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Biomedical subjects

W M Koch

Publications and source records attributed to W M Koch.

53 records · Page 3Linked to original sources

p53 gene mutations as markers of tumor spread in synchronous oral cancers.

OBJECTIVE: To demonstrate how genetic mutations may be used as specific markers for the study and management of head and neck squamous cell carcinomas. DESIGN: Mutations in the p53 gene were identified by DNA sequencing in synchronous primary head and neck squamous cell carcinomas from one patient. The polymerase chain reaction and mutant-specific oligomer probes were used to detect rare tumor cells in surgical margins, lymph nodes, and swabs of the oral cavity. PATIENTS: Selected from a consecutive series of individuals with head and neck squamous cell carcinomas at a tertiary referral center. RESULTS: Two synchronous primary invasive cancers displayed different missense mutations in the p53 gene. The mutated sequence from one primary tumor was detected in metastases from both sides of the neck. Infiltrating cells from this biologically aggressive tumor were also detected by a polymerase chain reaction-based assay in a histologically normal surgical margin, accurately predicting tumor recurrence. CONCLUSIONS: p53 gene mutations were useful as molecular markers to distinguish between tumors in this case. The potential utility of detection of tumor cells in surgical margins and saliva by molecular techniques merits further investigation.

Biomarkers, Tumor↗

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↗

Gene mutations in saliva as molecular markers for head and neck squamous cell carcinomas.

BACKGROUND: Cancer is caused by the accumulation of mutations that activate proto-oncogenes and inactivate tumor suppressor genes. The result is a clonal expansion of genetically identical daughter cells that eventually become clinical malignancies. The specific mutations acquired by the progenitor cell are like a fingerprint carried by each cell of the tumor. These mutations can serve as very specific markers for the presence of tumor cells in a background of normal cells. METHODS: Mutations in the p53 gene recovered from head and neck squamous cell carcinomas were sequenced, and these altered DNA sequences were used retrospectively as tumor-specific genetic markers for cancer cells in the patient's saliva. Cloned p53 sequences amplified by the polymerase chain reaction from DNA extracted from banked preoperative saliva specimens were screened for the presence of tumor-specific mutations using radiolabeled oligonucleotide probes. RESULTS: We identified tumor-specific mutations in preoperative saliva samples of 5 of the 7 patients evaluated (71%). CONCLUSIONS: These results suggest a potential for clinical applications of this novel approach to cancer detection using gene mutations as molecular markers for carcinomas.

Biomarkers, Tumor↗

Transdermal fentanyl.

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Administration, Cutaneous↗

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↗

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↗

Swallowing disorders. Diagnosis and therapy.

Normal swallowing is a complex, rapid neuromuscular function. Causes for dysfunctional swallowing are protean. Appropriate workup includes a careful history, thorough physical examination of the head and neck, videofluorographic swallowing study, and when appropriate, manometry and endoscopy under anesthesia. Many swallowing problems are not easily curable or reversible, but most patients experience some improvement through the intensive efforts of a multidisciplinary team. The otolaryngologist-head and neck surgeon plays a key role in both evaluation of patients with dysphagia and in surgical intervention for selected cases of cricopharyngeal motor dysfunction and chronic aspiration.

Deglutition↗

Frameless stereotaxic integration of CT imaging data: accuracy and initial applications.

To evaluate the spatial accuracy of a rapid interactive method of transferring computed tomographic (CT) information between its display on a computer screen to its source (test object, operating field), a multidimensional computer combined with a six-jointed position-sensing mechanical arm was tested with a Plexiglas model consisting of 50 rods of varied height and known location, a plastic replica of the skull, and, subsequently, three patients. The median error value between image and real location was 1-2 mm (P > .95), regardless of the registration target sites. The accuracy, however, increased with the selection of widespread registration points, and 95% of all errors were below 3.70 mm (P > .95). The results compare favorably with the four most commonly used stereotaxic framed units. A misregistration error of 0.3-2.2 mm was found during intraoperative correlation between anatomy on the CT display and actual anatomic location in the operative field.

Child↗

Complications and early outcome of anterior craniofacial resection.

OBJECTIVE: To evaluate the complications of anterior craniofacial resection and correlate their impact with tumor control status. DESIGN: We conducted a retrospective review of 32 consecutive, operable patients' records seen over a 6-year period, requiring 35 procedures. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Twenty-six patients (81%) had malignant lesions (esthesioneuroblastoma, squamous cell carcinoma, and a group of miscellaneous malignant tumors). Six patients had various benign neoplasms. INTERVENTION: The surgical approach involved bifrontal craniotomy coupled with lateral rhinotomy in 19 cases (61%), facial degloving in 10 cases (32%), a total rhinectomy in one case, and endoscopic sinusectomy without facial incision in two cases. OUTCOME MEASURE: Clinically noted complications and oncologic outcome. RESULTS: There was one avoidable perioperative death indirectly associated with the patient's procedure. Nine patients suffered significant intracranial neurological complications such as tension pneumocephalus and delayed epidural abscess. All of these complications were managed successfully. Of patients with malignant tumors, 13 (52%) are alive with no evidence of disease and one is alive with recurrence after a mean follow-up period of 28.9 months. The 10 patients who succumbed to disease had a mean postoperative survival of 22.9 months. CONCLUSIONS: In contrast to the perspective of only a decade ago, we conclude that craniofacial resection is a relatively safe, versatile, and effective procedure for surgical management of tumors involving the anterior skull base.

Adult↗

Utility of immediate on-site cytopathological procurement and evaluation in fine needle aspiration biopsy of head and neck masses.

The utility of on-site microscopic evaluation of fine needle aspirates (FNAs) of the head and neck was assessed by comparing the diagnostic yield in 336 specimens obtained with immediate on-site cytopathological procurement and evaluation to that achieved in 548 cases performed without immediate on-site evaluation. Three hundred six (91%) of 336 immediate evaluation specimens were adequate for cytopathologic diagnosis, compared to 391 (71%) of 548 specimens not evaluated immediately (P < .001, chi-squared test). The higher satisfactory rate in immediate evaluation cases was related primarily to 1. immediate reaspiration of the masses until sufficient cytopathologic material was obtained for diagnosis; and 2. optimal specimen preparation. It is concluded that immediate on-site cytopathological procurement and evaluation of fine needle aspirates of head and neck masses is a valuable practice which assures a higher yield of adequate specimens compared to biopsies taken without immediate evaluation. The technique of immediate on-site evaluation of FNAs is discussed and a cost-benefit analysis of immediate on-site evaluation of FNAs is presented.

Biopsy, Needle↗

Tympanoplasty in children. The Boston Children's Hospital experience.

Considerable controversy surrounds the subject of tympanoplasty in children. Conflicting opinions about the indications, patient selection, timing, and technique of surgery are supported by various published series of cases. The records of 64 consecutive tympanoplasty procedures performed at the Boston (Mass) Children's Hospital over a recent 6-year period were reviewed. The study was limited to cases of repair of uncomplicated perforation of pars tensa that did not require ossiculoplasty or mastoidectomy. Surgery was successful in 73% of cases. A number of factors that are postulated to affect the outcome of surgery have been analyzed to assess their utility in selecting successful surgical candidates. Only patient age at the time of surgery was found to have statistical significance. We conclude that tympanoplasty for repair of perforation is warranted for children 8 years of age and older.

Age Factors↗

Phase I-II study of advanced head and neck squamous cell carcinoma patients treated with recombinant human interferon gamma.

The association of immunodeficiency with head and neck squamous cell carcinoma has generated the concept of supplying immunologically active agents as a means of treating these cancers. One of the most active immunologic messengers is interferon gamma, which has been observed in our laboratories to also have a direct cytotoxic effect on cultures of squamous cell carcinoma derived from the head and neck. To test the feasibility of treating patients with advanced but resectable head and neck cancer with this agent, we designed a phase I-II trial of recombinant human interferon gamma using a 24-hour infusion repeated weekly for four times. In this study, both tumor and immunologic parameters were studied before and after treatment. Eight patients were entered into the study with the highest recombinant human interferon gamma dose attempted being 0.25 mg/m2 per 24 hours. Minimal side effects were observed. Three patients had clinically measurable responses, four had stabilization of disease, and one had progression while receiving treatment. Histopathologic results of treatment were similar to in vitro observations. Necrosis, as well as differentiation of tumor cells, was observed. In some tumors there was a marked decrease in cellularity without a change in tumor volume due to increased extracellular keratin deposition. Our study indicates that evaluation of adoptive immunotherapy trials in head and neck cancer needs to include parameters other than simple tumor regression as an end point, otherwise therapeutically important lymphokine-induced changes may be missed. Further evaluation of recombinant human interferon gamma and agents that induce human interferon gamma are warranted.

Adult↗

Lysis of squamous cell carcinoma via antibody-dependent cellular cytotoxicity.

We have developed a system in which antibody-dependent cellular cytotoxicity (ADCC) can be consistently demonstrated against squamous cell carcinoma (SCC) of the head and neck. Serum samples from patients with pemphigus vulgaris (PV) provided antibodies for ADCC. The effector cells were lymphocytes from the peripheral blood of healthy human donors. The SCC cell lines served as targets. Lysis of SCC, as measured by 51Cr release, was significantly enhanced by the presence of serum from patients with PV, but not by healthy human serum. Serum alone produced no target cell killing. Nonepithelial cell lines were not affected by the presence of PV antibodies. The results demonstrate that SCC is susceptible to ADCC. Thus, tumor-specific antibodies may have a role in the treatment of cancer of the head and neck. This system can serve as a positive control for further testing of ADCC against SCC.

Antibodies↗

Stevens-Johnson syndrome with supraglottic laryngeal obstruction.

Patients with the Stevens-Johnson syndrome or erythema multiforme exudativum may present to the otolaryngologist because of involvement of the mucosa of the upper aerodigestive tract. Stevens-Johnson syndrome is a symptom complex of uncertain cause that affects the eyes, skin, and mucous membranes throughout the body. The epithelial lesions progress from macules to bullae that desquamate, form pseudomembranes, and finally heal. Generally there is a prodromal period with fever and symptoms of an upper respiratory tract infection. The literature related to the otolaryngologic manifestations of the disease is reviewed and a case of Stevens-Johnson syndrome with early involvement of the supraglottic larynx is presented. The otolaryngologist should be aware of this syndrome and should be prepared to manage the possible airway compromise.

Adult↗

Induction of HLA-DR antigen on human squamous carcinoma by recombinant interferon gamma.

The antigen recognition system which plays the major role in immunologic attraction mechanisms, including graft rejection, is the class II major histocompatibility complex containing the HLA-DR locus. Few types of cells constitutively express this antigen, as it is a potent immunological activating signal usually confined to antigen processing cells, activated lymphocytes, and endothelium. Using indirect immunofluorescence, we have observed induction of the HLA-DR glycoprotein in selected head and neck squamous cell carcinoma tissue cultures treated with recombinant interferon gamma. This occurs in concert with growth arrest and morphological changes after rHuIFN-gamma treatment. This report describes the induction of a surface antigen that may have profound prognostic significance. Understanding the kinetics of HLA-DR induction will aid in the design and assessment of adoptive immunotherapy with rHuIFN-gamma.

Carcinoma, Squamous Cell↗

Carbon dioxide laser in removal of polytef paste.

Teflon injection is the most popular surgical technique for improvement of voice in patients with a unilaterally paralyzed larynx. The results with this method usually are good, but cases of overinjection with resultant poor voice, airway compromise, or both, do occur. The carbon dioxide laser has become a standard instrument for laryngeal surgery, and it might reasonably be used in attempts to correct the overinjected vocal cord. Realizing that Teflon could share flammable characteristics with other polymers, such as rubber and polyvinylchloride, we investigated the effect of the carbon dioxide laser on fresh polytef paste (Mentor O & O Inc, Hingham, Mass) before using it in a patient with an overinjected hemilarynx. Fresh paste was found to ignite after exposure to standard laser power at normal time settings, both in room air and in an oxygen-enriched atmosphere. To determine the effect of the laser on Teflon in situ, the paste was injected subcutaneously and intramuscularly into a rat. After a suitable interval of time, the Teflon was found to glow but not ignite when exposed to the laser under standard operating conditions. Only under high power in an oxygen-enriched environment did ignition occur. In our patient, the laser was used to incise the mucosa over the polytef granuloma, and standard microsurgical (nonlaser) techniques were used to complete the removal with good results. Laryngologists should be aware of the dangers of using the carbon dioxide laser on or near Teflon, especially in freshly injected vocal cords.

Carbon Dioxide↗