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Biomedical subjects

Eric M Genden

Publications and source records attributed to Eric M Genden.

At least 19 recordsLinked to original sources
PubMed2007

Interleukin-12 expression enhances vesicular stomatitis virus oncolytic therapy in murine squamous cell carcinoma.

OBJECTIVES: Replication-competent, vesicular stomatitis virus (VSV) has been demonstrated to be an effective oncolytic agent in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the use of combining these two approaches, an oncolytic VSV vector (rVSV-IL12) was designed to express the murine interleukin 12 (IL12) gene. This cytokine-carrying oncolytic virus was compared with an analogous noncytokine-carrying fusogenic virus (rVSV-F) in the treatment of murine SCC VII squamous cell carcinoma (SCC). STUDY DESIGN AND SETTING: The authors performed in vitro testing of recombinant VSV-F and recombinant VSV-IL12 in SCC cell lines. In vivo testing of multiple direct intratumoral injections of rVSV-F or rVSV-IL12 in an orthotopic floor of mouth murine model was performed. Each cell line was tested using rVSV-F or rVSV-IL12 at multiplicity of infection of 0.01. The ability of each virus to replicate was tested by real-time reverse transcriptase-polymerase chain reaction over 48 hours to determine viral copies of RNA. Cell survival was determined by MTT assay over 72 hours. IL12 expression by rVSV-IL12-treated cells was determined by enzyme-linked immunosorbent assay. RESULTS: Both viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. In an SCC VII orthotopic floor of mouth model in immunocompetent C3H/HeJ mice, multiple intratumoral injections with each virus caused a significant reduction in tumor volume when compared with saline injections alone. The rVSV-IL12-treated tumors showed a striking reduction in tumor volume when compared with rVSV-F and saline-treated tumors (P < .005). This striking reduction in tumor volume translated into a substantial survival benefit in rVSV-IL12-treated animals. No treatment-related toxicity was observed in either group. CONCLUSION/SIGNIFICANCE: rVSV-IL12 is a novel oncolytic vesicular stomatitis virus that effectively expresses IL12 and significantly enhances the treatment of head and neck murine carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of head and neck cancers.

Animals↗
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

Options for salvage after failed initial treatment of anterior vocal commissure squamous carcinoma.

Persistence or recurrent cancer in the anterior commissure (AC) after primary radiotherapy may remain localized to its pretreatment anatomical site. If so, endoscopic CO(2) laser excision, in experienced hands, may achieve complete tumor excision and result in cure for many patients. Occasionally, second and third recurrences may be similarly salvaged by further endoscopic surgery. The use of the vertical hemilaryngectomy is an alternative treatment for similar localized lesions, with a higher first time surgical tumor eradication rate, but with a more protracted hospitalization and a less satisfactory voice and swallowing outcome. In both types of such surgical salvage, CT scanning must demonstrate no evidence of cartilage invasion or destruction. When there is evidence of minimal thyroid cartilage invasion, then the supracricoid partial laryngectomy is an alternative conservation option, and is likely to result in a cure, with the retention of a voicing larynx without a stoma. When the tumor has increased in size from the original pretreatment dimension and/or site, then imaging must be used to identify possible cartilage invasion, in which case the likelihood of tumor eradication by endoscopic or external vertical partial laryngectomy is highly unlikely. The indications for the routine use of total laryngectomy for the treatment of recurrent or persistent cancer involving the AC must be reviewed; there is current evidence that cure can be achieved by a less radical procedure. However, total laryngectomy may remain the only treatment option for advanced or aggressive first time recurrence, or in patients who develop subsequent recurrence following previous less aggressive surgery (endoscopic or external).

Carcinoma, Squamous Cell↗
PubMed2006

Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: is it necessary for all?

In the absence of large-scale randomized trials evaluating dissection versus observation of the involved neck after neoadjuvant chemoradiotherapy, there is a need to collect data that will either support or ultimately refute a role for planned posttreatment neck dissection. A significant percentage of patients with extensive (N2 or N3) neck disease who demonstrate a complete response to chemoradiation therapy may harbor residual occult metastases, and identification of this subset of patients remains a clinical challenge. Because surgical salvage rates are greatly diminished when occult nodal disease becomes clinically manifest, planned posttreatment neck dissection is advocated but may not be necessary in all patients. The role of positron emission tomography chemoradiotherapy (PET-CT) in this scenario remains unproven but holds promise in being able to identify which patients may be harboring residual disease in the neck after chemoradiotherapy. The implementation of as yet unidentified molecular tumor markers in combination with PET-CT may ultimately prove to be effective in identifying patients who will best benefit from posttherapy neck dissection. Correlation of imaging results and pathologic node status will be important in determining the accuracy and, therefore, the value of this imaging modality for predicting the presence or absence of residual disease.

Carcinoma, Squamous Cell↗
PubMed2006

Preoperative selective venous sampling for nonlocalizing parathyroid adenomas.

INTRODUCTION: Preoperative parathyroid adenoma localization allows for a minimally invasive surgical approach. Current methods used for adenoma localization include ultrasound, sestamibi scan, and occasionally magnetic resonance imaging (MRI). In cases in which an adenoma is not localized after a radiologic work-up, the surgeon must perform a four-gland exploration. Preoperative selective venous sampling (SVS) has been described as a safe and clinically effective method to localize a parathyroid adenoma after failed exploration. The purpose of this study was to evaluate the efficacy of SVS as a primary localization technique in cases where conventional localization techniques have failed. MATERIALS AND METHODS: Fourteen patients with nonlocalizing parathyroid adenomas after ultrasonography, sestamibi scanning, and MRI were retrospectively reviewed. Eight patients underwent SVS prior to surgery and six patients underwent a four-gland neck exploration without preoperative SVS. The two groups were assessed for accuracy of the SVS in localizing the adenoma, operative time, length of hospitalization, and complications. RESULTS: All of the patients in the study underwent successful uncomplicated surgical parathyroidectomy. The SVS proved accurate in preoperatively localizing the adenoma in 7 of 8 patients and allowed for a minimally invasive approach in 87% of patients. The mean operative time was 33 minutes for the SVS group and 67 minutes in the non-SVS group. None of the patients in either group experienced procedural complications. CONCLUSION: This study suggests that preoperative SVS may represent a safe and effective method of preoperatively localizing the nonlocalized parathyroid adenoma. In cases where conventional radiologic techniques fail to localize an adenoma, SVS may obviate the need for a four-gland exploration.

Adult↗
PubMed2006

Allograft tracheoplasty technique for management of refractory tracheal stenosis.

OBJECTIVES: Extensive tracheal airway defects represent a clinical dilemma. Although resection and reanastomosis and staged tracheoplasty may prove beneficial in some cases, recurrent or extensive circumferential stenosis remains a reconstructive challenge. We report the use of the allograft tracheoplasty technique for the reconstruction of recurrent, extensive defects of the trachea and cricoid. METHODS: Nine consecutive patients with recurrent tracheal stenosis were treated with the two-stage allograft tracheoplasty technique. A retrospective review was performed to evaluate for prior surgery, length of stenosis, surgical technique, and outcome. All 9 patients underwent multiple surgical procedures for acquired tracheal stenosis (average, 3.4 procedures) before undergoing the allograft tracheoplasty technique. Before surgery, all patients were tracheotomy-dependent. RESULTS: The patients were assessed 8 to 39 months after allograft tracheoplasty. The primary airway disorders included postintubation stenosis (n = 6), surgical resection for malignancy (n = 1), and idiopathic stenosis (n = 2). Three defects involved 30% to 60% of the cricoid cartilage, and 4 defects were complete circumferential tracheal defects. Five patients underwent an island deltopectoral flap for closure of the tracheoplasty site. One patient had a superficial wound infection at the cartilage recipient site, and 1 patient had a hematoma at the deltopectoral flap donor site. All 9 patients were successfully decannulated without shortness of breath, stridor, or recurrent stenosis at the time of follow-up. CONCLUSIONS: Allograft tracheoplasty is a new technique for the reconstruction of recurrent tracheal stenosis. It appears to be reliable for extensive airway defects that are refractory to conventional tracheoplasty techniques.

Adult↗
PubMed2006

Role of the island deltopectoral flap in contemporary head and neck reconstruction.

OBJECTIVES: The deltopectoral flap (DP) was originally described 40 years ago for head and neck reconstruction. Since that time, use of pedicled myocutaneous flaps and free tissue transfer has supplanted the DP flap as a first-line reconstructive tool. The island DP flap, a variation of the DP flap wherein the skin bridge is de-epithelialized, provides a source of thin and pliable tissue that can be useful for select head and neck reconstruction. The purpose of this review is to assess the utility of the island DP flap in contemporary head and neck reconstruction. METHODS: A retrospective review of 16 consecutive cases utilizing the island DP flap was performed. Indications, complications, and outcome were reviewed in an effort to determine the role of the island DP in contemporary head and neck reconstruction. RESULTS: Sixteen island DP flap procedures were successfully performed in 16 patients for a variety of reconstructions, including esophageal, laryngeal, cutaneous, and pharyngeal defects. The donor skin paddles averaged 22.4 cm2 (range, 14 to 40.8 cm2). There were no recipient site complications; however, there was 1 donor site hematoma that was managed with drainage. In all 16 cases, the island DP flap provided an appropriate source of donor tissue for reconstruction of limited defects of the pharynx, esophagus, and skin of the neck. CONCLUSIONS: The island DP flap is a reliable donor site that provides an excellent source of thin and pliable tissue for limited defects of the head and neck.

Adult↗
PubMed2005

Referral guidelines for suspected cancer of the head and neck.

OBJECTIVE: To identify the impact of referral guidelines for head and neck cancer on the economics and effectiveness of the delivery of care. METHODS: A retrospective review of the literature was performed to examine the current referral guidelines and referral models that have impacted the delivery of care. RESULTS: Advances in technology and changes in the diagnostic work up of head and neck cancer require that common symptoms and presentations of head and neck cancer are made available to primary care physicians to improve the expeditious referral of head and neck cancer patients. CONCLUSION: Physician awareness and symptom guidelines may prove effective in expediting the care of patients with head and neck cancer.

Head and Neck Neoplasms↗
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

Reepithelialized orthotopic tracheal allografts expand memory cytotoxic T lymphocytes but show no evidence of chronic rejection.

BACKGROUND: Acute rejection of mouse tracheal allografts is characterized by infiltration of the lamina propria with CD4+/CD8+ T cells that leads to the destruction of the epithelium and luminal obliteration. The donor epithelium is progressively replaced by recipient-derived epithelium. Once allograft reepithelialization has occurred, immunosuppression can be withdrawn without inciting acute rejection. We hypothesize that reepithelialization will also prevent chronic rejection of the trachea after withdrawal of immunosuppression. METHODS: BALB/c tracheal grafts were transplanted orthotopically into allogeneic C57BL/6 recipients. Allografted mice were nonimmunosuppressed for 10 or 100 days or immunosuppressed with cyclosporine A continuously for 50 days and then withdrawn from immunosuppression for an additional 50 days. In addition, grafts from this group were then heterotopically retransplanted into isogenic C57BL/6 or allogeneic BALB/c recipients to assess their immunogenicity. RESULTS: Cyclosporine A-treated mice showed no signs of chronic rejection or priming of cellular immunity as measured by proliferation and cytokine secretion in a mixed leukocyte reaction. However, there was a notable expansion of memory CD8+ T cells specific for donor major histocompatibility complex. When these tracheal allografts were retransplanted heterotopically into C57BL/6 or BALB/c, they demonstrated reduced responses toward BALB/c and primed responses toward C57BL/6, respectively. These results suggest that the grafts express a chimeric phenotype consisting of both BALB/c and C57BL/6 antigens. CONCLUSION: These observations suggest that long-term withdrawal of immunosuppression does not lead to chronic tracheal rejection even in the presence of alloantigen specific cytotoxic T-lymphocyte responses and that the reepithelialized grafts may contain donor elements that impact the generation of immunity.

Animals↗
PubMed2005

Grisel's syndrome in head and neck practice.

Grisel's syndrome is a rare condition of uncertain etiology characterized by a non-traumatic atlanto-axial subluxation, secondary to an infection in the head and neck region. The authors discuss the history, pathogenesis, terminology, classification, clinical characteristics, diagnosis, treatment, prognosis and prevention of this syndrome.

Anti-Bacterial Agents↗
PubMed2005

Management of mandibular invasion: when is a marginal mandibulectomy appropriate?

There has been a great deal of controversy regarding the appropriate method of management of oral cavity and oropharyngeal tumors that invade the mandible. The inability to acquire intraoperative bone margins can make the decision process complex. Preoperative imaging offers several advantages, however, there is no single modality that has proven accurate. Intraoperative assessment has been suggested as a method of evaluation, however, this approach does not allow for preoperative planning. The following is a review of the current literature regarding mandibular invasion and the indications for a marginal mandibulectomy.

Carcinoma, Squamous Cell↗
PubMed2005

The role of the anterolateral thigh flap for pharyngoesophageal reconstruction.

OBJECTIVE: To elucidate the advantages and disadvantages of the anterolateral thigh flap (ALTF) for pharyngoesophageal reconstruction, we assessed this donor site and compared it with the radial forearm free flap (RFFF). DESIGN: Retrospective medical chart review. SETTING: Tertiary care referral center. SUBJECTS: Twenty-three consecutive patients who underwent pharyngoesophageal reconstruction using an ALTF or RFFF. INTERVENTION: Pharyngoesophageal reconstruction. MAIN OUTCOME MEASURES: Patient medical charts were assessed for age, histopathological diagnosis, preoperative treatment, surgical defect, tracheoesophageal speech, flap survival, donor and recipient site complications, and swallowing function. RESULTS: Twenty-three patients (12 who underwent reconstruction with ALTF and 11 with RFFF) were included in the study. Both donor sites provided adequate tissue for pharyngoesophageal reconstruction; however, the RFFF group demonstrated a higher rate of postoperative donor site complications including skin graft loss and extremity edema and stiffness. Postoperatively, the ALTF group demonstrated no gait disturbance and no donor site complications. All 23 patients in both groups were able to tolerate an unrestricted oral diet; however, 3 patients who underwent reconstruction with an RFFF experienced cervical esophageal stenosis, whereas only 1 patient with an ALTF experienced stenosis. CONCLUSION: In this preliminary series, the ALTF represents an excellent source of tissue for pharyngoesophageal reconstruction and is associated with a lower rate of donor site morbidity and anastomotic stenosis compared with the RFFF donor site.

Adult↗
PubMed2005

Reepithelialization of orthotopic tracheal allografts prevents rejection after withdrawal of immunosuppression.

Prior work has demonstrated that immunosuppressed orthotopic tracheal allografts undergo progressive reepithelialization over a 48-day period with recipient-derived tracheal epithelium. We hypothesized that reepithelialization of tracheal allografts would prevent rejection after withdrawal of immunosuppression. BALB/c murine tracheal grafts were transplanted orthotopically into either syngeneic or allogeneic C57/BL6 recipients. The recipients were either not immunosuppressed, immunosuppressed with cyclosporine A (10 mg/kg per day) continuously, or immunosuppressed for 48 days and then withdrawn from immunosuppression. The grafts were assessed for acute and chronic rejection 10 days and 50 days after immunosuppression withdrawal. The immunosuppressed allograft recipients maintained a ciliated epithelium acutely and chronically after immunosuppression withdrawal. Ten days after immunosuppression withdrawal, there was a mild cellular infiltrate, which resolved 50 days after withdrawal. Electron microscopy, lymphocyte subpopulation assays, and lamina propria analysis demonstrated that immunosuppression withdrawal did not result in tracheal allograft rejection. In vitro and in vivo assessments did not demonstrate evidence of systemic or local immune tolerance. We conclude that reepithelialization of orthotopic tracheal allografts with recipient-derived mucosa prevents rejection of allograft segments. Tracheal transplantation may require only transient immunosuppression, which can be withdrawn after tracheal reepithelialization.

Animals↗
PubMed2005

Fiberoptic endoscopic-assisted diverticulotomy: a novel technique for the management of Zenker's diverticulum.

Endoscopic diverticulotomy is rapidly becoming the procedure of choice for treatment of Zenker's diverticulum. The endoscopic approach has resulted in significant decreases in patient morbidity, time to resumption of oral intake, and overall cost as compared with open treatment. However, a small but significant patient population is unable to accommodate the rigid laryngoscope and therefore requires open treatment. We present a novel technique, flexible fiberoptic endoscopic-assisted diverticulotomy, for the management of patients who are unable to undergo rigid endoscopy.

Aged↗
PubMed2005

Treatment considerations for head and neck cancer in the elderly.

As life expectancy increases, surgeons can expect an increasing number of geriatric patients. In turn, the number of elderly patients presenting with head and neck cancer is likely to increase. Management of this subpopulation has become a source of debate because there is a paucity of randomized data regarding the effect of age on treatment response and morbidity associated with the treatment of head and neck cancer. The management of head and neck cancer in the elderly depends on the patient's age and general condition, the stage of disease, the effects of treatment on quality of life (such as speech and swallowing), patient and family wishes, and active physician participation in continued care. Elderly patient's comorbid conditions need appropriate attention especially if surgery is to be undertaken. The aim of this review is to examine the current literature in an attempt to develop an approach to the treatment of the elderly patient with head and neck cancer and to define the pertinent issues that require further study.

Age Factors↗
PubMed2004

The role of intraoperative rapid parathyroid hormone monitoring for predicting thyroidectomy-related hypocalcemia.

OBJECTIVE: To determine if the intraoperative rapid parathyroid hormone (PTH) assay can be used to accurately predict postoperative calcium levels following total or completion thyroidectomy. DESIGN: A prospective study. SETTING: Tertiary care referral center. PATIENTS: One hundred four patients following a total or completion thyroidectomy.Intervention Intraoperative rapid plasma PTH levels were determined for patients undergoing a total or completion thyroidectomy. MAIN OUTCOME MEASURES: Parathyroid hormone levels were recorded after the induction of anesthesia, before excision, and 5, 10, and 20 minutes after thyroidectomy. Postoperative calcium levels were monitored every 6 hours until hospital discharge. Intraoperative PTH levels were correlated with postoperative calcium levels and clinical symptoms of hypocalcemia. RESULTS: Twenty-two patients (21.2%) required short-term postoperative calcium supplementation, and 2 (1.9%) required long-term calcium replacement. There was a statistically significant difference between those patients requiring calcium replacement and those who did not require calcium supplementation, for postoperative total calcium level (7.2 vs 8.1 mg/dL [1.8 vs 2.0 mmol/L]; P<.001) and ionized calcium level (3.76 vs 4.36 mg/dL [0.94 vs 1.09 mmol/L]; P<.001). In addition, the PTH changes from baseline demonstrated statistically significant differences at 5, 10, and 20 minutes after the excision between the 2 groups (P<.005). In those patients requiring calcium supplementation, 14 (64%) of 22 demonstrated a change in PTH level at 20 minutes of greater than 75% from baseline, and in those patients who did not require postoperative calcium supplementation, 61 (74%) of 82 demonstrated a change in PTH level of less than 75% from baseline (P<.005). CONCLUSION: Intraoperative PTH monitoring may be a useful tool in identifying patients who will not require postoperative calcium supplementation following total or completion thyroidectomy.

Adolescent↗