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Biomedical subjects

David Goldenberg

Publications and source records attributed to David Goldenberg.

At least 19 recordsLinked to original sources
PubMed2007

Reduction of complication rate in percutaneous dilation tracheostomies.

INTRODUCTION: Percutaneous dilation tracheotomy (PDT) is now an accepted alternative to surgical tracheotomy in certain patients. We began performing these procedures in 2000 and use it regularly in select intensive care unit patients requiring prolonged intubation and mechanical ventilation. MATERIALS AND METHODS: A retrospective chart review of consecutive PDTs performed in the Department of Otolaryngology-Head and Neck Surgery at the John Hopkins Hospital between 2002 and 2005 was undertaken. Procedural and postoperative complications in an earlier group were compared with those in the later group for both frequency and severity. RESULTS: Three hundred eighteen PDTs were performed on intensive care patients during this time period. All were performed using the Ciaglia method and the Cook Blue Rhino (Cook Medical Products, Bloomington, IN) set under direct bronchoscopic visualization. In group A (first 159 patients), there were a total of 12 complications (7.5%), including six cases of perioperative hemorrhage, whereas in group B (second 159 PDTs), there were seven complications (4.4%) with no cases of perioperative hemorrhage. CONCLUSIONS: PDT provides an easy and convenient alternative to open tracheotomy (OT) and should be added to the otolaryngologist's armamentarium of surgical airway procedures. The complication rate of PDT is low and similar to that of open operative tracheotomy. However, with experience and the use of strict protocols in both patient selection and PDT procedure, the complication rate can be significantly reduced further both in frequency and severity, making it even safer than an open operative tracheotomy.

Adult↗
PubMed2007

Supracricoid laryngectomy outcomes: The Johns Hopkins experience.

OBJECTIVE: To report the oncologic and functional results from our experience in performing supracricoid laryngectomy (SCL) for selected patients with laryngeal cancer. STUDY DESIGN: Retrospective chart review. METHODS: Twenty-four consecutive patients who underwent SCL for laryngeal cancer in our institution from December 2000 to March 2006 have been reviewed. Reports of the site and extent of tumor, type of reconstruction, preoperative or postoperative radiotherapy, and the final histopathologic examination were reviewed. In addition, the reports of the preoperative examination, inpatient course, and postoperative follow-up were reviewed. RESULTS: A total of 24 patients were involved in the study; 19 had tumors involving the glottic region, and 5 patients had tumors involving both the glottic and supraglottic regions (transglottic). Ten patients had their SCL for postradiotherapy recurrence/persistence of disease. Eighteen patients underwent reconstruction through cricohyoidoepiglottopexy (CHEP), whereas six patients had cricohyoidopexy (CHP). Eleven patients had an arytenoid cartilage resected; 8 of 11 had CHEP, and 3 of 11 had CHP. All patients had a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement performed at the same time as the SCL. The median hospital stay period was 6 days. Twenty-three of 24 had successful tracheostomy tube decannulation, with a median time to decannulation of 37 days. The median time to removal of the PEG tube was 70 days. The complications with SCL were postoperative wound infection in two patients (SCL/CHP) and the need for completion total laryngectomy secondary to intractable aspiration in one patient with SCL/CHP. One patient with SCL/CHEP had a ruptured pexy and subsequently underwent a second reconstruction with successful tracheostomy and PEG tube removal. One of 24 patients is still PEG tube dependant, and he had postoperative radiotherapy. Fifteen patients underwent concurrent neck dissection. None of the patients had any local or regional recurrence, with a median follow-up period of 3 years. All final surgical margins were negative for tumor invasion. Three patients had postoperative radiotherapy, two patients because of nodal metastases in the excised lymph nodes and one because of perineural invasion on final histopathologic examination of the SCL specimen. There were no perioperative deaths. CONCLUSION: SCL with CHEP or CHP represents an effective technique that can be taught and effectively used to avoid a total laryngectomy while maintaining physiologic speech and swallowing in selected patients with advanced stage primary laryngeal cancer or recurrent/persistent laryngeal cancer after radiotherapy. There is a good functional recovery with acceptable morbidity and an excellent oncologic outcome when strict selection criteria are applied and a formal swallowing rehabilitation program is followed.

Adult↗
PubMed2006

Increased plasma DNA integrity index in head and neck cancer patients.

Analysis of the length of circulating DNA in plasma has been reported as a marker for solid tumor detection. We assessed the sensitivity and specificity of increased plasma DNA length to identify patients with head and neck squamous cell carcinoma (HNSCC) and monitor posttreatment disease status. Fifty-eight HNSCC patients with paired pre- and postoperative plasma and 47 plasma samples from control subjects were analyzed using quantitative PCR to determine plasma DNA integrity index. We found that the mean DNA integrity index was significantly greater in the plasma from HNSCC patients, 0.24 (95% CI: 0.11, 0.38), when compared to plasma from the control subjects, -2.24 (95% CI: -2.92, -1.56), p < 0.0001 using multivariate analysis. The optimal sensitivity (the value for which sensitivity equals specificity) was found at a plasma DNA integrity index of 0.82: sensitivity, 84.5%; specificity, 83%. However, there was no significant difference noted between pre- and postoperative DNA integrity index in plasma samples from HNSCC patients. This study shows that DNA integrity index in the plasma of the patients with HNSCC is increased in comparison with that in the plasma from non-HNSCC control subjects. Lack of normalization of plasma DNA integrity index after surgical resection implies the persistence of a population of cells with an altered pattern of DNA degradation despite removal of malignancy.

Adult↗
PubMed2006

The role of positron emission tomography and computed tomography fusion in the management of early-stage and advanced-stage primary head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the role of positron emission tomography and computed tomography (PET-CT) fusion in the management of early-stage and advanced-stage primary head and neck squamous cell cancer. DESIGN: Retrospective analysis, with a blinded evaluation of clinical data and formation of a treatment plan. SETTING: Single tertiary academic medical institution. Patients Thirty-six patients with previously untreated head and neck squamous cell carcinoma who underwent staging CT or magnetic resonance imaging of the neck prior to undergoing PET-CT as part of their initial diagnostic evaluation between July 2000 and January 2005. MAIN OUTCOME MEASURES: Confirmation or alteration of the treatment plan with the addition of the PET-CT information compared with traditional clinical and radiological data alone for early-stage and advanced-stage disease. When available, histopathological results were correlated with the PET-CT findings. RESULTS: Among the 36 patients, PET-CT provided additional information that confirmed the treatment plan in 25 patients (69%) and altered the treatment plan in 11 patients (31%). Six of 11 patients in the altered-treatment group had their tumors upstaged. Four of 8 patients with early-stage tumors had their treatment plan altered, compared with 7 of 28 patients with advanced-stage disease. Among 18 patients who underwent a surgical intervention for their primary tumor, PET-CT identified the primary tumor in all 18 patients and, based on histopathological findings, correctly staged the regional nodal disease in 9 of 16 patients who had their nodal disease addressed. CONCLUSION: The use of PET-CT is important in the initial treatment planning of early-stage and advanced-stage head and neck squamous cell carcinoma.

Adolescent↗
PubMed2006

Cystic metastasis from head and neck squamous cell cancer: a distinct disease variant?

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) commonly spreads to regional deep cervical nodes. In most cases, these metastases present as firm, solid masses in the designated lymph node chains. A distinct subset of metastatic nodes present as cystic masses, with most of the volume made up of a liquid center surrounded by a thin solid rim. It has been observed that certain squamous cell carcinoma (SCC) subsites are more likely to produce metastases that are cystic. These sites predominantly include primary tumors of tonsil tissue from Waldeyer's ring. In the past, these cystic cancers often have been erroneously diagnosed as branchiogenic carcinomas, that is, a branchial cleft cyst that has undergone malignant degeneration. Today, most authors have concluded that so-called branchiogenic carcinomas are actually cystic metastases in the neck probably arising from an oropharyngeal primary SCC. The purpose of this work is to consider the phenomenon of cystic lymph node metastasis in head and neck cancer in depth. METHODS: A review of the relevant English-language literature linking cystic metastasis and head and neck cancer was performed. RESULTS: These studies indicate that lateral cystic masses in adults often represent an occult primary cancer originating in the epithelium within Waldeyer's ring. CONCLUSIONS: Adult patients who are initially seen with a lateral cystic neck mass must be presumed to have a cancer until proven otherwise. The mass should be biopsied by fine-needle aspiration (FNA). However, negative FNA findings may be misleading; therefore, an excisional biopsy and examination under anesthesia with directed biopsies of Waldeyer's ring and bilateral tonsillectomy should be considered a part of the diagnostic workup.

Animals↗
PubMed2006

Oral complications of radiotherapy.

Radiotherapy-induced damage in the oral mucosa is the result of the deleterious effects of radiation, not only on the oral mucosa itself but also on the adjacent salivary glands, bone, dentition, and masticatory musculature and apparatus. Biological response modifiers, cytoprotective drugs, salivary-sparing radiation techniques, and surgery have been introduced to combat and, more importantly, to prevent, the development of these complications. Radiotherapy-induced oral complications are complex, dynamic pathobiological processes that lower the quality of life and predispose patients to serious clinical disorders. Here, we focus on these oral complications of radiotherapy, highlight preventive and therapeutic developments, and review the current treatment options available for these disorders.

Humans↗
PubMed2006

Squamous cell carcinoma of the sinonasal cavity arising as a second primary in individuals with head and neck cancer.

OBJECTIVES/HYPOTHESIS: Second primary tumors occur frequently in patients with head and neck carcinoma. This may be caused by generalized exposure to carcinogens resulting in "field cancerization" or to the individuals' generalized susceptibility to cancer. The paranasal sinuses are not commonly included in the sites considered at risk for this process. We therefore sought to assess the overall risk of contracting a primary cancer in this region after having a tumor elsewhere in the upper aerodigestive tract. STUDY DESIGN: Retrospective. METHODS: Two thousand four hundred seventy-five patients with squamous cell carcinoma of the upper aerodigestive tract were analyzed using a tumor registry at a tertiary care institution. RESULTS: Five (0.2%) patients were identified as having a second primary in the sinonasal tract. The average interval between the index and second primary tumors was 28.4 (range 8-60) months. All five patients presented with symptoms typical of sinus inflammatory disease and had advanced sinus lesions at the time of diagnosis. These findings are typical of those with sinonasal carcinoma in that they present with nonspecific signs and symptoms and were diagnosed with locally advanced disease despite being in a surveillance program for their index cancer. CONCLUSIONS: Although uncommon, the data reported here support inclusion of the sinonasal tract in these surveillance programs. This could result in earlier detection and greater opportunity for curative intervention.

Aged↗
PubMed2005

Somatic mutation and gain of copy number of PIK3CA in human breast cancer.

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. METHODS: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. RESULTS: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. CONCLUSION: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.

Apoptosis↗
PubMed2005

Molecular margin analysis predicts local recurrence after sublobar resection of lung cancer.

Sublobar resection for early-stage lung cancer has been used for patients who are not candidates for lobar resection. However, sublobar resection is associated with high local recurrence rates in the context of tumor-free parenchymal margins. The mechanism underlying this high recurrence rate is not well understood. We hypothesized that this elevated risk of local recurrence is due to undetected tumor cells present at parenchymal margins thought to be negative by conventional light microscopy. Thirteen of 44 patients who underwent sublobar resection for lung cancer were found to have a k-ras mutation at codon 12.1. A novel fluorescence-based assay for detection of rare copies of mutant DNA in a background of wild-type DNA, fluorescent gap ligase chain reaction, was used to quantitate the mutant/wild-type DNA in a range of 1 to 1/10,000 in histologically normal margins from these resections. Nine of 13 patients had at least one margin with the number of mutant cells over or equal to a threshold of 1/5,000, and of these, 6/9 (67%) recurred locally. None of the remaining 4 patients without mutant DNA in any surgical margin had evidence of recurrence. The higher rate of local recurrence associated with sublobar resection of lung cancer is likely due to the occult presence of tumor cells at resection margins. These occult tumor cells can be quantitated using a novel fluorescence-based assay and define a group of patients at high risk for local recurrence who are candidates for adjuvant therapy or more extensive resection. This methodology may be adaptable to a real-time format for intraoperative use.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Absence of V599E BRAF mutations in desmoplastic melanomas.

BACKGROUND: Desmoplastic melanoma is an uncommon variant of cutaneous melanoma that mimics soft tissue sarcoma both clinically and morphologically. An activating point mutation of the BRAF oncogene has been identified in a high proportion of conventional cutaneous melanomas, but its frequency in the desmoplastic subtype is not known. METHODS: The authors tested 12 desmoplastic melanoma specimens for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 of the BRAF gene using a newly developed assay that employs a novel primer extension method. They also tested 57 vertical growth phase cutaneous nondesmoplastic melanoma specimens. RESULTS: The 1796 T-->A mutation was detected in 23 of the 57 conventional cutaneous melanoma specimens but in none of the 12 desmoplastic melanoma specimens (40% vs. 0%; P=0.0006, Fisher exact 2-tailed test). CONCLUSIONS: The relative importance of BRAF mutational activation in melanocytic tumorigenesis clearly was not the same across the various subtypes of melanoma, even for melanomas of cutaneous origin that are associated with sun exposure. In contrast to conventional cutaneous melanomas, the desmoplastic variant frequently did not harbor an activating mutation of BRAF. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new therapeutic strategies are developed that target specific genetic alterations.

Female↗
PubMed2005

Reading performance in children with otitis media.

OBJECTIVE: To examine whether middle ear diseases and the associated hearing loss in early childhood affect reading performance later at school. STUDY DESIGN AND SETTING: One hundred and sixty children, 6.5 to 8 years of age, were enrolled in this study: 80 children with a history of recurrent infections and/or prolonged periods of effusions of the middle ear before the age of 5 years, and 80 healthy children without any history of middle ear disease. Data were collected from the medical records of the children. Every child underwent a complete otological and audiological evaluation, followed by special reading tests. RESULTS: The study group performed more poorly, in all reading tests, as compared to the controls ( P < 0.001). CONCLUSION: Children with recurrent or prolonged middle ear diseases during the first five years of life tend to be at greater risk for delayed reading than aged-matched controls with no previous middle ear diseases.

Child↗
PubMed2005

The role of positron emission tomography/computed tomography in the management of recurrent papillary thyroid carcinoma.

OBJECTIVES/HYPOTHESIS: The aim of the study was to evaluate the role of combined positron emission tomography/computed tomography (PET/CT) fusion imaging in the detection and management of recurrent papillary thyroid cancer. STUDY DESIGN: A retrospective analysis of 33 patients with suspected recurrent papillary thyroid carcinoma who had undergone PET/CT was performed. PET/CT was compared with standard imaging techniques in each patient to determine whether PET/CT contributed to the therapeutic management plan. Histopathological findings were correlated to PET/CT in patients who underwent surgery. METHODS: The senior author reviewed the charts of 33 patients with recurrent papillary thyroid carcinoma to determine the impact PET/CT had on management. PET/CT was compared with conventional imaging results. In surgical patients, PET/CT was compared with histopathological findings to determine its sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: In 67% of the cases (22 of 33), PET/CT supplied additional information that altered or confirmed the management plan. Twenty of 33 patients underwent surgery with 36 sites assessed by histopathological analysis. PET/CT correlated with histopathological findings in 25 of 36 distinct anatomical sites, with an accuracy of 70%. The sensitivity of PET/CT in identifying recurrence was found to be 66%, with a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 27%. CONCLUSION: Combined PET/CT fusion scanning was most useful in the detection and management of recurrent papillary thyroid cancer in patients who had average thyroglobulin levels greater than 10 ng/mL and when the tumor no longer concentrated radioactive iodine. In 100% of the cases in which PET/CT localized a region suspicious for malignancy, histopathological analysis confirmed the results. When PET/CT is positive, it is a powerful tool for predicting exact locations of recurrent papillary thyroid cancer, thus making it a reliable guide for surgical planning. PET/CT is a supplement to conventional imaging and fine-needle aspiration in the workup of recurrent papillary thyroid cancer. A negative finding on PET/CT is not sufficiently reliable to preclude further investigation and treatment.

Adult↗
PubMed2005

Colorimetric approach to high-throughput mutation analysis.

High-throughput genomic mutation screening for primary tumors has characteristically been expensive, labor-intensive, and inadequate to detect low levels of mutation in a background of wild-type signal. We present a new, combined PCR and colorimetric approach that is inexpensive, simple, and can detect the presence of 1% mutation in a background of wild-type. We compared manual dideoxy sequencing of p53 for eight lung cancer samples to a novel assay combining a primer extension step and an enzymatic colorimetric step in a 96-well plate with covalently attached oligonucleotide sequences. For every sample, we were able to detect the presence or absence of the specific mutation with a statistically significant difference between the sample optical density (OD) and the background OD, with a sensitivity and specificity of 100%. This assay is straightforward, accurate, inexpensive, and allows for rapid, high-throughput analysis of samples, making it ideal for genomic mutation or polymorphism screening studies in both clinical and research settings.

Biological Assay↗
PubMed2004

Exon 15 BRAF mutations are uncommon in melanomas arising in nonsun-exposed sites.

PURPOSE: An activating point mutation of the BRAF oncogene has been identified in a high proportion of cutaneous nevi and cutaneous melanomas, but its frequency in melanomas arising from the mucosa of head and neck is unknown. EXPERIMENTAL DESIGN: We tested 17 malignant mucosal melanomas of the head and neck for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using direct sequencing and a newly developed assay that uses a novel primer extension method (Mutector assay). We also tested 21 cutaneous melanomas, including 13 arising from sun-exposed sites and 8 from a nonsun-exposed site, the vulvar skin. RESULTS: The 1796T-->A mutation was detected in only 1 (6%) of the sinonasal melanomas. As for cutaneous melanomas, a BRAF mutation was detected in 8 (62%) of the tumors arising in sun-exposed sites but in none (0%) of vulvar melanomas. CONCLUSIONS: In contrast to cutaneous melanomas arising in sun-exposed sites, mucosal melanomas of the head and neck do not frequently harbor an activating mutation of BRAF. This finding additionally supports the view that the various subtypes of melanoma are not equivalent and that distinct genetic alterations may underlie well recognized differences in risk factors and behavioral patterns. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new strategies are developed that target specific genetic alterations.

Adenine↗
PubMed2004

Intraoperative molecular margin analysis in head and neck cancer.

BACKGROUND: Tumor-specific molecular alterations in surgical margins have been shown to predict risk of local recurrence. However, assays used for these analyses are time-consuming and therefore cannot be used in the intraoperative setting. OBJECTIVE: To detect and quantify tumor-specific methylated promoter sequences in surgical margins in a time frame suitable for intraoperative use. DESIGN: A novel quantitative methylation-specific polymerase chain reaction (QMSP) protocol. METHODS: A total of 13 patients with head and neck squamous cell carcinoma (HNSCC) were initially characterized for molecular alterations in their tumor at the time of biopsy. Six primary tumors were found to harbor promoter hypermethylation for p16 and O6-methylguanine-DNA-methyltransferase (MGMT) genes. Rapid QMSP was then used to identify promoter hypermethylation of these genes in the surgical margins. Results were compared with standard intraoperative histologic frozen section analysis and with conventional QMSP. RESULTS: Using our rapid QMSP assay, we found that 3 patients had methylation-positive margins. Tumor margins from 2 patients were methylated for p16 alone, and margins from 1 patient were methylated for p16 and MGMT simultaneously. Molecular margin analysis was completed in less than 5 hours, a time frame appropriate for selected major HNSCC resections that require combined primary tumor resection, cervical lymphadenectomy, and complex reconstruction. This technique was comparable in sensitivity to conventional QMSP. CONCLUSION: Rapid molecular margin analysis using QMSP is feasible and may be performed intraoperatively in selected patients with HNSCC that requires extensive resection.

Carcinoma, Squamous Cell↗
PubMed2004

Odontogenic ghost cell carcinoma.

BACKGROUND: Odontogenic ghost cell carcinoma (OGCC), a malignant counterpart of the calcifying odontogenic cyst (COC), is exceedingly rare. Previous descriptions of this tumor were based on identification of malignant histologic characteristics such as infiltration, cellular pleomorphism, numerous mitoses, and necrosis concurrent with classical benign COC or its solid benign variant, the odontogenic ghost cell tumor. METHODS: We present a case of a young Asian man who underwent multiple local excisions of a recurring maxillary COC. After one such excision, a rapid onset of painful swelling ensued, and the patient was referred to our institution for definitive surgery. RESULTS: The patient underwent a right subtotal maxillectomy. Intraoperatively, a 5-cm tumor was found to be extending into the right maxillary sinus and nasal cavity. The excised tumor was diagnosed as an OGCC. The tumor was excised with clear margins, and no adjunctive radiotherapy was given. The patient was free of residual or recurrent disease 18 months after surgery. CONCLUSION: On the basis of this case and prior cases found in the literature, OGCCs show a spectrum of growth from slow growing locally invasive tumors to highly aggressive, rapidly growing, infiltrative tumors. Wide local excision with histologically clean margins is the recommended mode of treatment. We recommend close long-term surveillance of recurrent or long-standing benign COCs and OGCC.

Adult↗
PubMed2004

Habitual risk factors for head and neck cancer.

UNLABELLED: Chronic tobacco smoking and alcohol consumption are well-established risk factors for the development of squamous cell carcinoma (SCC) of the head and neck. There are, however, a variety of other habitual and culturally based activities that are less commonly seen in the Western world and that are also risks factors for the development of this type of cancer. In this era of globalization, many of these habits have now crossed borders and appear in various areas throughout the world. This article reviews habitual and social risk factors for cancer of the head and neck, excluding smoking and alcohol consumption. These factors include chewing tobacco and snuff, areca nut in its various forms, Khat leaves, and the drinking of Mate. EBM RATING: D.

Areca↗