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W J Richtsmeier

Publications and source records attributed to W J Richtsmeier.

At least 19 recordsLinked to original sources
PubMed1998

Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer.

BACKGROUND: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS: Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS: Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS: Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

Aged↗
PubMed1998

Identification of sialyl Lewis-x in squamous cell carcinoma of the head and neck.

BACKGROUND: Sialyl Lewis-x (sLx) is a cellular adhesion molecule (CAM) that has been implicated in the inflammatory reaction and cancer metastasis. The sLx is the carbohydrate ligand of endothelial-selectin (E-selectin), an inducible vascular endothelial CAM. The role of sLx has been investigated in several cancers, and its presence has been correlated with advanced disease stage, decreased disease-free survival, and greater metastatic potential. A recent study has found that cultured head and neck (HN) squamous cell carcinoma (SCC) cell lines express sLx and that binding of these cells to cytokine activated endothelium correlates with the endothelial expression of E-selectin. The purpose of this study was to identify sLx in the tumors of patients with HNSCC and to see if the presence of sLx correlated with disease status. METHODS: We performed immunohistochemical (IHC) staining to detect the sLx antigen using the monoclonal antibody (MAb) KM-93. Eighty-two specimens of HNSCC that were obtained at the time of resection or biopsy were analyzed for sLx staining patterns and intensities. The clinical outcomes of survival, disease-free interval, and incidence of distant metastasis were then assessed to determine whether there was a correlation with sLx tumor expression. In addition, we analyzed specimens from metastatic HNSCC sites for expression of sLx. RESULTS: The sLx expression was identified in 62% of the primary tumor specimens and 87% of the metastatic tumor specimens analyzed by IHC. The staining pattern in the HNSCC tumors differed from that seen in normal squamous epithelium but was variable in both intensity and distribution. The sLx expression in the metastatic sites was higher than in the primary sites in 67% of the specimens (10 of 15). There was no correlation between sLx staining and disease status. CONCLUSIONS: The results of this study demonstrate that sLx is present in HNSCC and supports the data that show that sLx may play a role in the metastasis of HNSCC. Future studies are warranted to evaluate the role of sLx, E-selectin, and other CAMs in HNSCC.

Adolescent↗
PubMed1998

Long-term experience with endoscopic staple-assisted esophagodiverticulostomy for Zenker's diverticulum.

The authors have previously described the endoscopic staple-assisted esophagodiverticulostomy (ESED) technique for treatment of Zenker's diverticulum. In the initial series of six patients, ESED was shown to be safe and effective in the short term, with a significant reduction in hospital stay and convalescence as compared with other surgical techniques. This report documents the authors' long-term experience with ESED (average follow-up, 9.3 months; range, 1.5 to 25 months) and discusses the long-term results of this therapy, technical issues, and variations they have utilized, as well as the advantages and limitations of this approach. Thirty-six patients with Zenker's diverticula have been treated from March 1995 to March 1997. In 34 of the patients, ESED was accomplished, resulting in successful resolution of preoperative symptoms in 32 (94%). Two patients had persistent dysphagia after initial ESED; a revision ESED was successfully performed without complication in both. Two patients were unable to be treated with ESED because of inability to expose the diverticulum with the Weerda laryngoscope. Oral liquid diet has been resumed, on average, 0.8 days after surgery (range, 0 to 4 days), with solid diet resumed by day 5 (range, 1 to 14 days). The average hospital stay has been 1.3 days (range, 1 to 4 days). There have been no postoperative deaths, infections, or airway difficulties. Perioperative morbidity to date has included one case of iatrogenic pharyngeal perforation, one postoperative fever, one transient true vocal fold paralysis, and two dental injuries, with no long-term sequelae. The results support the use of ESED as the initial treatment of choice for patients with Zenker's diverticula.

Aged↗
PubMed1998

Fenretinide-induced apoptosis of human head and neck squamous carcinoma cell lines.

BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) has a high incidence of recurrence and associated second primary malignancy. The retinoid 13-cis-retinoic acid has been shown to be effective as both a chemopreventive and chemotherapeutic agent for HNSCC, but often with treatment-limiting toxicity. The synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide) (HPR) has significant antiproliferative activity against a number of animal and human malignancies and has been used in clinical trials as a chemopreventive agent in patients with breast and prostate cancer and oral leukoplakia. HPR has been shown to have a toxicity profile lower than that for other retinoids used in clinical trials. PURPOSE: The aim of this study was to investigate the effect of HPR on the growth of HNSCC cell lines in vitro. METHODS: Four HNSCC cell lines (JHU-011-SCC, JHU-020-SCC, JHU-022-SCC, and FaDu) were treated with a range of concentrations of HPR for various times. After HPR exposure, cell viability was determined by tetrazolium dye (MTT) colorimetric assay, comparing cell survival with that of untreated control cells. HPR-induced apoptosis was determined by flow-cytometric deoxyribonucleic acid cell-cycle analysis, ultrastructural analysis with electron microscopy, and deoxyribonucleic acid fragmentation detected by gel electrophoresis. RESULTS: HPR caused significant growth inhibition in three of the four HNSCC cell lines in a dose- and time-dependent fashion. In two cell lines (JHU-011-SCC, JHU-020-SCC) a significant antiproliferative effect was achieved between 1 and 2.5 micromol/L HPR after 72 hours of treatment. By deoxyribonucleic acid cell-cycle analysis, electron microscopy, and gel electrophoresis, HPR was shown to induce apoptosis in the JHU-011-SCC and JHU-020-SCC cell lines, but not in the FaDu cell line, which was insensitive to the growth inhibitory effect of HPR. CONCLUSIONS: This study has demonstrated that HPR reduces cell viability in HNSCC cells in vitro at clinically relevant doses, with the growth inhibition occurring through the induction of apoptosis.

Antineoplastic Agents↗
PubMed1997

Telescopic laryngeal and pharyngeal surgery.

Surgery of the hypopharynx and larynx has traditionally been performed with either direct, unaided vision or the operating microscope. We proposed to extend the surgical capability provided by angled Hopkins telescopes to the larynx and hypopharynx. Forty-eight cases in which rigid telescopes were employed primarily for intervention were reviewed. We found significant advantages of the telescopic system when performing procedures on surfaces that were not 90 degrees from the observer, such as the walls of the hypopharynx, the petiole of the epiglottis, the ventricle, and the posterior commissure. Both 30 degree and 70 degree telescopes were found useful, but required complementary instruments. The potassium titanyl phosphate laser's flexible fiber provided a distinct advantage in resecting lesions that presented on vertical surfaces. Telescopes also permitted the use of large instruments designed for intraperitoneal and intrathoracic surgery that blocked the view of the operating microscope. Telescopic pharyngeal and laryngeal visualization allowed surgical procedures complementary to more traditional forms of endoscopic surgery.

Adolescent↗
PubMed1996

Endoscopic staple-assisted esophagodiverticulostomy for Zenker's diverticulum.

We have used a new technique, endoscopic staple-assisted esophagodiverticulostomy (ESED), for the treatment of Zenker's diverticulum. This technique is a modification of the endoscopic approach first described by Mosher in 1917 and popularized by Dohlman and Mattsson in which the common wall between the esophagus and diverticulum was divided without mucosal closure. ESED differs in that an endosurgical stapler is used to create an esophagodiverticulostomy by dividing the common wall between the esophagus and diverticulum, with the mucosal and muscular edges sealed by the staples. We have performed this procedure in six patients, with no perioperative morbidity in any patient. All patients resumed oral intake on either the first or second postoperative day, with no evidence of fistula formation or mediastinitis. Hospital stay has averaged 2 days (range, 1 to 3 days). Patient follow-up after ESED averages 6 months and is available for five of the six patients treated. There has been complete resolution of pretreatment symptoms in these five patients, with resumption of regular diet between postoperative day 3 and day 14 (average, day 9). Our results demonstrate that ESED is a safe and effective treatment for Zenker's diverticulum. This endoscopic approach offers a number of advantages over previously used treatments for Zenker's diverticulum, including reduced morbidity, rapid convalescence, short hospitalization, brief operative time, and predictable resolution of symptoms.

Aged↗
PubMed1995

Interferon gamma enhances lymphokine-activated killer cell adhesion but not lysis of head and neck squamous cell carcinoma.

OBJECTIVES: To determine if treatment with recombinant human interferon gamma (rHuIFN-gamma) increases the adhesion to, and lysis of, head and neck squamous cell carcinoma (SCC) cells by lymphokine-activated killer (LAK) and peripheral blood mononuclear (PBM) effector cells in vitro and to evaluate the role of cell surface adhesion molecules in these processes. DESIGN: Two human SCC cell lines, JHU-020-SCC and JHU-022-SCC, were used. Lymphokine-activated killer cells were generated by interleukin-2 stimulation of PBM cells obtained from the hemapheresis blood donor packs of healthy individuals. Adhesion assays were performed to assess the level of binding of both effector populations to SCC cells, which were treated with either fresh media or rHuIFN-gamma (100 U/mL). Binding was measured by flow cytometric detection of effector cells labeled with fluorescein-conjugated anti-CD45 monoclonal antibody. Monoclonal antibodies to the cell adhesion molecules HLA-DR, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1 were used in blocking experiments to determine their contribution to the process of effector-SCC cell adhesion. Cytotoxicity experiments were performed using a colorimetric assay to determine the cytotoxic response generated by LAK and PBM cells against SCC cells, with and without prior rHuIFN-gamma treatment of the tumor cells. MAIN OUTCOME MEASURES: Effector cell binding level and percent cytotoxicity of SCC cells. RESULTS: Recombinant human interferon gamma treatment of JHU-020-SCC cells resulted in increased adhesion to both LAK cells and PBM cells (P < .001). The presence of anti-lymphocyte function-associated antigen 1 antibody resulted in elimination of the enhanced adhesion seen with rHuIFN-gamma pretreatment of SCC cells (P =.03), but antibody to intercellular adhesion molecule 1 and HLA-DR did not reduce the level of effector binding. The greatest cytotoxic response against both JHU-020-SCC and JHU-022-SCC was seen with LAK cells (P < or = .001). Pretreatment of tumor targets by rHuIFN-gamma (100 U/mL) resulted in no enhancement of cytotoxic response by either LAK or PBM cells; at the effector-target ratio of 30:1, there was a significant decrease in LAK cell-mediated cytotoxic response against rHuIFN-gamma-treated SCC cells (P < or = .02). CONCLUSIONS: Recombinant human interferon gamma treatment of head and neck SCC cells does increase binding of both LAK cells and PBM cells to tumor cells, in part via the lymphocyte function-associated antigen 1 ligand mechanism. The cytotoxic effect mediated by LAK cells against head and neck SCC cells is reduced after rHuIFN-gamma treatment, suggesting that the activity of this cytokine may be more important in regulating antigen-specific cytotoxic response mediated by cytotoxic T-lymphocytes.

Antineoplastic Agents↗
PubMed1995

Adhesion of head and neck squamous cell carcinoma to endothelial cells. The missing links.

OBJECTIVES: To examine the direct adhesion of head and neck squamous cell carcinoma (HNSCC) cells to basal and cytokine-activated human endothelial cells and to determine the cell adhesion molecules (CAMs) that mediate binding under these two conditions. DESIGN: Using an established model of tumor metastasis, the adhesion of four HNSCC cell lines to human umbilical vein endothelial cell (HUVEC) monolayers was examined, with and without pretreatment of HUVEC with tumor necrosis factor alpha (TNF-alpha). Surface CAM expression of HNSCC and HUVEC was determined by flow cytometry, and the results were used to direct studies of adhesion blocking using monoclonal antibodies. The contribution of various CAM to HNSCC binding of basal and cytokine-activated human endothelial cells in vitro was established. MAIN OUTCOME MEASURES: Adhesion of HNSCC to HUVEC monolayers was determined by a sodium chromate Cr 51-labeling assay in the presence or absence of monoclonal antibodies directed against specific CAMs. RESULTS: Four HNSCC cell lines were shown by flow cytometry to constitutively express the following CAMs: intercellular CAM-1, CD44, lymphocyte function-associated antigen-3, integrin chains alpha 6 and beta 1, and sialyl Lewis(x). No cell lines expressed lymphocyte function-associated antigen-1 or the integrin subunit alpha 4. Adhesion of JHU-011-SCC to TNF-alpha-activated HUVEC was enhanced above the untreated level in a time-dependent manner, with maximal adhesion at 12 hours. This increase correlated with endothelial-selectin expression by HUVEC and HNSCC expression of its ligand sialyl Lewis(x). Monoclonal antibody to sialyl Lewis(x) blocked the increased adhesion to TNF-alpha-activated HUVEC in two of four HNSCC cell lines. Monoclonal antibody to the alpha 6 integrin reduced binding to TNF-alpha-activated and non-activated HUVEC and to subendothelial matrix, but not to fibronectin. CONCLUSIONS: Studies of four HNSCC cell lines disclosed a consistent and distinctive pattern of adhesion molecule expression. The alpha 6 integrin subunit may be involved in direct adhesion to nonactivate and cytokine-activated endothelial cells or to laminin present on the endothelial surface. Sialyl Lewis(x) was more specifically involved in the increased adhesion to cytokine-activated HUVEC. This suggests that the sialyl Lewis(x)-endothelial-selectin ligand interaction may be important in facilitating HNSCC adhesion during metastasis to sites of active or chronic inflammation in vivo.

Carcinoma, Squamous Cell↗
PubMed1994

Otolaryngology--head and neck surgery.

p53 mutations are early events in the development of carcinoma of the head and neck. Cochlear implantation continues to influence rehabilitation of the profoundly deaf. Replacing cocaine with a combination of lidocaine and oxymetazoline for nasal procedures avoids potential abuse.

Otolaryngology↗
PubMed1994

Advantages of mandibular reconstruction with the titanium hollow screw osseointegrating reconstruction plate (THORP).

Alloplastic reconstruction following segmental mandibulectomy is a simple way to maintain mandibular segmental relationships, partially preserving form and function for many patients. This study is a retrospective review of 40 patients who had mandibular reconstruction with metal plates over a 6-year period (April 1986 through August 1992). The results of reconstruction with titanium hollow-screw osseointegrating reconstruction plates (THORP [n = 12]) and solid screw (SS) steel and titanium plates (n = 28) are compared. One THORP has been removed as compared to 14 SS plates. While the improved results with THORP may be attributable in part to its advanced design, the success of soft-tissue reconstruction and tumor extirpation are important factors in the early outcome seen in this series. Longer follow-up is needed to determine if THORP can serve as a permanent implant. THORP is the authors' method of choice for alloplastic mandibular reconstruction.

Adult↗
PubMed1994

Three-dimensional models for head and neck tumor treatment planning.

The authors have evaluated two types of practical maxillofacial model systems useful to the head and neck surgeon:1. plastic mandibular model generated by three-dimensional computerized tomography (CT) reconstruction, and 2. dental impression model of the maxilla. The first model is expensive and technology intensive; the second is simple but limited. Both three-dimensional models offer several advantages: 1. they provide segmental mandibular relationships that are not known because of oncologic restrictions or previous surgery; 2. they allow preoperative reconstructive planning including prosthesis fabrication and visualization of tumor extent not obvious by two dimensional imaging; and 3. they provide a permanent record for future needs or reconstructions. The disadvantages include cost, time, and possible inaccuracies secondary to image artifacts. We find both models to be of significant practical value in selected head and neck tumor patients.

Adenocarcinoma↗
PubMed1993

Induction of the intercellular adhesion molecule (ICAM-1) on squamous cell carcinoma by interferon gamma.

OBJECTIVE: To determine if the cell surface antigen, the intercellular adhesion molecule 1 (ICAM-1), is expressed on head and neck (H&N) squamous cell carcinoma (SCC) cell lines, and if treatment with interferon gamma (IFN-gamma) enhances the expression of the antigen. Intercellular adhesion molecule 1 mediates effector cell adhesion, activation, and function in inflammatory and immunologic reactions, and it may be important in the generation of antitumor immune surveillance and cytotoxicity against H&N SCC. MATERIALS: Four human SCC cell lines, JHU-011-SCC, JHU-020-SCC, JHU-022-SCC, and FaDu, established by explant technique from tumors of the upper aerodigestive tract, were utilized for these experiments. The cell lines were maintained and tested under standard tissue culture conditions. METHODS: Fluorescence-activated cell sorting and enzyme-linked immunosorbent assay were performed to identify the presence of ICAM-1 on the H&N SCC cell lines after staining with an anti-ICAM-1 monoclonal antibody (CD54). The SCC cell lines were treated with either fresh media or varying dosages (1 to 1000 U/mL) of recombinant human interferon gamma (rHuIFN-gamma) to determine constitutive and enhanced antigen expression. The kinetics of the response to rHuIFN-gamma were determined for the JHU-022-SCC cell line. The effect of the cytokines interleukin 1, interleukin 2, tumor necrosis factor alpha, and interferon alfa on ICAM-1 expression on JHU-022-SCC was also tested. MAIN OUTCOME MEASURE: Constitutive and enhanced ICAM-1 expression. RESULTS: Low levels of constitutive expression of ICAM-1 were identified on all four H&N SCC cell lines, with significantly enhanced expression seen after rHuIFN-gamma treatment (P = .0001). Maximally enhanced expression of the antigen on JHU-022-SCC occurred after treatment for 48 hours with 100 U/mL of rHuIFN-gamma (P = .0001). Induction of ICAM-1 expression was detectable after treatment with as little as 10 U/mL of rHuIFN-gamma (P < .001). Induction was also present after treatment with interleukin 1 and tumor necrosis factor alpha, but not with interleukin 2 or interferon alfa. CONCLUSIONS: Intercellular adhesion molecule 1 is constitutively expressed on H&N SCC cell lines, with enhanced expression seen after treatment with interferon gamma and other cytokines. This suggests that the antigen may be involved in the generation of an immune response against SCC of the H&N.

Carcinoma, Squamous Cell↗
PubMed1993

Comparison of intra-arterial and intravenous infusion of cisplatin for head and neck squamous cell carcinoma in a modified rat model.

To study intra-arterial infusion of chemotherapeutic agents, human squamous carcinoma cells were obtained from the FaDu cell line and were implanted in athymic rats (rnu/rnu). The xenografts were grown and then were reimplanted on a vascular pedicle and were completely isolated from the surrounding tissue. The vascular isolation of these pedicles was confirmed radiographically and histologically. After 26 days of growth, an osmotic pump was implanted to deliver either saline, intra-arterial cisplatin, or intravenous cisplatin to the vascular pedicle. Platinum levels were identified in the tumors following intra-arterial and intravenous infusions, demonstrating the usefulness of this model for delivery of antineoplastic agents. We were unable to detect differences between tumor groups for final tumor volume, tumor platinum levels, and tumor histology with the one-dose schedule used. We were able to show a remarkable uniformity of the tumor platinum levels with varying serum platinum levels with intra-arterial and intravenous infusion of cisplatin. The toxicity of each drug administration method was assessed by levels of renal platinum and rat serum creatinine and blood urea nitrogen. No differences in toxicity with the dose administrated. We believe the immunodeficient rat with a xenografted isolated vascular pedicle is an excellent model to study the effect of intra-arterial therapeutic modalities on head and neck squamous cell carcinoma.

Animals↗
PubMed1993

The effect of an acute fast on human head and neck carcinoma xenograft. Growth effects on an 'isolated tumor vascular pedicle' in the nude rat.

The effects of nutritional state on tumor growth are poorly understood. Most animal studies to date suggest an inhibitory effect of nutritional depletion on tumor growth and a stimulatory effect of nutritional repletion or overfeeding. We have modified an "isolated tumor vascular pedicle" model in the nude rat to study the growth and tumor-specific nutrient utilization of the FaDu cell line of human hypopharyngeal squamous carcinoma. Two weeks after tumor implantation, rats were randomized to either a fed or fasted study group for an additional 7 days. Tumors were significantly larger in the fasted group (0.602 +/- 0.215 g vs 0.362 +/- 0.104 g; P < .02). Whole blood nutrient gradients were determined across the tumor and systemic tissues in both groups. The nutrient gradients across these tissues were significantly different in the fed animals and approached statistical significance in the fasted animals. In addition, there appeared to be a greater utilization of glucose in the fed group (-0.401 +/- 0.904 mmol/L vs -0.298 +/- 0.589 mmol/L), while there was a greater production of lactate in the fasted group (0.798 +/- 0.518 mmol/L vs 0.046 +/- 0.639 mmol/L; P < .1). Flow cytometric analysis revealed no difference in the percentage of cells in any particular stage of the cell cycle between the two groups. These results suggest that the maintenance of adequate body weight may be beneficial not only to the nutrition of the cachectic tumor-bearing host but may also prevent a ketotic state or state of lipolysis that may be preferential to the tumor.

Acute Disease↗
PubMed1993

Case report.

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Diagnosis, Differential↗