gyrus, insula, putamen, and cingulate gyrus in the left hemisphere. The inferior frontal gyrus in the right hemisphere produced greater activity than the area of the left hemisphere during high and low pitch generation. These results suggest that a single-trial design is sensitive enough to begin to delineate a widespread network of activations in both hemispheres associated with vocal pitch variation.


Subject(s)
Brain Mapping , Brain/diagnostic imaging , Magnetic Resonance Imaging , Nerve Net/diagnostic imaging , Phonation/physiology , Adult , Female , Humans , Image Interpretation, Computer-Assisted , Male , Radionuclide Imaging
15.
BMC Cancer ; 9: 11, 2009 Jan 12.
Article in English | MEDLINE | ID: mdl-19138406

ABSTRACT

BACKGROUND: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. METHODS: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR. RESULTS: Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only GLUT3 showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. CONCLUSION: The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.


Subject(s)
Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Tongue Neoplasms/diagnosis , Tongue Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , DNA-Binding Proteins , Female , Glucose Transporter Type 3/genetics , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Prognosis , Proprotein Convertases/genetics , Serine Endopeptidases/genetics , Transcription Factors/genetics
16.
Otolaryngol Head Neck Surg ; 140(2): 218-23, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19201292

ABSTRACT

OBJECTIVE: To determine the rate and type of complications after craniofacial resection (CFR) during the most recent 10-year period in comparison to a historic control. METHODS: Patients underwent CFR in 1973-1995 ("earlier" period; n = 114) and in 1996-2005 ("later" period; n = 120) before and after a broad-spectrum antibiotic regime was used. RESULTS: In the later period patients had higher rates of comorbidity, dural invasion, high-grade malignancy, and wide resections (P < 0.02). Complications were identified in 52 percent of the early and 33 percent of the later groups (P = 0.002). There was 20 percent decrease in wound complications in the later period (P < 0.0001), but not in other complications. In the earlier period, complications were evenly distributed between patients younger and older than 50 years. However, in the later period, most complications occurred among elderly patients. Multivariate analysis revealed that a broad-spectrum antibiotic regime was associated with a lower complication rate (P = 0.02). CONCLUSIONS: Complication rates decreased during the last 10 years due to a decline in wound infections. Broad-spectrum antibiotic coverage probably contributed to this change.


Subject(s)
Cranial Fossa, Anterior , Facial Neoplasms/surgery , Postoperative Complications , Skull Base Neoplasms/surgery , Adult , Aged , Antibiotic Prophylaxis , Cohort Studies , Facial Neoplasms/mortality , Facial Neoplasms/pathology , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Skull Base Neoplasms/mortality , Skull Base Neoplasms/pathology
17.
Ann Otol Rhinol Laryngol ; 118(3): 218-26, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19374154

ABSTRACT

OBJECTIVES: We studied the effect of transforming growth factor (TGF)-beta on immortalized human vocal fold fibroblasts. METHODS: Normal human vocal fold fibroblasts were subjected to sequential lentiviral transduction with genes for human telomerase (hTERT) and SV40 large T antigen in order to produce an "immortalized" cell line of normal phenotype. After confirmation of vocal fold fibroblast transfection, these cells, referred to as HVOX, were treated with various concentrations of exogenous TGF-beta1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-beta signaling pathway were examined in this cell line. RESULTS: TGF-beta stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutively expressed type I and II TGF-beta receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-beta isoforms. Exogenous TGF-beta1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-beta increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-beta decreased TGF-beta1 gene expression. CONCLUSIONS: Insight into the underlying pathophysiology of vocal fold fibrosis is likely to yield improved therapeutic strategies to mitigate vocal fold scarring. Our data suggest that TGF-beta signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-beta may be a reasonable target for therapies to prevent and/or treat vocal fold fibrosis, given its putative role in both acute and chronic vocal fold injury, as well as its effects on vocal fold fibroblasts.


Subject(s)
Fibroblasts/drug effects , Fibroblasts/physiology , Transforming Growth Factor beta1/pharmacology , Vocal Cords/cytology , Vocal Cords/drug effects , Cell Culture Techniques , Cell Line , Cell Proliferation/drug effects , Collagen/metabolism , Dose-Response Relationship, Drug , Humans , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction/drug effects , Smad Proteins/metabolism
18.
Int J Radiat Oncol Biol Phys ; 70(5): 1365-72, 2008 Apr 01.
Article in English | MEDLINE | ID: mdl-18029108

ABSTRACT

PURPOSE: To analyze the recent experience of patients with adenoid cystic carcinoma treated with radiation therapy at Memorial Sloan-Kettering Cancer Center. METHODS AND MATERIALS: From 1990 to 2004, a total of 59 patients with a diagnosis of primary adenoid cystic carcinoma of the head and neck received radiation therapy at our institution. The subsite distribution was oral cavity, 28% (n = 17); paranasal sinuses, 22% (n = 13); parotid, 14% (n = 8); submandibular, 14% (n = 8); oropharynx, 10% (n = 6); sublingual, 3% (n = 2); nasopharynx, 3% (n = 2); and other, 5% (n = 3). T Stage distribution was T1, 34% (n = 20); T2, 19% (n = 11); T3, 14% (n = 8); and T4, 34% (n = 20). Twenty-nine percent of patients (n = 17) were treated with intensity-modulated radiation therapy; 25% (n =15), with three-dimensional conformal therapy, and the remainder, with conventional techniques. Ninety percent (n = 53) of patients received treatment including the base of skull. RESULTS: Median follow-up for surviving patients was 5.9 years. Five-year and 10-year rates of local control and distant metastases-free survival were 91%/81% and 81%/49%, respectively. Five-year and 10-year rates of disease-free and overall survival were 76%/40% and 87%/65%, respectively. On univariate analysis, stage T4 (p = 0.004) and gross/clinical nerve involvement (p = 0.002) were associated with decreased progression free survival, whereas stage T4 and lymph node involvement were associated with decreased overall survival (p = 0.046 and p < 0.001, respectively). CONCLUSIONS: Radiation therapy in combination with surgery produces excellent rates of local control, although distant metastases account for a high proportion of failures. Routine treatment to the base of skull reduces the significance of histologic perineural invasion, but major nerve involvement remains an adverse prognostic factor.


Subject(s)
Carcinoma, Adenoid Cystic/radiotherapy , Head and Neck Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Carcinoma, Adenoid Cystic/mortality , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Adenoid Cystic/secondary , Disease-Free Survival , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Radiation Injuries/complications , Radiotherapy, Conformal/methods , Retrospective Studies , Treatment Outcome
19.
J Nucl Med ; 49(4): 532-40, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18344440

ABSTRACT

UNLABELLED: For patients with locoregional advanced head and neck squamous cell carcinoma (HNSCC), concurrent chemoradiotherapy is a widely accepted treatment, but the need for subsequent neck dissection remains controversial. We investigated the clinical utility of 18F-FDG PET/CT in this setting. METHODS: In this Institutional Review Board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPPA)-compliant retrospective study, we reviewed the records of patients with HNSCC who were treated by concurrent chemoradiation therapy between March 2002 and December 2004. Patients with lymph node metastases who underwent 18F-FDG PET/CT > or = 8 wk after the end of therapy were included. 18F-FDG PET/CT findings were validated by biopsy, histopathology of neck dissection specimens (n = 18), or clinical and imaging follow-up (median, 37 mo). RESULTS: Sixty-five patients with a total of 84 heminecks could be evaluated. 18F-FDG PET/CT (visual analysis) detected residual nodal disease with a sensitivity of 71%, a specificity of 89%, a positive predictive value (PPV) of 38%, a negative predictive value (NPV) of 97%, and an accuracy of 88%. Twenty-nine heminecks contained residual enlarged lymph nodes (diameter, > or =1.0 cm), but viable tumor was found in only 5 of them. 18F-FDG PET/CT was true-positive in 4 and false-positive in 6 heminecks, but the NPV was high at 94%. Fifty-five heminecks contained no residual enlarged nodes, and PET/CT was true-negative in 50 of these, yielding a specificity of 96% and an NPV of 98%. Lack of residual lymphadenopathy on CT had an NPV of 96%. Finally, normal 18F-FDG PET/CT excluded residual disease at the primary site with a specificity of 95%, an NPV of 97%, and an accuracy of 92%. CONCLUSION: In patients with HNSCC, normal 18F-FDG PET/CT after chemoradiotherapy has a high NPV and specificity for excluding residual locoregional disease. In patients without residual lymphadenopathy, neck dissection may be withheld safely. In patients with residual lymphadenopathy, a lack of abnormal 18F-FDG uptake in these nodes also excludes viable tumor with high certainty, but confirmation of these data in a prospective study may be necessary before negative 18F-FDG PET/CT may become the only, or at least most-decisive, criterion in the management of the neck after chemoradiotherapy.


Subject(s)
Fluorodeoxyglucose F18 , Head and Neck Neoplasms/therapy , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Combined Modality Therapy , Female , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Humans , Lymphatic Metastasis , Male , Middle Aged , Neck/diagnostic imaging , Retrospective Studies
20.
Pediatr Blood Cancer ; 50(1): 167-9, 2008 Jan.
Article in English | MEDLINE | ID: mdl-16856154

ABSTRACT

Extrarenal extracranial malignant rhabdoid tumors (MRT) are extremely rare and typically lethal. No consensus exists on an optimal treatment approach, and, in particular, the role of radiation therapy (RT) is poorly defined. We report on three children who underwent multimodality treatment including surgery, chemotherapy (CMT), and RT. Two of these patients are alive and without evidence of disease 6(1/2) and 7 years after diagnosis and one has expired. Our limited experience suggests that RT in the setting of CMT and surgery has the potential to prolong survival with acceptable toxicity, but outcomes are inconsistent and further study is necessary.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Rhabdoid Tumor/radiotherapy , Child , Combined Modality Therapy , Diseases in Twins , Female , Head and Neck Neoplasms/genetics , Humans , Infant , Rhabdoid Tumor/genetics
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