Biomedical subjects

Carl E Silver

Publications and source records attributed to Carl E Silver.

At least 19 recordsLinked to original sources

PubMed2007

Phase II clinical trial of parenteral hydroxyurea and hyper-fractionated, accelerated external beam radiation therapy in patients with advanced squamous cell carcinoma of the head and neck: toxicity and efficacy with continuous ribonucleoside reductase inhibition.

BACKGROUND: Almost all concurrent chemoradiation regimens for head and neck are platinum based; however, cisplatin is associated with severe renal, oto-, and neurotoxicity. Hydroxyurea (HU) has been associated with fewer irreversible toxicities. We obtained HU in parenteral form to be administered continually during the radiation treatment. Intravenous HU promised better pharmacokinetics and cell cycle blockade. METHODS: Participants had biopsy-proven, untreated squamous cell carcinoma of the oral cavity, oropharynx (stage IV) and hypopharynx (stages II-IV). Radiation therapy consisted initially of 74.4 Gy administered in twice daily 1.2-Gy fractions. After 20 patients, the radiation dose was reduced to 60.0 Gy, and another 16 patients were enrolled. RESULTS: Patients received HU by Continuous Ambulatory Drug Delivery (CADD) pump on a daily x5 schedule during radiation therapy. Because of persistent long-term dysphagia, after 20 patients, the dose of external beam radiation therapy was reduced from 74 to 60 Gy, and the duration of concurrent HU was correspondingly reduced. The new regimen was much better tolerated. The median survival for the group as a whole was 30 months. Within this small study, there were no significant differences in survival, regional control, or local control between the 2 groups. CONCLUSIONS: Lower doses of concurrent parenteral HU and hyper-fractionated radiation therapy are tolerable and promising.

Aged↗

PubMed2006

Preliminary multi-institutional prospective pathologic and molecular studies support preservation of sublevel IIB and level IV for laryngeal squamous carcinoma with clinically negative neck.

Level II-IV selective neck dissection, often performed bilaterally, has become the procedure of choice for elective dissection of the clinically negative (N0) neck in the treatment of laryngeal cancer. The most significant morbidity of this procedure is dysfunction of the accessory nerve, incurred by the necessity of mobilization and retraction of the nerve in order to remove the contents of sublevel IIB. Other morbidity includes possible injury to the phrenic nerve and chylous fistula. These complications are associated with the dissection of level IV. A number of prospective multi-institutional studies of the distribution of cervical lymph node metastases in the neck indicate that lymph nodes in sublevel IIB and level IV are rarely involved in cases of laryngeal cancer with N0 neck. Information was obtained by the study of neck dissection specimens by conventional light microscopy, and by molecular analysis of the specimens. Molecular analysis reveals a significant number of metastases that are not discovered by light microscopy, and is thus essential for this type of evaluation. The authors conclude that these preliminary studies indicate that it is safe and appropriate to eliminate dissection of sublevel IIB and level IV from the elective neck dissection performed for laryngeal cancer with N0 neck. This practice will reduce both operating time and morbidity, particularly accessory nerve dysfunction, without compromising the oncologic result. Further prospective studies are needed to confirm these conclusions.

Carcinoma, Squamous Cell↗

PubMed2006

Evolution of the management of laryngeal cancer.

The treatment of laryngeal cancer has evolved through several phases, starting with wide extirpative surgical resection, and evolving through an era of conservation surgery and, finally, planned treatment using modalities of irradiation, chemotherapy and surgery in various combinations. Attempts to extirpate laryngeal cancer date to the nineteenth century, but only by the mid-twentieth century did advances in anesthesia, blood transfusion and antibiotics, make this surgery safe and reliable. Techniques of partial laryngectomy by external approach developed in the second half of the twentieth century, and endoscopic use of the laser refined the concept and provided a new paradigm for surgical treatment, particularly for early lesions. During most of this era, radiation was employed as an alternative method of treatment, with surgery reserved for salvage of radiation failure. By the last decade of the twentieth century, and to the present time, the value of combined modality therapy, using planned combinations of irradiation, chemotherapy and surgery became the standard of care for advanced laryngeal cancer, permitting maximal laryngeal preservation with the highest attainable cure rates.

Antineoplastic Agents↗

PubMed2006

Neck dissection: then and now.

The significance of metastatic disease in the lymph nodes of the neck as a critical independent prognostic factor in head and neck cancer has long been appreciated. Although 19th century surgeons attempted to remove involved cervical lymph nodes at the time of resection of the primary cancer, a systematic approach to en bloc removal of cervical lymph node disease, described in detail by Jawdyński in 1888 and popularized and illustrated by Crile in the early 20th century, provided consistent and more effective treatment, and forms the basis of our current techniques. During the first half of the 20th century, developments included preservation of the accessory nerve in selected cases, elective neck dissection performed in association with resection of various primary tumors, bilateral neck dissection and limited neck dissection. The greatest impetus to the status of radical neck dissection came from Martin, whose technique consisted of resection of all lymph nodes from level I-V together with the accessory nerve, internal jugular vein, sternocleidomastoid muscle and various other structures in a single block of resected tissue. Martin's technical precepts were followed until the latter part of the 20th century when modifications in technique began to find general acceptance. The first description of an effective technique of modified radical neck dissection was published in Spanish by Suárez, in 1963. This technique, which preserves important structures, such as the internal jugular vein, sternocleidomastoid muscle and accessory nerve, was refined and popularized by various authors who published their results in the English language literature during the period from 1964 through 1990 and beyond. Modified or "functional" neck dissection avoids much of the morbidity of radical neck dissection while achieving equivalent degrees of control of regional disease in properly selected cases. By the late 20th century, the concept of selective neck dissection, consisting of resection of only the nodal groups at greatest risk for metastasis from a given primary site, was studied and developed. These limited dissections are now widely employed for elective, and in properly selected cases, therapeutic treatment and staging of the neck, and have been proposed for limited cervical recurrences after various chemoradiation protocols. Prospective studies have demonstrated similar rates of neck recurrence and survival after elective selective neck dissection compared to elective modified radical neck dissection. Other modifications and factors applied to treatment of cervical lymph node disease include the use of adjuvant and neo-adjuvant radiation and chemotherapy, a revised system for classification of neck dissections, the identification of various adverse prognostic factors such as extracapsular spread and extranodal soft tissue deposits, application of sentinel lymph node biopsy to staging of the neck, the use of immunohistochemical and molecular techniques for identification of lymph node metastases not detectable by light microscopy, and the possibility of endoscopic neck dissection. The authors conclude that neck dissection, as evolved over the past century, is a fundamental tool in management of patients with head and neck cancer, but is still a work in progress.

Head and Neck Neoplasms↗

PubMed2005

Neck dissection: past, present and future?

With the exception of distant metastasis, the presence of cervical lymph node metastasis is the single most adverse independent prognostic factor in head and neck squamous cell carcinoma. Surgical removal of metastatic cervical lymph nodes had been attempted during the late nineteenth century, with varying techniques and poor results. A systematic approach to en bloc removal of cervical lymph node disease, described in detail by Jawdyński at the end of the nineteenth century and popularized and illustrated by Crile in the early twentieth century, provided consistent and more effective treatment and forms the basis of our current techniques. The concepts of radical neck dissection, employed extensively by Martin, were followed with almost religious consistency by most head and neck surgeons until the late twentieth century, when the principles of 'functional' neck dissection, developed by Suárez and popularized by Bocca, Gavilán, Ballantyne, Byers and others, led to the acceptance of modified radical neck dissection as treatment for lymph node disease in various stages. More recently, selective neck dissection, involving removal of nodes confined to the levels at greatest risk of metastasis from primary tumours at various sites, has become accepted practice for elective and, in some instances, therapeutic treatment of the neck. In the future, sentinel lymph node biopsy and the use of molecular pathological analyses may be employed to predict the presence of occult cervical disease, thus directing therapy to patients at greatest risk and sparing those without regional metastasis.

Carcinoma, Squamous Cell↗

PubMed2005

Management of the N0 neck--reference or preference.

For patients with squamous cell carcinoma of the upper aerodigestive tract, appropriate management of the regional lymph nodes is an important and often controversial issue that has significant influence on survival. Over the years radical treatment either by surgery or radiotherapy contributed to improvement in prognosis. Recently, a more conservative approach has achieved a similar level of cancer control with less morbidity. This review considers the issues of selection of patients for treatment of the neck, choice of modality and extent of therapy, treatment of the contralateral neck, management of recurrence and influence of the site and status of the primary lesion.

Carcinoma, Squamous Cell↗

PubMed2005

Elective and therapeutic selective neck dissection.

Selective neck dissection is a modification of the more comprehensive modified radical or radical neck dissection that is designed to remove only those nodal levels considered to be at risk for harboring nodal metastases. The role of selective neck dissection continues to evolve: while initially designed as a staging and diagnostic procedure for patients without clinical evidence of nodal disease, a growing body of literature suggests that selective neck dissection has a therapeutic role in patients with clinical and histologic evidence of nodal metastases. The rationale behind selective neck dissection, its application in the clinically negative but histologically node-positive neck and the extended application of selective neck dissection in patients with clinical evidence of nodal disease are discussed.

Carcinoma, Squamous Cell↗

PubMed2005

New molecular diagnostic methods in head and neck cancer.

Initial cancer evaluation includes assessment of histologic appearance, tumor grading, assessment of lymph node status, and presence of metastasis. However, traditional diagnostic methods such as histopathology and radiology are not sensitive enough to detect small numbers of cancer cells and are limited in their ability to predict response to treatment. Recently, there has been considerable progress in molecular diagnostics in these areas. Using molecular-based technologies, it is now possible to detect cancer early in asymptomatic individuals, identify minimal residual disease at histopathologic normal surgical margins, more precisely assess tumor burden in cancer patients, and more accurately assess the prognosis of the patients. Examples of these applications in the evaluation of head and neck cancer are reviewed here. However, despite the great promise of these new molecular approaches for cancer detection, much of the current technology limits their implementation into routine clinical use.

Biomarkers, Tumor↗

PubMed2004

Techniques for radiofrequency ablation of head and neck tumors.

OBJECTIVES: To describe the various techniques that have been developed for application of radiofrequency ablation in the palliative treatment of recurrent and advanced head and neck malignant tumors. DESIGN: Case series with a follow-up of 3 to 18 months. SETTING: Faculty practice, research protocol, tertiary care academic medical center. PATIENTS: Fifteen treatments were administered over a 3-year period to 12 patients with advanced and/or recurrent tumors. Eleven tumors were squamous cell carcinomas of the oral cavity, oropharynx, and maxillary sinus, and 1 tumor was a medullary thyroid carcinoma. Three of the 12 patients were treated on 2 separate occasions. Patients were selected as a referred sample and sent specifically for treatment with radiofrequency ablation because they were not candidates for the standard curative options of radiation or surgery. No patient refused enrollment, nor were any patients withdrawn because of adverse events. INTERVENTION: Radiofrequency ablation is a method of localized hyperthermia resulting in tissue necrosis. Ninety to 150 W of energy is applied, achieving intratumoral temperatures of 60 to 110 degrees C for 5 to 15 minutes per ablation. Techniques have been developed to apply radiofrequency ablation under direct vision, endoscopically, percutaneously, and with ultrasound and computed tomographic guidance. RESULTS: The radiofrequency ablation probe was accurately placed and treatment administered on 15 occasions. No perioperative deaths occurred. One patient suffered a stroke. Subjective patient improvement was reported with regard to pain (n=9), appearance (n=3), and function (n=4).

Aged↗

PubMed2002

Radiofrequency ablation of head and neck tumors: dramatic results from application of a new technology.

BACKGROUND: Radiofrequency ablation (RFA) is a new treatment modality used over the past decade predominantly in the treatment of unresectable liver tumors. We find no prior reported series on the use of RFA for malignant tumors of the head and neck. METHODS: Four patients with recurrent tongue tumors not amenable to standard surgical or radiation therapy were treated with RFA administered transorally, endoscopically, or percutaneously. RESULTS: There was no perioperative mortality. Significant palliation was achieved consisting of substantial reduction in tumor size and alleviation of tumor-induced pain. One patient has survived for 8 months with no progression of tumor. Three patients had complications, including line sepsis, pneumonia, and enlargement of an orocutaneous fistula. CONCLUSIONS: RFA was relatively straightforward to apply, achieved substantial palliation, and was associated with minimal perioperative morbidity and no mortality. It might easily be combined with other therapies such as chemotherapy, immunotherapy, or radiation. Further investigation is necessary and ongoing.

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PubMed2002