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H Goepfert

Publications and source records attributed to H Goepfert.

At least 73 records · Page 4Linked to original sources
PubMed1995

Sequential loss of heterozygosity at microsatellite motifs in preinvasive and invasive head and neck squamous carcinoma.

Studies of sequential molecular alterations in noninvasive and invasive head and neck squamous carcinoma are few in number. Consequently, the genetic changes associated with the neoplastic transformation of these carcinomas have not been defined. To identify chromosomal alterations in preinvasive and invasive head and neck squamous carcinoma, we analyzed DNA from microdissected normal squamous epithelium, severe dysplasia, and invasive carcinoma samples from 20 patients for loss of heterozygosity (LOH) at microsatellite loci by multiplex PCR. Twenty-five microsatellite repeats on chromosomes 3p, 5q, 8p, 9p and 9q, 11q, 17p, 17q, and 18p and 18q regions were used. In informative cases, LOH in noninvasive lesions was observed in 9p (28%), 9q and 18q (10%), 11q and 17p (7%), and 3p and 18p (5%). A high incidence of LOH in invasive carcinoma was observed at 9p (72%), 8p (53%), 3p (47%), 9q (35%), and 11q (33%). LOH was also associated with DNA aneuploidy, high tumor stage, and poor histological differentiation. Our results indicate that: (a) the high incidence of LOH at loci on chromosomes 9p, 8p, 3p, 9q, and 11q implicate these regions in head and neck squamous carcinoma tumorigenesis; (b) 9p loci alterations are manifested in the early development of these tumors; (c) LOH is correlated with poor prognostic clinicopathological factors; and (d) LOH at 8p loci appears to be associated with the tumor's aggressive features.

Adult↗
PubMed1995

In vivo molecular therapy with p53 adenovirus for microscopic residual head and neck squamous carcinoma.

Developing gene therapy strategies may allow contemporary medicine to reassess its management of solid malignancies. We have demonstrated previously that the wild-type p53 adenovirus (Ad5CMV-p53) suppressed the growth of established tumors of the head and neck. In this paper we develop a microscopic residual model which mimics the postsurgical environment of head and neck cancer patients with advanced disease. Using this squamous cell carcinoma of the head and neck model, we prevented the establishment of tumors in nude mice in which tumor cells had been s.c. implanted by transiently introducing exogenous wild-type p53 via an adenoviral vector 2 days following tumor cell implantation. These effects were vector dose dependent but independent on the endogenous wild-type or mutated p53 status of the cells. Importantly, karyotypically normal and nontumorigenic fibroblast cell lines are inert to the p53 adenovirus treatment. These results pave the ground work for further development of molecular therapy for head and neck cancer and other solid malignancies.

Adenoviridae↗
PubMed1995

Laryngeal preservation for advanced laryngeal and hypopharyngeal cancers.

OBJECTIVE: To compare a single institutional experience with combination chemotherapy and radiation for laryngeal preservation with historical age-, sex-, stage-, and site-matched controls who underwent laryngectomy for cancer of the larynx or hypopharynx. DESIGN: Fifty-five patients with stage III or IV laryngeal and hypopharyngeal squamous carcinoma were prospectively entered into a protocol to receive three cycles of cisplatin (+/- bleomycin sulfate) and fluorouracil and radiation therapy from 1986 to 1991 (group 1). Following two cycles of chemotherapy, the clinical tumor response was assessed and responders received a third cycle of chemotherapy followed by definitive radiation therapy. Nonresponders underwent surgical salvage. Two patients in the surgical control group were matched to each protocol patient (n = 110, group 2) regarding site, stage, sex, and age (+/- 7 years) without knowledge of patient outcome. SETTING: A tertiary cancer referral center, The University of Texas M. D. Anderson Cancer Center, Houston. RESULTS: Following chemotherapy, the tumor response rate for group 1 was complete in 38% and partial in 31%. With a median follow-up of 24 months (group 1) and 37 months (group 2), the Kaplan-Meier 2-year disease-specific survival for group 1 and 2 was 63% and 74%, respectively (P = .251). Among group 1 patients, 67% retained their larynges. Local recurrences were more frequent among the laryngeal preservation group (P = .001), whereas distant metastasis was more frequent among controls (P = .35). Thirty-three percent (18/55) of group 1 patients required total laryngectomy. Examining these subsets of patients showed that of the 67% (n = 37) of patients who retained their larynges, their 2-year survival was 56%, not significantly different from their respective controls (n = 74), 71%. Additionally, 2-year survival among the 18 group 1 patients who required salvage laryngectomy was 75% as compared with 80% for their matched controls (n = 36). CONCLUSIONS: These results document the results of chemotherapy and radiation therapy in the treatment of patients with advanced laryngeal and hypopharyngeal cancers in preserving the larynx. Although local control is significantly compromised among these patients, there is no compromise in overall survival when combined with prompt surgical salvage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Split-thickness skin graft donor site management. A randomized prospective trial comparing a hydrophilic polyurethane absorbent foam dressing with a petrolatum gauze dressing.

OBJECTIVE: Traditionally, skin graft donor sites have been covered with fine-mesh gauze dressings, and a dry eschar has been allowed to form. Newer dressings that can provide a moist wound environment may facilitate reepithelialization. We compared a hydrophilic semipermeable absorbent polyurethane foam dressing that provides a moist wound environment with a petrolatum gauze dressing for donor sites. DESIGN: Prospective randomized trial; follow-up at 14 days. SETTING: Department of head and neck surgery in a tertiary care center. PATIENTS: Sixty-eight eligible patients received one of the two dressings. Harvested skin grafts were 0.375-mm (0.015-in) thick; donor site surface areas were recorded. At postoperative day 14, the dressings were removed, and wound epithelialization was scored: 1, none; 2, scattered or spotty; and 3, complete. Donor site and operative site pain intensities were assessed by a visual numeric scale: none (0) to the worst (100) experienced over the preceding 24-hour period. Pain scores were available for 58 patients. MAIN OUTCOME MEASURES: Dressings were compared based on these criteria: healing at 14 days, infection, and donor site and operative site pain. RESULTS: A healing score of 3 was seen in 37% (14/38) of patients with hydrophilic semipermeable absorbent polyurethane foam dressings and in 17% (5/30) of patients with petrolatum gauze dressings (P = .06) by day 14. Overall, however, mean healing scores were similar in both groups. Mean healing scores for the patients who received a hydrophilic semipermeable absorbent polyurethane foam dressing was 2.3 (SD = 0.6) vs 2.2 (SD = 0.6) for patients who received the petrolatum gauze dressing (P = .20). Numbers of days required for complete epithelialization in these groups were 20.6 (SD = 10.1) and 19.3 (SD = 5.1), respectively (P = .49). One infection occurred in the group who received the petrolatum gauze dressing. The mean maximum pain intensity scores were lower for those who were given the hydrophilic semipermeable absorbent polyurethane foam dressing on postoperative days 1 through 3 (P = .003, .03, and .04, respectively). Pain increased with a larger donor site surface area for the patients with the petrolatum gauze dressing but not for the patients with the hydrophilic semipermeable absorbent polyurethane foam dressing. CONCLUSIONS: The hydrophilic semipermeable absorbent polyurethane foam dressing appears to have potential advantages over the petrolatum gauze dressing; it produces less initial patient donor site discomfort and tends to produce more complete donor site healing by postoperative day 14.

Absorption↗
PubMed1995

Outcome and complications of extended cranial-base resection requiring microvascular free-tissue transfer.

OBJECTIVES: To determine the complications of extensive cranial-base resection requiring free-tissue transfer (FTT) and the effect of these resections on local control and survival among patients with malignant neoplasms of the skull base. BACKGROUND: Before the advent of FTT, cranial-base surgery was often limited by our inability to adequately repair defects comprising communication between the central nervous system and upper aerodigestive tract. The use of FTT in cranial-base resections was therefore assessed to determine whether the improved procedure (ie, extensive resections) would improve local control and prolong survival. DESIGN: A retrospective review of 39 consecutive craniofacial resections with FTT reconstruction in patients with malignant neoplasms involving the cranial base. PATIENTS: All 39 patients had malignant neoplasms, including 20 squamous cell carcinomas, eight basal cell carcinomas, two melanomas, two neuroendocrine carcinomas, two adenoid cystic carcinomas, and various other malignant neoplasms. Resections involved the anterior, middle, or posterior cranial fossa in 19 patients (49%), 10 patients (26%), and three patients (8%) of cases, respectively. The remaining seven surgeries (18%) involved resection of more than one of these cranial base sites. RESULTS: Early (< 14 days after surgery) complications occurred in 14 (36%) of 39 patients. Major complications included failure of microvascular anastomosis (n = 1), pneumonitis (n = 3), perioperative myocardial infarction (n = 1), and cerebrovascular accident (n = 1). The microvascular anastomosis failure was promptly treated with surgical intervention. Two patients (5%) experienced late postoperative complications; one had cellulitis at the donor site, and the other had pneumonitis. No perioperative deaths or complications such as meningitis, epidural abscess, or tension pneumocephalus occurred. The 2-year disease-specific survival rate was 55%, and the 2-year local control rate, 49%; both were determined by the Kaplan-Meier method. The nine patients who died of their disease had a median survival of 9 months. Log-rank testing showed that pathologically positive margins and transdural pathology were the most significant predictors of local recurrence and death of disease. CONCLUSIONS: Contemporary surgical approaches provide an opportunity for wide surgical excision of dura and skull-base structures that normally separate the intracranial and extracranial cavities. These major skull-base resections can be reconstructed safely and effectively with FTT. Patients with malignant neoplasms of the dura and skull base should be approached with the understanding that transdural disease portends an increased risk of local recurrence and death of disease.

Adolescent↗
PubMed1995

Glutathione s-transferase genotypes as risk factors for head and neck cancer.

BACKGROUND: Several enzymatic systems, including glutathione S-transferases, are involved in the metabolism of environmental agents. The absence of glutathione S-transferases mu (GSTM1) and theta (GSTT1) results in decreased detoxification of carcinogens, for example, chemicals in cigarette smoke. These metabolic deficiencies may predispose individuals to the development of smoking-related tumors, such as cancers of the lung, head and neck, and bladder. METHODS: The glutathione S-transferase genotypes of 186 previously untreated patients with squamous cell carcinoma of the head and neck and 42 healthy controls were determined with polymerase chain reaction (PCR) methodologies. Lymphocytes separated from heparinized peripheral blood or whole blood extracts served as sources of genomic DNA. The presence or absence of the gene-specific PCR products revealed the positive or negative genotypes, respectively. RESULTS: The absence of the GSTM1 genotype conferred an odds ratio of 2.37, and the 95% confidence interval (CI) was 1.20 to 4.67. The absence of the GSTT1 gene conferred an odds ratio of 1.47 (CI 0.71 to 3.02). In the population of 42 patients and their matched 42 controls, the absence of the GSTM1 and GSTT1 genotypes conferred odds ratios of 3.10 (CI 1.24 to 7.75) and 2.18 (CI 0.91 to 5.23), respectively. CONCLUSIONS: Despite the small study size, our preliminary data suggest that genetically determined factors of carcinogen metabolism may be associated with increased risk for head and neck cancer.

Base Composition↗
PubMed1995

RET proto-oncogene mutations in multiple endocrine neoplasia type 2 and medullary thyroid carcinoma.

The identification of RET proto-oncogene mutations in patients with MEN2 2 years ago was a watershed event in the management of this genetic cancer syndrome. The identification of a finite number of mutations that together causes more than 95% of hereditary and 15-25% of sporadic MTC has made it possible to develop simple and definitive tests to screen individuals at risk for this tumour syndrome. The impact of this technology is enormous. It is now possible to reassure 50% of family members at risk that they, and their children, do not have to worry about developing MTC. In the other 50% who are gene carriers, it is now possible to approach clinical management with greater certainty and plot strategies that are likely to result in a greater percentage of curative therapy. It seems likely that this technology will also have an impact on the management of sporadic MTC, although it is still too early to define a specific role for mutational analysis in these patients, except to exclude hereditary disease. The identification of specific mutations causative for MTC makes it possible to conceive future strategies for the treatment or prevention of MTC and to further extend the impact of these exciting findings.

Carcinoma, Medullary↗
PubMed1995

Clinical use of molecular information in the management of multiple endocrine neoplasia type 2A.

One hundred and ninety-seven members of 28 kindreds with multiple endocrine neoplasia type 2A (MEN 2A) were screened for RET proto-oncogene exon 10 and 11 mutations. Seventy-one known affected individuals had mutations of codons 609, 618, 620 or 634, whereas 53 unaffected individuals had no abnormalities. Nineteen out of 54 individuals of unknown status, mostly children, had RET mutations. Four of these children had thyroidectomy based on this analysis and were found to have C-cell abnormalities. We identified one false negative mutation analysis because of a codon 691 polymorphism. We conclude that RET mutational analysis is a cost-effective and accurate method for determination of gene carrier status in MEN 2A.

Amino Acid Sequence↗
PubMed1995

"Inflammatory pseudotumor": what is it? How does it behave?

Inflammatory pseudotumor, as a histologic diagnosis and carrying with it the prospect of a benign clinical course, is rather firmly entrenched as a pulmonary lesion. Extrapulmonic forms, however, are farraginous and, as reported, have included lesions having few, or even none, of the histologic features of those in the lungs. For those more closely aligned with the fibroblastic or myofibroblastic phase of the lung lesions, their biologic behavior can belie their histology in that they can be locally aggressive and metastasize as sarcomas. For those tumors in the upper airway, and especially in the abdomen, pathologists should be very circumspect in the use of inflammatory pseudotumor as a diagnosis, and clinicians should not be lulled into denying the extrapulmonic forms their due respect.

Granuloma, Plasma Cell↗
PubMed1995

Radiation therapy in the management of paragangliomas of the temporal bone.

The use of radiation therapy for the treatment of paragangliomas of the temporal bone remains controversial. Few studies exist that provide sufficient information on staging the long-term follow-up to clarify this issue. A retrospective study was undertaken of 38 patients with temporal bone paragangliomas treated with radiation therapy between 1956 and 1991. All patients received radiation therapy, either as a primary modality (14 patients), in combination treatment with surgery (13 patients), or as salvage therapy (11 patients). Mean disease stage (Fisch classification system) for each group was C2, B, and C1, respectively. The follow-up period ranged from 1 to 27 years (median 11.5 yr). Local control was achieved in 79% of the primary radiation therapy group, 100% of the combined treatment group, and 91% of the salvage therapy group. Complications resulting from radiation therapy were few and minor. This study demonstrates that the use of radiation therapy for temporal bone paragangliomas offers effective local control as a primary treatment modality, in combination with surgery, and as salvage therapy with few long-term complications.

Adult↗
PubMed1994

Postoperative radiotherapy for cutaneous melanoma of the head and neck region.

PURPOSE: To assess the efficacy and toxicity of elective-adjunctive radiotherapy given in five 6-Gy fractions to patients with cutaneous melanoma of the head and neck at high risk for local-regional relapse. METHODS AND MATERIALS: From 1983 to August 1992, 174 patients (132 men and 42 women) were enrolled. The ages ranged from 16 to 89 years (median: 54 years). One group (n = 79) received elective irradiation after wide local excision of lesions > or = 1.5 mm thick, or Clark's level IV-V, a second group (n = 32) received adjunctive irradiation after excision of primary lesions plus limited neck dissection, and a third group (n = 63) received irradiation after neck dissection for nodal relapse. Each group had a projected local-regional recurrence rate of approximately 50%. The radiotherapy consisted of five fractions of 6 Gy each, specified at Dmax, delivered twice a week, to a total dose of 30 Gy in 2.5 weeks. Electron beams of appropriate energies were used whenever possible. Junction lines between adjoining fields were moved twice to minimize dose heterogeneity. Patients were seen at regular intervals to assess disease status and therapy-related complications. Patients who relapsed were treated as indicated by the clinical status. RESULTS: With a median follow-up of 35 months, 111 of 174 patients were alive. The disease recurred above the clavicles only in six patients, at distant sites in 58 patients, and both local-regionally and at distant sites in nine patients. The actuarial 5-year local-regional control (LRC) and survival rates for the whole group were 88% and 47%, respectively. The thickness of the primary lesion, presence of more than three positive nodes, and extracapsular extension did not influence the LRC rate after radiotherapy (range: 85-92%). However, lesion thickness strongly affected the 5-year survival rate of group 1 patients (i.e., 100% for < or = 1.5 mm thick, but Clark's level IV, 72% for > 1.5-4 mm, and 30% for > 4 mm). In groups 2 and 3, the 5-year survival rate of patients with > three involved nodes was lower than that of patients with one to three positive nodes (23% vs. 39%). The acute tolerance to adjunctive radiotherapy was excellent. Late radiation complications were observed in only three patients. These were moderate neck fibrosis, mild ipsilateral hearing impairment, and transient exposure of external auditory canal cartilage. CONCLUSION: The safety of this hypofractionated radiotherapy regimen in the management of cutaneous melanoma was established in this study. The overall 5-year actuarial LRC rate of 88% was much higher than that of our historical group and that reported in the literature (50%). The survival rate of patients with lesion of 1.5-4 mm thickness was also higher than that observed in other series. Based on these results a prospective randomized study to further define the role of adjunctive postoperative radiotherapy is planned.

Adolescent↗
PubMed1994

Growth suppression of human head and neck cancer cells by the introduction of a wild-type p53 gene via a recombinant adenovirus.

Mutations of the p53 gene constitute one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN). In this study, we introduced wild-type p53 into two separate SCCHN cell lines via a recombinant adenoviral vector, Ad5CMV-p53. Northern blotting showed that following infection by the wild-type p53 adenovirus (Ad5CMV-p53), cells produced up to 10-fold higher levels of exogenous p53 mRNA than cells treated with vector only (without p53). Western blotting showed that the increased levels of p53 protein produced in the Ad5CMV-p53-infected cells were a reflection of p53 mRNA expression. In vitro growth assays revealed growth arrest following Ad5CMV-p53 infection as well as cell morphological changes consistent with apoptosis. In vivo studies in nude mice with established s.c. squamous carcinoma nodules showed that tumor volumes were significantly reduced in mice that received peritumoral infiltration of Ad5CMV-p53. These data suggest that Ad5CMV-p53 may be further developed as a potential novel therapeutic agent for SCCHN since introduction of wild-type p53 into SCCHN cell lines attenuates their replication and tumor growth.

Adenoviridae↗
PubMed1994

A single center's experience with 308 free flaps for repair of head and neck cancer defects.

Since its inception at our institution in 1988, microvascular reconstructive surgery has become an integral part of the treatment of head and neck cancer patients. This review of 308 free flaps performed over the last 4 years was done to evaluate the complication and flap loss rates and to investigate which factors may contribute to these rates. The overall complication rate was 36.1 percent, the vessel thrombosis rate was 6.8 percent, the flap loss rate was 5.5 percent, and the flap salvage rate was 19.0 percent. Multifactorial analysis of delayed reconstruction, tobacco use, alcohol consumption, previous radiation therapy, previous surgery, and use of vein grafts showed that only previous surgery and the use of vein grafts led to significantly higher rates of flap loss (p < 0.01 for both).

Adolescent↗
PubMed1993

Polymerase chain reaction-based restriction fragment length polymorphism analysis of the short arm of chromosome 3 in primary head and neck squamous carcinoma.

BACKGROUND: Deletion or loss of heterozygosity (LOH) at the polymorphic loci on the short arm of chromosome 3 has been reported in a large number of renal cell, small cell lung, non-small cell lung, and cervical carcinomas, suggesting the presence of one or more putative tumor suppressor genes at chromosome 3p. Similar studies in primary head and neck carcinoma are lacking. METHODS: To investigate the possibility of chromosome 3p deletions, the authors applied a polymerase chain reaction (PCR)-based, restriction fragment length polymorphism analysis, in conjunction with conventional Southern blot techniques, to DNA samples of matched normal mucosa and head and neck squamous cell carcinomas from 18 patients. The authors also assessed the merit of the PCR-based assay as a rapid screening tool, particularly in assaying limited tissue samples. RESULTS: Constitutional heterozygosity at the polymorphic loci varied in the 18 normal samples that the authors studied: 12 at the D3F15S2 locus (on telomeric 3p21), 7 at the D3S32 locus (on centromeric 3p21), and 9 at the THRB locus (on 3p24). In 18 matched carcinoma specimens, LOH (deletion) was observed at D3S32 in 0 of 7, at D3F15S2 in 9 of 12 (75%), and at THRB in 3 of 9 cases (33%). CONCLUSIONS: The results of the PCR-based assay and Southern blotting were completely concordant in all specimens the authors studied. This study indicates that deletion at 3p is a frequent abnormality in primary head and neck carcinoma and that the most common deletion region is telomeric to D3S32. The authors also observed an apparent correlation among poor histologic differentiation, DNA aneuploidy, and 3p deletions. Most poorly and moderately differentiated and aneuploid carcinomas manifested the 3p deletion. Therefore, the authors suggest an association between deletion at 3p and aggressive biologic behavior.

Aged↗